Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - A systematic review with meta-analysis and trial sequential analysis.

PubMed

Sjövall, Fredrik; Perner, Anders; Hylander Møller, Morten

2017-04-01

To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Thirteen RCTs (n = 2633) were included; all were judged as having high risk of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95-1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area, indicating that a 20% relative risk difference in mortality may be excluded between the two groups. For the other outcomes, TSA indicated lack of data and high risk of random errors. This systematic review of RCTs with meta-analysis and TSA demonstrated no differences in mortality or other patient-important outcomes between empirical mono- vs. combination antibiotic therapy in adult ICU patients with severe sepsis. The quantity and quality of data was low without firm evidence for benefit or harm of combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Family Therapy and Group Counseling: Therapeutic Factors and the Chemically Dependent Adolescent.

ERIC Educational Resources Information Center

Weis, David M.; And Others

1988-01-01

Suggests a combination of family therapy and group counseling in the treatment of chemically dependent adolescents. Explores the development of the individual in the family and examines the literature on therapeutic factors present in group and family therapy. Includes example for practitioners interested in combining group and family therapy…

Neutron therapy for salivary and thyroid gland cancer

NASA Astrophysics Data System (ADS)

Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

2016-08-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Neutron therapy for salivary and thyroid gland cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gribova, O. V., E-mail: gribova79@mail.ru; Choynzonov, E. L., E-mail: nii@oncology.tomsk.ru; National Research Tomsk Polytechnic University, Lenina Avenue 30, Tomsk, 634050

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Music Therapy: A Career in Music Therapy

MedlinePlus

... combination with doctoral study in related areas. Degree Equivalent Training in Music Therapy P ersonal qualifications include ... the student completes only the coursework necessary for equivalent music therapy training without necessarily earning a second ...

Single vs. combination immunotherapeutic strategies for glioma

PubMed Central

Chandran, Mayuri; Candolfi, Marianela; Shah, Diana; Mineharu, Yohei; Yadav, Vivek; Koschmann, Carl; Asad, Antonela S.; Lowenstein, Pedro R.; Castro, Maria G.

2017-01-01

Introduction Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific featuresmay substantially improve upon existing treatments. Areas covered Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review we discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While we describe a limited number of combination immunotherapies which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration. PMID:28286975

A Systematic Review of Clinical Practice Guidelines' Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism.

PubMed

Kraut, Eyal; Farahani, Pendar

2015-12-04

Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

PubMed

Dournon, E; Mayaud, C; Wolff, M; Schlemmer, B; Samuel, D; Sollet, J P; Levasseur-Rajagopalan, P

1990-10-01

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

PubMed Central

Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n = 35) and control group (n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications. PMID:29785195

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

PubMed

Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

Combination Controversies: Checkpoint Inhibition Alone or in Combination for the Treatment of Melanoma?

PubMed

Warner, Allison Betof; Postow, Michael A

2018-05-15

The immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have dramatically improved outcomes for patients with metastatic melanoma; however, not all patients benefit from monotherapy with these agents. To address this issue, complementary combinations of immunotherapy are increasingly being explored as a strategy to improve outcomes. However, combinatorial approaches come with heightened risk of toxicity. In this review, we highlight combinations for which there are prospective data from clinical trials. The combinations discussed include ipilimumab plus anti-programmed death 1 agents, ipilimumab plus granulocyte-macrophage colony-stimulating factor, checkpoint inhibitor plus talimogene laherparepvec, ipilimumab plus chemotherapy, checkpoint inhibitor plus BRAF/MEK targeted therapy, and checkpoint inhibition plus radiation therapy. We discuss data regarding the efficacy and toxicity of combination therapy, and we identify clinical scenarios that may favor treatment with combination therapy.

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

PubMed

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months. Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Persistent use of against-label statin-fibrate combinations from 2003-2009 despite United States Food and Drug Administration dose restrictions.

PubMed

Alford, Julie C; Saseen, Joseph J; Allen, Richard R; Nair, Kavita V

2012-07-01

To describe the prevalence of prescribing against-label statin-fibrate combination therapy. Retrospective cohort study. Medstat MarketScan Commercial Claims and Encounter database. Adults (aged 18-89 yrs) who were prescribed statin-fibrate combination therapy between January 1, 2003, and June 30, 2009, had pharmacy claims demonstrating two or more concurrently filled prescriptions for a statin and a fibrate, and had continuous insurance enrollment for at least 12 months. Claims data were used to identify patients with dyslipidemia based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. National Drug Codes were used to describe concurrent statin-fibrate combination therapy. The primary outcome was recent use of against-label statin-fibrate combination therapy, defined as use during the last 18 months (January 1, 2008-June 30, 2009) of the study period. Patients were stratified according to statin and dosage to identify against-label combination use (e.g., simvastatin > 10 mg/day with gemfibrozil). Within the recent-use period, 131,394 patients were prescribed concurrent statin-fibrate combination therapy; of these patients, 13,420 (10.2%) had against-label therapy. Simvastatin-gemfibrozil accounted for 8978 (66.9%) of all against-label combinations. Of all 9877 simvastatin-gemfibrozil combinations prescribed in the recent-use period (both on-label and against-label use), 8978 (90.9%) were against label. The secondary outcome was prevalence of against-label statin-fibrate combination therapy on an annual basis: 15.5% in 2003, 18.7% in 2004, 9.1% in 2005, 8.3% in 2006, 9.2% in 2007, and 9.8% in 2008. Against-label statin-fibrate combination therapy continues to be prescribed despite established United States Food and Drug Administration (FDA) dose restrictions. Nearly every time the simvastatin-gemfibrozil combination was prescribed, it was against label because simvastatin exceeded the maximum dose restriction. Updated simvastatin labeling in June 2011 includes additional maximum dose restrictions and new contraindications, which include gemfibrozil. Different approaches in clinical practice are needed to ensure adherence with the revised FDA labeling. © 2012 Pharmacotherapy Publications, Inc. All rights reserved.

Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease.

PubMed

Rojas-Reyes, Maria Ximena; García Morales, Olga M; Dennis, Rodolfo J; Karner, Charlotta

2016-06-06

The long-acting bronchodilator tiotropium and single-inhaler combination therapy of inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) are commonly used for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than administering the individual components. To assess relative effects of the following treatments on markers of exacerbations, symptoms, quality of life and lung function in patients with COPD.• Tiotropium plus LABA/ICS versus tiotropium.• Tiotropium plus LABA/ICS versus LABA/ICS. We searched the Cochrane Airways Group Specialised Register of Trials (April 2015), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal and reference lists of relevant articles. We included parallel, randomised controlled trials (RCTs) lasting three months or longer conducted to compare ICS and LABA combination therapy in addition to inhaled tiotropium versus tiotropium alone or combination therapy alone. We independently assessed trials for inclusion, then extracted data on trial quality and outcome results. We contacted study authors to ask for additional information. We collected trial information on adverse effects. Tiotropium plus LABA/ICS versus tiotropiumWe included six studies (1902 participants) with low risk of bias that compared tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy versus tiotropium alone. Investigators found no statistically significant differences in mortality between treatments (odds ratio (OR) 1.80, 95% confidence interval (CI) 0.55 to 5.91; two studies; 961 participants), a reduction in all-cause hospitalisations with the use of combined therapy (tiotropium + LABA/ICS) (OR 0.61, 95% CI 0.40 to 0.92; two studies; 961 participants; number needed to treat for an additional beneficial outcome (NNTB) 19.7, 95% CI 10.75 to 123.41). The effect on exacerbations was heterogeneous among trials and was not meta-analysed. Health-related quality of life measured by St. George's Respiratory Questionnaire (SGRQ) showed a statistically significant improvement in total scores with use of tiotropium + LABA/ICS compared with tiotropium alone (mean difference (MD) -3.46, 95% CI -5.05 to -1.87; four studies; 1446 participants). Lung function was significantly different in the combined therapy (tiotropium + LABA/ICS) group, although average benefit with this therapy was small. None of the included studies included exercise tolerance as an outcome.A pooled estimate of these studies did not show a statistically significant difference in adverse events (OR 1.16, 95% CI 0.92 to 1.47; four studies; 1363 participants), serious adverse events (OR 0.86, 95% CI 0.57 to 1.30; four studies; 1758 participants) and pneumonia (Peto OR 1.62, 95% CI 0.54 to 4.82; four studies; 1758 participants). Tiotropium plus LABA/ICS versus LABA/ICSOne of the six studies (60 participants) also compared combined therapy (tiotropium + LABA/ICS) versus LABA/ICS therapy alone. This study was affected by lack of power; therefore results did not allow us to draw conclusions for this comparison. In this update, we found new moderate-quality evidence that combined tiotropium + LABA/ICS therapy compared with tiotropium plus placebo decreases hospital admission. Low-quality evidence suggests an improvement in disease-specific quality of life with combined therapy. However, evidence is insufficient to support the benefit of tiotropium + LABA/ICS for mortality and exacerbations (moderate- and low-quality evidence, respectively). Of note, not all participants enrolled in the included studies would be candidates for triple therapy according to current international guidance.Compared with the use of tiotropium plus placebo, tiotropium + LABA/ICS-based therapy does not increase undesirable effects such as adverse events or serious non-fatal adverse events.

Risks and safety of combination therapy for hypothyroidism.

PubMed

Jonklaas, Jacqueline

2016-08-01

Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

State-of-the-art: Immunosuppression and biologic therapy.

PubMed

Sandborn, William J

2010-01-01

Azathioprine and 6-mercaptopurine are orally administered immunosuppressive drugs which are effective for the treatment of Crohn's disease and ulcerative colitis. Azathioprine is rapidly converted to 6-mercaptopurine after administration. 6-Mercaptopurine is then either converted to the putative active metabolites, the 6-thioguinine nucleotides, or inactivated by the enzyme xanthine oxidase to 6-thiouric acid or alternatively inactivated to 6-methylmercaptopurine by the enzyme thiopurine methyltransferase. Thiopurine methyltransferase activity is genetically determined, with one in 300 patients having low or absent enzyme activity, one in 10 patients having intermediate enzyme activity, and 9 in 10 patients having normal enzyme activity. Patients with intermediate or low thiopurine methyltransferase activity are at risk for early leukopenia. Higher erythrocyte 6-thioguinine nucleotide concentrations are associated with a greater likelihood of clinical response. Azathioprine is modestly effective for Crohn's disease and ulcerative colitis. Toxicity associated with azathioprine includes infection and lymphoma. Anti-TNF therapy with infliximab, adalimumab, and certolizumab pegol is effective for induction and maintenance treatment of Crohn's disease, and infliximab is effective for ulcerative colitis. Toxicity associated with anti-TNF therapy includes infection and lymphoma. Combination therapy with infliximab and azathioprine is more effective for inducing and maintaining steroid-free remission and mucosal healing then monotherapy with either drug alone. Strategies to reduce immunogenicity of anti-TNF agents include combination therapy with azathioprine and administration of a loading dose followed by systematic maintenance dosing. Higher serum trough concentrations of infliximab occur more frequently in patients receiving combination therapy with azathioprine and are associated with better clinical outcomes. Combination therapy is associated with an increased relative risk of opportunistic infection, but is not associated with an increased absolute risk of serious infection. Clinical practice should change such that combination therapy with an anti-TNF agent and azathioprine replace azathioprine in patients failing first line therapy with mesalamine and/or steroids. Copyright © 2010 S. Karger AG, Basel.

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiniker, Susan M., E-mail: shiniker@stanford.edu; Reddy, Sunil A.; Maecker, Holden T.

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasismore » measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.« less

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis

PubMed Central

Wang, Jianrong; Lu, Wenxia; Li, Jingjing; Zhang, Rong; Zhou, Yuqing; Yin, Qin; Zheng, Yuanyuan; Wang, Fan; Xia, Yujing; Chen, Kan; Li, Sainan; Liu, Tong; Lu, Jie; Zhou, Yingqun; Guo, Chuan-Yong

2017-01-01

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs. β-blocker monotherapy, with inconsistent results. The aim of the present study was to assess the efficacy of the RAAS inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for hepatic vein pressure gradient (HVPG) reduction in cirrhosis. Studies were obtained using PubMed, Embase, Medline and Cochrane library databases up to July 2015, and the weighted mean difference (WMD) in HVPG reduction was used as a measure of treatment efficacy. In total, three studies (91 patients) were included. When compared to the β-blocker monotherapy, the RAAS inhibitor and β-blocker combination therapy resulted in a significant HVPG reduction [WMD 1.70; 95% confidence interval (CI): 0.52–2.88]. However, there was no significant difference in the heart rate reduction between the monotherapy and combination therapy groups (WMD −0.11; 95% CI: −3.51–3.29). In addition, no significant difference in the hemodynamic response was observed between the two groups (WMD 1.46; 95% CI: 0.93–2.30). In conclusion, the RAAS inhibitor and β-blocker combination therapy reduces portal hypertension significantly and to a greater extent than β-blocker monotherapy. Both therapies reduced the heart rate to similar levels; however, the RAAS inhibitor and β-blocker combination therapy reduced the mean arterial pressure to a greater extent. Due to the limited number of studies included, the data available do not allow a satisfactory comparison of adverse events. Moreover, further larger-scale trials are required in order to strengthen the results of the present study. PMID:28565796

Combined treatment in punctate inner choroidopathy

PubMed Central

Terelak-Borys, Barbara; Zagajewska, Katarzyna; Jankowska-Lech, Irmina; Tesla, Piotr; Grabska-Liberek, Iwona

2016-01-01

Purpose The purpose of this study was to describe a combination treatment for choroidal neovascular (CNV) membrane, secondary to punctate inner choroidopathy (PIC). Patient and methods A 44-year-old female patient was diagnosed with PIC complicated by the development of recurrent juxtafoveal neovascular membrane. The treatment included a sequence of monotherapy regimens: systemic steroid therapy, photodynamic therapy, and intravitreal injections of vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF). Owing to the CNV membrane resistance to various types of monotherapy, a combination treatment consisting of local injections of steroid underneath the Tenon’s capsule and intravitreal anti-VEGF injections was used. Results Systemic steroid therapy resulted in rapid local improvement with a very short remission period. No positive effects of photodynamic therapy were observed. Sequential anti-VEGF injections led to remission periods of several months. Permanent regression of CNV membrane was achieved following combined local application of steroid and intravitreal anti-VEGF injections. Conclusion A combination treatment including steroid and anti-VEGF medication characterized by anti-inflammatory and antiangiogenic effects may be a very beneficial option for the treatment of recurrent CNV membrane as a complication of PIC. PMID:27729795

Dacarbazine combined targeted therapy versus dacarbazine alone in patients with malignant melanoma: a meta-analysis.

PubMed

Jiang, Guan; Li, Rong-Hua; Sun, Chao; Liu, Yan-Qun; Zheng, Jun-Nian

2014-01-01

Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27-2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14-1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10-1.36), vomiting (combined RR = 1.73, 95% CI: 1.41-2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42-2.16) compared to the group for DTIC alone. These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.

FAST INdiCATE Trial protocol. Clinical efficacy of functional strength training for upper limb motor recovery early after stroke: neural correlates and prognostic indicators.

PubMed

Pomeroy, Valerie M; Ward, Nick S; Johansen-Berg, Heidi; van Vliet, Paulette; Burridge, Jane; Hunter, Susan M; Lemon, Roger N; Rothwell, John; Weir, Christopher J; Wing, Alan; Walker, Andrew A; Kennedy, Niamh; Barton, Garry; Greenwood, Richard J; McConnachie, Alex

2014-02-01

Functional strength training in addition to conventional physical therapy could enhance upper limb recovery early after stroke more than movement performance therapy plus conventional physical therapy. To determine (a) the relative clinical efficacy of conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy for upper limb recovery; (b) the neural correlates of response to conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy; (c) whether any one or combination of baseline measures predict motor improvement in response to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Randomized, controlled, observer-blind trial. The sample will consist of 288 participants with upper limb paresis resulting from a stroke that occurred within the previous 60 days. All will be allocated to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Functional strength training and movement performance therapy will be undertaken for up to 1·5 h/day, five-days/week for six-weeks. Measurements will be undertaken before randomization, six-weeks thereafter, and six-months after stroke. Primary efficacy outcome will be the Action Research Arm Test. Explanatory measurements will include voxel-wise estimates of brain activity during hand movement, brain white matter integrity (fractional anisotropy), and brain-muscle connectivity (e.g. latency of motor evoked potentials). The primary clinical efficacy analysis will compare treatment groups using a multilevel normal linear model adjusting for stratification variables and for which therapist administered the treatment. Effect of conventional physical therapy combined with functional strength training versus conventional physical therapy combined with movement performance therapy will be summarized using the adjusted mean difference and 95% confidence interval. To identify the neural correlates of improvement in both groups, we will investigate associations between change from baseline in clinical outcomes and each explanatory measure. To identify baseline measurements that independently predict motor improvement, we will develop a multiple regression model. © 2013 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

2017-06-01

The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

The Clinical Management of Multiple Melanoma Brain Metastases: A Systematic Review

PubMed Central

Goyal, Sharad; Silk, Ann W.; Tian, Sibo; Mehnert, Janice; Danish, Shabbar; Ranjan, Sinthu; Kaufman, Howard L.

2017-01-01

Importance The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery and whole brain radiation. Several new classes of agents have revolutionized the treatment of metastatic melanoma allowing for subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving. Objective To review the current evidence regarding the treatment of MBM from melanoma. Evidence Review The Pubmed database was searched using combinations of search terms and synonyms for melanoma, brain metastases, radiation, chemotherapy, immunotherapy and targeted therapy published between January 1, 1995 and January 1, 2015. Articles were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a clinical trial, large observational study, or retrospective study focusing on melanoma brain metastases. Of 2243 articles initially identified, 110 were selected for full review. Of these, the most pertinent 76 articles were included. Findings Patients with newly diagnosed MBM can be treated with various modalities, either alone or in combination. Level 1 evidence supports the use of radiosurgery alone, whole brain radiation therapy (WBRT), and radiosurgery with WBRT. Though the addition of WBRT to SRS improves the overall brain relapse rate, WBRT has no significant impact on overall survival and has detrimental neurocognitive outcomes. Cytotoxic chemotherapy has largely been ineffective; targeted therapies and immunotherapies have reported to have high response rates and deserve further attention in the setting of larger clinical trials. Further studies are needed to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. Conclusions and Relevance At this time, the standard management for patients with MBM from melanoma includes SRS, WBRT, or combination of both. Emerging data exists to support the notion that SRS in combination with targeted therapies or immune therapy may obviate the need for whole brain radiation and prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. PMID:26181286

Is fixed combination therapy appropriate for initial hypertension treatment?

PubMed

Elliott, William J

2002-08-01

Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.

PubMed

LoRusso, Patricia M; Canetta, Renzo; Wagner, John A; Balogh, Erin P; Nass, Sharyl J; Boerner, Scott A; Hohneker, John

2012-11-15

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies. ©2012 AACR.

The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review

PubMed Central

Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein

2016-01-01

Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser’s wavelength and nanoparticle’s properties more animal studies and clinical trials are required as a lack of perfect studies PMID:27330701

Systemic and topical drugs for aging skin.

PubMed

Kockaert, Michael; Neumann, Martino

2003-08-01

The rejuvenation of aging skin is a common desire for our patients, and several options are available. Although there are some systemic methods, the most commonly used treatments for rejuvenation of the skin are applied topically. The most frequently used topical drugs include retinoids, alpha hydroxy acids (AHAs), vitamin C, beta hydroxy acids, anti-oxidants, and tocopherol. Combination therapy is frequently used; particularly common is the combination of retinoids and AHAs. Systemic therapies available include oral retinoids and vitamin C. Other available therapies such as chemical peels, face-lifts, collagen, and botulinum toxin injections are not discussed in this article.

The effect of combined therapies on recovery after acquired brain injury: Systematic review of preclinical studies combining enriched environment, exercise, or task-specific training with other therapies.

PubMed

Malá, Hana; Rasmussen, Camilla Pihl

2017-01-01

Acquired brain injuries (ABI) have devastating effects for the affected individual as well as society. Many studies have investigated the effect of different monotherapies. However, functional recovery is typically only partial. One possible strategy to promote a greater degree of recovery is to apply monotherapies in combination with one or more treatments. The objective of this systematic review is to investigate if approaches combining enriched environment (EE), exercise, or task-specific training with other monotherapies, further enhance the degree of recovery after ABI. Scopus, PsychINFO, and PubMed databases were searched in March 2016 with the following search strings: exercise (or) enriched environment (or) environmental enrichment (or) rehabilitation (and) traumatic brain injury (or) ischemia (or) stroke (and) rat (or) rodent. Studies were included if they (1) were in English, (2) used adult animals subjected to brain injury, (3) included EE, and/or exercise, and/or task-specific training as post-injury treatment strategies, (4) included at least one group receiving another monotherapy. Out of 2.168 hits, 29 studies fulfilled the inclusion criteria. Despite several trends for enhanced recovery after combined therapies, this systematic review of 29 studies does not indicate that combined therapies confer consistent combined effects on motor, cognitive, or cerebral recovery according to present criteria for combined effect. Combined treatments continue to provide hope for enhanced recovery after ABI, however, the research area is in its infancy. This systematic review does not provide conclusive evidence. This is likely due to sparse knowledge regarding optimal treatment parameters. Combined treatments, however, hold the best promise regarding treatment of the complex changes induced by ABI.

[Restoring of the speech functions in patients with aphasia in the early rehabilitation period of ischemic stroke].

PubMed

Kotov, S V; Belova, Yu A; Shcherbakova, M M; Chervinskaya, A D; Isakova, E V; Volchenkova, T V

To study the efficacy of combined therapy including daily sessions and two 10-day injections of the drug cellex in patients with aphasia in the early rehabilitation period of ischemic stroke (II). Forty patients in the early rehabilitation period of II in the basin of the left middle cerebral artery with moderate to severe aphasia were studied. Twenty patients received combined therapy, including daily sessions with a speech therapist-aphasiologist within 10 days using the improved method, then a self-study using educational materials and two 10-day injections of cellex. Other 20 patients received only speech therapy. To assess the efficacy of therapy, the automated "Program of examination of patients with aphasia", Goodglass-Kaplan scale, modified Rankin scale were used. There was a significant improvement of speech functions, communicative abilities and functional recovery (p<0.01) in patients of both groups. However, a significantly greater level of rehabilitation (p<0.05) was noted in patients treated with combined therapy included two courses of cellex. The results allow to recommend the inclusion of cellex in the complex rehabilitation of patients with post-stroke speech disorders.

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder

PubMed Central

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-01-01

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy. PMID:22696635

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder.

PubMed

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-04-19

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy.

Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

PubMed

2000-07-07

To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

PubMed Central

Jiang, Guan; Li, Rong-Hua; Sun, Chao; Liu, Yan-Qun; Zheng, Jun-Nian

2014-01-01

Background Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. Methods We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Results Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone. Conclusion These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion. PMID:25502446

Effects of low-dose light-emitting-diode therapy in combination with water bath for atopic dermatitis in NC/Nga mice.

PubMed

Kim, Chang-Hyun; Cheong, Kyung Ah; Lim, Won Suk; Park, Hyung-Moo; Lee, Ai-Young

2016-01-01

Light-emitting diode (LED) phototherapy and water bath therapy have beneficial effect on atopic dermatitis (AD)-like skin disease. However, not all current treatments work well and alternative therapies are need. The contribution of combination therapy with low-dose 850 nm LED and water bath was investigated on dermatophagoides farina (Df)-induced dermatitis in NC/Nga mice. Low-dose LED (10, 15, and 20 J/cm(2) ) irradiation, water bath (36 ± 1°C) were administered separately and together to the Df-induced NC/Nga mice in acrylic jar once a day for 2 weeks. Combined therapy with low-dose LED therapy and water bath therapy significantly ameliorated the development of AD-like skin lesions. These effects were correlated with the suppression of total IgE, NO, histamine, and Th2-mediated immune responses. Furthermore, combination therapy significantly reduced the infiltration of inflammatory cells and the induction of thymic stromal lymphopoietin (TSLP) in the skin lesions. The beneficial therapeutic effects of this combination therapy might regulate by the inhibition of various immunological responses including Th2-mediated immune responses, inflammatory mediators such as IgE, histamine, and NO, as well as inflammatory cells. The combination therapy of LED and water bath might be used as an efficacious, safe, and steroid-free alternative therapeutic strategy for the treatment of AD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Manual therapy, exercise therapy or combined treatment in the management of adult neck pain - A systematic review and meta-analysis.

PubMed

Fredin, Ken; Lorås, Håvard

2017-10-01

Neck pain is a common and often disabling musculoskeletal condition. Two therapies frequently prescribed for its management are manual therapy (MT) and exercise therapy (ET), and combining these treatment approaches are common. To assess whether or not combined treatment consisting of MT and ET is more effective than either therapy alone in relieving pain and improving function in adult patients with grade I-II neck pain. Systematic review with meta-analysis. A systematic search on EMBASE, MEDLINE, AMED, CENTRAL and PEDro were performed until June 2017. Randomized controlled trials with adult grade I-II neck pain patients were included if they investigated the combined effect of MT and ET to the same ET or MT alone, and reported pain intensity or disability on numerical scales. Quality of life was assessed as a secondary outcome. Quality of the included trials was assessed with the PEDro scale, and the quality of evidence was assessed with GRADE. 1169 articles were screened, and 7 studies were included, all of which investigated the addition of ET to MT. Only very small and non-significant between group differences was found on pain intensity at rest, neck disability, and quality of life at immediate post-treatment, 6 months, and 12 months follow-up. The quality of evidence was moderate for pain-at-rest outcomes and moderate too low for neck disability and quality of life outcomes. Combined treatment consisting of MT and ET does not seem to be more effective in reducing neck pain intensity at rest, neck disability or improving quality of life in adult patients with grade I-II neck pain, than ET alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

PubMed

Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-01-01

Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Systematic review on randomized controlled clinical trials of acupuncture therapy for neurovascular headache.

PubMed

Zhao, Lei; Guo, Yi; Wang, Wei; Yan, Li-juan

2011-08-01

To evaluate the effectiveness of acupuncture as a treatment for neurovascular headache and to analyze the current situation related to acupuncture treatment. PubMed database (1966-2010), EMBASE database (1986-2010), Cochrane Library (Issue 1, 2010), Chinese Biomedical Literature Database (1979-2010), China HowNet Knowledge Database (1979-2010), VIP Journals Database (1989-2010), and Wanfang database (1998-2010) were retrieved. Randomized or quasi-randomized controlled studies were included. The priority was given to high-quality randomized, controlled trials. Statistical outcome indicators were measured using RevMan 5.0.20 software. A total of 16 articles and 1 535 cases were included. Meta-analysis showed a significant difference between the acupuncture therapy and Western medicine therapy [combined RR (random efficacy model)=1.46, 95% CI (1.21, 1.75), Z=3.96, P<0.0001], indicating an obvious superior effect of the acupuncture therapy; significant difference also existed between the comprehensive acupuncture therapy and acupuncture therapy alone [combined RR (fixed efficacy model)=3.35, 95% CI (1.92, 5.82), Z=4.28, P<0.0001], indicating that acupuncture combined with other therapies, such as points injection, scalp acupuncture, auricular acupuncture, etc., were superior to the conventional body acupuncture therapy alone. The inclusion of limited clinical studies had verified the efficacy of acupuncture in the treatment of neurovascular headache. Although acupuncture or its combined therapies provides certain advantages, most clinical studies are of small sample sizes. Large sample size, randomized, controlled trials are needed in the future for more definitive results.

Breast Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Breast cancer treatment commonly includes various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy is influenced by clinical and pathology features. Get detailed information about breast cancer in this summary for clinicians.

Treatment of dyslipidemia in HIV-infected patients.

PubMed

Sekhar, Rajagopal V; Balasubramanyam, Ashok

2010-08-01

Patients infected with HIV are at high risk for dyslipidemia, insulin resistance and cardiovascular disease. Therapies to reverse these risks are complex, sometimes controversial, and not uniformly effective. Pathophysiology of the lipid abnormalities in HIV is discussed, including the causes of alterations in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and insulin resistance. We discuss the therapy of dyslipidemia in HIV using a combination of available clinical evidence and expert opinion based on extensive clinical experience, with discussions of lifestyle intervention and diet, conventional pharmacotherapy with lipid-lowering medications including statins, fibrates, niacin and thiazolidinediones for dyslipidemia, and newer therapeutic approaches including omega fatty acids, acipimox, growth hormone and leptin. A detailed understanding of the pathophysiology and rational or evidence-based approach to therapy of lipid abnormalities in patients infected with HIV. Treatment of dyslipidemia in patients with HIV is challenging and complicated by the risk of drug interactions. Appropriate therapy requires a sound understanding of pathophysiology and the principles of pharmacological and nonpharmacological therapeutic interventions. An evidence-based approach that combines lifestyle changes and drugs that are both safe and effective, singly and in combination, is described.

Two is better than one; toward a rational design of combinatorial therapy.

PubMed

Chen, Sheng-Hong; Lahav, Galit

2016-12-01

Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness of Behavioral Therapy for Chronic Low Back Pain: A Component Analysis.

ERIC Educational Resources Information Center

Turner, Judith A.; And Others

1990-01-01

Evaluated effects of group behavioral therapy including aerobic exercise, behavioral therapy alone, and aerobic exercise alone on pain and physical and psychological disability among mildly disabled chronic low-back-pain patients (n=96). The combined behavioral therapy and exercise group improved significantly more pretreatment to posttreatment…

Inappropriate combination of warfarin and aspirin.

PubMed

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-03-01

A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety

PubMed Central

Walkup, John T.; Albano, Anne Marie; Piacentini, John; Birmaher, Boris; Compton, Scott N.; Sherrill, Joel T.; Ginsburg, Golda S.; Rynn, Moira A.; McCracken, James; Waslick, Bruce; Iyengar, Satish; March, John S.; Kendall, Philip C.

2009-01-01

Background Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. Methods In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. Results The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Conclusions Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) PMID:18974308

Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety.

PubMed

Walkup, John T; Albano, Anne Marie; Piacentini, John; Birmaher, Boris; Compton, Scott N; Sherrill, Joel T; Ginsburg, Golda S; Rynn, Moira A; McCracken, James; Waslick, Bruce; Iyengar, Satish; March, John S; Kendall, Philip C

2008-12-25

Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) 2008 Massachusetts Medical Society

Efficacy and tolerability of rasagiline in daily clinical use--a post-marketing observational study in patients with Parkinson's disease.

PubMed

Reichmann, H; Jost, W H

2010-09-01

The MAO-B inhibitor rasagiline is indicated for the treatment of idiopathic Parkinson's disease (PD), and its use is supported by evidence from large-scale, controlled clinical studies. The post-marketing observational study presented here investigated the efficacy and tolerability of rasagiline treatment (monotherapy or combination therapy) in daily clinical practice. The study included patients with idiopathic PD who received rasagiline (recommended dose 1 mg, once daily) as monotherapy or combination therapy. The treatment and observation period was approximately 4 months. Outcome measures included the change from baseline in the Columbia University Rating Scale (CURS), the Unified PD Rating Scale fluctuation subscale, daily OFF time (patient home diaries) and the PD Questionnaire-39. Adverse drug reactions/adverse events (ADRs/AEs) and the physician's global judgement of tolerability and efficacy were also examined. Overall, 754 patients received rasagiline during the study. Patients treated with rasagiline (monotherapy or combination therapy) showed significant improvements from baseline in symptom severity (including classical motor and non-classical motor/non-motor symptoms) and quality of life (QoL). Patients receiving combination therapy also experienced significant reductions in daily OFF time. Tolerability was rated as good/very good in over 90% of patients. In daily clinical practice, monotherapy or combination therapy with rasagiline is able to improve PD symptoms, reduce OFF time, and improve QoL, whilst demonstrating favourable tolerability. In addition, rasagiline has a simple dosing schedule of one tablet, once daily, with no titration. These results are consistent with the pivotal rasagiline clinical studies (TEMPO, LARGO and PRESTO).

A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

PubMed Central

Gau, Susan Shur-Fen; Méndez, Luis; Montgomery, William; Monk, Julie A.; Altin, Murat; Wu, Shenghu; Lin, Chaucer C.H.; Dueñas, Héctor J.

2013-01-01

Abstract Objective The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods Literature databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success. PMID:23560600

A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).

PubMed

Pohl, Gerhardt M; Van Brunt, David L; Ye, Wenyu; Stoops, William W; Johnston, Joseph A

2009-06-08

Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy. Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for ADHD medication during the study period July 2003 to June 2004, and continuous enrollment 6 months prior to and throughout the study period. Dispensing events were grouped into 6 categories: atomoxetine (ATX), long-acting stimulants (LAS), intermediate-acting stimulants (IAS), short-acting stimulants (SAS), bupropion (BUP), and Alpha-2 Adrenergic Agonists (A2A). Events were assigned to calendar months, and months with combined use from multiple categories within patient were identified. Predictors of combination therapy for LAS and for ATX were modeled for patients covered by commercial plans using logistic regression in a generalized estimating equations framework to adjust for within-patient correlation between months of observation. Factors included age, gender, presence of the hyperactive component of ADHD, prior diagnoses for psychiatric disorders, claims history of recent psychiatric visit, insurance plan type, and geographic region. There were 18,609 patients identified representing a total of 11,886 months of therapy with ATX; 40,949 months with LAS; 13,622 months with IAS; 38,141 months with SAS; 22,087 months with BUP; and 1,916 months with A2A. Combination therapy was present in 19.7% of continuing months (months after the first month of therapy) for ATX, 21.0% for LAS, 27.4% for IAS, 23.1% for SAS, 36.9% for BUP, and 53.0% for A2A.For patients receiving LAS, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having comorbid depression, or having point-of-service coverage versus a Health Maintenance Organization (HMO) resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD.For patients receiving ATX, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having a hyperactive component to ADHD, or having comorbid depression resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD. ATX and LAS are the most likely drugs to be used as monotherapy. Factors predicting combination use were similar for months in which ATX was used and for months in which LAS was used except that a hyperactive component to ADHD predicted increased combination use for ATX but not for LAS.

Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

PubMed Central

So, Charlotte H.; Eckman, Mark H.

2016-01-01

Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events. PMID:27665101

Valsartan combination therapy in the management of hypertension – patient perspectives and clinical utility

PubMed Central

Nash, David T; McNamara, Michael S

2009-01-01

The morbidity and mortality benefits of lowering blood pressure (BP) in hypertensive patients are well established, with most individuals requiring multiple agents to achieve BP control. Considering the important role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of hypertension, a key component of combination therapy should include a RAAS inhibitor. Angiotensin receptor blockers (ARBs) lower BP, reduce cardiovascular risk, provide organ protection, and are among the best tolerated class of antihypertensive therapy. In this article, we discuss two ARB combinations (valsartan/hydrochlorothiazide [HCTZ] and amlodipine/valsartan), both of which are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy and as initial therapy in patients likely to need multiple drugs to achieve BP goals. Randomized, double-blind studies that have assessed the antihypertensive efficacy and safety of these combinations in the first-line treatment of hypertensive patients are reviewed. Both valsartan/HCTZ and amlodipine/valsartan effectively lower BP and are well tolerated in a broad range of patients with hypertension, including difficult-to-treat populations such as those with severe BP elevations, prediabetes and diabetes, patients with the cardiometabolic syndrome, and individuals who are obese, elderly, or black. Also discussed herein are patient-focused perspectives related to the use of valsartan/HCTZ and amlodipine/valsartan, and the rationale for use of single-pill combinations as one approach to enhance patient compliance with antihypertensive therapy. PMID:21949614

Comparison possibilities of ultrasound and its combination with laser in surgery and therapy

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Menyaev, Yulian A.; Kabisov, Ruslan K.; Alkov, Sergey V.; Nesterov, A. V.; Loshchilov, Vladimir I.; Suen, James Y.

2000-05-01

This article presents the further developments of combined laser-ultrasound medical technologies with paying attention the possibility ultrasound in surgery and therapy. The analyses of main effects at the low frequency ultrasonic treatment of biotissues including cavitation, acoustic streams, acoustic pressure, mechanical influence etc are analyzed. The main promising areas of application of low frequency ultrasound are considered including bactericidal treatment of infections wounds, spray treatment of wounds in head and neck surgery, tumor treatment etc. In particular the clinical result of using ultrasonic devices based on imposing ultrasonic oscillations in a range of 22-66 kHz on a cutting instrument with a special form, radiation intensity up to 10 W/cm2 and oscillation amplitude up to 40-60 micrometers with respect to oncology for halt bleeding from a tumor, liquidating pain, acoustic denervation are presented. Some limitation of medical application of ultrasound are discussed and perspective combination with laser for increasing efficiency of new combined technologies are found. Among them: combination photodynamic therapy and ultrasonic treatment of tumors, laser-ultrasonic treatment of infections wounds including using spray, laser-ultrasonic drug delivery. The preliminary result of experimental study of some of above-mentioned technologies are presented.

SOP conservative (medical and mechanical) treatment of erectile dysfunction.

PubMed

Porst, Hartmut; Burnett, Arthur; Brock, Gerald; Ghanem, Hussein; Giuliano, Francois; Glina, Sidney; Hellstrom, Wayne; Martin-Morales, Antonio; Salonia, Andrea; Sharlip, Ira

2013-01-01

Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation. © 2013 International Society for Sexual Medicine.

Is the BTS/SIGN guideline confusing? A retrospective database analysis of asthma therapy.

PubMed

Covvey, Jordan R; Johnston, Blair F; Wood, Fraser; Boyter, Anne C

2013-09-01

The British guideline on the management of asthma produced by the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN) describes five steps for the management of chronic asthma. Combination therapy of a long acting β2-agonist (LABA) and an inhaled corticosteroid (ICS) is recommended as first-line therapy at step 3, although the dose of ICS at which to add a LABA is subject to debate. To classify the inhaled therapy prescribed to patients with asthma in NHS Forth Valley according to two interpretations of the BTS/SIGN guideline and to evaluate the use of combination therapy in this population. A retrospective analysis including patients from 46 general practitioner surgeries was conducted. Patients with physician diagnosed asthma were classified according to the BTS/SIGN guideline based on treatment prescribed during 2008. Patient characteristics were evaluated for the overall step classification, and specifically for therapy in step 3. 12,319 patients were included. Guideline interpretation resulted in a shift of 9.2% of patients (receiving medium-dose ICS alone) between steps 2 and 3. The largest proportion of patients (32.3%) was classified at step 4. Age, sex, smoking status, chronic obstructive pulmonary disease co-morbidity, and utilisation of short-acting β2-agonists and oral corticosteroids all correlated with step; however, no differences in these characteristics were evident between low-dose combination therapy and medium-dose ICS alone at step 3. Further studies are needed to evaluate prescribing decisions in asthma. Guideline recommendations regarding the use of ICS dose escalation versus combination therapy need to be clarified relative to the published evidence.

Effects of Aquatic Therapy and Land-Based Therapy versus Land-Based Therapy Alone on Range of Motion, Edema, and Function after Hip or Knee Replacement: A Systematic Review and Meta-analysis.

PubMed

Gibson, Alison J; Shields, Nora

2015-01-01

To determine whether aquatic therapy in combination with land-based therapy improves patient outcomes after hip or knee arthroplasty compared with land-based therapy alone. For this systematic review, six online databases (MEDLINE, CINAHL, AMED, EMBASE, Cochrane, and PEDro) were searched from the earliest date available until September 2013. Controlled trials published in English in a peer-reviewed journal that compared aquatic therapy in combination with land-based therapy with land-based therapy alone were included; trial quality was assessed using the PEDro scale. Data were presented as standardized mean differences (SMDs), their associated 95% CIs, and meta-analyses. Three small trials of moderate quality were included in the qualitative analysis. Meta-analysis of two of these studies found moderate-quality evidence that aquatic therapy in combination with land-based therapy improves functional outcomes (SMD=0.53; 95% CI, 0.03-1.03), knee range of motion (measured in knee or hip arthroplasty; SMD=0.78; 95% CI, 0.27-1.29), and edema (SMD=-0.66; 95% CI, -1.16 to -0.15) compared with land-based therapy alone. The results for improved functional outcomes were not considered clinically significant. It is not possible to draw confident conclusions from this review because of the small number of studies of limited quality and the modest differences found. Further studies of sound methodological quality are required to confirm the results. Economic analysis alongside randomized controlled trials is needed to examine the cost-effectiveness of these clinical outcomes.

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival.

PubMed

Sexe, R; Miedema, B W

1993-07-01

The risk of malignant disease arising in rectal mucosa is high. Surgery is the most effective form of treatment but results in cure in only 50% of patients. Adjuvant preoperative radiation therapy reduces the likelihood of local recurrence but does not improve survival rates. Fluorouracil is the most effective agent for adjuvant chemotherapy and slightly improves survival when given after surgery. Combining radiation therapy with chemotherapy appears to have a synergistic effect, and recent studies show that providing this combination after surgery improves survival. Future trends in the treatment of rectal cancer are expected to include expanded use of local excision to preserve anal sphincter function, preoperative use of a combination of radiation therapy and chemotherapy, perioperative use of chemotherapy combined with immunostimulating therapy, and use of tumor antibodies for diagnostic and therapeutic purposes.

Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy.

PubMed

Ren, Feifeng; Tang, Lin; Cai, Yin; Yuan, Xin; Huang, Wenhan; Luo, Lei; Zhou, Jun; Zheng, Yaning

2015-05-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin-angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN. Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI + ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI). In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups. Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.

Quality of Artemisinin-based Combination Therapy for malaria found in Ghanaian markets and public health implications of their use.

PubMed

Tivura, Mathilda; Asante, Isaac; van Wyk, Albert; Gyaase, Stephaney; Malik, Naiela; Mahama, Emmanuel; Hostetler, Dana M; Fernandez, Facundo M; Asante, Kwaku Poku; Kaur, Harparkash; Owusu-Agyei, Seth

2016-10-28

Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regulatory bodies and law enforcement agencies. The presence and prevalence of substandard and counterfeit Artemisinin-based Combination Therapies need to be determined on open markets in Ghana; a review of the current policy; identifying any gaps and making recommendations on actions to be taken in addressing gaps identified are essential as the data provided and recommendations made will help in ensuring effective control of malaria in Ghana. A field survey of antimalarial drugs was conducted in the central part of Ghana. The amount of active pharmaceutical ingredient in each Artemisinin-based Combination Therapy sample identified in the survey was measured using high performance liquid chromatographic analyses. Active pharmaceutical ingredient within the range of 85-115 % was considered as standard and active pharmaceutical ingredient results out of the range were considered as substandard. All samples were screened to confirm stated active pharmaceutical ingredient presence using mass spectrometry. A total of 256 Artemisinin-based Combination Therapies were purchased from known medicine outlets, including market stalls, hospitals/clinics, pharmacies, drug stores. Artemether lumefantrine (52.5 %) and artesunate amodiaquine (43.2 %) were the predominant Artemisinin-based Combination Therapies purchased. Of the 256 Artemisinin-based Combination Therapies purchased, 254 were tested, excluding two samples of Artesunate-SP. About 35 % of Artemisinin-based Combination Therapies were found to be substandard. Nine percent of Artemisinin-based Combination Therapies purchased were past their expiry date; no counterfeit (falsified) medicine samples were detected by either high performance liquid chromatographic or mass spectrometry. A high proportion of Artemisinin-based Combination Therapies sold in central Ghana were found to be substandard. Manufacturing of medicines that do not adhere to good manufacturing practices may have contributed to the poor quality of the Artemisinin-based Combination Therapies procured. A strict law enforcement and quality monitoring systems is recommended to ensure effective malaria case management as part of malaria control.

[Clinical usefulness of the combined empirical therapy with flomoxef and fosfomycin for intractable respiratory tract infections. With a background of increasing MRSA incidence].

PubMed

Shimada, K; Kudoh, S; Hayashi, I; Shishido, H; Fukuchi, Y; Suzuki, H; Oritsu, M; Nakada, K; Sano, Y; Goto, H

1994-10-01

We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

What Is Acute Respiratory Distress Syndrome?

MedlinePlus

... used for ARDS include: ■■ Breathing support from a mechanical ventilator combined with oxygen therapy (See ATS fact sheets on Mechanical Ventilation and Oxygen Therapy at www. thoracic.org/ ...

Treatment of murine invasive candidiasis with amphotericin B and cilofungin: evidence for enhanced activity with combination therapy.

PubMed Central

Sugar, A M; Goldani, L Z; Picard, M

1991-01-01

The in vivo interactions of cilofungin, an echinocandin antifungal agent, and amphotericin B, a polyene derivative, in a murine model of disseminated candidiasis have been investigated. While single therapy with either drug alone prolonged survival of infected mice, kidney colony counts were not appreciably reduced. In contrast, combination therapy, especially at higher doses of both drugs, resulted in significant prolongation of survival and suppression of growth of yeast cells in the kidneys. Combination therapy of experimental candidiasis with cilofungin and amphotericin B did not result in antagonism; rather, additive or synergistic effects were seen. Future preclinical work with other echinocandin and polyene derivatives should include studies evaluating the in vivo interactions of both classes of compounds. PMID:1759836

Neutron therapy of resistant thyroid gland cancer

NASA Astrophysics Data System (ADS)

Choynzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Lisin, V. A.; Novikov, V. A.; Musabaeva, L. I.

2017-09-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons c. The study included 45 patients with thyroid gland cancers who received the combined modality treatment and radiation therapy alone with the use of 6.3 MeV fast neutrons generated within U-120 cyclotron. The clinical trial of neutron-photon therapy used alone and in combination with the surgery for the patients with aggressive forms of thyroid cancer showed feasibility of increasing the effectiveness of treatment due to the reduction in the incidence of local recurrences. In addition, satisfactory treatment tolerance and absence of severe specific complications dictate the necessity of prospective studies to improve treatment outcomes.

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM. PMID:20694078

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Safety of regular formoterol or salmeterol in children with asthma: an overview of Cochrane reviews

PubMed Central

Cates, Christopher J; Oleszczuk, Marta; Stovold, Elizabeth; Wieland, L. Susan

2014-01-01

Background Two large surveillance studies in adults with asthma have found an increased risk of asthma-related mortality in those who took regular salmeterol as monotherapy in comparison to placebo or regular salbutamol. No similar sized surveillance studies have been carried out in children with asthma, and we remain uncertain about the comparative safety of regular combination therapy with either formoterol or salmeterol in children with asthma. Objectives We have used the paediatric trial results from Cochrane systematic reviews to assess the safety of regular formoterol or salmeterol, either as monotherapy or as combination therapy, in children with asthma. Methods We included Cochrane reviews relating to the safety of regular formoterol and salmeterol from a search of the Cochrane Database of Systematic Reviews conducted in May 2012, and ran updated searches for each of the reviews. These were independently assessed. All the reviews were assessed for quality using the AMSTAR tool. We extracted the data relating to children from each review and from new trials found in the updated searches (including risks of bias, study characteristics, serious adverse event outcomes, and control arm event rates). The safety of regular formoterol and salmeterol were assessed directly from the paediatric trials in the Cochrane reviews of monotherapy and combination therapy with each product. Then monotherapy was indirectly compared to combination therapy by looking at the differences between the pooled trial results for monotherapy and the pooled results for combination therapy. The comparative safety of formoterol and salmeterol was assessed using direct evidence from trials that randomised children to each treatment; this was combined with the result of an indirect comparison of the combination therapy trials, which represents the difference between the pooled results of each product when randomised against inhaled corticosteroids alone. Main results We identified six high quality, up to date Cochrane reviews. Four of these related to the safety of regular formoterol or salmeterol (as monotherapy or combination therapy) and these included 19 studies in children. We added data from two recent studies on salmeterol combination therapy in 689 children which were published after the relevant Cochrane review had been completed, making a total of 21 trials on 7474 children (from four to 17 years of age). The two remaining reviews compared the safety of formoterol with salmeterol from trials randomising participants to one or other treatment, but the reviews only included a single trial in children in which there were 156 participants. Only one child died across all the trials, so impact on mortality could not be assessed. We found a statistically significant increase in the odds of suffering a non-fatal serious adverse event of any cause in children on formoterol monotherapy (Peto odds ratio (OR) 2.48; 95% confidence interval (CI) 1.27 to 4.83, I2 = 0%, 5 trials, N = 1335, high quality) and smaller increases in odds which were not statistically significant for salmeterol monotherapy (Peto OR 1.30; 95% CI 0.82 to 2.05, I2 = 17%, 5 trials, N = 1333, moderate quality), formoterol combination therapy (Peto OR 1.60; 95% CI 0.80 to 3.28, I2 = 32%, 7 trials, N = 2788, moderate quality) and salmeterol combination therapy (Peto OR 1.20; 95% CI 0.37 to 2.91, I2 = 0%, 5 trials, N = 1862, moderate quality). We compared the pooled results of the monotherapy and combination therapy trials. There was no significant difference between the pooled ORs of children with a serious adverse event (SAE) from long-acting beta2-agonist beta agonist (LABA) monotherapy (Peto OR 1.60; 95% CI 1.10 to 2.33, 10 trials, N = 2668) and combination trials (Peto OR 1.50; 95% CI 0.82 to 2.75, 12 trials, N = 4,650). However, there were fewer children with an SAE in the regular inhaled corticosteroid (ICS) control group (0.7%) than in the placebo control group (3.6%). As a result, there was an absolute increase of an additional 21 children (95% CI 4 to 45) suffering such an SAE of any cause for every 1000 children treated over six months with either regular formoterol or salmeterol monotherapy, whilst for combination therapy the increased risk was an additional three children (95% CI 1 fewer to 12 more) per 1000 over three months. We only found a single trial in 156 children comparing the safety of regular salmeterol to regular formoterol monotherapy, and even with the additional evidence from indirect comparisons between the combination formoterol and salmeterol trials, the CI around the effect on SAEs is too wide to tell whether there is a difference in the comparative safety of formoterol and salmeterol (OR 1.26; 95% CI 0.37 to 4.32). Authors’ conclusions We do not know if regular combination therapy with formoterol or salmeterol in children alters the risk of dying from asthma. Regular combination therapy is likely to be less risky than monotherapy in children with asthma, but we cannot say that combination therapy is risk free. There are probably an additional three children per 1000 who suffer a non-fatal serious adverse event on combination therapy in comparison to ICS over three months. This is currently our best estimate of the risk of using LABA combination therapy in children and has to be balanced against the symptomatic benefit obtained for each child. We await the results of large on-going surveillance studies to further clarify the risks of combination therapy in children and adolescents with asthma. The relative safety of formoterol in comparison to salmeterol remains unclear, even when all currently available direct and indirect trial evidence is combined. PMID:23076961

Topical treatment and combination approaches for vitiligo: new insights, new developments.

PubMed

Hossani-Madani, A R; Halder, R M

2010-02-01

Despite much research done involving elucidation of the pathogenesis of vitiligo, a precise cause is still not known. Prevalent hypotheses include the autoimmune, genetic, neural, self-destruction, growth factor deficiency, viral, and convergence theories, which have served as the basis for treatment formulation. Topical therapies have been a mainstay of vitiligo treatment, with or without phototherapy. Topical treatments used in the treatment of vitiligo include steroids, calcineurin inhibitors, vitamin D analogues, pseudocatalase, and depigmenting agents. Combination therapies are used to improve the success rate of repigmentation. In this article, we have examined randomized controlled trials utilizing topical treatments used as monotherapy or combination therapy. Although psoralen and khellin can be used as topical agents, used in conjunction with UV radiation, we have not included them in the review due to their inability to be used as monotherapy. We have also excluded less used or ineffective topical agents, such as melagenina, topical phenylalanine, topical L-DOPA, coal tar, anacarcin forte oil and topical minoxidil. According to current guidelines, a less than two month trial of potent or very potent topical corticosteroids or topical calcineurin inhibitors may be used for therapy of localized vitiligo (<20% skin surface area). Combinations of topical corticosteroids with excimer laser and UVA seem to be more effective than steroids alone. Pseudocatalase plus NB-UVB does not seem to be more effective than placebo with NB-UVB. Combinations of vitamin D analogues have varied efficacy based on which type is used and the type of UV light. Efficacy of calcineurin inhibitor combinations also vary based on the type used and UV light combined, with tacrolimus being more effective with excimer laser. Pimecrolimus has been effective with NB-UVB and excimer laser on facial lesions, and microdermabrasion on localized areas.

Efficacy and Safety of Saxagliptin as Add-On Therapy in Type 2 Diabetes

PubMed Central

Neumiller, Joshua J.

2014-01-01

In Brief Combination therapy for type 2 diabetes using agents with complementary mechanisms of action may improve glycemic control to a greater extent than monotherapy and allow the use of lower doses of antihyperglycemic medications. Dipeptidyl peptidase-4 inhibitors, including saxagliptin, are recommended as add-on therapy to metformin and as part of two- or three-drug combinations in patients not meeting individualized glycemic goals with metformin alone or as part of a dual-therapy regimen. This article reviews the efficacy and safety of saxagliptin as an add-on therapy to metformin, glyburide, a thiazolidinedione, or insulin (with or without metformin) and as a component of triple therapy with metformin and a sulfonylurea. PMID:25646943

Bruton tyrosine kinase inhibition in chronic lymphocytic leukemia.

PubMed

Maddocks, Kami; Jones, Jeffrey A

2016-04-01

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and remains incurable outside of the setting of allogeneic stem cell transplant. While the standard therapy for both initial and relapsed CLL has traditionally included monoclonal antibody therapy in combination with chemotherapy, there are patients with high-risk disease features including unmutated IgVH, del(11q22) and del(17p13) that are associated with poor overall responses to these therapies with short time to relapse and shortened overall survival. Additionally, many of these therapies have a high rate of infectious toxicity in a population already at increased risk. Targeting the B-cell receptor (BCR) signaling pathway has emerged as a promising therapeutic advance in a variety of B-cell malignancies, including CLL. Bruton agammaglobulinemia tyrosine kinase (Btk) is a tyrosine kinase in the BCR pathway critical to the survival of both normal and malignant B cells and inhibition of this kinase has shown to block the progression of CLL. Ibrutinib, a first in class oral inhibitor of Btk, has shown promise as a very effective agent in the treatment of CLL-in both relapsed and upfront therapy, alone and in combination with other therapies, and in patients of all-risk disease-which has led to its approval in relapsed CLL and as frontline therapy in patients with the high-risk del(17p13) disease. Several studies are ongoing to evaluate the efficacy and safety of ibrutinib in combination with chemotherapy as frontline treatment for CLL and investigation into newer-generation Btk inhibitors is also underway. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Aquatic Therapy and Land-Based Therapy versus Land-Based Therapy Alone on Range of Motion, Edema, and Function after Hip or Knee Replacement: A Systematic Review and Meta-analysis

PubMed Central

Shields, Nora

2015-01-01

ABSTRACT Purpose: To determine whether aquatic therapy in combination with land-based therapy improves patient outcomes after hip or knee arthroplasty compared with land-based therapy alone. Methods: For this systematic review, six online databases (MEDLINE, CINAHL, AMED, EMBASE, Cochrane, and PEDro) were searched from the earliest date available until September 2013. Controlled trials published in English in a peer-reviewed journal that compared aquatic therapy in combination with land-based therapy with land-based therapy alone were included; trial quality was assessed using the PEDro scale. Data were presented as standardized mean differences (SMDs), their associated 95% CIs, and meta-analyses. Results: Three small trials of moderate quality were included in the qualitative analysis. Meta-analysis of two of these studies found moderate-quality evidence that aquatic therapy in combination with land-based therapy improves functional outcomes (SMD=0.53; 95% CI, 0.03–1.03), knee range of motion (measured in knee or hip arthroplasty; SMD=0.78; 95% CI, 0.27–1.29), and edema (SMD=−0.66; 95% CI, −1.16 to −0.15) compared with land-based therapy alone. The results for improved functional outcomes were not considered clinically significant. Conclusions: It is not possible to draw confident conclusions from this review because of the small number of studies of limited quality and the modest differences found. Further studies of sound methodological quality are required to confirm the results. Economic analysis alongside randomized controlled trials is needed to examine the cost-effectiveness of these clinical outcomes. PMID:25931664

Dapagliflozin and saxagliptin tablets for adults with type 2 diabetes.

PubMed

Scheen, André J

2017-12-01

Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly). Expert commentary: Conclusions drawn from clinical trials investigating combination with the separate drugs are considered to apply to the fixed-dose combination (FDC) that demonstrates bioequivalence. Dual saxagliptin/dapagliflozin therapy is more potent than either monotherapy and can be used as an initial combination or a stepwise sequential approach. Dual therapy is generally well tolerated and may be used in special populations, with some limitations because of the presence of dapagliflozin. However, the latter may offer some advantages because of multiple effects attributed to SGLT2i. The best place of this dual combination for the management of T2D and the profile of patients who will make the most of this combined therapy remains to be defined.

Emerging monoclonal antibodies for the treatment of renal cell carcinoma (RCC).

PubMed

Atkins, Michael B; Philips, George K

2016-09-01

Advanced renal cell carcinoma (RCC) was considered refractory to most cancer therapies until the 1980s, after which immune modulating agents and targeted agents were developed. Recently the rapid development of therapeutic monoclonal antibodies targeting immune checkpoint pathways has provided significant clinical benefit in patients with many distinct cancer types. Nivolumab, an anti-PD1 monoclonal antibody showed improvement in response rate and overall survival in patients with previously treated RCC and received US FDA approval in late 2015. Current efforts with anti-PD1-based therapy include combinations with ipilimumab and with VEGF pathway blockers in the hopes on building on the activity of single agent therapy. We describe our current understanding of tumor immunology including the basis of the tumor-specific immune response and the adaptive mechanisms used by the tumor for immune escape. We describe the mechanisms of action as well as the therapeutic application of the antibodies, ipilimumab, nivolumab and atezolizumab in patients with RCC. We identify key areas of active research in biomarker development and combination therapies. Clinical trials and the field of RCC therapeutics are expected to move in the direction of combination therapies using immune checkpoint inhibitors, extending overall survival as a benchmark for new drug approvals, and biomarker validation for improved selection of patients for specific therapies.

[The results of the combined application of extracorporeal shock-wave therapy and radon baths during the rehabilitative treatment of the patients presenting with gonarthrosis].

PubMed

Razumov, A N; Puriga, A O; Yurova, O V

2015-01-01

Osteoarthritis (OA) is one of the leading diseases of the musculoskeletal system and the main cause of arthritic joint damage. The objective of the present study was to evaluate the effectiveness of the combined application of radon baths and shock-wave therapy in the patients suffering from knee OA. The study involved 75 patients at the age of 35 to 62 years with the confirmed diagnosis of stage II and III gonarthrosis; they were divided into 3 groups. The patients of the main group received the combined treatment including extracorporeal shock-wave therapy and radon baths The patients comprising the group of comparison were given the course of radon therapy alone while those in the control group were offered the standard treatment including physiotherapy, magnetic therapy, and NSAIDs. The study has demonstrated the high effectiveness of the combined application of the radon baths and extracorporeal shock-wave therapy for the rehabilitation of the patients with deforming arthrosis of the knee that was apparent from the substantial decrease of pain syndrome, the increase of the range of motions in the knee joints, and the overall improvement of the quality of life. These beneficial changes persisted for a period of up to 6 months. The results of the present study give reason to recommend the proposed method of the remedial treatment for the wide practical application as a component in the framework of the medical rehabilitation programs.

The role of combination medical therapy in the treatment of acromegaly.

PubMed

Lim, Dawn Shao Ting; Fleseriu, Maria

2017-02-01

Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis.

PubMed

Tang, Kai; Si, Jun-Kang; Guo, Da-Dong; Cui, Yan; Du, Yu-Xiang; Pan, Xue-Mei; Bi, Hong-Sheng

2015-01-01

To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV). A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis. Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study. IVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis

PubMed Central

Tang, Kai; Si, Jun-Kang; Guo, Da-Dong; Cui, Yan; Du, Yu-Xiang; Pan, Xue-Mei; Bi, Hong-Sheng

2015-01-01

AIM To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV). METHODS A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis. RESULTS Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study. CONCLUSION IVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV. PMID:26558226

Intense pulsed light, near infrared pulsed light, and fractional laser combination therapy for skin rejuvenation in Asian subjects: a prospective multi-center study in China.

PubMed

Tao, Li; Wu, Jiaqiang; Qian, Hui; Lu, Zhong; Li, Yuanhong; Wang, Weizhen; Zhao, Xiaozhong; Tu, Ping; Yin, Rui; Xiang, Leihong

2015-09-01

Ablative skin rejuvenation therapies have limitations for Asian people, including post-inflammatory hyperpigmentation and long down time. Non-ablative lasers are safer but have limited efficacy. This study is to investigate the safety and efficacy of a combination therapy consisting of intense pulsed light (IPL), near infrared (NIR) light, and fractional erbium YAG (Er:YAG) laser for skin rejuvenation in Asian people. This study recruited 113 subjects from six sites in China. Subjects were randomly assigned to a full-face group, who received combination therapy, and split-face groups, in which one half of the face received combination therapy and the other half received IPL monotherapy. Each subject received five treatment sessions during a period of 90 days. Subjects were followed up at 1 and 3 months post last treatment. Three months after last treatment, the full-face group (n = 57) had a global improvement rate of 29 % and 29 % for wrinkles, 32 % for skin texture, 33 % for pigment spots, 28 % for pore size, respectively. For patients in the split-face groups (n = 54), monotherapy side had a global improvement rate of 23 % and 20 % for wrinkles, 27 % for skin texture, 25 % for pigment spots, 25 % for pore size, respectively. Both combination therapy and monotherapy resulted in significant improvements at the follow-up visits compared to baseline (P < 0.001). Combination therapy showed significantly greater improvements compared to monotherapy at two follow-up visits (P < 0.05). Combination therapy is a safe and more effective strategy than IPL monotherapy for skin rejuvenation in Asian people.

Inappropriate combination of warfarin and aspirin

PubMed Central

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-01-01

Objective: A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). Methods: This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Results: Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). Conclusion: The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV. (Anatol J Cardiol 2016; 16: 189-96) PMID:26467380

Vaginal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Vaginal cancer treatment options include a variety of surgical procedures, topical chemotherapy, radiation therapy, and combination radiation therapy. Get detailed treatment information for newly diagnosed and recurrent vaginal cancer in this summary for clinicians.

[Herpetic infection in patients with psoriasis: the improvement of therapy].

PubMed

Shul'diakov, A A; Barkhatova, T S; Satarova, S A; Perminova, T A

2012-01-01

The aim of the study was to estimate the efficacy of liniment cycloferon included in combined therapy of herpetic infection in 30 patients with psoriasis divided into 2 groups. Combined treatment of patients with recurrent herpetic infection promoted elimination of general infection syndrome, shortened duration of eruption and local inflammation, accelerated epithelization of herpetic erosion, and decreased the frequency of relapses during the follow-up.

[Infrared radiation and magnetic field therapy ameliorates cartilage damage in rabbits with knee osteoarthritis].

PubMed

Sun, Jia-li; Fan, Jian-zhong; Song, Gui-zhi; Tan, Xiao-ming; Peng, Nan

2007-12-01

To evaluate the effect of infrared radiation and magnetic field therapy on cartilage damage in rabbits with knee osteoarthritis. Knee osteoarthritis was induced in 24 adult New Zealand rabbits by prolonged fixation of the knee joint in extension for 6 weeks. The rabbits were subsequently randomized into control group (without treatment), infrared therapy group, magnetic field therapy group and the combined infrared and magnetic field therapy group. At the end of the first, second and third weeks of the therapy, respectively, 2 rabbits from each group were sacrificed to observe the general changes and histopathology of the condylar cartilage of the femur, and the findings were assessed using Mankin scores. Compared with other groups, the rabbits in the combined therapy group showed significantly milder cartilage damage (including injury of the cartilage surface and chondrocyte's proliferation and disarrangement) with significantly lower Mankin scores (P<0.05). No significant differences were found in the findings between the two groups with exclusive infrared or magnetic field therapy (P>0.1). Combined infrared and magnetic field therapy can effectively alleviate cartilage destruction, shortens the disease course and enhance the therapeutic effects in rabbits with knee osteoarthritis.

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

PubMed

Christophorou, D; Funakoshi, N; Duny, Y; Valats, J-C; Bismuth, M; Pineton De Chambrun, G; Daures, J-P; Blanc, P

2015-04-01

The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use. © 2015 John Wiley & Sons Ltd.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation

PubMed Central

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong

2017-01-01

Background A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. Objective This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Methods Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Results Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil (p<0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. Conclusion A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL. PMID:28566902

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

PubMed

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong; Lee, Won-Soo

2017-06-01

A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil ( p <0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

Phosphatidylserine-targeting antibodies augment the anti-tumorigenic activity of anti-PD-1 therapy by enhancing immune activation and downregulating pro-oncogenic factors induced by T-cell checkpoint inhibition in murine triple-negative breast cancers.

PubMed

Gray, Michael J; Gong, Jian; Hatch, Michaela M S; Nguyen, Van; Hughes, Christopher C W; Hutchins, Jeff T; Freimark, Bruce D

2016-05-11

The purpose of this study was to investigate the potential of antibody-directed immunotherapy targeting the aminophospholipid phosphatidylserine, which promotes immunosuppression when exposed in the tumor microenvironment, alone and in combination with antibody treatment towards the T-cell checkpoint inhibitor PD-1 in breast carcinomas, including triple-negative breast cancers. Immune-competent mice bearing syngeneic EMT-6 or E0771 tumors were subjected to treatments comprising of a phosphatidylserine-targeting and an anti-PD-1 antibody either as single or combinational treatments. Anti-tumor effects were determined by tumor growth inhibition and changes in overall survival accompanying each treatment. The generation of a tumor-specific immune response in animals undergoing complete tumor regression was assessed by secondary tumor cell challenge and splenocyte-produced IFNγ in the presence or absence of irradiated tumor cells. Changes in the presence of tumor-infiltrating lymphocytes were assessed by flow cytometry, while mRNA-based immune profiling was determined using NanoString PanCancer Immune Profiling Panel analysis. Treatment by a phosphatidylserine-targeting antibody inhibits in-vivo growth and significantly enhances the anti-tumor activity of antibody-mediated PD-1 therapy, including providing a distinct survival advantage over treatment by either single agent. Animals in which complete tumor regression occurred with combination treatments were resistant to secondary tumor challenge and presented heightened expression levels of splenocyte-produced IFNγ. Combinational treatment by a phosphatidylserine-targeting antibody with anti-PD-1 therapy increased the number of tumor-infiltrating lymphocytes more than that observed with single-arm therapies. Finally, immunoprofiling analysis revealed that the combination of anti-phosphatidylserine targeting antibody and anti-PD-1 therapy enhanced tumor-infiltrating lymphocytes, and increased expression of pro-immunosurveillance-associated cytokines while significantly decreasing expression of pro-tumorigenic cytokines that were induced by single anti-PD-1 therapy. Our data suggest that antibody therapy targeting phosphatidylserine-associated immunosuppression, which has activity as a single agent, can significantly enhance immunotherapies targeting the PD-1 pathway in murine breast neoplasms, including triple-negative breast cancers.

[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy].

PubMed

Kochetkov, A V; Gorbunov, F E; Minenkov, A A; Strel'tsova, E N; Filina, T F; Krupennikov, A I

2000-01-01

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Spotlight on fluticasone furoate/umeclidinium/vilanterol in COPD: design, development, and potential place in therapy.

PubMed

Lal, Chitra; Strange, Charlie

2017-01-01

COPD is characterized by persistent airflow obstruction caused by exposure to irritants including cigarette smoke, dust, and fumes. According to the latest GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines, a combination of inhaled corticosteroids, long-acting β 2 agonists, and long-acting muscarinic receptor antagonists can be used for group D COPD patients who are at high risk for exacerbations. Umeclidinium/fluticasone furoate/vilanterol is one such triple-combination therapy currently under development with some completed and several ongoing clinical trials. This review paper summarizes the pharmacologic profiles of these medications and highlights findings from clinical trials, including safety and efficacy data, while speculating on the role of this therapy in current treatment for COPD.

Androgen excess: Investigations and management.

PubMed

Lizneva, Daria; Gavrilova-Jordan, Larisa; Walker, Walidah; Azziz, Ricardo

2016-11-01

Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. Copyright © 2016. Published by Elsevier Ltd.

Molecular profiling of childhood cancer: Biomarkers and novel therapies.

PubMed

Saletta, Federica; Wadham, Carol; Ziegler, David S; Marshall, Glenn M; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D; Byrne, Jennifer A

2014-06-01

Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

Effectiveness of Combined Therapy with Pirfenidone and Erythromycin for Unclassifiable Interstitial Pneumonia Induced by HTLV-1-associated Bronchioloalveolar Disorder (HABA)

PubMed Central

Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko

2017-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003

Accessing Transgenerational Themes Through Dreamwork.

ERIC Educational Resources Information Center

Andrews, Jennifer; And Others

1988-01-01

Proposes use of dreamwork to evoke historical patterns or transgenerational themes. Describes new variant of dreamwork which combines aspects of both gestalt and family systems therapies. Implications of therapeutic dramatization for couple therapy are suggested. Examples are included. (Author/NB)

Photodynamic therapy in combination with ranibizumab versus ranibizumab monotherapy for wet age-related macular degeneration: A systematic review and meta-analysis.

PubMed

Su, Yongxian; Wu, Jiawei; Gu, Yu

2018-06-01

To evaluate the efficacy and safety between photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) and ranibizumab monotherapy in treating wet age-related macular degeneration (AMD). A systematic search was performed in the PubMed, Embase, Web of Science and the Cochrane Library databases through December 31, 2017. The methodological quality of the references was evaluated according to the Cochrane quality assessment. RevMan 5.3 software was used to perform the meta-analysis. Eight RCTs involving 817 participants were included. Wet AMD eyes in the mono-group achieved better best-corrected vision acuity (BCVA) than the combination group in month 12 (WMD = -0.19, 95% CI = -0.32 to -0.06, P = 0.004, I 2  = 18%). The proportion of patients gaining more than 15 letters from baseline in the mono-group was larger than that in the combination group (RR = 0.70, 95% CI: 0.56 to 0.87, P = 0.001). However, the number of ranibizumab injections with combination therapy was smaller than that with mono-therapy (MD = -1.13, 95% CI: -2.11 to -0.15, P = 0.02, I 2  = 85%). No significant differences were observed in the proportions of patients losing more than 15 letters, central retinal thickness (CRT), lesion size of choroidal neovascularization (CNV) and adverse events. Combination therapy decreased the number of injections of ranibizumab, although its BCVA improvement was inferior to that of monotherapy over 12 months of follow-up. Given the inherent limitations of the included trials, more studies are needed to further validate and update the findings in this area. Copyright © 2018 Elsevier B.V. All rights reserved.

Creating genetic resistance to HIV.

PubMed

Burnett, John C; Zaia, John A; Rossi, John J

2012-10-01

HIV/AIDS remains a chronic and incurable disease, in spite of the notable successes of combination antiretroviral therapy. Gene therapy offers the prospect of creating genetic resistance to HIV that supplants the need for antiviral drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based therapeutics. Combinations of therapeutic genes against viral and host targets are designed to improve the overall antiviral potency and reduce the likelihood of viral resistance. In cell-based therapies, therapeutic genes are expressed in gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV-resistant immune system. Such strategies must promote the selective proliferation of the transplanted cells and the prolonged expression of therapeutic genes. This review focuses on the current advances and limitations in genetic therapies against HIV, including the status of several recent and ongoing clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intensified Voice Therapy: A New Model for the Rehabilitation of Patients Suffering from Functional Dysphonias

ERIC Educational Resources Information Center

Fischer, Michael J.; Gutenbrunner, Christoph; Ptok, Martin

2009-01-01

The objective of this study was to evaluate a new intervention for chronic dysphonias, consisting of a 2-week outpatient treatment period using intensified voice therapy combined with elements of physical medicine, including physiotherapy (orthotherapy, detonisation and training of the trunk muscles, respiratory therapy and others), manual therapy…

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

PubMed

Cecchini, Jérôme; Tuffet, Samuel; Sonneville, Romain; Fartoukh, Muriel; Mayaux, Julien; Roux, Damien; Kouatchet, Achille; Boissier, Florence; Tchir, Martial; Thyrault, Martial; Maury, Eric; Jochmans, Sebastien; Mekontso Dessap, Armand; Brun-Buisson, Christian; de Prost, Nicolas

2017-05-01

Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. To evaluate the effect of antimicrobial strategy on ICU mortality. Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P  =   0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P  =   0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P  =   0.02]. Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Myofunctional therapy improves adherence to continuous positive airway pressure treatment.

PubMed

Diaféria, Giovana; Santos-Silva, Rogerio; Truksinas, Eveli; Haddad, Fernanda L M; Santos, Renata; Bommarito, Silvana; Gregório, Luiz C; Tufik, Sergio; Bittencourt, Lia

2017-05-01

Few studies have investigated myofunctional therapy in patients with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the effect of myofunctional therapy on continuous positive airway pressure (CPAP) adherence. The study was registered at ClinicalTrials.gov (NCT01289405). Male patients with OSAS were randomly divided into four treatment groups: placebo, patients undergoing placebo myofunctional therapy (N = 24); myofunctional therapy, undergoing myofunctional therapy (N = 27); CPAP, undergoing treatment with CPAP (N = 27); and combined, undergoing CPAP therapy and myofunctional therapy (N = 22). All patients underwent evaluations before and after 3 months of treatment evaluation and after 3 weeks of washout. Evaluations included Epworth sleepiness scale (ESS), polysomnography, and myofunctional evaluation. The 100 men had a mean age of 48.1 ± 11.2 years, body mass index of 27.4 ± 4.9 kg/m 2 , ESS score of 12.7 ± 3.0, and apnea-hypopnea index (AHI) of 30.9 ± 20.6. All treated groups (myofunctional therapy, CPAP, and combined myofunctional therapy with CPAP) showed decreased ESS and snoring, and the myofunctional therapy group maintained this improvement after the "washout" period. AHI reduction occurred in all treated groups and was more significant in CPAP group. The myofunctional therapy and combined groups showed improvement in tongue and soft palate muscle strength when compared with the placebo group. The association of myofunctional therapy to CPAP (combined group) showed an increased adherence to CPAP compared with the CPAP group. Our results suggest that in patients with OSAS, myofunctional therapy may be considered as an adjuvant treatment and an intervention strategy to support adherence to CPAP.

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer.

PubMed

Bonomi, P D; Gandara, D; Hirsch, F R; Kerr, K M; Obasaju, C; Paz-Ares, L; Bellomo, C; Bradley, J D; Bunn, P A; Culligan, M; Jett, J R; Kim, E S; Langer, C J; Natale, R B; Novello, S; Pérol, M; Ramalingam, S S; Reck, M; Reynolds, C H; Smit, E F; Socinski, M A; Spigel, D R; Vansteenkiste, J F; Wakelee, H; Thatcher, N

2018-06-14

Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or anti-angiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results. Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥ 200) and/or gene copy numbers of EGFR (e.g., ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥ 10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with anti-angiogenic agents. Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or anti-angiogenic agents remain limited.

Effects of Additional Intra-aortic Balloon Counter-Pulsation Therapy to Cardiogenic Shock Patients Supported by Extra-corporeal Membranous Oxygenation

PubMed Central

Lin, Lian-Yu; Liao, Che-Wei; Wang, Chih-Hsien; Chi, Nai-Hsin; Yu, Hsi-Yu; Chou, Nai-Kuan; Hwang, Juey-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien; Chen, Yih-Sharng

2016-01-01

Extra-corporeal membranous oxygenation (ECMO) has been applied in patients with cardiopulmonary failure. One critical drawback of peripheral ECMO is an increase in left ventricular (LV) afterload which could be counterbalanced by the combination of intra-aortic balloon counter-pulsation (IABP) therapy. We hypothesized that an add-on therapy with IABP could improve outcomes in patients receiving ECMO support. We included patients (>18 years old) from 2002 to 2013 requiring ECMO support due to cardiogenic shock in a medical center. A total of 529 patients (227 ECMO alone and 302 combined IABP plus ECMO) were included. The mortality rates at 2 weeks (48.5 vs. 47.7%) after ECMO implantation were not different between the two groups (ECMO vs. combined group). After adjustment for propensity score and potential confounders, the odds ratios of outcomes within 14 days (combined group vs. ECMO) for poor LV systolic function, high preload, multi-organ failure and mortality were not different. The results remained similar for subgroup analysis. Compared with ECMO alone, combined IABP and ECMO treatment did not improve outcomes in patients with circulatory failure. PMID:27032984

Effects of physiotherapy combined with sirolimus in a patient with vascular malformation: A case report.

PubMed

Akbayrak, Türkan; Orhan, Ceren; Baran, Emine; Kaya, Serap; Coskun, Gürsoy; Varan, Ali

2016-01-01

The aim of the present case report was to investigate the effects of a physiotherapy program combined with sirolimus in a child patient with upper extremity edema and joint limitation due to low-flow vascular malformation. This case report included an 11-year-old male patient (26 kg, 130 cm) diagnosed with congenital lymphovascular malformation on the left and right chest. The patient, who had edema on the upper left extremity and experienced joint limitations, was administered complete decongestive therapy (CDT) and manual therapy in combination with sirolimus. Physiotherapy included a total of 24 sessions, 3 sessions a week for 8 weeks. Following the physiotherapy, the patient was assigned to a home therapy program, and then the maintenance phase of the CDT was initiated. Evaluations were carried out at baseline, at the end of week 8, and after 12 months. Following the physiotherapy program combined with sirolimus, a decrease in extremity volume, an increase in joint movement range, and an improvement in disease-related complaints were observed. Physiotherapy methods combined with sirolimus may be an effective treatment method in patients with vascular malformations. However, further studies with larger sample size are warranted.

Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of combination therapy with colistin plus β-lactams.

PubMed

Ribera, Alba; Benavent, Eva; Lora-Tamayo, Jaime; Tubau, Fe; Pedrero, Salvador; Cabo, Xavier; Ariza, Javier; Murillo, Oscar

2015-12-01

In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options. This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion. Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%. We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

PubMed

Dhir, Mashaal; Melin, Alyson A; Douaiher, Jeffrey; Lin, Chi; Zhen, Weining Ken; Hussain, Shahid M; Geschwind, Jean-Francois H; Doyle, Maria B Majella; Abou-Alfa, Ghassan K; Are, Chandrakanth

2016-06-01

To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

Parathyroid hormone plus alendronate in osteoporosis: a meta-analysis of randomized controlled trials.

PubMed

Zhang, Qinggang; Qian, Jing; Zhu, Yuchang

2015-01-01

Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy of PTH with alendronate will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy of PTH with alendronate in the treatment of patients with osteoporosis. A comprehensive literature search of PubMed, Embase, and Web of Science was conducted to identify relative studies. Eligible studies were randomized controlled trials (RCT), which assessed the efficacy of combination therapy in patients with osteoporosis. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using of random-effects or fixed-effects model, depending on the heterogeneity between the included studies. Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy of PTH with alendronate resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95% CI: 1.58, 3.31; P = 0.000), but not in lumbar spine (WMD = -0.83, 95% CI: -3.48, 1.81; P = 0.538), femoral neck (WMD = -0.99, 95% CI: -2.04, 0.07; P = 0.068), and total hip (WMD = -0.06, 95% CI: -0.93, 0.81; P = 0.892). The subgroup analysis based on the dosage and schedule of PTH, study duration, gender of patients, and anabolic agents, were conducted. And results revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 μg (WMD = 2.33, 95% CI: 1.24, 3.43; P = 0.000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95% CI: 1.00, 3.47; P = 0.000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95% CI: 0.63, 2.53; P = 0.001). However, the combination of PTH of 40 μg with alendronate produced a decrease in the BMD at spine (WMD = -4.56, 95% CI: -7.56, -1.56; P = 0.003) and femoral neck (WMD = -5.82, 95% CI: -9.91, -1.72; P = 0.005). Our findings indicated that the addition of alendronate to PTH in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip.

[Combination of periodontal, orthodontic and endodontic therapy in upper anterior teeth with hopeless prognosis and long-time follow-up: a case report].

PubMed

Li, Y; Xu, L; Zhou, Y H; Ouyang, X Y; Cao, T

2017-08-18

It is complicated to decide the treatment plan of hopeless anterior teeth in esthetic zone due to severe periodontitis, periodontal-endodontic combined lesion or teeth trauma. The optional treatment plan for this kind of teeth includes retention after periodontal treatment, extraction and implant treatment, extraction and prosthodontic treatment and so on. To make an appropriate treatment plan, patients' periodontal conditions, periodontal biotype, local anatomy, esthetic demand, economic condition and social psychological status should be comprehensively considered. A combine of periodontal, endodontic and orthodontic therapy may achieve a good treatment effect in hopeless anterior teeth with severe periodontal destruction, tooth extrusion and occlusal trauma. In this case, a 20-year-old female who presented with symptoms of bleeding on brushing and upper incisors loosening for 1 month came to the Department of Periodontology, Peking University School and Hospital of Stomatology. The clinical examinations revealed that the patient's right upper incisor had signs of mobility (III°), intrusion of 1-2 mm, and probing depth (PD) of 9-10 mm. The periapical radiograph showed that the alveolar bone of right upper incisor absorbed horizontally to the apex. And the patients showed Angle II° malocclusion with II° overbite in anterior teeth and maxillary protrusion. A diagnosis of aggressive periodontitis and Angle II° malocclusion was made. The treatment of this patient lasts for 5 years which include periodontal initial therapy, orthodontic therapy, guided tissue regeneration (GTR) of right upper incisor and supportive periodontal therapy and the clinical result is fine. A hopeless upper incisor was successfully retained and the longtime clinical condition was stable. The strategy of retention of hopeless upper anterior teeth, the relationship of periodontal treatment and orthodontic treatment, and the indications of periodontal and orthodontic combined therapy were also discussed on the basis of this case. Generally, the positive factors in retention of hopeless teeth includes young age, absence of systemic conditions, strong motivation for maintaining the tooth, single root anatomy, integrated dentition, good response to cause-related therapy, intrabony alveolar bone defect, thick periodontal biotype, and regular supportive periodontal therapy. And in the progress of orthodontic therapy, regular supportive periodontal therapy and good plaque control is extremely important.

Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

PubMed Central

Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

2011-01-01

Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors. PMID:24212824

Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

PubMed

Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

2017-08-28

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

PubMed

Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

2015-08-01

SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy. © The Author(s) 2014.

Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

PubMed

Nakanishi, Asako; Hakamada, Arata; Isoda, Ken-ichi; Mizutani, Hitoshi

2005-05-01

Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

Combination therapy with clomiphene citrate and anastrozole is a safe and effective alternative for hypoandrogenic subfertile men.

PubMed

Alder, Nathan J; Keihani, Sorena; Stoddard, Gregory J; Myers, Jeremy B; Hotaling, James M

2018-06-06

To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow-ups. Treatment side effects were recorded; prostatic-specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t-test and Wilcoxon's signed-rank test. A total of 51 men were included, with a mean age of 35.4 ± 7.4 years and a mean body mass index of 35.0 ± 8.0 kg/m 2 . After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.

PubMed

Baracat, Felipe; Moura, Eduardo; Bernardo, Wanderley; Pu, Leonardo Zorron; Mendonça, Ernesto; Moura, Diogo; Baracat, Renato; Ide, Edson

2016-06-01

Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy. Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials. Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone. Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

[Spasmodic hemiplegia after stroke treated with scalp acupuncture, music therapy and rehabilitation: a randomized controlled trial].

PubMed

Jia, Chengjie; Zhang, Hongru; Ni, Guangxia; Zhang, Yinan; Su, Bin; Xu, Xinlei

2017-12-12

To evaluate the differences in the clinical therapeutic effects on spasmodic hemiplegia after stroke among the alliance therapy of scalp acupuncture, music therapy combined with rehabilitation, the simple rehabilitation therapy and the combination of music therapy and rehabilitation. A total of 76 patients of post-stroke spasmodic hemiplegia were randomized into a rehabilitation group (25 cases), a combination group with music therapy and rehabilitation (25 cases) and an alliance therapy group with scalp acupuncture, music therapy and rehabilitation (26 cases). In the rehabilitation group, the routine rehabilitation therapy was applied, including the removal of various incentives that cause spasm, the correction of body position and the physical therapy. In the combination group, the music therapy was added on the basis of the treatment as the rehabilitation group. The music physician used the rhythmic auditory stimulation, the patterned sensory enhancement and the therapeutic instrumental music playing to set up the task in the treatment. In the alliance therapy group, scalp acupuncture was added on the basis of the treatment as the combination group. The anterior oblique line of vertex-tempora (MS 6) and the posterior oblique line of vertex-tempora (MS 7) on the contralateral side were selected and stimulated with penetrating needling technique. The needles were retained. During the needling retaining, the needles were rotated once every 10 min, for 2 min each time. The treatment was given one session a day, totally for 5 sessions a week, continuously for 4 weeks. The Fugl-Meyer assessment (FMA), Barthel index (BI) and the modified Ashworth scale (MAS) of the affected elbow and the passive knee movement at static condition were observed in the patients before and after treatment. The results of FMA, BI and MAS were not different before treatment in the patients among the three groups (all P >0.05), indicating the comparability among groups. After treatment, FMA and BI scores were all increased apparently in the three groups as compared with those before treatment (all P <0.05). MAS grade was reduced remarkably as compared with that before treatment (all P <0.05). After treatment, FMA and BI scores in the alliance therapy group were higher than those in the combination group and the rehabilitation group (all P <0.05). FMA and BI scores in the combination group were higher than those in the rehabilitation group (both P <0.05). MAS grade in the alliance therapy group was lower than those in the combination group and the rehabilitation group (both P <0.05). MAS grade in the combination group was lower than that in the rehabilitation group ( P <0.05). The alliance therapy with scalp acupuncture, music therapy and rehabilitation achieve the remarkable clinical therapeutic effects on post-stroke spasmodic hemiplegia as compared with the routine rehabilitation and the combination of music therapy and rehabilitation.

Targeted cancer therapy--are the days of systemic chemotherapy numbered?

PubMed

Joo, Won Duk; Visintin, Irene; Mor, Gil

2013-12-01

Targeted therapy or molecular targeted therapy has been defined as a type of treatment that blocks the growth of cancer cells by interfering with specific cell molecules required for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells as with traditional chemotherapy. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the growing relevance of this therapeutic approach. Targeted cancer therapies, also referred to as "Personalized Medicine", are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The objective of personalized medicine is the identification of patients that would benefit from a specific treatment based on the expression of molecular markers. Examples of this approach include bevacizumab and olaparib, which have been designated as promising targeted therapies for ovarian cancer. Combinations of trastuzumab with pertuzumab, or T-DM1 and mTOR inhibitors added to an aromatase inhibitor are new therapeutic strategies for breast cancer. Although this approach has been seen as a major step in the expansion of personalized medicine, it has substantial limitations including its high cost and the presence of serious adverse effects. The Cancer Genome Atlas is a useful resource to identify novel and more effective targets, which may help to overcome the present limitations. In this review we will discuss the clinical outcome of some of these new therapies with a focus on ovarian and breast cancer. We will also discuss novel concepts in targeted therapy, the target of cancer stem cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Gene Therapy for Brain Cancer: Combination Therapies Provide Enhanced Efficacy and Safety

PubMed Central

Candolfi, Marianela; Kroeger, Kurt M.; Muhammad, A.K.M.G.; Yagiz, Kader; Farrokhi, Catherine; Pechnick, Robert N.; Lowenstein, Pedro R.; Castro, Maria G.

2009-01-01

Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults. Despite significant advances in treatment and intensive research, the prognosis for patients with GBM remains poor. Therapeutic challenges for GBM include its invasive nature, the proximity of the tumor to vital brain structures often preventing total resection, and the resistance of recurrent GBM to conventional radiotherapy and chemotherapy. Gene therapy has been proposed as a useful adjuvant for GBM, to be used in conjunction with current treatment. Work from our laboratory has shown that combination of conditional cytotoxic with immunotherapeutic approaches for the treatment of GBM elicits regression of large intracranial tumor masses and anti-tumor immunological memory in syngeneic rodent models of GBM. In this review we examined the currently available animal models for GBM, including rodent transplantable models, endogenous rodent tumor models and spontaneous GBM in dogs. We discuss non-invasive surrogate end points to assess tumor progression and therapeutic efficacy, such as behavioral tests and circulating biomarkers. Growing preclinical and clinical data contradict the old dogma that cytotoxic anti-cancer therapy would lead to an immune-suppression that would impair the ability of the immune system to mount an anti-tumor response. The implications of the findings reviewed indicate that combination of cytotoxic therapy with immunotherapy will lead to synergistic antitumor efficacy with reduced neurotoxicity and supports the clinical implementation of combined cytotoxic-immunotherapeutic strategies for the treatment of patients with GBM. PMID:19860655

Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

PubMed

Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

2017-06-01

Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

Combined treatment modalities for age related macular degeneration.

PubMed

Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

2011-02-01

Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder.

PubMed

Ozbaran, Burcu; Kose, Sezen; Yuzuguldu, Onur; Atar, Burcu; Aydin, Cahide

2015-01-01

Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) includes stimulant and non-stimulant medications. Our purpose in this study is to investigate efficacy, safety and tolerability of combined methylphenidate and atomoxetine pharmacotherapy. We included 12 patients of the 824 patients with ADHD using methylphenidate and atomoxetine combined therapy between the years 2010 and 2014. Kiddie-SADS, Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale, Child Behavior Checklist, Clinic Global Impression Scale Severity and Impression (CGIS-S-I) scales were used. Patients were between the ages of 7 and 17 years. Before combined pharmacotherapy the CGIS-S score mean was 5.08. Mean CGIS-S score after the combined pharmacotherapy was 3.08 (P = 0.03; -2,980). The most common side effects were irritability (n = 5, 41.6%), appetite reduction (n = 3, 25%), palpitations (n = 2, 16.7%), headache (n = 1, 8.3%). Nine of these 12 patients showed significant improvement in their symptoms, combined therapy enhanced the effectiveness of monotherapy.

Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections.

PubMed

Grossman, Chagai; Keller, Nathan; Bornstein, Gil; Ben-Zvi, Ilan; Koren-Morag, Nira; Rahav, Galia

2017-06-01

Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia. A cross-sectional study was conducted during January 2010-December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed. A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2-23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination. Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

[Individual parameters of general low-frequency magnetic therapy as a possibility for improving the clinical efficacy of the combined treatment of patients with essential arterial hypertension].

PubMed

Fedotov, V D; Maslov, A G; Lobkaeva, E P; Krylov, V N; Obukhova, E O

2012-01-01

A new approach is proposed for the choice of low-frequency magnetic therapy on an individual basis using the results of analysis of heart rhythm variability. The clinical efficiency of low-frequency magnetic therapy incorporated in the combined treatment of 65 patients aged between 25 and 45 years with essential arterial hypertension was estimated. The statistically significant positive effects of the treatment included normalization of blood pressure and characteristics of heart rhythm variability as well as resolution of clinical symptoms of vegetative dysregulation.

Cervical Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Cervical cancer treatment modalities include surgery, radiation therapy, chemotherapy and targeted therapy. They may be used alone or in combination depending on tumor volume, spread pattern, and FIGO staging. Get detailed information about cervical cancer treatment in this summary for clinicians.

Pituitary Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Pituitary tumors treatment can include surgery, radiation therapy, and medical therapy, either alone or in combination. Treatment is individualized and is dictated by the type of tumor, its location, and hormonal expression. Get detailed treatment information in ths summary for clinicians.

Novel anti-malarial combinations and their toxicity.

PubMed

Angus, Brian

2014-05-01

Artemisinin combination therapy for the treatment of uncomplicated malaria includes artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine and dihydroartemisinin plus piperaquine. These drugs are safe and efficacious at present. The emergence of artemisinin resistant parasites in SE Asia means that there is a need to optimise drug dosing and investigate novel therapies to maintain the impressive reduction in malaria mortality which has been seen in the past decade.

Advantages and Disadvantages of Combined Chemotherapy with Carmustine Wafer and Bevacizumab in Patients with Newly Diagnosed Glioblastoma: A Single-Institutional Experience.

PubMed

Akiyama, Yukinori; Kimura, Yuusuke; Enatsu, Rei; Mikami, Takeshi; Wanibuchi, Masahiko; Mikuni, Nobuhiro

2018-05-01

To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016. Twenty-five patients who underwent resection without BCNU implantation between 2010 and 2012 were enrolled as a control group; these patients were treated with the Stupp regimen and did not receive bevacizumab. This retrospective study included evaluation of progression-free survival and overall survival, plus comparisons between the combined therapy group and the control group. There were no significant differences in age, sex, Karnofsky Performance Status on admission, isocitrate dehydrogenase 1/2 mutation ratio, or resection rate between the combined and standard therapy groups. The median overall survival in the combined therapy group and control group was 24.2 months and 15.30, respectively (P = 0.027). The median progression-free survival was 16.8 months and 7.30 months, respectively (P = 0.009). Overall, the incidence of adverse events leading to discontinuation of the study drug was similar between the treatment groups, except for infection, which was more common in the combined treatment group and required repeat surgery. The combined therapy showed higher efficacy compared with standard therapy in patients with GBM. Therefore, combined therapy seems to be effective with an acceptable toxicity profile. Copyright © 2018 Elsevier Inc. All rights reserved.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

PubMed

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Reducing the rehospitalization risk after a manic episode: A population based cohort study of lithium, valproate, olanzapine, quetiapine and aripiprazole in monotherapy and combinations.

PubMed

Wingård, Louise; Bodén, Robert; Brandt, Lena; Tiihonen, Jari; Tanskanen, Antti; Kieler, Helle; Andersen, Morten; Reutfors, Johan

2017-08-01

Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited. We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors. The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy). Register data does not provide information on all clinical parameters affecting treatment choices. One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode. Copyright © 2017 Elsevier B.V. All rights reserved.

Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis.

PubMed

Clowse, Megan E B; Feldman, Steven R; Isaacs, John D; Kimball, Alexandra B; Strand, Vibeke; Warren, Richard B; Xibillé, Daniel; Chen, Yan; Frazier, Donald; Geier, Jamie; Proulx, James; Marren, Amy

2016-08-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta. The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting. Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up. Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up. The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.

Treatment of melasma with topical agents, peels and lasers: an evidence-based review.

PubMed

Rivas, Shelly; Pandya, Amit G

2013-10-01

Melasma is an acquired disorder of hyperpigmentation occurring on the face and predominantly affecting women of childbearing age. It is a chronic, often relapsing condition with a negative impact on quality of life. Current treatments for melasma are unsatisfactory. The aim of this article was to conduct an evidence-based review of interventions available for the treatment of melasma. A systematic literature search was performed using PubMed and the keywords 'melasma' or 'chloasma' in the title. The search was further refined by using a filter for 'controlled clinical trials' and 'randomized controlled trial'. The included studies were used to develop recommendations for treatment. The electronic search yielded a total of 80 citations. Forty studies were included in this review, which had a total of 2,912 participants. Three different therapeutic modalities were investigated-topical agents, chemical peels, and laser and light therapies. Topical depigmenting agents were found to be the most effective in treating moderate-to-severe melasma, with combination therapies, such as triple-combination therapy (hydroquinone, tretinoin, and fluocinolone acetonide), yielding the best results. Chemical peels as well as laser and light therapies were found to have moderate benefit but more studies are needed to determine their efficacy and long-term safety. Adverse events associated with treatment were mild and short-lasting and included skin irritation, dryness, burning, and erythema. The data could not be statistically pooled because of the heterogeneity of treatments and lack of consistency across study designs. Topical combination therapies were found to be more effective than monotherapy. Triple combination therapy was found to be the most effective, but approximately 40 % of patients develop erythema and peeling. Chemical peels and laser and light therapies produced mixed results, with increased risk of irritation and subsequent hyperpigmentation, particularly in darker-skinned individuals. Hence, current treatments available for melasma remain unsatisfactory. Many of the studies lacked long-term follow-up. Limitations of current literature include the heterogeneity of study designs, small sample sizes, and poor follow-up rates. Additional evidence for the effects and role of sunscreens is needed. Categorization or stratification of demographic data should also be included in future studies, such as age, melasma type, and duration of melasma prior to initiation of treatment. Patient's perception of improvement versus investigator's assessment of improvement should also be included in future studies and standardized methods of study design and assessment of outcomes are needed to form definitive conclusions on the efficacy of different treatment modalities.

Use and Characteristics of Antipsychotic/Methylphenidate Combination Therapy in Children and Adolescents with a Diagnosis of Attention-Deficit/Hyperactivity Disorder.

PubMed

Scholle, Oliver; Banaschewski, Tobias; Enders, Dirk; Garbe, Edeltraut; Riedel, Oliver

2018-05-16

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently have comorbidities that are potential indications for antipsychotics (APs). Some studies have suggested that the combined use of methylphenidate (MPH) and APs is increasing in this population group. Longitudinal analyses and in-depth investigations on the substance level are lacking. This study aimed to estimate the cumulative proportion of concomitant AP/MPH use in children and adolescents with ADHD over a follow-up of up to 9 years and to describe patient characteristics stratified by specific AP drug. Based on claims data, concomitant AP/MPH use was identified among 67,595 children and adolescents with ADHD starting MPH treatment between 2005 and 2013. Characteristics and diagnoses-including those indicating appropriateness of AP use according to approved indications and/or guidelines-were examined at the time of first AP/MPH combination therapy. In addition, subsequent use of AP/MPH combination therapy was evaluated. The cumulative proportion of individuals with any AP/MPH combination therapy rose to over 6% within 9 years after initiating MPH. The most frequent APs first used in combination with MPH were risperidone (72%), pipamperone (15%), and tiapride (8%). Percentages of psychiatric hospitalization in the year preceding the first combination therapy with MPH were 33%, 43%, and 19%, respectively. The proportion of individuals with potentially appropriate use was high (>72%) in risperidone/MPH and tiapride/MPH and low (15%) in pipamperone/MPH combination users. Conduct disorders and tic disorders were frequent in users who were prescribed MPH with risperidone and tiapride, respectively. One-quarter of patients with AP/MPH combination therapy were one-time-only combination users. Our study suggests that a considerable proportion of children and adolescents with ADHD receive MPH in combination with APs and that this is a factor not only during the first years of MPH treatment. ADHD guidelines should specify algorithms concerning the use of AP medication.

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

PubMed Central

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

[Changes of twenty-four-hour profile blood pressure and its correction of patients with arterial hypertension on the background of combined antihypertensive therapy application].

PubMed

Solomennchuk, T M; Slaba, N A; Prots'ko, V V; Bedzaĭ, A O

2014-01-01

The aim of this research was the study of efficiency and endurance antihypertensive therapy on the basis of fixed combination of enalapril and hydrochlorothiazide (HCTZ) and enalapril and HCTZ in combination with amlodipine according to the twenty-four-hour (? day-and-night) monitoring of blood pressure (? 24H BPM) of patients with arterial hypertension (AH) 2-3 severity. The study included 33 patients with 2-3 grade of hypertension (average age--54,40 ± 3.45 years). All patients performed ? 24H BPM before treatment and after 12 weeks of therapy. The combination of enalapril and HCTZ allowed to achieve target levels of blood pressure in 79% of patients, amlodipine additional purpose--in 86% of patients. We found that this therapy has a corrective effect on daily blood pressure profile, significantly reducing the load pressure and blood pressure variability. During treatment with the combination of enalapril and HCTZ combination of enalapril, HCTZ with amlodipine optimal daily profile of blood pressure after 12 weeks of reaching respectively 63.1% and 71.4% of patients. The treatment with combination of enalapril and HCTZ and adding of amlodipine is characterized by good endurance and high adherence to treatment.

Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study.

PubMed

Sitbon, Olivier; Jaïs, Xavier; Savale, Laurent; Cottin, Vincent; Bergot, Emmanuel; Macari, Elise Artaud; Bouvaist, Hélène; Dauphin, Claire; Picard, François; Bulifon, Sophie; Montani, David; Humbert, Marc; Simonneau, Gérald

2014-06-01

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH. ©ERS 2014.

Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy.

PubMed

Keating, Gillian M

2009-06-18

Losartan/hydrochlorothiazide (HCTZ) [Hyzaar(R)] is a fixed-dose combination of the angiotensin II receptor antagonist (angiotensin receptor blocker [ARB]) losartan and the thiazide diuretic HCTZ. It is indicated for the treatment of hypertension (including as initial therapy in severe hypertension) and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan/HCTZ is an effective combination therapy, lowering blood pressure (BP) to a greater extent than losartan or HCTZ alone in patients with hypertension. Other ARB/HCTZ fixed-dose combinations generally lowered BP to a greater extent than losartan/HCTZ in patients with hypertension, although whether this translates into improvements in cardiovascular outcomes is not known. In the LIFE study, losartan-based therapy was associated with a lower incidence of cardiovascular morbidity and mortality than atenolol-based therapy, mainly as a result of a reduced risk of stroke; the incidence of new-onset diabetes mellitus was also lower with losartan-based therapy. Losartan/HCTZ is a well tolerated combination therapy. Thus, losartan/HCTZ remains an important option in the treatment of hypertension, as well as being indicated to reduce stroke risk in patients with hypertension and LVH.

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

PubMed

Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

2017-02-01

To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

A novel bFGF-GH injection therapy for two patients with severe ischemic limb pain.

PubMed

Ito, Naomi; Saito, Shigeru; Yamada, Makiko Hardy; Koizuka, Shiro; Obata, Hideaki; Nishikawa, Koichi; Tabata, Yasuhiko

2008-01-01

Severe ischemic pain is difficult to treat with a single therapy. Although modern angiogenic therapies have been used in patients with peripheral arterial occlusive diseases, a regimen combining novel angiogenic therapy and classic nerve blocks, including sympathectomy, has not been discussed to date. In this case report, we present two patients with peripheral arterial occlusive disease who were first treated with medication and lumbar sympathectomy, and then with a novel gelatin hydrogel drug-delivery system loaded with basic fibroblast growth factor. The gelatin hydrogel combined with recombinant basic fibroblast growth factor was injected intramuscularly into the ischemic limbs. In the first patient, with arteriosclerosis obliterans, a foot ulcer was healed, and the original score for resting pain (visual analogue scale, 5/10) was decreased to 0/10. In the second patient, with Buerger's disease, a large toe ulcer was healed, and his resting pain (visual analogue scale, 8/10) was decreased to 1/10. Some other parameters, such as skin surface temperature, transcutaneous oxygen partial pressure, and pain-free walking distance, were also improved in both patients after the combined therapy. A multimodal approach is necessary to treat severe ischemic pain. Novel angiogenic therapy combined with nerve blocks seems to be a promising option in patients with severe pain.

Ezetimibe-Statin Combination Therapy.

PubMed

Nußbaumer, Barbara; Glechner, Anna; Kaminski-Hartenthaler, Angela; Mahlknecht, Peter; Gartlehner, Gerald

2016-07-01

To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

PubMed

Suii, Hirokazu; Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin

PubMed Central

Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was −3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only −1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV. PMID:29375917

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial.

PubMed

Brummel, N E; Girard, T D; Ely, E W; Pandharipande, P P; Morandi, A; Hughes, C G; Graves, A J; Shintani, A; Murphy, E; Work, B; Pun, B T; Boehm, L; Gill, T M; Dittus, R S; Jackson, J C

2014-03-01

Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial

PubMed Central

Brummel, N.E.; Girard, T.D.; Ely, E.W.; Pandharipande, P.P.; Morandi, A.; Hughes, C.G.; Graves, A.J.; Shintani, A.K.; Murphy, E.; Work, B.; Pun, B.T.; Boehm, L.; Gill, T.M.; Dittus, R.S.; Jackson, J.C.

2013-01-01

PURPOSE Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3-months, we also assessed cognitive, functional and health-related quality of life outcomes. Data are presented as median [interquartile range] or frequency (%). RESULTS Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% [92–100%] of study days beginning 1.0 [1.0–1.0] day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients and 42/43 (98%) of cognitive plus physical therapy patients on 17% [10–26%], 67% [46–87%] and 75% [59–88%] of study days, respectively. Cognitive, functional and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment and benefits of cognitive therapy in the critically ill is needed. PMID:24257969

Immunosuppression in inflammatory bowel disease: traditional, biological or both?

PubMed

Van Assche, Gert; Vermeire, Séverine; Rutgeerts, Paul

2009-07-01

To focus on the emerging clinical evidence for the use of traditional immunosuppressives and biologicals in the treatment of inflammatory bowel disease. Evidence published this year indicates that in Crohn's disease the early use of combined infliximab and purine analogues before the introduction of steroid therapy induces faster steroid-free remission and improves mucosal healing. We have also learned that, in patients with Crohn's disease who are naïve to traditional immunosuppressive therapy, combined infliximab and azathioprine improves clinical and mucosal healing outcomes at 6 months. On the contrary, in patients already exposed to traditional immunosuppressives prior to starting infliximab, withdrawal of azathioprine or methotrexate after 6 months of combined scheduled infliximab maintenance with these agents does not affect outcomes after 2 years of continued infliximab therapy. Finally, several important studies on the safety of immunosuppressives including anti-tumour necrosis factor agents have been published. The cumulative body of evidence suggests that combined immunosuppressive therapy in patients with inflammatory bowel disease increases toxicity. Treatment paradigms for traditional immunosuppressives and biologicals in inflammatory bowel disease are evolving, and the choice of therapy becomes highly dependent on the drugs previously used and disease severity.

[Platelet aggregation and antiplatelet agents in acute coronary syndromes].

PubMed

Collet, Jean-Philippe; Choussat, Rémi; Montalescot, Gilles

2004-03-01

Antiplatelet agents are the cornerstone therapy of acute coronary syndromes. In the setting of ST elevation myocardial infarction, antiplatelet therapy prevent the prothrombotic effect of reperfusion therapy including thrombolysis and primary percutaneous coronary intervention. In non ST-elevation acute coronary syndromes, antiplatelet therapy prevent s complete coronary thrombotic occlusion and therefore the occurrence of ST elevation myocardial infarction. Antiplatelet agent benefit is related to the patient's risk profile. It is well established that combined antiplatelet therapy is the most effective in high risk patients. Several important issues have to be faced including the identification of non responders, dose adjustment and the management of temporary interruption of antiplatelet agents in stable coronary artery disease patients.

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

PubMed

Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

2014-11-30

Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when outcomes were measured on different scales. We included eleven studies, involving 1307 participants in this review. We also identified one ongoing study, and two additional ongoing studies that may be eligible for inclusion. Studies recruited participants with different severities of disorder and with a variety of comorbid disorders, including anxiety and substance use disorder, therefore limiting the comparability of the results. Regarding the risk of bias in studies, just under half the studies had adequate allocation concealment (there was insufficient information to determine allocation concealment in the remainder), outcome assessors were blind to the participants' intervention in six studies, and in general, studies reported on incomplete data analysis methods, mainly using intention-to-treat (ITT) analyses. For the majority of outcomes there were no statistically significant differences between the interventions compared. There was limited evidence (based on two studies involving 220 participants) that antidepressant medication was more effective than psychotherapy on measures of clinician defined remission immediately post-intervention (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the medication group and 53.7% in the psychotherapy group rated as being in remission. There was limited evidence (based on three studies involving 378 participants) that combination therapy was more effective than antidepressant medication alone in achieving higher remission from a depressive episode immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of participants treated with combination therapy and 57.8% of participants treated with medication, rated as being in remission. There was no evidence to suggest that combination therapy was more effective than psychological therapy alone, based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI 0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in various ways across studies and could not be combined in meta-analyses. However, some trials measured suicidal ideation using standardised assessment tools suitable for meta-analysis. In one study involving 188 participants, rates of suicidal ideation were significantly higher in the antidepressant medication group (18.6%) compared with the psychological therapy group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at six to nine months (OR 0.26, 95% CI 0.07 to 0.98), with 13.6% of participants in the medication group and 3.9% of participants in the psychological therapy group reporting suicidal ideation. It was unclear what the effect of combination therapy was compared with either antidepressant medication alone or psychological therapy alone on rates of suicidal ideation. The impact of any of the assigned treatment packages on drop out was also mostly unclear across the various comparisons in the review.Limited data and conflicting results based on other outcome measures make it difficult to draw conclusions regarding the effectiveness of any specific intervention based on these outcomes. There is very limited evidence upon which to base conclusions about the relative effectiveness of psychological interventions, antidepressant medication and a combination of these interventions. On the basis of the available evidence, the effectiveness of these interventions for treating depressive disorders in children and adolescents cannot be established. Further appropriately powered RCTs are required.

A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study.

PubMed

Kant, S B; van den Kerckhove, E; Colla, C; Tuinder, S; van der Hulst, R R W J; Piatkowski de Grzymala, A A

2018-01-01

Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars. Fifty-eight patients with hypertrophic scars ( n  = 31) and keloid scars ( n  = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly ( P  < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3-4 months, 4-6 months, and >12 months after start of therapy in both keloids and hypertrophic scars. This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.Level of evidence: Level IV, therapeutic study.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Newer influenza antivirals, biotherapeutics and combinations.

PubMed

Hayden, Frederick G

2013-01-01

This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high-risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host-directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host-directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. © 2012 Blackwell Publishing Ltd.

Trial Protocol: Cognitive functional therapy compared with combined manual therapy and motor control exercise for people with non-specific chronic low back pain: protocol for a randomised, controlled trial.

PubMed

Belache, Fabiana Terra Cunha; Souza, Cíntia Pereira de; Fernandez, Jessica; Castro, Julia; Ferreira, Paula Dos Santos; Rosa, Elizana Rodrigues de Sousa; Araújo, Nathalia Cristina Gimenez de; Reis, Felipe José Jandre; Almeida, Renato Santos de; Nogueira, Leandro Alberto Calazans; Correia, Luís Cláudio Lemos; Meziat-Filho, Ney

2018-06-11

Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy is an intervention that deals with potentially modifiable multidimensional aspects of pain (eg, provocative cognitive, movement and lifestyle behaviours). There is evidence (from a single randomised, controlled trial) that cognitive functional therapy is better than combined manual therapy and motor control exercise. However, this study had significant methodological shortcomings including the failure to carry out an intention-to-treat analysis and a considerable loss of follow-up of participants. It is important to replicate this study in another domain through a randomised clinical trial with similar objectives but correcting these methodological shortcomings. To investigate the efficacy of cognitive functional therapy compared to combined manual therapy and exercise on pain and disability at 3 months in patients with chronic non-specific low back pain. Two-group, randomised, multicentre controlled trial with blinded assessors. One hundred and forty-eight participants with chronic low back pain that has persisted for >3months and no specific spinal pathology will be recruited from the school clinic of the Centro Universitário Augusto Motta and a private clinic in the city of Rio de Janeiro, Brazil. Four to 10 sessions of cognitive functional therapy. The physiotherapists who will treat the participants in the cognitive functional therapy group have previously attended 2 workshops with two different tutors of the method. Such physiotherapists have completed 106 hours of training, including workshops and patient examinations, as well as conducting a pilot study under the supervision of another physiotherapist with>3 years of clinical experience in cognitive functional therapy. Four to 10 sessions of combined manual therapy and motor control exercises. Participants in the combined manual therapy and exercise group will be treated by two physiotherapists with an average of >10years of clinical experience in manual therapy and motor control exercises, including isolated contractions of the deep abdominal muscles. The primary outcome measures will be pain intensity and disability 3 months after randomisation. Secondary outcomes will be pain and disability assessed 6 and 12 months after randomisation, and both global perceived effect and patient satisfaction at 3, 6 and 12 months after randomisation. The potential outcome mediators will be assessed at 3 and 6 months after randomisation, with brief screening questions for anxiety, social isolation, catastrophisation, depression, fear of movement, stress and sleep. Non-specific predictors and moderators will include age, gender, duration of chronic low back pain, chronicity risk (Örebro and Start Back score), number of pain areas, stressful life event, MRI scan imaging, and family history. Intention-to-treat analysis will be performed. Linear mixed models will be used to compare the mean differences in pain intensity, disability and global perceived effect between the intervention arms. The analysis of the effect of potential mediators of the treatment will be performed using the causal mediation methods described by Imai and colleagues. The baseline variables will be evaluated as predictors and moderators of treatment, including terms and interaction models. A level of statistical significance of 5% will be used in the analysis. All the analyses will be performed using RStudio. This study will investigate whether the results of the first cognitive functional therapy randomised clinical trial are reproducible. The present study will have a sample size capable of detecting clinically relevant effects of the treatment with a low risk of bias. In pragmatic terms, this clinical trial is designed to reproduce the intervention as it would be performed in clinical practice by a trained physiotherapist who works with cognitive functional therapy, which increases the relevance of this study. The combined manual therapy and exercise group comprises an intervention strategy widely used by physiotherapists to treat low back pain. As evidence of efficacy is still limited, the results of a randomised, controlled clinical trial of high methodological quality will help physiotherapists in clinical decision-making. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Modena, Tiziana; Conti, Bice; Benazzo, Francesco; Gastaldi, Giulia; Genta, Ida

2017-01-01

A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue regeneration. This mini-review is focused on the combination of the local delivery of antibiotic agents with bone regenerative therapy for the treatment of a severe bone infection such as osteomyelitis. The review includes a brief explanation of scaffolds for bone regeneration including scaffolds characteristics and types, a focus on severe bone infections (especially osteomyelitis and its treatment), and a literature review of local antibiotic delivery by the combination of scaffolds and drug-delivery systems. Some examples related to published studies on gentamicin sulfate-loaded drug-delivery systems combined with scaffolds are discussed, and future perspectives are highlighted. PMID:29231857

Combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation versus placebo in type 2 diabetes.

PubMed

Bay, Roohallah; Bay, Fatemeh

2011-09-01

Type 2 diabetes is one of the most widespread diseases in the world. The main aim of this research was to evaluate the effect of combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation (TM) on the blood sugar (BS) level in comparison with placebo in type 2 diabetic patients. We used "convenience sampling" for selection of patients with type 2 diabetes; 20 patients were recruited. For collection of data, we used an identical quasi-experimental design called "nonequivalent control group." Therapy sessions each lasting 60-90 min were carried out on 10 successive days. We prescribed 2 capsules (containing 3g of wheat flour each) for each member of the placebo group (one for evening and one for morning). Pre-tests, post-tests, and follow-up tests were conducted in a medical laboratory recognized by the Ministry of Health and Medical Education of Iran. Mean BS level in the post-tests and follow-up tests for the experimental group was reduced significantly in comparison with the pre-tests whereas in the placebo group no changes were observed. Combined therapy including acupressure therapy, hypnotherapy, and TM reduced BS of type 2 diabetic patients and was more effective than placebo therapy on this parameter. Copyright © 2011. Published by Elsevier B.V.

Polymer-Based Nanocarriers for Co-Delivery and Combination of Diverse Therapies against Cancers

PubMed Central

Yan, Guowen; Li, Aihua; Zhang, Aitang; Sun, Yong; Liu, Jingquan

2018-01-01

Cancer gives rise to an enormous number of deaths worldwide nowadays. Therefore, it is in urgent need to develop new therapies, among which combined therapies including photothermal therapy (PTT) and chemotherapy (CHT) using polymer-based nanocarriers have attracted enormous interest due to the significantly enhanced efficacy and great progress has been made so far. The preparation of such nanocarriers is a comprehensive task involving the cooperation of nanomaterial science and biomedicine science. In this review, we try to introduce and analyze the structure, preparation and synergistic therapeutic effect of various polymer-based nanocarriers composed of anti-tumor drugs, nano-sized photothermal materials and other possible parts. Our effort may bring benefit to future exploration and potential applications of similar nanocarriers. PMID:29401694

The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy.

PubMed

Moore, Colin; Kosgodage, Uchini; Lange, Sigrun; Inal, Jameel M

2017-08-01

There is an urgent need to develop new combination therapies beyond existing surgery, radio- and chemo-therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immunosuppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis. One promising cancer immunotherapy discussed uses cationic liposomes carrying tumour RNA (RNA-lipoplexes) to provoke a strong anti-viral-like (cytotoxic CD8 + ) anti-tumour immune response. Mesenchymal stem cell-derived EMVs, with their capacity to migrate towards inflammatory areas including solid tumours, have also been used. As tumour EMVs clearly exacerbate the tumour microenvironment, another therapy option could involve EMV removal. Affinity-based methods to deplete EMVs, including an immunodepletion, antibody-based affinity substrate, are therefore considered. Finally EMV and exosome-mimetic nanovesicles (NVs) delivery of siRNA or chemotherapeutic drugs that target tumours using peptide ligands for cognate receptors on the tumour cells are discussed. We also touch upon the reversal of drug efflux in EMVs from cancer cells which can sensitize cells to chemotherapy. The use of immunotherapy in combination with the advent of EMVs provides potent therapies to various cancers. © 2017 UICC.

Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

The incidence of photodamaged skin and skin lesions of all degrees of severity, from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic keratoses are pathologic, reflecting damage of essential skin cell functions and potentially progressing to invasive squamous cell carcinoma (SCC). The rate of progression is uncertain but may be as high as 10%. Because it is impossible to predict which AKs will progress to SCC, all lesions should be treated. Options include topical therapies, cryotherapy, curettage, and photodynamic therapy. Unfortunately, many individuals do not seek treatment or avoid it because of irritation, discomfort, and concern for scarring. Combining field-directed therapy and cryotherapy has been more effective than cryotherapy alone. Incorporating patient education with treatment may optimize outcomes. We propose a comprehensive 5-step approach for managing AK lesions and photodamaged skin that includes periodic clinical skin examinations; treating AK lesions with a combination of field- and lesion-directed therapy; and patient education regarding sun-protective measures and regular skin self-examinations.

The Effect of Orthodontic Therapy on Periodontal Health: A Review of the Literature

PubMed Central

Alfuriji, Samah; Alhazmi, Nora; Alhamlan, Nasir; Al-Ehaideb, Ali; Alruwaithi, Moatazbellah; Alkatheeri, Nasser; Geevarghese, Amrita

2014-01-01

Objectives. This review aims to evaluate the effect of orthodontic therapy on periodontal health. Data. Original articles that reported on the effect of orthodontic therapy on periodontal health were included. The reference lists of potentially relevant review articles were also sought. Sources. A literature search was conducted using the databases, Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies. The search was carried out by using a combined text and the MeSH search strategies: using the key words in different combinations: “periodontal disease,” “orthodontics” and “root resorption.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Articles published only in English language were included. Letters to the Editor, historical reviews and unpublished articles were not sought. Conclusions. Within the limitations of the present literature review, it was observed that there is a very close inter-relationship between the periodontal health and the outcome of orthodontic therapy. PMID:24991214

[The assessment of the effectiveness of fenspiride (erespal) for the combined treatment of the patients presenting with exudative otitis media].

PubMed

Mel'chinskiĭ, A N; Vasilenko, D Iu; Kiseleva, G V

2013-01-01

The objective of the present work was to estimate the effectiveness and safety of combined anti-inflammatory therapy of exudative otitis media with the use of fenspiride (erespal). The study included 75 patients of whom 35 (group 1) were given standard therapy supplemented by erespal (80 mg thrice daily); the remaining patients receiving standard therapy alone formed group 2 (control). The patients treated with erespal reported the subjective improvement of hearing and reduced congestion on days 7 - 8. Similar changes in group 2 occurred on day 10. It is concluded that the use of erespal for the combined treatment of the patients presenting with exudative otitis media reduces the duration of hospital stay, accelerates recovery, and promotes rapid normalization of hearing.

Newer influenza antivirals, biotherapeutics and combinations

PubMed Central

Hayden, Frederick G.

2012-01-01

Please cite this paper as: Hayden FG. (2012) Newer Influenza Antivirals, Biotherapeutics and Combinations. Influenza and Other Respiratory Viruses 7(Suppl. 1), 63–75. This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high‐risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host‐directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host‐directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed. PMID:23279899

Modeling combination therapy for breast cancer with BET and immune checkpoint inhibitors.

PubMed

Lai, Xiulan; Stiff, Andrew; Duggan, Megan; Wesolowski, Robert; Carson, William E; Friedman, Avner

2018-05-07

CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor. The model shows that the two drugs are positively correlated in the sense that the tumor volume decreases as the dose of each of the drugs is increased. The model also considers the effect of the combined therapy on levels of myeloid-derived suppressor cells (MDSCs) and the overexpression of TNF-[Formula: see text], which may predict gastrointestinal side effects of the combination.

Treatment of selective mutism based on cognitive behavioural therapy, psychopharmacology and combination therapy - a systematic review.

PubMed

Østergaard, Kasper Rud

2018-05-01

Selective mutism (SM) is a debilitating childhood anxiety disorder characterized by a persistent lack of speech in certain social settings and is considered hard to treat. Cognitive behavioral therapy (CBT) and pharmacological treatments are the best described treatments in the literature. To test whether there is evidence on treatment based on CBT, medication or a combination of these. Systematic and critical review of the literature on CBT and/or pharmacological treatments of SM. Literature was sought on PubMed, Embase and Psycinfo in March 2017. Of the included studies, six examined CBT, seven pharmacologic treatment and two a combination of these. Using CBT 53/60 children improved symptomatically whilst respectively 55/67 and 6/7 improved using pharmacologic- and combination-treatment. Pharmacologic treatment and especially CBT showed promising results supported by some degree of evidence, which combination treatment lacks. Yet small numbers, few RCTs, heterogeneous study designs, lack of consistent measures, short treatment and follow-up periods, generally limits the evidence. This needs focus in future research.

Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

PubMed

Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

2016-06-01

Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

PubMed Central

Bai, Wenxia; Wang, Shudong; An, Shanshan; Guo, Mengjie; Gong, Guangming; Liu, Wenya; Ma, Shaoxin; Li, Xin; Fu, Jihua; Yao, Wenbing

2018-01-01

This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure. PMID:29643988

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria.

PubMed

Stickles, Allison M; Smilkstein, Martin J; Morrisey, Joanne M; Li, Yuexin; Forquer, Isaac P; Kelly, Jane X; Pou, Sovitj; Winter, Rolf W; Nilsen, Aaron; Vaidya, Akhil B; Riscoe, Michael K

2016-08-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria

PubMed Central

Smilkstein, Martin J.; Morrisey, Joanne M.; Li, Yuexin; Forquer, Isaac P.; Kelly, Jane X.; Pou, Sovitj; Winter, Rolf W.; Nilsen, Aaron; Vaidya, Akhil B.

2016-01-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. PMID:27270285

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

PubMed

Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

2017-07-01

Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials. Morin M, Carroll M-S, Bergeron S. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia. Sex Med Rev 2017;5:295-322. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

PubMed

Nkoli Mandoko, P; Sinou, V; Moke Mbongi, D; Ngoyi Mumba, D; Kahunu Mesia, G; Losimba Likwela, J; Bi Shamamba Karhemere, S; Muepu Tshilolo, L; Tamfum Muyembe, J-J; Parzy, D

2018-06-01

Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. We performed a cross-sectional survey of 404 pharmacies. Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[The effects of combination therapy with 5-reductase inhibitor and -blocker on the prognosis of BPH].

PubMed

Neimark, A I; Davydov, A V; Aliev, R T

2018-05-01

Benign prostatic hyperplasia (BPH) is a polyethological disease of elderly and old men. The symptomatic pharmacological treatment of BPH involves the use of drugs that reduce either the dynamic component of obstruction or the size of the prostate (a mechanical component of obstruction). 5-reductase inhibitors (5-ARI) and -blockers are considered first-line therapy in the management of prostate adenoma. To investigate the efficacy of combination therapy with Fokusin and Penester in BPH patients. The study is based on the analysis of medical records of 67 BPH patients aged over 50 years. All patients included in the study were randomized to 3 groups and had comparable age, sex, clinical manifestations and severity of the disease. Group 1 comprised 21 patients (mean age 63.8+/-9.7 years), who received a 5-reductase inhibitor (5-ARI) Pentester (Sanofi, France) 5 mg once daily. Group 2 included 22 patients (mean age 65.2+/-7.8 years), who received an -blocker Fokusin (Sanofi, France) 0.4 mg once a day. Group 3 comprised 24 patients (mean age 64.2+/-8.6 years) who received combination therapy with 5-reductase inhibitor (5-ARI) (Penester 5 mg once daily) and blocker (Fokusin 0.4 mg once daily). The study findings showed that in comparison with monotherapy, the concurrent administration of Fokusin and Penester was more effective in reducing the clinical manifestations of BPH, slowing the growth of adenomatous tissue thus reducing the size of the enlarged prostate. Combination therapy with Fokusin and Penester can be recommended to improve the treatment results of BPH patients.

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review

PubMed Central

Ogawa, Kohei; Mizuno, Ken-ichi; Shinagawa, Yoko; Kobayashi, Yuji; Abe, Hiroyuki; Watanabe, Yukari; Takahashi, Shunsaku; Hayashi, Kazunao; Yokoyama, Junji; Takeuchi, Manabu; Yamagiwa, Satoshi; Sato, Yuichi; Terai, Shuji

2016-01-01

Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently. PMID:27642293

Acarbose plus metformin fixed-dose combination in the management of type 2 diabetes.

PubMed

Joshi, Shashank R; Ramachandran, Ambady; Chadha, Manoj; Chatterjee, Sudip; Rathod, Rahul; Kalra, Sanjay

2014-08-01

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Concerns in the management of diabetes include drug-induced hypoglycemia, poor control of postprandial blood glucose level and weight gain. A carbohydrate-rich diet can cause more load on the intestinal cells producing α-glucosidase. Many patients need combination treatment based on their level of glycemic control and other associated parameters. In such cases, a therapy that provides effective glycemic control with minimal or no risk of adverse events like hypoglycemia or weight gain is highly desired. The chances of cardiovascular events are high in diabetes patients; hence, medicines providing benefits beyond glycemic control such as reduced cardiovascular risk factors may be ideal in such patients. Current available data are related to the rationale and clinical trials on the fixed-dose combination of acarbose plus metformin in management of type 2 diabetes. Combination therapy is routinely prescribed in the management of T2DM. Drugs with complimentary mechanisms should be used to maximize the efficacy of combination therapy. The combination of metformin and acarbose is a rational therapy because of their different and complimentary mechanisms of action, which provides effective glycemic control with additional cardiovascular benefits and minimizes adverse events.

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

PubMed Central

Fleischmann, Roy; Wollenhaupt, Jürgen; Takiya, Liza; Maniccia, Anna; Kwok, Kenneth; Wang, Lisy; van Vollenhoven, Ronald F

2017-01-01

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies. Methods Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months. Results Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching. Conclusion Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment regimens. Safety was consistent over 96 months. Clinical trial registration NCT00413699 (Pre-results) and NCT00661661 (Results). PMID:29435359

RF waveguide phase-directed power combiners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nantista, Christopher D.; Dolgashev, Valery A.; Tantawi, Sami G.

2017-05-02

High power RF phase-directed power combiners include magic H hybrid and/or superhybrid circuits oriented in orthogonal H-planes and connected using E-plane bends and/or twists to produce compact 3D waveguide circuits, including 8.times.8 and 16.times.16 combiners. Using phase control at the input ports, RF power can be directed to a single output port, enabling fast switching between output ports for applications such as multi-angle radiation therapy.

Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, C-H; Cheong, K A; Park, C D; Lee, A-Y

2012-05-01

Tacrolimus (FK-506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)-like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK-506 in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK-506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2-mediated cytokines and chemokines, CD3(+) T cells and CLA(+) T cells. Combined therapy using glucosamine plus FK-506 improved the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3(+) T cells and CLA(+) cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Somatic Treatments for Mood Disorders

PubMed Central

Rosa, Moacyr A; Lisanby, Sarah H

2012-01-01

Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID:21976043

Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zech, N; Hansen, E; Bernardy, K; Häuser, W

2017-02-01

This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library, MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCTs) comparing GI/H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3-month follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI).Seven RCTs with 387 subjects were included into a comparison of GI/H versus controls. There was a clinically relevant benefit of GI/H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy. Acceptability at the end of treatment for GI/H was not significantly different to the control. Two RCTs with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow-up. No study reported on safety. GI/H hold promise in a multicomponent management of fibromyalgia. We provide a systematic review with meta-analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural therapy in reducing key symptoms of fibromyalgia. © 2016 European Pain Federation - EFIC®.

Economic evaluations of fluticasone-propionate/salmeterol combination therapy for chronic obstructive pulmonary disease: a review of published studies.

PubMed

Roberts, M H; Borrego, M E; Kharat, A A; Marshik, P L; Mapel, D W

2016-01-01

This review identifies and evaluates the comprehensive reporting of peer-reviewed economic evaluations of the effectiveness of fluticasone-propionate/salmeterol combination (FSC) therapy for maintenance treatment of chronic obstructive pulmonary disease (COPD). Economic evaluations were included if published in English since 2003. Evaluation categories included in the review were cost-effectiveness, cost-utility, and cost-consequence analyses. FSC is cost-effective in comparison to short-acting bronchodilators (SABDs). Cost and outcome differences between FSC and other long-acting therapies were modest. Studies exhibited large variations in populations, designs and environment, limiting the ability to draw conclusions. Many new maintenance treatments for COPD have been approved since 2010. Most have yet to be compared to older treatments like FSC. Evaluations are needed that consider costs and outcomes from a societal perspective (e.g., patients' ability to keep working) and evaluations that include subgroup analyses to investigate differential impacts according to clusters of patient characteristics.

In vitro therapeutic effect of PDT combined with VEGF-A gene therapy

NASA Astrophysics Data System (ADS)

Lecaros, Rumwald Leo G.; Huang, Leaf; Hsu, Yih-Chih

2014-02-01

Vascular endothelial growth factor A (VEGF-A), commonly known as VEGF, is one of the primary factors that affect tumor angiogenesis. It was found to be expressed in cancer cell lines including oral squamous cell carcinoma. Photodynamic therapy (PDT) is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates oxygen-independent hypoxic conditions to tumor. Another emerging treatment to cure cancer is the use of interference RNA (e.g. siRNA) to silence a specific mRNA sequence. VEGF-A was found to be expressed in oral squamous cell carcinoma and overexpressed after 24 hour post-PDT by Western blot analysis. Cell viability was found to decrease at 25 nM of transfected VEGF-A siRNA. In vitro combined therapy of PDT and VEGF-A siRNA showed better response as compared with PDT and gene therapy alone. The results suggest that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.

Combination therapy in hypertension: an Asia-Pacific consensus viewpoint.

PubMed

Abdul Rahman, Abdul Rashid; Reyes, Eugenio B; Sritara, Piyamitr; Pancholia, Arvind; Van Phuoc, Dang; Tomlinson, Brian

2015-05-01

Hypertension incurs a significant healthcare burden in Asia-Pacific countries, which have suboptimal rates of blood pressure (BP) treatment and control. A consensus meeting of hypertension experts from the Asia-Pacific region convened in Hanoi, Vietnam, in April 2013. The principal objectives were to discuss the growing problem of hypertension in the Asia-Pacific region, and to develop consensus recommendations to promote standards of care across the region. A particular focus was recommendations for combination therapy, since it is known that most patients with hypertension will require two or more antihypertensive drugs to achieve BP control, and also that combinations of drugs with complementary mechanisms of action achieve BP targets more effectively than monotherapy. The expert panel reviewed guidelines for hypertension management from the USA and Europe, as well as individual Asia-Pacific countries, and devised a treatment matrix/guide, in which they propose the preferred combination therapy regimens for patients with hypertension, both with and without compelling indications. This report summarizes key recommendations from the group, including recommended antihypertensive combinations for specific patient populations. These strategies generally entail initiating therapy with free drug combinations, starting with the lowest available dosage, followed by treatment with single-pill combinations once the BP target has been achieved. A single reference for the whole Asia-Pacific region may contribute to increased consistency of treatment and greater proportions of patients achieving BP control, and hence reducing hypertension-related morbidity and mortality.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

PubMed

Biondi, Bernadette; Wartofsky, Leonard

2012-07-01

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

Near-infrared light-responsive nanomaterials in cancer therapeutics.

PubMed

Shanmugam, Vijayakumar; Selvakumar, S; Yeh, Chen-Sheng

2014-09-07

Noninvasive techniques, such as breath tests (urea breath test), blood pressure measurements using a sphygmomanometer and electrocardiography, were employed by a physician to perform classical diagnosis. The use of state-of-the-art noninvasive therapies at the organ level in modern medicine has gradually become possible. However, cancer treatment demands spatially and temporally controlled noninvasive therapy at the cell level because nonspecific toxicity often causes complicated side effects. To increase survival in cancer patients further, combination therapy and combination drugs are explored which demand high specificity to avoid combined-drug side effects. We believe that high specificity could be obtained by implementing near-infrared (NIR) light-assisted nanoparticles in photothermal therapy, chemotherapy, and photodynamic therapy. To refine this therapy and subsequently achieve high efficiency, novel nanomaterials have been designed and modified either to enhance the uptake and drug delivery to the cancer site, or control treatment to administer therapy efficiently. These modifications and developments have been demonstrated to achieve spatial and temporal control when conducting an in vivo xenograft, because the NIR light penetrated effectively the biological tissue. The nanoplatforms discussed in this review are grouped under the following subheadings: Au nanorods (NRs), Au nanoshells, other Au-related nanomaterials, graphene oxide, upconversion nanoparticles, and other related materials (including materials such as CuS, Fe3O4-related systems, and carbon nanotubes (CNTs)).

Stereotactic body radiation therapy for oligometastases.

PubMed

Lo, Simon S; Fakiris, Achilles J; Teh, Bin S; Cardenes, Higinia R; Henderson, Mark A; Forquer, Jeffrey A; Papiez, Lech; McGarry, Ronald C; Wang, Jian Z; Li, Kaile; Mayr, Nina A; Timmerman, Robert D

2009-05-01

The standard treatment for metastatic cancer is systemic therapy. However, in a subset of patients with limited extracranial metastases or oligometastases, local ablative therapy in combination with systemic therapy may improve treatment outcomes. Stereotactic body radiation therapy (SBRT) has emerged as a novel approach for local ablation of extracranial oligometastases. There is a good body of experience in the use of SBRT for the treatment of oligometastases in various sites including the lung, the liver and the spine with promising results. This article provides an overview of the use of SBRT in the management of extracranial oligometastases.

Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma.

PubMed

Sonpavde, Guru; Pond, Gregory R; Choueiri, Toni K; Mullane, Stephanie; Niegisch, Guenter; Albers, Peter; Necchi, Andrea; Di Lorenzo, Giuseppe; Buonerba, Carlo; Rozzi, Antonio; Matsumoto, Kazumasa; Lee, Jae-Lyun; Kitamura, Hiroshi; Kume, Haruki; Bellmunt, Joaquim

2016-04-01

Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Data were available from eight trials including 370 patients; two trials (n=109) evaluated single-agent chemotherapy with docetaxel (n=72) and cremophor-free paclitaxel (n=37), and six trials (n=261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n=99 and n=24), paclitaxel-cyclophosphamide (n=32), paclitaxel-ifosfamide-nedaplatin (n=45), docetaxel-ifosfamide-cisplatin (n=26), and paclitaxel-epirubicin (n=35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p=0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Strategies for treatment of dystonia.

PubMed

Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

2016-03-01

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Improving patient outcomes to targeted therapies in melanoma.

PubMed

Eroglu, Zeynep; Smalley, Keiran S M; Sondak, Vernon K

2016-06-01

The arrival of targeted therapies has led to significant improvements in clinical outcomes for patients with BRAFV600 mutated advanced melanoma over the past five years. In several clinical trials, BRAF and MEK inhibitors have shown improvement in progression free and overall survival, along with much higher tumor response rates in comparison to chemotherapy, with the combination of these drugs superior to monotherapy. These agents are also being tested in earlier-stage patients, in addition to alternative dosing regimens and in combinations with other therapeutics. Efforts are also ongoing to expand the success found with targeted therapies to other subtypes of melanoma, including NRAS and c-kit mutated melanomas, uveal melanomas, and BRAF/NRAS wild type melanomas. Expert Commentary: We aim to provide an overview of clinical outcomes with targeted therapies in melanoma patients.

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

Treatment of psoriasis and long-term maintenance using 308 nm excimer laser, clobetasol spray, and calcitriol ointment: a case series.

PubMed

Wong, Jillian W; Nguyen, Tien V; Bhutani, Tina; Koo, John Y M

2012-08-01

Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.

Online learning: the potential for occupational therapy education.

PubMed

Hollis, Vivien; Madill, Helen

2006-01-01

Online learning continues to have a significant impact on higher education. Increasingly students seek a combination of online learning and face-to-face instruction at undergraduate and graduate levels and occupational therapists ask for online continuing professional development opportunities. However, occupational therapy educators have been slow to adopt web-based instructional technology. This paper presents background information on the use of web-based learning in the general sphere of higher education and outlines the current range of usage in occupational therapy education. Research findings are presented to stimulate discussion regarding online learning and occupational therapy professional socialisation, student satisfaction and outcomes. There is a fine line between full and partial online course delivery, so research on technology-enhanced campus-based delivery is also included in the review. Evidence suggests that blending combinations of technologies with computer mediated learning enhances interaction and could address the higher order learning needs of professional programmes such as occupational therapy.

Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

PubMed Central

Quirk, Shannon K.; Shure, Anna K.; Agrawal, Devendra K.

2015-01-01

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies as well as specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

Various treatment options for benign prostatic hyperplasia: A current update

PubMed Central

Shrivastava, Alankar; Gupta, Vipin B.

2012-01-01

In benign prostatic hyperplasia (BPH) there will be a sudden impact on overall quality of life of patient. This disease occurs normally at the age of 40 or above and also is associated with sexual dysfunction. Thus, there is a need of update on current medications of this disease. The presented review provides information on medications available for BPH. Phytotherapies with some improvements in BPH are also included. Relevant articles were identified through a search of the English-language literature indexed on MEDLINE, PUBMED, Sciencedirect and the proceedings of scientific meetings. The search terms were BPH, medications for BPH, drugs for BPH, combination therapies for BPH, Phytotherapies for BPH, Ayurveda and BPH, BPH treatments in Ayurveda. Medications including watchful waitings, Alpha one adrenoreceptor blockers, 5-alpha reductase inhibitors, combination therapies including tamsulosin-dutasteride, doxazosin-finasteride, terazosin-finasteride, tolterodine-tamsulosin and rofecoxib-finasteride were found. Herbal remedies such as Cernilton, Saxifraga stolonifera, Zi-Shen Pill (ZSP), Orbignya speciosa, Phellodendron amurense, Ganoderma lucidum, Serenoa Repens, pumpkin extract and Lepidium meyenii (Red Maca) have some improvements on BPH are included. Other than these discussions on Ayurvedic medications, TURP and minimally invasive therapies (MITs) are also included. Recent advancements in terms of newly synthesized molecules are also discussed. Specific alpha one adrenoreceptor blockers such as tamsulosin and alfuzosin will remain preferred choice of urologists for symptom relief. Medications with combination therapies are still needs more investigation to establish as preference in initial stage for fast symptom relief reduced prostate growth and obviously reduce need for BPH-related surgery. Due to lack of proper evidence Phytotherapies are not gaining much advantage. MITs and TURP are expensive and are rarely supported by healthcare systems. PMID:22923974

Antiparasitic Therapy

PubMed Central

Kappagoda, Shanthi; Singh, Upinder; Blackburn, Brian G.

2011-01-01

Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world's poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis. PMID:21628620

A systematic review of goal directed fluid therapy: rating of evidence for goals and monitoring methods.

PubMed

Wilms, Heath; Mittal, Anubhav; Haydock, Matthew D; van den Heever, Marc; Devaud, Marcello; Windsor, John A

2014-04-01

To review the literature on goal directed fluid therapy and evaluate the quality of evidence for each combination of goal and monitoring method. A search of major digital databases and hand search of references was conducted. All studies assessing the clinical utility of a specific fluid therapy goal or set of goals using any monitoring method were included. Data was extracted using a pre-determined pro forma and papers were evaluated using GRADE principles to assess evidence quality. Eighty-one papers met the inclusion criteria, investigating 31 goals and 22 methods for monitoring fluid therapy in 13052 patients. In total there were 118 different goal/method combinations. Goals with high evidence quality were central venous lactate and stroke volume index. Goals with moderate quality evidence were sublingual microcirculation flow, the oxygen extraction ratio, cardiac index, cardiac output, and SVC collapsibility index. This review has highlighted the plethora of goals and methods for monitoring fluid therapy. Strikingly, there is scant high quality evidence, in particular for non-invasive G/M combinations in non-operative and non-intensive care settings. There is an urgent need to address this research gap, which will be helped by methodologies to compare utility of G/M combinations. Copyright © 2014 Elsevier Inc. All rights reserved.

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

PubMed

Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

2016-01-01

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.

Practical Applications for Single Pill Combinations in the Cardiovascular Continuum

PubMed Central

Iellamo, Ferdinando; Werdan, Karl; Narkiewicz, Krzysztof; Rosano, Giuseppe

2017-01-01

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include standard to lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure. PMID:28785474

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials.

PubMed

Zhao, Ming; Chen, Jia-Yi; Chu, Yu-Dong; Zhu, Ya-Bin; Luo, Lin; Bu, Shi-Zhong

2018-06-01

To evaluate the efficacy of α-lipoic acid (ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy (DPN). The electronic databases of PubMed, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were (diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND (α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat. All of the eligible studies met the following inclusion criteria: (1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN. (2) The minimum duration of treatment was 2 weeks. (3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria. (4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV and peroneal SNCV. Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies (RR = 1.29, 95% CI: 1.21-1.38; RR = 1.43, 95% CI: 1.34-1.54, respectively). ALA plus epalrestat combination therapy also significantly improved median MNCV (WMD = 5.41, 95% CI: 2.07-8.75), median SNCV (WMD = 5.87, 95% CI: 1.52-10.22), peroneal MNCV (WMD = 5.59, 95% CI: 2.70-8.47) and peroneal SNCV (WMD = 4.57, 95% CI: 2.46-6.68). : ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-01-01

Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID:27559448

Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

PubMed

Inui, Naoki

2017-05-01

Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

Metastatic adenocarcinoma of mammary-like glands of the vulva successfully treated with surgery and hormonal therapy.

PubMed

Benito, Virginia; Arribas, Sara; Martínez, David; Medina, Norberto; Lubrano, Amina; Arencibia, Octavio

2013-01-01

Vulvar cancer is a rare malignancy; most tumors are squamous cell type while adenocarcinomas are rare. Primary adenocarcinomas of the vulva predominantly include extramammary Paget's disease and sweat gland carcinomas. Greene first described a rare form of adenocarcinoma in 1936, which was called adenocarcinoma of mammary-like glands of the vulva because of its morphologic and immunohistochemical resemblance to breast adenocarcinomas. In the management of this entity, varying combinations of surgery, radiation therapy, systemic chemotherapy and/or hormonal therapy may be used, as in patients with orthotopic breast carcinoma. However, hormonal therapy leads the way in patients with positive hormonal receptors, where other therapies cannot be used due to comorbidities or advanced age. We present the first reported case of an elderly patient with metastatic vulvar adenocarcinoma arising from mammary-like glands, successfully treated with a combination of surgery and hormonal therapy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Simplification of antiviral hepatitis C virus therapy to support expanded access in resource-limited settings.

PubMed

Ford, Nathan; Swan, Tracy; Beyer, Peter; Hirnschall, Gottfried; Easterbrook, Philippa; Wiktor, Stefan

2014-11-01

Currently, access to treatment for HCV is limited, with treatment rates lowest in the more resource-limited countries, including those countries with the highest prevalence. The use of oral DAAs has the potential to provide treatment at scale by offering opportunities to simplify drug regimens, laboratory requirements, and service delivery models. Key desirable characteristics of future HCV treatment regimens include high efficacy, tolerability, pan-genotype activity, short treatment duration, oral therapy, affordability, and availability as fixed-dose combination. Using such a regimen, HCV treatment delivery could be greatly simplified. Treatment could be initiated following confirmation of the presence of viraemia, with an initial assessment of the stage of liver disease. A combination DAA therapy that is safe and effective across genotypes could remove the need for genotyping and intermediary viral load assessments for response-guided therapy and reduce the need for adverse event monitoring. Simpler, safer, shorter therapy will also facilitate simplified service delivery, including task shifting, decentralization, and integration of treatment and care. The opportunity to scale up HCV treatment using such delivery approaches will depend on efforts needed to guarantee that the new DAAs are affordable in low-income settings. This will require the engagement of all stakeholders, ranging from the companies developing these new treatments, WHO and other international organizations, including procurement and funding mechanisms, governments and civil society. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

PubMed

Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

2013-01-01

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

[The long-term results of the application of the combined rehabilitative treatment in the patients presenting with knee osteoarthrosis].

PubMed

Razumov, A N; Purigа, A O; Yurova, O V

2015-01-01

The rehabilitative treatment of the patients suffering from knee osteoarthrosis (OA) up-to-date remains one of the most important medical and social problems of modern medicine due to the high prevalence of this disease, heavy morbidity, and the significant deterioration of the quality of the patients' life. The objective of the present study was to evaluate the long-term results of the combined application of radon and extracorporeal shock-wave therapy for the rehabilitation of the patients presenting with knee OA. The study involved 75 patients at the age from 35 to 62 years with the confirmed diagnosis of stage II and III knee osteoarthrosis. They were divided into 3 groups. Those comprising the main group received extracorporeal shock-wave therapy in combination with the treatment based on the use of radon baths. The patients included in the group of comparison were given a course of radon therapy alone while the patients of the control group received the standard treatment including physiotherapy, magnetic therapy, and the use of non-steroidal anti-inflammatory drugs (NSAIDs). The study has demonstrated the high effectiveness of the combined application of the radon baths and extracorporeal shock-wave therapy that was manifested as the substantial decrease of pain intensity, the increased range of motion in the knee joints, and the improvement of the general quality of life. These beneficial effects persisted during a period of up to 12 months. The stable remission was documented in 82% of the patients comprising the main group. The data obtained give reason to recommend the method employed in the present study for the extensive practical application at different stages of medical rehabilitation of the patients presenting with knee osteoarthrosis.

Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis

PubMed Central

Inomata, Minoru; Nishioka, Yasuhiko; Azuma, Arata

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. The molecular mechanisms involved in the progression of IPF are not fully understood; however, the platelet-derived growth factor (PDGF)/PDGF receptor pathway is thought to play a critical role in fibrogenesis of the lungs. Other growth factors, including fibroblast growth factor and vascular endothelial growth factor, are also thought to contribute to the pathogenesis of pulmonary fibrosis. Nintedanib is an inhibitor of multiple tyrosine kinases, including receptors for PDGF, fibroblast growth factor, and vascular endothelial growth factor. In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily. Pirfenidone, another antifibrotic drug, was shown to limit the decline in pulmonary function in patients with IPF in the ASCEND trial. Combination therapy with nintedanib and pirfenidone is anticipated, although further evaluation of its long-term safety is needed. There is limited evidence for the safety of the combination therapy although a Phase II trial conducted in Japan demonstrated that combination therapy with nintedanib and pirfenidone was tolerable for 1 month. Available antifibrotic agents (ie, pirfenidone and N-acetylcysteine) have limited efficacy as single therapies for IPF; therefore, further study of combination therapy with antifibrotic agents is needed. PMID:26346347

Current management of hepatocellular carcinoma: An Eastern perspective

PubMed Central

Yim, Hyung Joon; Suh, Sang Jun; Um, Soon Ho

2015-01-01

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress. PMID:25852267

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID:22315271

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

PubMed Central

Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

2014-01-01

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. Conclusions: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile. PMID:25266247

Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.

PubMed

Jonklaas, Jacqueline; Bianco, Antonio C; Bauer, Andrew J; Burman, Kenneth D; Cappola, Anne R; Celi, Francesco S; Cooper, David S; Kim, Brian W; Peeters, Robin P; Rosenthal, M Sara; Sawka, Anna M

2014-12-01

A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non-levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine-liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.

Combined therapy with gas gangrene antitoxin and recombinant human soluble thrombomodulin for Clostridium perfringens sepsis in a rat model.

PubMed

Hifumi, Toru; Nakano, Daisuke; Chiba, Joe; Takahashi, Motohide; Yamamoto, Akihiko; Fujisawa, Yoshihide; Kawakita, Kenya; Kuroda, Yasuhiro; Nishiyama, Akira

2018-01-01

Cases of Clostridium perfringens septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group). After α-toxin injection, mortality and platelet counts, and hemolysis were observed for 6 h. The fibrin/fibrinogen degradation products (FDP), and plasma high-mobility group box 1 (HMGB1) were also measured at 6 h. The combination group demonstrated 100% survival compared with 50% survival in the α-toxin group and demonstrated significantly improved hemolysis, platelet counts, and lactate levels compared with those in the α-toxin group (p < .01). The FDP and HMGB1 levels in the combination therapy group were significantly lower than those in the α-toxin group (p < .05). Combination therapy with GGA and rTM administration is applicable as adjunct therapy for fatal C. perfringens sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calcium-based biomaterials for diagnosis, treatment, and theranostics.

PubMed

Qi, Chao; Lin, Jing; Fu, Lian-Hua; Huang, Peng

2018-01-22

Calcium-based (CaXs) biomaterials including calcium phosphates, calcium carbonates, calcium silicate and calcium fluoride have been widely utilized in the biomedical field owing to their excellent biocompatibility and biodegradability. In recent years, CaXs biomaterials have been strategically integrated with imaging contrast agents and therapeutic agents for various molecular imaging modalities including fluorescence imaging, magnetic resonance imaging, ultrasound imaging or multimodal imaging, as well as for various therapeutic approaches including chemotherapy, gene therapy, hyperthermia therapy, photodynamic therapy, radiation therapy, or combination therapy, even imaging-guided therapy. Compared with other inorganic biomaterials such as silica-, carbon-, and gold-based biomaterials, CaXs biomaterials can dissolve into nontoxic ions and participate in the normal metabolism of organisms. Thus, they offer safer clinical solutions for disease theranostics. This review focuses on the state-of-the-art progress in CaXs biomaterials, which covers from their categories, characteristics and preparation methods to their bioapplications including diagnosis, treatment, and theranostics. Moreover, the current trends and key problems as well as the future prospects and challenges of CaXs biomaterials are also discussed at the end.

Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

PubMed

Ascierto, Paolo A; Agarwala, Sanjiv; Botti, Gerardo; Cesano, Alessandra; Ciliberto, Gennaro; Davies, Michael A; Demaria, Sandra; Dummer, Reinhard; Eggermont, Alexander M; Ferrone, Soldano; Fu, Yang Xin; Gajewski, Thomas F; Garbe, Claus; Huber, Veronica; Khleif, Samir; Krauthammer, Michael; Lo, Roger S; Masucci, Giuseppe; Palmieri, Giuseppe; Postow, Michael; Puzanov, Igor; Silk, Ann; Spranger, Stefani; Stroncek, David F; Tarhini, Ahmad; Taube, Janis M; Testori, Alessandro; Wang, Ena; Wargo, Jennifer A; Yee, Cassian; Zarour, Hassane; Zitvogel, Laurence; Fox, Bernard A; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena

2016-11-15

The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 (PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i) multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and T cell receptor (TCR) modified T cells; (ii) tumor heterogeneity including changes in antigenic profiles over time and location in individual patient; and (iii) a variety of immune-suppressive mechanisms in the tumor microenvironment (TME) including T regulatory cells (Treg), myeloid derived suppressor cells (MDSC) and immunosuppressive cytokines. In addition, complex interaction of tumor-immune system further increases the level of difficulties in the process of biomarkers development and their validation for clinical use. Recent clinical trial results have highlighted the potential for combination therapies that include immunomodulating agents such as anti-PD-1 and anti-CTLA-4. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well. These agents are also being tested in combination with targeted therapies to improve upon shorter-term responses thus far seen with targeted therapy. Various locoregional interventions that demonstrate promising results in treatment of advanced melanoma are also integrated with immunotherapy agents and the combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for melanoma patients' population. This meeting's specific focus was on advances in immunotherapy and combination therapy for melanoma. The importance of understanding of melanoma genomic background for development of novel therapies and biomarkers for clinical application to predict the treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into personalized-medicine approach for treatment of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. We also discussed the requirements for pre-analytical and analytical as well as clinical validation process as applied to biomarkers for cancer immunotherapy. The concept of the fit-for-purpose marker validation has been introduced to address the challenges and strategies for analytical and clinical validation design for specific assays.

Combining Active Immunization with Monoclonal Antibody Therapy to Facilitate Early Initiation of a Long-acting Anti-methamphetamine Antibody Response

PubMed Central

Hambuchen, Michael D.; Carroll, F. Ivy; Rüedi-Bettschen, Daniela; Hendrickson, Howard P.; Hennings, Leah J.; Blough, Bruce E.; Brieaddy, Lawrence E.; Pidaparthi, Ramakrishna R.; Owens, S. Michael

2015-01-01

We hypothesized that an anti-METH mAb could be used in combination with a METH-conjugate vaccine (MCV) to safely improve the overall quality and magnitude of the anti-METH immune response. The benefits would include immediate onset of action (from the mAb), timely increases in the immune responses (from the combined therapy) and duration of antibody response that could last for months (from the MCV). A novel METH-like hapten (METH-SSOO9) was synthesized and then conjugated to immunocyanin monomers of Keyhole limpet hemocyanin (ICKLH) to create the MCV, ICKLH-SOO9. The vaccine, in combination with previously discovered anti-METH mAb7F9, was then tested in rats for safety and potential efficacy. The combination antibody therapy allowed safe achievement of an early high anti-METH antibody response, which persisted throughout the study. Indeed, even after four months the METH vaccine antibodies still had the capacity to significantly reduce METH brain concentrations resulting from a 0.56 mg/kg METH dose. PMID:25973614

The Environmental Impact on Occupational Therapy Interventions.

PubMed

Skubik-Peplaski, Camille Louise; Howell, Dana; Hunter, Elizabeth

2016-01-01

The purpose of this study was to investigate how the environment influenced the intervention choices occupational therapists made for patients recovering from a stroke in an inpatient rehabilitation hospital. Three occupational therapists were observed providing intervention for six patients over a 16-month period. Treatment spaces included a therapy gym, gym with kitchen combination, and a home-like space. Furniture was added to the therapy gym to be more home-like midway through the study. Observations included therapist selection of treatment location and interventions, and observational data of the environment and interactions among therapists and patients. This study found that inpatient rehabilitation environments did influence interventions. The occupational therapists provided therapy in the standard therapy gym environment most often, whether it was enhanced to be more home-like or not, and predominately used preparatory methods.

[Recent Advances in Immunotherapy for Non-Small Cell Lung Cancer].

PubMed

Muto, Satoshi; Suzuki, Hiroyuki

2018-02-01

Cancer immunotherapy for non-small cell lung cancer began around 1970 with nonspecific immunomodulators and cytokine therapies. This has since developed into cell therapy including lymphokine-activated killer cells(LAK)and tumor infiltrating lymphocytes(TIL), as well as cancer vaccine therapy. However, no clear indication of effectiveness has been reported. Despite the high expectation over the effectiveness of cancer vaccine therapy, the treatment strategy was deemed unsuccessful, and focus turned to the study of immune escape mechanism, which is now regarded as standard treatment for non-small cell lung cancer. With the advent of immune checkpoint inhibitors, cancer immunotherapy has finally become a standard treatment for non-small cell lung cancer. There are still several obstacles to overcome including the identification of a predictive biomarker for improved efficacy, as well as the establishment of multidrug or multimodality combination therapy. PD-L1 expression is currently used as a predictive biomarker for anti-PD-1 therapy, but does not meet the expectations of the aimed results. Although tumor mutation burden is considered another promising biomarker, there remain clinical problems, for example the need of next generation sequencer. It was reported that combination therapy of immune checkpoint inhibitor after chemoradiation therapy was also effective. However, it remains unclear of what is required to further improve the clinical effects. In this article, we will review the history of cancer immunotherapy for non-small cell lung cancer and discuss the future prospects.

Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes.

PubMed

Courson, Alesa; Jones, G Morgan; Twilla, Jennifer D

2016-06-01

Rifaximin is approved for the reduction of hepatic encephalopathy (HE) recurrence in patients with chronic liver disease (CLD); however, few studies have evaluated the benefit of adding rifaximin to lactulose for treatment of acute HE. The aim of this study was to determine the impact of combination therapy with lactulose and rifaximin on hospital length of stay (LOS) and readmission rates. A retrospective study of patients admitted to an adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis, Tennessee, between 2007 and 2012 was conducted. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) coding for liver cirrhosis. Of the 173 patients included, 87 (50%) received lactulose monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy escalation. Median LOS was 6 days in monotherapy group and 8 days in combination group (P = .9). At 180 days, patients receiving combination therapy had fewer readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02). Addition of rifaximin to lactulose for treatment of acute HE did not reduce hospital LOS; however, it did result in lower readmission rates for HE at 180 days. © The Author(s) 2015.

A Combined Pharmacokinetic and Radiologic Assessment of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Response to Chemoradiation in Locally Advanced Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semple, Scott; Harry, Vanessa N. MRCOG.; Parkin, David E.

2009-10-01

Purpose: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. Methods and Materials: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic andmore » pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. Results: Pretherapy radiologic parameters and pharmacokinetic K{sup trans} correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. Conclusions: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.« less

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

PubMed

Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

2018-05-01

Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

Initiating therapy: when to start, what to use.

PubMed

Hirsch, Martin S

2008-05-15

Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a benefit to therapy during primary infection, results are inconclusive. Once begun, treatment probably should be continued indefinitely, since its potential advantages disappear over time if treatment is stopped. Recent studies suggest that cART may be useful at higher CD4 cell count thresholds than are currently recommended in several guidelines. Several regimens are acceptable as initial therapy, with tenofovir/emtricitabine/efavirenz favored by many because of potency and ease of administration. Other favored regimens include combinations of 2 nucleoside (or nucleotide) reverse-transcriptase inhibitors and a ritonavir-boosted protease inhibitor. Some new antiretroviral drugs under study, particularly integrase inhibitors, may prove useful in treatment-naive patients.

[Pay more attention to the standardized oncologic assessment of gastric cancer prior to starting therapy].

PubMed

Ji, Jiafu; Shan, Fei

2015-02-01

With the development of specialized gastric cancer oncology, multidisciplinary treatment(MDT) model has been widely accepted and implemented. Reasonable combination of comprehensive therapy and individualized treatment can really benefit patients, but its premise is comprehensive and detailed assessment of the tumor. We must pay more attention to the standardized oncologic assessment of gastric cancer prior to starting therapy, including staging, resectability assessment, and the pathological and molecular features.

Comparison of cephalonium alone and in combination with an internal teat sealant for dry cow therapy in seasonally calving dairy cows.

PubMed

Bates, A J; Chambers, G; Laven, R A

2016-03-01

To assess the effect of combining an internal teat sealant (ITS) and a long-acting cephalonium-based dry cow therapy (DCT) on the prevalence of cows with a somatic cell count (SCC) >150,000 cells/mL 60-80 days after calving, and the incidence of clinical mastitis diagnosed by farm staff in the first 100 days after calving. Cows from a spring-calving, pasture-based, dairy farm in the South Canterbury region of New Zealand were randomly allocated to receive cephalonium DCT (n=289) or cephalonium and internal teat sealant (n=304) at the end of lactation. Cows were inspected twice daily by farm staff during the dry period and following calving for signs of mastitis. Individual SCC were determined from herd tests conducted in the previous lactation and following calving. Logistic regression models were used to determine relationships with the prevalence of cows with a SCC >150,000 cells/mL after calving, and survival analysis was used to model time to the first case of clinical mastitis following calving at the cow and quarter level. The OR for a cow with a SCC >150,000 cells/mL after calving, including age and individual SCC in the preceding lactation in the model, was 0.53 (95% CI=0.32-0.89) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.017). At the cow level, including age and preceding SCC in the model, the hazard ratio for diagnosis of clinical mastitis by farm staff in the first 100 days of lactation was 0.60 (95% CI=0.39-0.98) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.04). At the quarter level, the hazard ratio for diagnosis of clinical mastitis, with age included in the model, was 0.41 (95% CI=0.23-0.74) for the combination therapy compared to cephalonium alone (p<0.001). The combination of internal teat sealant and cephalonium DCT was more effective than cephalonium alone at reducing clinical mastitis diagnosed by farm staff in the 100 days after calving, and the prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving. This study adds to the evidence that the prevention of intra mammary infections throughout the dry period and up to calving by using combination therapy is important in reducing the incidence of farmer-diagnosed clinical mastitis and prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving.

Cognitive and affective benefits of combination therapy with galantamine plus cognitive rehabilitation for Alzheimer's disease.

PubMed

Tokuchi, Ryo; Hishikawa, Nozomi; Matsuzono, Kosuke; Takao, Yoshiki; Wakutani, Yosuke; Sato, Kota; Kono, Syoichiro; Ohta, Yasuyuki; Deguchi, Kentaro; Yamashita, Toru; Abe, Koji

2016-04-01

The aim of the present study was to compare the effects of a galantamine only therapy and a combination therapy with galantamine plus ambulatory cognitive rehabilitation for Alzheimer's disease patients. For this retrospective cohort study, we enrolled 86 patients with Alzheimer's disease, dividing them into two groups - a galantamine only group (group G, n = 45) and a combination with galantamine plus ambulatory rehabilitation group (group G + R, n = 41). The present cognitive rehabilitation included a set of physical therapy, occupational therapy and speech therapy for 1-2 h once or twice a week. We compared the Mini-Mental State Examination and Frontal Assessment Battery for cognitive assessment, and Geriatric Depression Scale, Apathy Scale, and Abe's Behavioral and Psychological Symptoms of Dementia score for affective assessment in two groups over 6 months. The baseline Mini-Mental State Examination score was 20.2 and 18.7 in groups G and G + R, respectively. Other baseline data (Frontal Assessment Battery, Geriatric Depression Scale, Apathy Scale, and Abe's Behavioral and Psychological Symptoms of Dementia) were not different between the two groups. Although group G kept all the scores stable until 6 months of the treatment, the Apathy Scale score showed a significant improvement in group G + R as early as 3 months, followed by the Mini-Mental State Examination and Frontal Assessment Battery improvements at 6 months (*P = 0.04 and *P = 0.02, respectively). The Geriatric Depression Scale and Abe's Behavioral and Psychological Symptoms of Dementia did not show any changes. The combination therapy of galantamine plus ambulatory cognitive rehabilitation showed a superior benefit both on cognitive and affective functions than galantamine only therapy in Alzheimer's disease patients. © 2015 Japan Geriatrics Society.

Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial.

PubMed

Roehrborn, Claus G; Barkin, Jack; Siami, Paul; Tubaro, Andrea; Wilson, Timothy H; Morrill, Betsy B; Gagnier, R Paul

2011-03-01

• To investigate the influence of baseline variables on the 4-year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)-related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both. • The 4-year Combination of Avodart® and Tamsulosin (CombAT) study was a multicenter, randomized, double-blind, parallel-group study of clinical outcomes in men aged ≥ 50 years with symptomatic (International Prostate Symptom Score [IPSS]≥ 12) BPH, with prostate-specific antigen (PSA) levels of ≥ 1.5 ng/mL and ≤ 10 ng/mL, and a prostate volume (PV) of ≥ 30 mL. • Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. • The primary endpoint was time to first AUR or BPH-related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health-related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q(max) ] and body-mass index [BMI]) on the incidence of AUR or BPH-related surgery, clinical progression of BPH, and symptoms were performed. • There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. • Regardless of baseline subgroup, the incidence of AUR or BPH-related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. • Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH-related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P ≤ 0.001). • Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of < 20 or IPSS HRQL score of < 4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of < 40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. • Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of ≥ 20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of < 40 mL) and compared with dutasteride in most subgroups. • Men with a baseline PV of ≥ 40 mL and any baseline PSA level of ≥1.5 ng/mL had greater reductions in the RR of AUR or BPH-related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. • These analyses support the long-term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality

PubMed Central

McIntyre, Alan; Harris, Adrian L

2015-01-01

Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6–8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. PMID:25700172

[The use of mood stabilizers in preventive treatment of patients with schizoaffective disorders].

PubMed

Chritinin, D F; Sumarokova, M A

2014-01-01

To study an effect of combination therapy consisting of mood stabilizers on the quality of remission in patients with schizoaffective disorders. Authors examined 56 outpatients with ICD-10 diagnosis of schizoaffective disorder (F25). Patients in remission received anti-relapse therapy with antipsychotics and were not treated with mood stabilizers for at least two years, and then they received a combined anti-relapse therapy, including both antipsychotics and mood stabilizers. The combined use of pharmacotherapy creates a better remission. No statistically significant differences in the effect of different groups of mood stabilizers on the average duration of remission are identified. The inclusion of mood stabilizers in the scheme of preventive treatment has no effect on the average duration of subsequent hospitalization. Mood stabilizers are effective in the prevention of suicidal behavior in patients with schizoaffective disorder, they reduce the risk of disability in patients with schizoaffective disorder and increase compliance.

Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

PubMed

Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

2014-04-01

Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

PubMed

Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

2018-06-09

Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-analysis.

PubMed

Lai, Andrew; Lipka, Seth; Kumar, Ambuj; Sethi, Sajiv; Bromberg, David; Li, Nanxing; Shen, Huafeng; Stefaniwsky, Lilia; Brady, Patrick

2018-04-01

More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis. Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement. While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.

Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases.

PubMed

Koutsilieris, Michael; Mitsiades, Constantine S; Bogdanos, John; Dimopoulos, Theodoros; Karamanolakis, Dimitrios; Milathianakis, Constantine; Tsintavis, Athanassios

2004-07-01

Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy). Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days). Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse. The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.

Platelet rich plasma for the management of hair loss: Better alone or in combination?

PubMed

Anitua, Eduardo; Pino, Ander; Jaén, Pedro; Navarro, Mª Rogelia

2018-06-14

Platelet-rich plasma (PRP) and autologous protein-based treatments have recently emerged as a potential therapeutic approach for hair loss-related disorders including androgenetic alopecia and alopecia areata. The safety and efficacy of repeated intradermal injections of PRP has proved to promote hair growth in a number of randomized clinical trials. Biologically active proteins and cytokines released upon platelet activation have shown to induce folliculogenesis and activate the anagen growing phase of dormant bulbs. Interestingly, further studies have revealed that combining PRP with other hair loss-related products may enhance the final performance of the treatment. These synergistic approaches include Food and Drug Administration (FDA) approved drugs such as finasteride or minoxidil, bioactive macromolecules and cell-based therapies. Here, recent research involving alone or combined therapy with platelet-rich plasma for the management of hair loss-related disorders are outlined and future prospects are discussed. © 2018 Wiley Periodicals, Inc.

Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN–JDRF Type 1 Diabetes Combination Therapy Assessment Group

PubMed Central

Matthews, J B; Staeva, T P; Bernstein, P L; Peakman, M; von Herrath, M

2010-01-01

Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper. PMID:20629979

Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment.

PubMed

Kim, J H; Park, H Y; Jung, M; Choi, E H

2013-01-01

Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method. To evaluate the cutaneous effects of an AMTS in combination with topical tretinoin. Twelve hairless mice were divided into two groups, and the dorsal skin of each mouse was marked down the centre. The first group was treated with the AMTS plus 0.025% tretinoin on one side of the back, and with 0.025% tretinoin only on the other side. The other group was treated with the AMTS and vehicle on one side, while the other side was left untreated. The effects on cutaneous regeneration and the treatment side-effects were evaluated by functional assessment including transepidermal water loss and skin hydration, and by histopathology including epidermal and dermal thickness, and density of collagen fibres. Western blotting and real-time reverse transcriptase PCR were also performed to determine protein and mRNA expression of procollagen type 1 and matrix metalloproteinase-13. Compared with the individual treatments (the AMTS alone or tretinoin alone) the combination of tretinoin plus the AMTS produced greater dermal regeneration as a result of increased proliferation of collagen fibres. This combination therapy did not result in treatment-related adverse effects. An AMTS combined with topical tretinoin is a safe and effective method for skin regeneration, which works by increasing collagen production, and might be a new therapeutic option for regenerative therapy. © The Author(s). CED © 2012 British Association of Dermatologists.

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

PubMed

Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

2015-03-01

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy.

PubMed

Chowdhury, P S; Chamoto, K; Honjo, T

2018-02-01

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell. © 2017 The Association for the Publication of the Journal of Internal Medicine.

An open trial of outpatient group therapy for bulimic disorders: combination program of cognitive behavioral therapy with assertive training and self-esteem enhancement.

PubMed

Shiina, Akihiro; Nakazato, Michiko; Mitsumori, Makoto; Koizumi, Hiroki; Shimizu, Eiji; Fujisaki, Mihisa; Iyo, Masaomi

2005-12-01

The purposes of this study were to examine the therapeutic efficacy of combined group cognitive behavioral therapy (CGCBT) and to explore the characteristics of the patients who failed to complete it. Our group cognitive behavioral therapy combined with assertiveness training for alexithymia and self-esteem enhancement therapy were attended over a 10-week period. Twenty-five participants were enrolled in the study. The clinical symptoms were assessed before and after treatment, using rating scales including the Eating Disorder Inventory-2, the Bulimic Investigatory Test, Edinburgh, the Toronto Alexithymia Scale, the Rosenberg Self-Esteem Scale, and Global Assessment of Functioning. Sixteen participants (64%) completed the CGCBT program. Completion of the CGCBT resulted in significant improvements in reducing binge-eating behavior and improving social functioning. Eight patients (32%) significantly improved using the Clinical Global Impression Change (CGI-C). Stepwise logistic regression analysis of the results indicated that a lower age (P=0.04) and psychiatric comorbidity (P=0.06) were predictors of dropout from the CGCBT program. Our CGCBT program is a promising first-line treatment for bulimic outpatients. Lower age and the presence of comorbidity had effects on dropout rates.

Update on therapy for narcolepsy.

PubMed

Thorpy, Michael J

2015-05-01

Narcolepsy is a severe, incurable, neurological disorder that is treated by pharmacological management of its symptoms. The main symptoms are excessive daytime sleepiness (EDS) and cataplexy, although addition symptoms that may require treatment include sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. Sodium oxybate and modafinil/armodafinil are the first-line treatments for EDS, and sodium oxybate for cataplexy. Sodium oxybate treats all the symptoms of narcolepsy, whereas modafinil is effective for EDS only. Alternative medications for EDS include methylphenidate or amphetamines such as dextroamphetamine, lisdexamfetamine, methamphetamine, or combination amphetamine salts. Non-FDA approved medications for cataplexy include norepinephrine reuptake inhibitors such as venlafaxine or atomoxetine. Combination therapy can be more effective for sleepiness such as sodium oxybate and modafinil/armodafinil. Medication for narcolepsy is generally well tolerated and usually required life-long although does not eliminate all symptoms of narcolepsy.

Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2018-05-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. © 2018 Wiley Periodicals, Inc.

What interventions can improve quality of life or psychosocial factors of individuals with knee osteoarthritis? A systematic review with meta-analysis of primary outcomes from randomised controlled trials.

PubMed

Briani, Ronaldo Valdir; Ferreira, Amanda Schenatto; Pazzinatto, Marcella Ferraz; Pappas, Evangelos; De Oliveira Silva, Danilo; Azevedo, Fábio Mícolis de

2018-03-16

To systematically review evidence of primary outcomes from randomised controlled trials (RCTs) examining the effect of treatment strategies on quality of life (QoL) or psychosocial factors in individuals with knee osteoarthritis (OA). Systematic review with meta-analysis. Medline, Embase, SPORTDiscus, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science were searched from inception to November 2017. We included RCTs investigating the effect of conservative interventions on QoL or psychosocial factors in individuals with knee OA. Only RCTs considering these outcomes as primary were included. Pooled data supported the use of exercise therapy compared with controls for improving health-related and knee-related QoL. There was limited evidence that a combined treatment of yoga, transcutaneous electrical stimulation and ultrasound may be effective in improving QoL. Limited evidence supported the use of cognitive behavioural therapies (with or without being combined with exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress. Exercise therapy (with or without being combined with other interventions) seems to be effective in improving health-related and knee-related QoL or psychosocial factors of individuals with knee OA. In addition, evidence supports the use of cognitive behavioural therapies (with or without exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress in individuals with knee OA. CRD42016047602. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

PubMed

Peluso, Rosario; Caso, Francesco; Costa, Luisa; Sorbo, Dario; Carraturo, Nello; Di Minno, Matteo Nicola Dario; Carraturo, Federica; Oriente, Alfonso; Balestrieri, Umberto; Minicucci, Annamaria; Del Puente, Antonio; Scarpa, Raffaele

2016-01-01

To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Defense Force Management: Occupation Distribution and Composition.

DTIC Science & Technology

1992-03-01

diitteseilss lyve medicine, veterinary medicine. optometry, phlysilolgy. diet therapy . medical equipmerint main- s2. Clericaj/Personne-Includes combined...Includes ecology, zoý- 61. Health Services Administration Officers-4n. ology, botany, horticulture , conservatioand at cludles all medical and health

Structure of the physical therapy benefit in a typical Blue Cross Blue Shield preferred provider organization plan available in the individual insurance market in 2011.

PubMed

Sandstrom, Robert W; Lehman, Jedd; Hahn, Lee; Ballard, Andrew

2013-10-01

The Affordable Care Act of 2010 establishes American Health Benefit Exchanges. The benefit design of insurance plans in state health insurance exchanges will be based on the structure of existing small-employer-sponsored plans. The purpose of this study was to describe the structure of the physical therapy benefit in a typical Blue Cross Blue Shield (BCBS) preferred provider organization (PPO) health insurance plan available in the individual insurance market in 2011. A cross-sectional survey design was used. The physical therapy benefit within 39 BCBS PPO plans in 2011 was studied for a standard consumer with a standard budget. First, whether physical therapy was a benefit in the plan was determined. If so, then the structure of the benefit was described in terms of whether the physical therapy benefit was a stand-alone benefit or part of a combined-discipline benefit and whether a visit or financial limit was placed on the physical therapy benefit. Physical therapy was included in all BCBS plans that were studied. Ninety-three percent of plans combined physical therapy with other disciplines. Two thirds of plans placed a limit on the number of visits covered. The results of the study are limited to 1 standard consumer, 1 association of insurance companies, 1 form of insurance (a PPO), and 1 PPO plan in each of the 39 states that were studied. Physical therapy is a covered benefit in a typical BCBS PPO health insurance plan. Physical therapy most often is combined with other therapy disciplines, and the number of covered visits is limited in two thirds of plans.

[How to Increase the Effectiveness of Antihypertensive Therapy in Clinical Practice: Results of the Russian Observational Program FORSAZH].

PubMed

Glezer, M G; Deev On Behalf Of The Participants Of The Program, A D

2016-01-01

im of the study - to evaluate the possibility of increasing the effectiveness of antihypertensive therapy by simplifying regimens, improving knowledge and practical skills of the doctors on the use of modern tactical approaches to treatment as well as patients education methods of measuring blood pressure (BP), the principles of a healthy lifestyle and explain the need to follow the prescribing physician. Post-marketing observational discovery program FORSAZH held in 29 cities of the Russian Federation. Participation in the program received 442 physician (internists and general practitioners), which included 1969 patients with prior failure of combination antihypertensive therapy. Patients in 86% of cases took the free combination, 14% - fixed combinations of drugs. The change of the treatment on reception of a preparation containing a fixed combination of perindopril/indapamide (10 mg/2.5 mg) after 3 months led to decrease in systolic blood pressure by an average of 39.5 mm Hg, diastolic - 18.7 per mm Hg. The frequency of achieving the target BP <140 mm Hg and 90 it was 76%. Marked reduction in BP and frequency to achieve the target BP is not dependent on additional training of physicians and patients, the use of prior therapy in free or fixed combination, but depended on the initial degree of increase in BP and duration of therapy. Predictors of failure to achieve target BP were age, male gender, low initial adherence, good health, a higher baseline BP, elevated cholesterol levels, body weight, heart rate and decreased glomerular filtration rate. Adherence to therapy patients (on a scale of Morisky-Green) and health assessment on a visual analog scale significantly increased. This tactic has been a change of therapy is not only effective but also safe. Adverse events were reported in 28 patients (1.4% of the total number of observed cases) and only 1 case required dose reduction due to development of clinically manifested hypotension. In enhancing the effectiveness of the treatment of patients with hypertension was decisive simplification of drug therapy through the use of a fixed combination of perindopril A/indapamide.

Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors.

PubMed

Bland, Christopher M; Bookstaver, P Brandon; Lu, Z Kevin; Dunn, Brianne L; Rumley, Kathey Fulton

2014-10-01

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P = 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P = 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P = 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Sound waves and antineoplastic drugs: The possibility of an enhanced combined anticancer therapy.

PubMed

Feril, Loreto B; Kondo, Takashi; Umemura, Shin-Ichiro; Tachibana, Katsuro; Manalo, Angelo H; Riesz, Peter

2002-12-01

Kremkau wrote a historical review of the use of ultrasound in cancer therapy in 1979((1)) In 1990, Kondo and Kano published a Japanese review of the implications of the thermal and nonthermal effects of ultrasound in the treatment of cancer(2)). Again in 2000, Kondo et al reviewed the therapeutic applications of ultrasound and shock wave, emphasizing their thermal and cavitational effects(3)). Here we focus on the effects of ultrasound or shock waves in combination with anticancer agents, emphasizing their mechanisms of action and interaction. Most of the studies cited here reported promising results. Although the extent of the augmented combined effects in vivo is limited, synergism is the rule in vitro. In addition to the thermal effect of ultrasound, cavitational effects undoubtedly played a major role in both ultrasound and, more prominently, in shock wave therapy. Although the mechanism of the nonthermal noncavitational effects on biological processes is obscure, several factors, including temperature and the occurrence of cavitation and inertial cavitation, probably coexist and blend with these other effects. Magnification of anticancer activity results mainly from increased localization of drugs or other agents in vivo and increased intracellular permeabilisation both in vivo and in vitro. On the other hand, sublethal damage caused by ultrasound or shock waves may render cells more susceptible, to the effects of the agents, and both may act together, further amplifying these effects. We thus conclude that proper combination of an appropriate agent and ultrasound or shock wave should help improve cancer therapy by minimizing the side effects of drugs by lowering the effective dose and reducing the systemic concentration while increasing the efficiency of the therapy as a whole. Future studies should reveal specific conditions in this combined therapy that will lead to optimal outcome.

Gastrointestinal Bleeding in Cirrhotic Patients with Portal Hypertension

PubMed Central

Biecker, Erwin

2013-01-01

Gastrointestinal bleeding related to portal hypertension is a serious complication in patients with liver cirrhosis. Most patients bleed from esophageal or gastric varices, but bleeding from ectopic varices or portal hypertensive gastropathy is also possible. The management of acute bleeding has changed over the last years. Patients are managed with a combination of endoscopic and pharmacologic treatment. The endoscopic treatment of choice for esophageal variceal bleeding is variceal band ligation. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the time point of endoscopy. The first-line treatment for primary prophylaxis of esophageal variceal bleeding is nonselective beta blockers. Pharmacologic therapy is recommended for most patients; band ligation is an alternative in patients with contraindications for or intolerability of beta blockers. Treatment options for secondary prophylaxis include variceal band ligation, beta blockers, a combination of nitrates and beta blockers, and combination of band ligation and pharmacologic treatment. A clear superiority of one treatment over the other has not been shown. Bleeding from portal hypertensive gastropathy or ectopic varices is less common. Treatment options include beta blocker therapy, injection therapy, and interventional radiology. PMID:27335828

Massage therapy for people with HIV/AIDS.

PubMed

Hillier, Susan L; Louw, Quinette; Morris, Linzette; Uwimana, Jeanine; Statham, Sue

2010-01-20

Infection with human immunodeficency virus (HIV) and acquired immunodeficency syndrome (AIDS) is a pandemic that has affected millions of people globally. Although major research and clinical initiatives are addressing prevention and cure strategies, issues of quality of life for survivors have received less attention. Massage therapy is proposed to have a positive effect on quality of life and may also have a positive effect on immune function through stress mediation. The objective of this systematic review was to examine the safety and effectiveness of massage therapy on quality of life, pain and immune system parameters in people living with HIV/AIDS. A comprehensive search strategy was devised incorporating appropriate terms for HIV/AIDS, randomised controlled trials (RCTs), massage therapy and the pertinent measures of benefit. All electronic databases identified were searched in November 2008, including Cochrane Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE, AIDSearch, CINAHL, HEALTHSTAR, PsycLIT, AMED, Current Contents, AMI, NLM GATEWAY, LILACS, IndMed, SOCIOFILE, SCI, SSCI, ERIC and DAI. We also reviewed relevant published and unpublished conference abstracts and proceedings and scrutinised reference lists from pertinent journals. There were no language or date restrictions. Studies were identified by two reviewers based on trial design (RCTs) and participants (ie, people of any age with HIV/AIDS, at any stage of the disease) who had undergone an intervention that included massage therapy for the identified aims of improving quality of life and activity and participation levels, improving immune function, reducing pain and improving other physiological or psychological impairments. Two reviewers independently identified included studies and extracted relevant data. Two other reviewers independently reviewed the included studies for risk of bias. All data and risk of bias judgements were entered into Revman (v5) and meta-analyses were conducted where appropriate. Twelve papers were identified, from which four were included. The remaining eight papers were excluded predominantly due to inappropriate methodology. The four included studies were highly clinically heterogenous, investigating a range of age groups (ie, children, adolescents and adults) across the disease spectrum from early HIV through late-stage AIDS. The settings were either community or palliative care, and the outcome measures were a combination of quality of life and immunological function. The trials were judged to be at moderate risk of bias mostly because of incomplete reporting. For quality of life measures, the studies reported that massage therapy in combination with other modalities, such as meditation and stress reduction, are superior to massage therapy alone or to the other modalities alone. The quality of life domains with significant effect sizes included self-reported reduced use of health care resources, improvement in self-perceived spiritual quality of life and improvement in total quality of life scores. One study also reported positive changes in immune function, in particular CD4+ cell count and natural killer cell counts, due to massage therapy, and one study reported no difference between people given massage therapy and controls in immune parameters. Adverse or harmful effects were not well reported. There is some evidence to support the use of massage therapy to improve quality of life for people living with HIV/AIDS (PLWHA), particularly in combination with other stress-management modalities, and that massage therapy may have a positive effect on immunological function. The trials are small, however, and at moderate risk of bias. Further studies are needed using larger sample sizes and rigorous design/reporting before massage therapy can be strongly recommended for PLWHA.

Ciclosporin use in multi-drug therapy for meningoencephalomyelitis of unknown aetiology in dogs.

PubMed

Adamo, P F; Rylander, H; Adams, W M

2007-09-01

To evaluate the efficacy and safety of ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole in dogs with diagnosis of meningoencephalomyelitis of unknown aetiology. Medical records of 10 dogs diagnosed with meningoencephalomyelitis of unknown aetiology and treated with ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole were reviewed at the Veterinary Medical Teaching Hospital, University of Wisconsin-Madison. Laboratory abnormalities, side effects, clinical and cerebrospinal fluid responses to treatment and association between blood ciclosporin level and response to treatment were evaluated. Histopathological diagnosis was available in three patients. No significant abnormalities were detected on serial complete blood count and serum chemistry panel in any of the dogs. Side effects of ciclosporin therapy included excessive shedding, gingival hyperplasia and hypertrichosis. Overall median survival time for all dogs in the study was 930 days (range, 60 to more than 1290 days). In all dogs, serial cerebrospinal fluid analysis showed a marked improvement in the inflammation. Results suggest that ciclosporin either alone or in combination with ketoconazole may be a safe and effective treatment for meningoencephalomyelitis of unknown aetiology in dogs.

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

Nonstatin therapies for management of dyslipidemia: a review.

PubMed

Sando, Karen R; Knight, Michelle

2015-10-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe-statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: a systematic review.

PubMed

Cup, Edith H; Pieterse, Allan J; Ten Broek-Pastoor, Jessica M; Munneke, Marten; van Engelen, Baziel G; Hendricks, Henk T; van der Wilt, Gert J; Oostendorp, Rob A

2007-11-01

To summarize and critically appraise the available evidence on exercise therapy and other types of physical therapies for patients with neuromuscular diseases (NMD). Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Medline, CINAHL, EMBASE (Rehabilitation and Physical Medicine), and reference lists of reviews and articles. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), and other designs were included. Study participants had to have any of the following types of NMD: motoneuron diseases, disorders of the motor nerve roots or peripheral nerves, neuromuscular transmission disorders, or muscle diseases. All types of exercise therapy and other physical therapy modalities were included. Outcome measures had to be at the level of body functions, activities, or participation according to the definitions of the International Classification of Functioning, Disability and Health (ICF). Two reviewers independently decided on inclusion or exclusion of articles and rated the methodologic quality of the studies included. All RCTs, CCTs, and other designs only if of sufficient methodologic quality were included in a best evidence synthesis. A level of evidence was attributed for each subgroup of NMD and each type of intervention. Initially 58 studies were included: 12 RCTs, 5 CCTs, and 41 other designs. After methodologic assessment, 19 other designs were excluded from further analysis. There is level II evidence ("likely to be effective") for strengthening exercises in combination with aerobic exercises for patients with muscle disorders. Level III evidence ("indications of effectiveness") was found for aerobic exercises in patients with muscle disorders and for the combination of muscle strengthening and aerobic exercises in a heterogeneous group of muscle disorders. Finally, there is level III evidence for breathing exercises for patients with myasthenia gravis and for patients with myotonic muscular dystrophy. Adverse effects of exercise therapy were negligible. The available evidence is limited, but relevant for clinicians. Future studies should be preferably multicentered, and use an international classification of the variables of exercise therapy and an ICF core set for NMD in order to improve comparability of results.

Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy

PubMed Central

Neukam, Karin; Munteanu, Daniela I.; Rivero-Juárez, Antonio; Lutz, Thomas; Fehr, Jan; Mandorfer, Mattias; Bhagani, Sanjay; López-Cortés, Luis F.; Haberl, Annette; Stoeckle, Marcel; Márquez, Manuel; Scholten, Stefan; de los Santos-Gil, Ignacio; Mauss, Stefan; Rivero, Antonio; Collado, Antonio; Delgado, Marcial; Rockstroh, Juergen K.; Pineda, Juan A.

2015-01-01

Background and Aims Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. Methods In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Results Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. Conclusion The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable. PMID:25923540

RNA Interference Therapies for an HIV-1 Functional Cure.

PubMed

Scarborough, Robert J; Gatignol, Anne

2017-12-27

HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be achieved, several approaches to reach a functional cure (control of HIV-1 replication in the absence of drug therapy) are also under investigation. One of these approaches is the transplant of HIV-1 resistant cells expressing anti-HIV-1 RNAs, proteins or peptides. Small RNAs that use RNA interference pathways to target HIV-1 replication have emerged as competitive candidates for cell transplant therapy and have been included in all gene combinations that have so far entered clinical trials. Here, we review RNA interference pathways in mammalian cells and the design of therapeutic small RNAs that use these pathways to target pathogenic RNA sequences. Studies that have been performed to identify anti-HIV-1 RNA interference therapeutics are also reviewed and perspectives on their use in combination gene therapy to functionally cure HIV-1 infection are provided.

Evaluation of nitazoxanide for the treatment of disseminated cystic echinococcosis: report of five cases and literature review.

PubMed

Pérez-Molina, José A; Díaz-Menéndez, Marta; Gallego, José I; Norman, Francesca; Monge-Maillo, Begoña; Ayala, Ana Pérez; López-Vélez, Rogelio

2011-02-01

We aimed to evaluate the effectiveness of nitazoxanide in disseminated cystic echinococcosis (DCE) that failed to respond to surgical and antiparasitic therapy. We report on seven patients (five of them with bony involvement): two cases from the literature and five patients who were included in a compassionate trial of nitazoxanide therapy in our hospital. Median follow-up time until nitazoxanide therapy was 12 years and all patients had received prior medical treatment and extensive surgery. Nitazoxanide (500 mg/12 h) in combination with albendazole, with/without praziquantel, was administered for 3-24 months. Three patients improved: one with muscle involvement (clinico-radiological response), one with lung involvement (radiological response), and another with soft tissue and bony involvement (clinico-radiological response of soft tissue cysts). There was one discontinuation after 15 days of starting therapy. Nitazoxanide combination therapy could have a role in the treatment of DCE when there is no bony involvement. Long-term safety profile seems to be favorable.

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy

PubMed Central

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

Objectives: The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. Methods: This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. Results: One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Conclusion: Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss. PMID:25878638

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy.

PubMed

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review

PubMed Central

Watanabe, Norio; Churchill, Rachel; Furukawa, Toshi A

2007-01-01

Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone. Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials. Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6–12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment. One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials. Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects. PMID:17501985

Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis.

PubMed

Ma, Dongfeng; Zhang, Zhijun; Zhang, Xiangrong; Li, Lingjiang

2014-06-01

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.

The role of insulin pump therapy for type 2 diabetes mellitus.

PubMed

Landau, Zohar; Raz, Itamar; Wainstein, Julio; Bar-Dayan, Yosefa; Cahn, Avivit

2017-01-01

Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study.

PubMed

Kopylov, Uri; Papamichael, Konstantinos; Katsanos, Konstantinos; Waterman, Matti; Bar-Gil Shitrit, Ariella; Boysen, Trine; Portela, Francisco; Peixoto, Armando; Szilagyi, Andrew; Silva, Marco; Maconi, Giovanni; Har-Noy, Ofir; Bossuyt, Peter; Mantzaris, Gerassimos; Barreiro de Acosta, Manuel; Chaparro, Maria; Christodoulou, Dimitrios K; Eliakim, Rami; Rahier, Jean-Francois; Magro, Fernando; Drobne, David; Ferrante, Marc; Sonnenberg, Elena; Siegmund, Britte; Muls, Vinciane; Thurm, Tamara; Yanai, Henit; Dotan, Iris; Raine, Tim; Levin, Avi; Israeli, Eran; Ghalim, Fahd; Carbonnel, Franck; Vermeire, Severine; Ben-Horin, Shomron; Roblin, Xavier

2017-09-01

Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Cardiotoxicity of Anticancer Drugs: The Need for Cardio-Oncology and Cardio-Oncological Prevention

PubMed Central

Pennesi, Giuseppina; Donatelli, Francesco; Cammarota, Rosaria; De Flora, Silvio; Noonan, Douglas M.

2010-01-01

Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications. PMID:20007921

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

PubMed Central

Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

PubMed

Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

[Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

PubMed

Schlenk, R F; Döhner, K; Döhner, H

2013-02-01

Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

PubMed

Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

2015-11-03

Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

PubMed

Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis.

PubMed

Luo, L; Yuan, X; Huang, W; Ren, F; Zhu, H; Zheng, Y; Tang, L

2015-05-01

Hypercholesterolaemia is a pivotal risk factor for cardiovascular and cerebrovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with ezetimibe. Combination therapy is more effective because of its complementary approach, which has major benefits for patients with unmanageable lipid levels. Extensive application of combination therapy has resulted in an increased incidence of side-effects, which has raised our concern. To evaluate the evidence associated with the safety of coadministration of ezetimibe with statins. Three electronic databases were searched (PubMed, EMBASE and Cochrane Library) from January 2002 to October 2014. Two independent reviewers critically identify randomised controlled trials (RCT), extracted the data and assessed trial quality. A total ot 20 RCT met inclusion criteria, including 14,856 patients. A fixed-effects model was used for meta-analysis to assess the safety of combination therapy. Coadministration of ezetimibe and statins did not result in significant increases in total adverse events (30% vs 29%, P = 0.34), serious adverse events (2% vs 1.6%, P = 0.81), treatment discontinuations (3.5% vs 2.9%, P = 0.22), gastrointestinal adverse events (5% vs 4%, P = 0.08), allergic reactions or rashes (0.9% vs 1.3%, P = 0.33), creatine kinase > 10 × upper limit of normal (ULN) (0.2% vs 0.2%, P = 0.86), alanine aminotransferase > 3 × ULN (0.5% vs 0.4%, P = 0.96) and aspartate aminotransferase > 3 × ULN (0.4% vs 0.4%, P = 0.58). The incidence of adverse events was similar between ezetimibe-statin combination therapy and statin monotherapy; thus, we recommend combination therapy for patients with hypercholesterolaemia at high risk for cardiovascular and cerebrovascular disease. © 2015 Royal Australasian College of Physicians.

Pains, joys, and secrets: nurse-led group therapy for older adults with depression.

PubMed

Nance, Douglas C

2012-02-01

This is the first study of nurse-led group therapy in Mexico. Forty-one depressed older adults with a median age of 71 participated in nurse-led cognitive behavioral group therapy once a week for 12 weeks. Participants' scores on the Patient Health Questionaire-9 showed mild to moderate improvement. Participants experienced positive results in personal growth, changing negative thoughts, and relationships with family. An important therapeutic factor was the support of fellow group members. The nurses experienced positive personal and professional growth. Difficulties included physician resistance and a too-rigid cognitive behavioral group therapy model. A combination of cognitive behavioral therapy and supportive group therapy is recommended.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

PubMed Central

Moeinian, Mahsa; Ghasemi-Niri, Seyedeh Farnaz; Mozaffari, Shilan; Abdolghaffari, Amir Hossein; Baeeri, Maryam; Navaea-Nigjeh, Mona; Abdollahi, Mohammad

2014-01-01

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model. METHODS: Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon. RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO. CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting. PMID:25152589

Is there a role for rifampicin, ofloxacin and minocycline (ROM) therapy in the treatment of leprosy? Systematic review and meta-analysis.

PubMed

Setia, Maninder S; Shinde, Santosh S; Jerajani, Hemangi R; Boivin, Jean-François

2011-12-01

A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients. Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients. Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups. Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy. © 2011 Blackwell Publishing Ltd.

Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder.

PubMed

Waxmonsky, James G; Waschbusch, Daniel A; Pelham, William E; Draganac-Cardona, Lillian; Rotella, Bryan; Ryan, Lynn

2010-11-01

To evaluate the effects of atomoxetine alone and in combination with behavior therapy on the school functioning of children with attention-deficit/hyperactivity disorder (ADHD). Most atomoxetine studies have not assessed school functioning other than by measuring the change in ADHD symptoms. Combining behavior therapy with atomoxetine may be particularly beneficial for the academic domain as medication has not been found to produce sustained benefits in this realm. However, there is little research examining the effects of combining atomoxetine and behavior therapy. In an 8-week open-label trial, 56 children aged 6-12 years with ADHD diagnosed according to DSM-IV-TR were randomly assigned to receive atomoxetine and behavior therapy or atomoxetine alone. Behavior therapy consisted of an 8-week parenting course, a child social skills course, and a teacher-implemented daily report card of classroom behavior. The primary outcome was direct observation of the subject's classroom behavior. Secondary outcomes included change in ADHD symptoms and functioning at home and school. All data were collected between March 2007 and May 2008. Classroom observations showed that atomoxetine decreased rule violations (P < .0001). Moreover, atomoxetine was associated with significant improvements in ADHD and oppositional defiant disorder symptoms at home and school and enhanced functioning in both domains (Impairment Rating Scale: all P < .001). Combined treatment led to greater improvements in parent-rated symptoms of inattention (P < .01), problem behaviors (P < .001), and academic impairment (P < .05). However, teachers did not report significant group differences. Atomoxetine improved ADHD symptoms and classroom functioning as measured by parents, teachers, and direct observation. The addition of behavior therapy led to further improvements at home but not at school. clinicaltrials.gov Identifier: NCT00918567. © Copyright 2010 Physicians Postgraduate Press, Inc.

Gene therapy in pancreatic cancer

PubMed Central

Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

2014-01-01

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

Combination Therapy of Rosuvastatin and Ezetimibe in Patients with High Cardiovascular Risk.

PubMed

Yang, Young-June; Lee, Sang-Hak; Kim, Byung Soo; Cho, Yun-Kyeong; Cho, Hyun-Jai; Cho, Kyoung Im; Kim, Seok-Yeon; Ryu, Jae Kean; Cho, Jin-Man; Park, Joong-Il; Park, Jong-Seon; Park, Chang Gyu; Chun, Woo Jung; Kim, Myung-A; Jin, Dong-Kyu; Lee, Namho; Kim, Byung Jin; Koh, Kwang Kon; Suh, Jon; Lee, Seung-Hwan; Lee, Byoung-Kwon; Oh, Seung-Jin; Jin, Han-Young; Ahn, Youngkeun; Lee, Sang-Gon; Bae, Jang-Ho; Park, Woo Jung; Lee, Sang-Chol; Lee, Han Cheol; Lee, Jaewon; Park, Cheolwon; Lee, Backhwan; Jang, Yangsoo

2017-01-01

The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk. This was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed. The percentage change of LDL-C ranged from -45% to -56% (mean, -51%) in the monotherapy groups and from -58% to -63% (mean, -60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart (P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups (P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups. Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

PubMed

Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

2014-02-01

Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

NASA Astrophysics Data System (ADS)

Velikaya, V. V.; Musabaeva, L. I.; Lisin, V. A.; Startseva, Zh. A.

2016-08-01

The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru; National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050

The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

Clinical Management of HIV Drug Resistance

PubMed Central

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

PubMed

El-Hamamsy, Manal H; Elsisi, Gihan H; Eldessouki, Randa; Elmazar, Mohamed M; Taha, Ahmed S; Awad, Basma F; Elmansy, Hossam

2016-08-01

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014. The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.

The novel language-systematic aphasia screening SAPS: screening-based therapy in combination with computerised home training.

PubMed

Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

2018-03-01

SAPS-'Sprachsystematisches Aphasiescreening'-is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment foci from the individual performance profile. However, SAPS has not yet been evaluated in combination with the new SAPS-based treatment. To replicate the practicality of SAPS and to investigate the effectiveness of a SAPS-based face-to-face therapy combined with computerised home training in a feasibility study. To examine the soundness of the treatment design, to determine treatment-induced changes in patient performance as measured by SAPS, to assess parallel changes in communicative abilities, and to differentiate therapy effects achieved by face-to-face therapy versus add-on effects achieved by later home training. Sixteen participants with post-stroke aphasia (PWAs) were included into the study. They were administered the SAPS and communicative testing before and after the treatment regimen. Each PWA received one therapy session followed by home training per day, with the individual treatment foci being determined according to initial SAPS profile, and duration of treatment and possible change of focus dependent on performance assessed by continuous therapy monitoring. The combination of therapy and home training based on the SAPS was effective for all participants. We showed significant improvements for impairment-based SAPS performance and, with high inter-individual variability, in everyday communication. These two main targets of speech and language therapy were correlated and SAPS improvements after therapy were significantly higher than after home training. SAPS offers the assessment of an individual performance profile in order to derive sufficiently diversified, well-founded and specific treatment foci and to follow up changes in performance. The appending treatment regimen has shown to be effective for our participants. Thus, the study revealed feasibility of our approach. © 2017 Royal College of Speech and Language Therapists.

The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients.

PubMed

Minozzi, M; Nordio, M; Pajalich, R

2013-02-01

Women with Polycystic Ovarian Syndrome (PCOS) present several factors that increase the cardiovascular risk, such as insulin resistance and dyslipidemia. Myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. However, their effects on dyslipidemia are less clear. The aim of the present study was to evaluate whether the combined therapy myo-inositol plus D-chiro-inositol (in a in a physiological ratio of 40:1) improve the metabolic profile, therefore, reducing cardiovascular risk in PCOS patients. Twenty obese PCOS patients [BMI 33.7 ± 6 kg/m2 (mean ± SD)] were recruited. The lipid profile was assessed by measuring total cholesterol, LDL, HDL and triglycerides before and after 6 months treatment with the combined therapy. Secondary end points included changes in BMI, waist-hip ratio, percentage of body fat, HOMA-IR and blood pressure. The combined therapy myo-inositol and D-chiro-inositol improved LDL levels (3.50 ± 0.8 mmol/L versus, 3 ± 1.2 mmol/L p < 0.05), HDL (1.1 mmol/L ± 0.3 versus 1.6 mmol/L ± 0.4 p < 0.05) and triglycerides (2.3 ± 1.5 mmol/L versus 1.75 ± 1.9 mmol/L p < 0.05). Furthermore, significant improvements in HOMA-IR were also observed. The combined therapy myo-inositol plus D-chiro-inositol is able to improve the metabolic profile of PCOS women, therefore, reducing the cardiovascular risk.

Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis

PubMed Central

Fu, Shufang; Wen, Xin; Han, Fei; Long, Yin; Xu, Gaosi

2017-01-01

The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4.20; 95% confidential intervals (CI) -5.44 to -2.97; I2, 29.7%] and diastolic blood pressure (DBP: WMD, -2.09; 95% CI -2.90 to -1.27; I2, 0%) when compared with ACEIs or ARBs monotherapy, but with significantly increased the risk of hyperkalaemia [relative risk (RR), 1.45; 95% CI 1.28 to 1.64; I2,10.6 %] and kidney injury ( RR, 1.92; 95% CI 1.14 to 3.21; I2, 0%). Besides, there was no significant difference in the incidence of major cardiovascular events (RR, 0.95; 95% CI 0.89 to 1.02; I2, 0%) between the combined therapy and ACEIs or ARBs monotherapy. In conclusion, this meta-analysis demonstrated that aliskiren in combination therapy with ACEs/ARBs could control BP effectively, but is associated with increasing risks of hyperkalaemia and kidney injury, and have no benefit in preventing of major cardiovascular events. PMID:29179525

Trial of Music, Sucrose, and Combination Therapy for Pain Relief during Heel Prick Procedures in Neonates.

PubMed

Shah, Swapnil R; Kadage, Shahajahan; Sinn, John

2017-11-01

To compare the effectiveness of music, oral sucrose, and combination therapy for pain relief in neonates undergoing a heel prick procedure. This randomized, controlled, blinded crossover clinical trial included stable neonates >32 weeks of postmenstrual age. Each neonate crossed over to all 3 interventions in random order during consecutive heel pricks. A video camera on mute mode recorded facial expressions, starting 2 minutes before until 7 minutes after the heel prick. The videos were later analyzed using the Premature Infant Pain Profile-Revised (PIPP-R) scale once per minute by 2 independent assessors, blinded to the intervention. The PIPP-R scores were compared between treatment groups using Friedman test. For the 35 participants, the postmenstrual age was 35 weeks (SD, 2.3) with an average weight of 2210 g (SD, 710). The overall median PIPP-R scores following heel prick over 6 minutes were 4 (IQR 0-6), 3 (IQR 0-6), and 1 (IQR 0-3) for the music, sucrose, and combination therapy interventions, respectively. The PIPP-R scores were significantly lower at all time points after combination therapy compared with the groups given music or sucrose alone. There was no difference in PIPP-R scores between the music and sucrose groups. In relatively stable and mature neonates, the combination of music therapy with sucrose provided better pain relief during heel prick than when sucrose or music was used alone. Recorded music in isolation had a similar effect to the current gold standard of oral sucrose. www.anzctr.org.au ACTRN12615000271505. Copyright © 2017 Elsevier Inc. All rights reserved.

[Comparison on Endoscopic Hemoclip and Hemoclip Combination Therapy in Non-variceal Upper Gastrointestinal Bleeding Patients Based on Clinical Practice Data: Is There Difference between Prospective Cohort Study and Randomized Study?].

PubMed

Lee, Su Hyun; Jung, Jin Tae; Lee, Dong Wook; Ha, Chang Yoon; Park, Kyung Sik; Lee, Si Hyung; Yang, Chang Heon; Park, Youn Sun; Jeon, Seong Woo

2015-08-01

Endoscopic hemoclip application is an effective and safe method of endoscopic hemostasis. We conducted a multicenter retrospective study on hemoclip and hemoclip combination therapy based on prospective cohort database in terms of hemostatic efficacy not in clinical trial but in real clinical practice. Data on endoscopic hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively collected from February 2011 to December 2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were enrolled in this study. Subjects were divided into three groups: Group 1 (n = 62), hemoclipping only; group 2 (n = 88), hemoclipping plus epinephrine injection; and group 3 (n = 36), hemocliping and epinephrine injection plus other endoscopic hemostatic modalities. Primary outcomes included rebleeding, other therapeutic management, hospitalization period, fasting period and mortality. Secondary outcomes were bleeding associated mortality and overall mortality. Active bleeding and peptic ulcer bleeding were more common in group 3 than in group 1 and in group 2 (p <œ 0.001). However, primary outcomes (rebleeding, other management, morbidity, hospitalization period, fasting period and mortality) and secondary outcomes (bleeding associated mortality and total mortality) were not different among groups. Combination therapy of epinephrine injection and other modalities with hemoclips did not show advantage over hemoclipping alone in this prospective cohort study. However, there is a tendency to perform combination therapy in active bleeding which resulted in equivalent hemostatic success rate, and this reflects the role of combination therapy in clinical practice.

Combined autophagy and proteasome inhibition

PubMed Central

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-01-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy. PMID:24991834

Gaining ground on a cure through synergy: combining checkpoint inhibitors with cancer vaccines.

PubMed

Vreeland, T J; Clifton, G T; Herbert, G S; Hale, D F; Jackson, D O; Berry, J S; Peoples, G E

2016-12-01

The approval of multiple checkpoint inhibitors (CPIs) for the treatment of advanced malignancies has sparked an explosion of research in the field of cancer immunotherapy. Despite the success of these medications, a large number of patients with advanced malignancy do not benefit from therapy. Early research indicates that a therapeutic combination of cancer vaccines with checkpoint inhibitors may lead to synergistic effects and higher response rates than monotherapy. Areas covered: This paper summarizes the previously completed and ongoing research on this exciting combination, including the use of the tumor lysate, particle-loaded dendritic cell (TLPLDC) vaccine combined with checkpoint inhibitors in advanced melanoma. Expert commentary: Increasing experience with CPIs has led to improved understanding of which patients may benefit and it is increasingly clear that the presence of a pre-existing immune response to the tumor, along with tumor-infiltrating lymphocytes, is key to the success of CPIs. One exciting possibility for the future is the addition of a cancer vaccine to CPI therapy, eliciting these crucial T cells, which can then be augmented and protected by the CPI. A number of current and future studies are addressing this very exciting combination therapy.

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Multifunctional hollow gold nanoparticles designed for triple combination therapy and CT imaging.

PubMed

Park, Jaesook; Park, Jin; Ju, Eun Jin; Park, Seok Soon; Choi, Jinhyang; Lee, Jae Hee; Lee, Kyoung Jin; Shin, Seol Hwa; Ko, Eun Jung; Park, Intae; Kim, Chulhee; Hwang, Jung Jin; Lee, Jung Shin; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

2015-06-10

Hollow gold nanoparticles (HGNP) are a novel class of hybrid metal nanoparticles whose unique optical and morphological properties have spawned new applications including more effective cancer therapy. The shell thickness of HGNPs can tune the surface plasmon resonance to the near infrared light, resulting in photothermal ablation of tumors with optimal light penetration in tissue. The hollow cavity within a HGNP is able to accommodate a high payload of chemotherapeutic agents. They have also been used for enhancing radiosensitization in tumors during radiotherapy due to the high X-ray absorption capability of gold particles. However, no report has yet been published that utilize HGNPs for the triple combination therapy and CT imaging. In this study, we synthesized HGNPs which exhibit better response to radiation for therapy and imaging and demonstrated the effects of combined chemotherapy, thermal and radiotherapy. This combination strategy presented delayed tumor growth by 4.3-fold and reduced tumor's weight by 6.8-fold compared to control tumors. In addition, we demonstrated the feasibility of HGNP as a CT imaging agent. It is expected that translating these capabilities to human cancer patients could dramatically increase the antitumor effect and potentially overcome resistance to chemotherapeutic agents and radiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.

PubMed

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Morris, David Lawson

2014-11-12

Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from cell cycle arrest, apoptosis and autophagy. Towards the development of novel strategies for the enhancement of microscopic cytoreduction, our results lay the basis for further evaluation of this formulation in locoregional approaches to peritoneal surface malignancies and carcinomatosis.

Treatment of Helicobacter pylori infection: Current status and future concepts

PubMed Central

Yang, Jyh-Chin; Lu, Chien-Wei; Lin, Chun-Jung

2014-01-01

Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies. PMID:24833858

Novel nonstatin strategies to lower low-density lipoprotein cholesterol.

PubMed

Davidson, Michael H

2009-01-01

There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins. Several novel agents have been developed to lower LDL-C, either as monotherapy or in combination with statins. These novel therapies include squalene synthase inhibitors, microsomal triglyceride transfer protein inhibitors, and antisense apolipoprotein B. Although each of these novel therapies effectively lowers LDL-C, challenges remain in the clinical development to assess long-term safety.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Wright, Nicola; Jarvis, Morag C; Rees, Karen; Ebrahim, Shah; Huffman, Mark D

2014-01-01

Background Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. Objectives To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. Selection criteria We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. Data collection and analysis Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 > 50%). Main results We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38, N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs. Authors' conclusions Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes. PMID:24737108

Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint.

PubMed

Gwyn, Jennifer C V; Thomas, Mark R; Kirchhof, Paulus

2017-07-01

Patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy to reduce the risk of subsequent myocardial infarction (MI) and stent thrombosis. Approximately 5-10% of patients undergoing PCI also have atrial fibrillation (AF). Patients with AF have an additional requirement for anticoagulation, as dual antiplatelet therapy alone is insufficient to adequately reduce the risk of stroke in patients with AF. However, it is now well established that combining anticoagulants with dual antiplatelet therapy also causes a significant increase in the risk of bleeding. Hence, there is great interest in discovering the optimal blend of antiplatelet therapy and oral anticoagulation in this situation, aiming to reduce the risk of stent thrombosis, recurrent MI, and stroke, while also minimizing the risk of bleeding. Recent studies have experimented with combining oral anticoagulation with a single antiplatelet agent, rather than combining oral anticoagulation with dual antiplatelet therapy. These studies show that this reduces the risk of bleeding but are underpowered to determine whether this still provides as much cardiovascular benefit. This review summarizes the currently available evidence on this topic and highlights the key questions that remain to be answered including ongoing clinical trials in the field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Response of spinal myoclonus to a combination therapy of autogenic training and biofeedback.

PubMed

Sugimoto, Koreaki; Theoharides, Theoharis C; Kempuraj, Duraisamy; Conti, Pio

2007-10-12

Clinical evidence indicates that certain types of movement disorders are due to psychosomatic factors. Patients with myoclonic movements are usually treated by a variety of therapeutic agents. Autogenic training (AT), a recognized form of psychosomatic therapies, is suitable for certain types of neurological diseases. We describe a patient with myoclonus who failed to respond to conventional medical therapy. His symptoms were exaggerated by psychogenic factors, especially anger. A 42-year-old man was admitted to our hospital, Preventive Welfare Clinic, for severe paroxysmal axial myoclonus of the left shoulder and abdominal muscles. The initial diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus". The myoclonic movements did not occur during sleep but were aggravated by bathing, alcohol drinking, and anger. Psychological examination indicated hostile attribution. Although considered not to be a case of psychogenic myoclonus, a "psychogenic factor" was definitely involved in the induction of the organic myoclonus. The final diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus accompanied by features of psychosomatic disorders". The patient underwent psychosomatic therapy including AT and surface electromyography (EMG)-biofeedback therapy and treatment with clonazepam and carbamazepine. AT and EMG-biofeedback resulted in shortening the duration and reducing the amplitude and frequency of the myoclonic discharges. Psychosomatic therapy with AT and surface EMG-biofeedback produced excellent improvement of myoclonic movements and allowed the reduction of the dosage of conventional medications.

Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients.

PubMed

Uchiwa, Hiroki; Kai, Hisashi; Iwamoto, Yoshiko; Anegawa, Takahiro; Kajimoto, Hidemi; Fukuda, Kenji; Imaizumi, Tsutomu; Fukumoto, Yoshihiro

2018-01-01

Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.

Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.

1982-05-01

A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications,more » possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity.« less

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) in clinical practice in patients with vascular diseases or type 2 diabetes mellitus.

PubMed

Lafeber, Melvin; Grobbee, Diederick E; Spiering, Wilko; van der Graaf, Yolanda; Bots, Michiel L; Visseren, Frank L J

2013-10-01

Based on guidelines, patients with established cardiovascular disease are likely to already receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacological agents into a cardiovascular polypill could be considered in these patients to reduce prescription gaps and non-adherence. We aimed to assess the prevalence of the combined use of aspirin, statin, and BP-lowering agents in patients with established cardiovascular diseases or type 2 diabetes mellitus (DM2) in the period 1996-2009. In total, 5702 patients with coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial occlusive disease (PAOD), abdominal aortic aneurysm (AAA) or, DM2 were included in the period 1996-2009. The overall use of combination therapy with aspirin, statin, and ≥ 1 BP-lowering agent increased substantially from 9% in 1996 to 66% in 2009 and ≥ 2 BP-lowering agents increased from 1% to 47%. In 2009, combination therapy with ≥ 1 BP-lowering agent was used by 83% of those with CAD, 48% of those with CVD, 43% of those with PAOD, 36% of the patients with AAA, and 19% of the patients with DM2. In most patient groups, obesity, metabolic syndrome, hypertension concomitant CAD, CVD, or DM2 were related to the use of combination therapy in models adjusted for age and gender. A high proportion of patients with established cardiovascular diseases already uses a combination of pharmacological agents. Introduction of a polypill in high-risk patients might be feasible to reduce prescription gaps and increase adherence to indicated therapy.

The Effects of Parent Participation on Child Psychotherapy Outcome: A Meta-Analytic Review

ERIC Educational Resources Information Center

Dowell, Kathy A.; Ogles, Benjamin M.

2010-01-01

Forty-eight child psychotherapy outcome studies offering direct comparisons of an individual child treatment group to a combined parent-child/family therapy treatment group were included in this meta-analytic review. Results indicate that combined treatments produced a moderate effect beyond the outcomes achieved by individual child treatments,…

Interstitial cystitis

MedlinePlus

... symptoms get better. Reduce or stop consuming caffeine, chocolate, carbonated beverages, citrus drinks, and foods with a ... pelvic floor muscle spasms. MEDICINE AND PROCEDURES Combination therapy may include medicines such as: Pentosan polysulfate sodium, ...

Effect of speech therapy as adjunct treatment to continuous positive airway pressure on the quality of life of patients with obstructive sleep apnea.

PubMed

Diaferia, Giovana; Badke, Luciana; Santos-Silva, Rogerio; Bommarito, Silvana; Tufik, Sergio; Bittencourt, Lia

2013-07-01

Patients with obstructive sleep apnea (OSA) exhibit reduced quality of life (QoL) due to their daytime symptoms that restricted their social activities. The available data for QoL after treatment with continuous positive airway pressure (CPAP) are inconclusive, and few studies have assessed QoL after treatment with speech therapy or other methods that increase the tonus of the upper airway muscles or with a combination of these therapies. The aim of our study was to assess the effect of speech therapy alone or combined with CPAP on QoL in patients with OSA using three different questionnaires. Men with OSA were randomly allocated to four treatment groups: placebo, 24 patients had sham speech therapy; speech therapy, 27 patients had speech therapy; CPAP, 27 patients had treatment with CPAP; and combination, 22 patients had treatment with CPAP and speech therapy. All patients were treated for 3 months. Participants were assessed before and after treatment and after 3 weeks of a washout period using QoL questionnaires (Functional Outcomes of Sleep Questionnaire [FOSQ], World Health Organization Quality of Life [WHOQoL-Bref], and Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]). Additional testing measures included an excessive sleepiness scale (Epworth sleepiness scale [ESS]), polysomnography (PSG), and speech therapy assessment. A total of 100 men aged 48.1±11.2 (mean±standard deviation) years had a body mass index (BMI) of 27.4±4.9 kg/m(2), an ESS score of 12.7±3.0, and apnea-hypopnea index (AHI) of 30.9±20.6. After treatment, speech therapy and combination groups showed improvement in the physical domain score of the WHOQoL-Bref and in the functional capacity domain score of the SF-36. Our results suggest that speech therapy alone as well as in association with CPAP might be an alternative treatment for the improvement of QoL in patients with OSA. Copyright © 2013 Elsevier B.V. All rights reserved.

Concordant Occipital and Supraorbital Neurostimulation Therapy for Hemiplegic Migraine; Initial Experience; A Case Series

PubMed Central

Will, Kelly R.; Conidi, Frank; Bulger, Robert

2015-01-01

Introduction Hemiplegic migraine is a particularly severe form of the disease that often evolves to a debilitating chronic illness that is resistant to commonly available therapies. Peripheral neurostimulation has been found to be a beneficial therapy for some patients among several diagnostic classes of migraine, but its potential has not been specifically evaluated for hemiplegic migraine. Materials and Methods Four patients with hemiplegic migraine were treated with concordant, combined occipital and supraorbital neurostimulation over periods ranging 6–92 months. The clinical indicators followed included assessments of headache frequency and severity, frequency of hemiplegic episodes, functional impairment, medication usage, and patient satisfaction. Results All reported a positive therapeutic response, as their average headache frequency decreased by 92% (30 to 2.5 headache days/month); Visual Analog Score by 44% (9.5 to 5.3); frequency of hemiplegic episodes by 96% (7.5 to 0.25 hemiplegic episodes/month); headache medication usage by 96% (6 to 0.25 daily medications); and Migraine Disability Assessment score by 98% (249 to 6). All were satisfied and would recommend the therapy, and all preferred combined occipital–supraorbital neurostimulation to occipital neurostimulation alone. Conclusions Concordant combined occipital and supraorbital neurostimulation may provide effective therapy for both the pain and motor aura in some patients with hemiplegic migraine. PMID:25688595

CD28z CARs and Armored CARs

PubMed Central

Pegram, Hollie J.; Park, Jae H.; Brentjens, Renier J.

2015-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whilst promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate “armored CAR T cells” which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors or monoclonal antibodies are aimed at improving the anti-tumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include utilizing dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel “armored CAR T cell” approaches for improving anti-tumor efficacy therapy. PMID:24667958

CD28z CARs and armored CARs.

PubMed

Pegram, Hollie J; Park, Jae H; Brentjens, Renier J

2014-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whereas promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate "armored CAR T cells," which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors, or monoclonal antibodies, are aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include using dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel armored CAR T cell approaches for improving antitumor efficacy therapy.

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment.

PubMed

McLean, Leon P; Cross, Raymond K

2014-03-01

Crohn's disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered.

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

PubMed Central

McLean, Leon P; Cross, Raymond K

2014-01-01

Crohn’s disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered. PMID:24490595

[Physiotherapy for juvenile idiopathic arthritis].

PubMed

Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

2012-07-01

Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

An updated review of the efficacy of cupping therapy.

PubMed

Cao, Huijuan; Li, Xun; Liu, Jianping

2012-01-01

Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted.

Diabetic and Nondiabetic Gastroparesis.

PubMed

McCallum; Brown

1998-12-01

Nutritional support is essential in treating patients with gastroparesis. Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation. Enteral feeding should be introduced in the event of weight loss or persistent vomiting. Medical therapy is usually necessary early in treatment. Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron. If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects. Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance. Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities. Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective. While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis. Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms. Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin. In the future, gastric pacing may become an effective option for patients not responding to medical therapy. Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed. Both procedures should be reserved for centers that specialize in severe gastric motility disorders.

Combined oral contraceptives and/or antiandrogens versus insulin sensitizers for polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Luque-Ramírez, Manuel; Nattero-Chávez, Lía; Ortiz Flores, Andrés E; Escobar-Morreale, Héctor F

2017-12-27

Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic approaches for adult patients not seeking fertility include combined oral contraceptives (COC), antiandrogens (AA) and/or insulin sensitizers, although these practices are supported by limited high-quality evidence. We aimed to assess the efficacy and safety of these common treatments for PCOS by conducting a meta-analysis of RCTs with the following review questions: Which is the more appropriate therapeutic approach for hyperandrogenic symptoms, hyperandrogenemia, and ovulatory dysfunction in adult women with PCOS not seeking fertility; What is the impact on classic cardiometabolic risk factors of the more common treatments used in those women; Does the combination of the antiandrogenic therapy plus metformin have any impact on efficacy or cardiometabolic profile? We searched PubMed and EMBASE for articles published up to 16 September 2017. After deleting duplicates, the abstracts of 1522 articles were analysed. We subsequently excluded 1446 articles leaving 76 studies for full-text assessment of eligibility. Of them, 43 articles were excluded. Hence, 33 studies and 1521 women were included in the quantitative synthesis and in the meta-analyses. Meta-analyses calculated mean differences (MD), standardized mean differences (SMD), odds ratio (OR) and 95% CIs. Heterogeneity and inconsistency across studies was assessed by χ2 test and Higgins's I2 statistics. Quality and risk of bias of individual studies were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. We then used the approach recommended by the Grading of Recommendations, Assessments, Development, and Evaluation (GRADE) group to indicate the global quality of evidence for a selection of primary outcomes. Regarding efficacy, the MD in hirsutism score between COC and/or AA and metformin were not significant. The exclusion of one single study including most women with severe hirsutism yielded a significant effect in favour of COC and/or AA. When only those studies including an AA were compared with metformin, there were significant differences favouring antiandrogenic therapy. The combination of COC and/or AA with metformin was similar to COC and/or AA therapy alone in the whole group of patients. Post-intervention OR for the presence of regular menses favoured COC therapy. In terms of cardiometabolic impact, the MD in BMI were in favour of metformin. The negative effect of COC therapy on BMI was blunted by its combination with metformin. The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA. The combination of COC and/or AA and metformin decreased MD in HOMA with respect to antiandrogenic therapy alone. There were no significant post-intervention SMD in circulating glucose levels between COC and/or AA and metformin. However, adding metformin to COC and/or AA yielded a beneficial effect on fasting glucose levels. Post-intervention OR for abnormal glucose tolerance showed no significant differences between COC and/or AA and metformin, although after excluding studies including an AA as a comparator (without COC) a significant effect in favour of metformin therapy was observed. There were no significant differences among therapies in lipid profile, blood pressure or prevalence of hypertension. The global quality of evidence was very low when addressing the impact of the treatments explored on prevalence of hypertension and lipid profiles, low in the case of hirsutism, BMI and blood pressure values, and high for endometrial protection and glucose tolerance. These data provide further scientific evidence for the choice of treatment of women with PCOS. COC and AA are more effective than metformin for hyperandrogenic symptoms and endometrial protection. Their combination with metformin adds a positive effect on BMI and glucose tolerance. CRD42016053457. © The Author(s) 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery.

PubMed

Mitchell, L Brent

2011-01-01

Postoperative atrial fibrillation and atrial flutter (POAF) are the most common complications of cardiac surgery that require intervention or prolong intensive care unit and total hospital stay. For some patients, these tachyarrhythmias have important consequences including patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events including stroke, exposure to the risks of antiarrhythmic treatments, longer hospital stay, and increased health care costs. We conclude that prevention of POAF is a worthwhile exercise and recommend that the dominant therapy for this purpose be β-blocker therapy, especially the continuation of β-blocker therapy that is already in place. When β-blocker therapy is contraindicated, amiodarone prophylaxis is recommended. If both of these therapies are contraindicated, therapy with either intravenous magnesium or biatrial pacing is suggested. Patients at high risk of POAF may be considered for first-line amiodarone therapy, first-line sotalol therapy, or combination prophylactic therapy. The treatment of POAF may follow either a rate-control approach (with the dominant therapy being β-blocking drugs) or a rhythm-control approach. Anticoagulation should be considered if persistent POAF lasts >72 hours and at the point of hospital discharge. The ongoing need for any POAF treatment (including anticoagulation) should be reconsidered 6-12 weeks after the surgical procedure. Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Multimodal Surgical and Medical Treatment for Extensive Rhinocerebral Mucormycosis in an Elderly Diabetic Patient: A Case Report and Literature Review

PubMed Central

Pirrello, Roberto; Guadagnino, Giuliana; Richiusa, Pierina; Lo Casto, Antonio; Sarno, Caterina; Moschella, Francesco; Cabibi, Daniela

2014-01-01

Diabetes is a well-known risk factor for invasive mucormycosis with rhinocerebral involvement. Acute necrosis of the maxilla is seldom seen and extensive facial bone involvement is rare in patients with rhino-orbital-cerebral mucormycosis. An aggressive surgical approach combined with antifungal therapy is usually necessary. In this report, we describe the successful, personalized medical and surgical management of extensive periorbital mucormycosis in an elderly diabetic, HIV-negative woman. Mono- or combination therapy with liposomal amphotericin B (L-AmB) and posaconazole (PSO) and withheld debridement is discussed. The role of aesthetic plastic surgery to preserve the patient's physical appearance is also reported. Any diabetic patient with sinonasal disease, regardless of their degree of metabolic control, is a candidate for prompt evaluation to rule out mucormycosis. Therapeutic and surgical strategies and adjunctive treatments are essential for successful disease management. These interventions may include combination therapy. Finally, a judicious multimodal treatment approach can improve appearance and optimize outcome in elderly patients. PMID:24982678

Acupuncture therapy for sudden sensorineural hearing loss: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhang, Xin-chang; Xu, Xiu-ping; Xu, Wen-tao; Hou, Wen-zhen; Cheng, Ying-ying; Li, Chang-xi; Ni, Guang-xia

2015-01-01

Acupuncture has commonly been used in China, either alone or in combination with Western medicine, to treat sudden sensorineural hearing loss (SSHL). The purpose of this systematic review is to assess the efficacy and safety of acupuncture therapy for patients with SSHL. We searched PubMed, the Cochrane Library, Embase, China National Knowledge Internet (CNKI), Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical literature service system (SinoMed) to collect randomized controlled trials of acupuncture for SSHL published before July 2014. A meta-analysis was conducted according to the Cochrane systematic review method using RevMan 5.2 software. The evidence level for each outcome was assessed using the GRADE methodology. Twelve trials involving 863 patients were included. A meta-analysis showed that the effect of manual acupuncture combined with Western medicine comprehensive treatment (WMCT) was better than WMCT alone (RR 1.33, 95%CI 1.19-1.49) and the same as the effect of electroacupuncture combined with WMCT (RR 1.33, 95%CI 1.19-1.50). One study showed a better effect of electroacupuncture than of WMCT (RR 1.34, 95%CI 1.24-1.45). For mean changes in hearing over all frequencies, the meta-analysis showed a better effect with the combination of acupuncture and WMCT than with WMCT alone (MD 10.85, 95%CI 6.84-14.86). However, the evidence levels for these interventions were low or very low due to a high risk of bias and small sample sizes in the included studies. There was not sufficient evidence showing that acupuncture therapy alone was beneficial for treating SSHL. However, interventions combining acupuncture with WMCT had more efficacious results in the treatment of SSHL than WMCT alone. Electroacupuncture alone might be a viable alternative treatment besides WMCT for SSHL. However, given that there were fewer eligible RCTs and limitations in the included trials, such as methodological drawbacks and small sample sizes, large-scale RCTs are required to confirm the current findings regarding acupuncture therapy for SSHL.

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

PubMed

Ueda, Tamenobu; Kai, Hisashi; Imaizumi, Tsutomu

2012-07-01

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy for Atrial Fibrillation as a Test Case

PubMed Central

Li, Guowei; Thabane, Lehana; Delate, Thomas; Witt, Daniel M.; Levine, Mitchell A. H.; Cheng, Ji; Holbrook, Anne

2016-01-01

Objectives To construct and validate a prediction model for individual combined benefit and harm outcomes (stroke with no major bleeding, major bleeding with no stroke, neither event, or both) in patients with atrial fibrillation (AF) with and without warfarin therapy. Methods Using the Kaiser Permanente Colorado databases, we included patients newly diagnosed with AF between January 1, 2005 and December 31, 2012 for model construction and validation. The primary outcome was a prediction model of composite of stroke or major bleeding using polytomous logistic regression (PLR) modelling. The secondary outcome was a prediction model of all-cause mortality using the Cox regression modelling. Results We included 9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In the derivation cohort (n = 4632), there were 136 strokes (2.94%), 280 major bleedings (6.04%) and 1194 deaths (25.78%) occurred. In the prediction models, warfarin use was not significantly associated with risk of stroke, but increased the risk of major bleeding and decreased the risk of death. Both the PLR and Cox models were robust, internally and externally validated, and with acceptable model performances. Conclusions In this study, we introduce a new methodology for predicting individual combined benefit and harm outcomes associated with warfarin therapy for patients with AF. Should this approach be validated in other patient populations, it has potential advantages over existing risk stratification approaches as a patient-physician aid for shared decision-making PMID:27513986

Epigenetic therapy with inhibitors of histone methylation suppresses DNA damage signaling and increases glioma cell radiosensitivity.

PubMed

Gursoy-Yuzugullu, Ozge; Carman, Chelsea; Serafim, Rodolfo Bortolozo; Myronakis, Marios; Valente, Valeria; Price, Brendan D

2017-04-11

Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance. Here, we demonstrate that inhibitors of the H4K20 methyltransferase SETD8 (UNC-0379) and the H3K9 methyltransferase G9a (BIX-01294) are effective radiosensitizers of human glioma cells. UNC-0379 blocked H4K20 methylation and reduced recruitment of the 53BP1 protein to DSBs, although this loss of 53BP1 caused only limited changes in radiosensitivity. In contrast, loss of H3K9 methylation through G9a inhibition with BIX-01294 increased radiosensitivity of a panel of glioma cells (SER2Gy range: 1.5 - 2.9). Further, loss of H3K9 methylation reduced DSB signaling dependent on H3K9, including reduced activation of the Tip60 acetyltransferase, loss of ATM signaling and reduced phosphorylation of the KAP-1 repressor. In addition, BIX-0194 inhibited DSB repair through both the homologous recombination and nonhomologous end-joining pathways. Inhibition of G9a and loss of H3K9 methylation is therefore an effective approach for increasing radiosensitivity of glioma cells. These results suggest that combining inhibitors of histone methyltransferases which are critical for DSB repair with radiation therapy may provide a new therapeutic route for sensitizing gliomas and other tumors to radiation therapy.

Systemic medications: clinical significance in periodontics.

PubMed

Ciancio, Sebastian G

2002-05-01

Systemic medications are of value as adjuncts to periodontal therapy. These medications can be divided into two major categories: antibiotics and agents for host modulation. Antibiotics have been shown to be valuable adjuncts in specialized types of periodontal disease, such as localized and generalized aggressive periodontitis, and of possible value in severe chronic periodontitis. Antibiotics have been studied individually, in combination and in sequential therapy. Host modulators include Periostat, non-steroidal anti-inflammatory agents, alendronate (Fosamax), hormone replacement therapy and anti-arthritic medications. These agents produce their beneficial effects by a variety of mechanisms of action, including inhibition of matrix metalloproteinases, inhibition of prostaglandin production, stimulation of osteoblasts, inhibition of osteoclasts, and other anti-inflammatory mechanisms of action.

[Treating vaginismus in Turkish women].

PubMed

Gül, V; Ruf, G D

2009-03-01

Vaginismus is a sexual dysfunction involving various branches of medicine, including psychiatry and gynaecology. Psychiatric help is sought in only a small proportion of cases, although it is probable that the psychopathological aetiology is more frequent than generally recognized. This article deals with the causes and psychological circumstances in four Turkish couples who presented with unconsummated marriage for 3 to 7 years. Vaginismus F52.5 to the ICD-10 is a sexual dysfunction characterised as: deep anxiety about coitus leading to extreme spasm of musculature making coitus impossible or extremely unpleasant and painful. Four Turkish couples with unconsummated marriage due to the female partners' penetration phobia were included to this study. A patient-oriented multidimensional individual treatment (combination therapy) is a cost effective, short-term (typically 10- to 12-week) treatment model for both partners. It includes some elements of cognitive behavioural therapy and systemic partner therapy which were considered not radically different from previous therapeutic strategies. Results were successful in all cases; the couples were extremely satisfied with having a normal sex life for the first time. This led to desired pregnancies and avoiding of possible breakdown of their families. The couples did well with combination behavioural therapy. This methodology is discussed in its various aspects and with a cultural background. We also emphasise the need for physicians to be mindful of cases of vaginismus requiring psychiatric intervention rather than gynaecological treatment.

Potent Antitumor Effects of Combination Therapy With IFNs and Monocytes in Mouse Models of Established Human Ovarian and Melanoma Tumors

PubMed Central

Nakashima, Hideyuki; Miyake, Kotaro; Clark, Christopher R; Bekisz, Joseph; Finbloom, Joel; Husain, Syed R.; Baron, Samuel; Puri, Raj K.; Zoon, Kathryn C.

2012-01-01

Interferon-activated monocytes are known to exert cytocidal activity against tumor cells in vitro. Here, we have examined whether a combination of IFN-α2a and IFN-γ and human monocytes mediate significant antitumor effects against human ovarian and melanoma tumor xenografts in mouse models. OVCAR-3 tumors were treated i.t. with monocytes alone, IFN-α2a and IFN-γ alone or combination of all three on day 0, 15 or 30 post-tumor implantation. Mice receiving combination therapy beginning day 15 showed significantly reduced tumor growth and prolonged survival including complete regression in 40% mice., Tumor volumes measured on day 80 in mice receiving combination therapy (206 mm3) were significantly smaller than those of mice receiving the IFNs alone (1041 mm3), monocytes alone (1111 mm3) or untreated controls (1728 mm3). Similarly, combination therapy with monocytes and IFNs of much larger tumor also inhibited OVCAR-3 tumor growth. Immunohistochemistry studies showed a large number of activated macrophages (CD31+/CD68+) infiltrating into OVCAR-3 tumors and higher densities of IL-12, IP10 and NOS2, markers of M1 (classical) macrophages in tumors treated with combination therapy compared to the controls. Interestingly, IFNs activated macrophages induced apoptosis of OVCAR-3 tumor cells as monocytes alone or IFNs alone did not mediate significant apoptosis. Similar antitumor activity was observed in the LOX melanoma mouse model, but not as profound as seen with the OVCAR-3 tumors. Administration of either mixture of monocytes and IFN-α2a or monocytes and IFN-γ did not inhibit Lox melanoma growth; however a significant inhibition was observed when tumors were treated with a mixture of monocytes, IFN-α2a and IFN-γ. These results indicate that monocytes and both IFN-α2a and IFN-γ may be required to mediate profound antitumor effect against human ovarian and melanoma tumors in mouse models. PMID:22159517

Artificial intelligence in drug combination therapy.

PubMed

Tsigelny, Igor F

2018-02-09

Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.

PubMed

Negahban, Hossein; Rezaie, Solmaz; Goharpey, Shahin

2013-12-01

The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis. The secondary aim was to investigate whether combination of both massage and exercise has an additive effect. Randomized controlled pilot trial with repeated measurements and blinded assessments. Local Multiple Sclerosis Society. A total of 48 patients with multiple sclerosis were randomly assigned to four equal subgroups labelled as massage therapy, exercise therapy, combined massage-exercise therapy and control group. The treatment group received 15 sessions of supervised intervention for five weeks. The massage therapy group received a standard Swedish massage. The exercise therapy group was given a combined set of strength, stretch, endurance and balance exercises. Patients in the massage-exercise therapy received a combined set of massage and exercise treatments. Patients in the control group were asked to continue their standard medical care. Pain, fatigue, spasticity, balance, gait and quality of life were assessed before and after intervention. Massage therapy resulted in significantly larger improvement in pain reduction (mean change 2.75 points, P = 0.001), dynamic balance (mean change, 3.69 seconds, P = 0.009) and walking speed (mean change, 7.84 seconds, P = 0.007) than exercise therapy. Patients involved in the combined massage-exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy (mean change, 1.67 points, P = 0.001). Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.

Aplastic anemia.

PubMed

Usuki, Kensuke

2016-01-01

Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications. The most effective immunosuppressive therapy is a combination of anti-thymocyte globulin and cyclosporine. This treatment is also effective against the secondary, drug-induced and hepatitis-associated forms of aplastic anemia. In the management of aplastic anemia, a treatment is selected from among these options depending on the disease severity and the age of the individual case. The thrombopoietin receptor agonist eltrombopag appears to be effective and to provide tri-lineage recovery of hematopoiesis in some cases. Indications for its use are expected to expand in Japan.

Controlled Trial of Very Low Calorie Diet, Behavior Therapy, and Their Combination in the Treatment of Obesity.

ERIC Educational Resources Information Center

Wadden, Thomas A; Stunkard, Albert J.

1986-01-01

Assessed the effectiveness of a combined program of very low calorie diet and behavior therapy in treating obesity. Combined treatment and behavior therapy alone subjects maintained weight losses; none of the diet alone subjects met the criterion used to define maintenance. Only those receiving behavior therapy alone and combined treatment showed…

Hypothyroidism following treatment for head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrabec, D.P.; Heffron, T.J.

One hundred ninety-six head and neck patients were studied to determine the effects of radiation therapy and surgery on thyroid function. Serum thyroid-stimulating hormone (TSH) levels were obtained as a screening test for primary hypothyroidism. Elevated TSH levels were found in 57 of the 196 patients (29.1%). The highest incidence of abnormal TSH values (66%) occurred in the group treated with combination radiation therapy and surgery, including partial thyroidectomy. TSH levels rose early in the posttreatment period with 60% of the abnormal values occurring within the first three posttreatment years. Posttreatment thyroid dysfunction was twice as common in women (48.6%)more » as in men (25.4%). When serum thyroxine levels by radioimmunoassay (T4RIA) were correlated with the elevated serum TSH levels, a similar pattern was seen with 65% of the patients in Group 3 having a decreased T4RIA level indicating overt hypothyroidism. Pretreatment levels of thyroid function including thyroid antibody studies should be established for all patients. Serial TSH levels should be done every three months during the first three posttreatment years and semiannually thereafter as long as the patient will return for follow-up care. All patients treated with combination radiation therapy and surgery who develop elevated TSH levels should be treated with thyroid replacement therapy. Patients receiving radiation therapy alone should receive replacement thyroid therapy if they develop a depressed T4RIA value or a pattern of gradually increasing TSH levels.« less

Recommendations for physical therapists on the treatment of lumbopelvic pain during pregnancy: a systematic review.

PubMed

van Benten, Esther; Pool, Jan; Mens, Jan; Pool-Goudzwaard, Annelies

2014-07-01

Systematic review of the literature. To review and assess the peer-reviewed literature on the effectiveness of physical therapy interventions in treating lumbopelvic pain during pregnancy. Current guidelines on interventions for lumbopelvic pain during pregnancy differ in their recommendations for assessment and intervention. Recent publications may allow revising current recommendations for the treatment of this complex problem. An electronic search strategy was conducted in PubMed, PEDro, Scopus, and CINAHL of literature published from January 1992 to November 2013. Two authors independently assessed all abstracts for eligibility. Articles were independently rated for quality by 2 authors, using the Cochrane Back Review Group criteria for methodological quality. Where possible, effect sizes were calculated for the different interventions. A total of 22 articles (all randomized controlled trials) reporting on 22 independent studies were included. Overall, the methodological quality of the studies was moderate. Data for 4 types of interventions were considered: a combination of interventions (7 studies, n = 1202), exercise therapy (9 studies, n = 2149), manual therapy (5 studies, n = 360), and material support (1 study, n = 115). All included studies on exercise therapy, and most of the studies on interventions combined with patient education, reported a positive effect on pain, disability, and/or sick leave. Evidence-based recommendations can be made for the use of exercise therapy for the treatment of lumbopelvic pain during pregnancy. Therapy, level 1a-. J Orthop Sports Phys Ther 2014;44(7):464-473. Epub 10 May 2014. doi:10.2519/jospt.2014.5098.

The efficacy of tramadol/acetaminophen combination tablets (Ultracet®) as add-on and maintenance therapy in knee osteoarthritis pain inadequately controlled by nonsteroidal anti-inflammatory drug (NSAID).

PubMed

Park, Kyung-Su; Choi, Jin-Jung; Kim, Wan-Uk; Min, June-Ki; Park, Sung-Hwan; Cho, Chul-Soo

2012-02-01

The purpose of this study is to compare the efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) with that of nonsteroidal anti-inflammatory drugs (NSAIDs) as maintenance therapy following tramadol/APAP and NSAID combination therapy in knee osteoarthritis (OA) pain which was inadequately controlled by NSAIDs. Subjects with knee OA for over 1 year and moderate pain (numerical rating scale [NRS] ≥5) despite at least 4 weeks' NSAID therapy (meloxicam 7.5 mg or 15 mg qd or aceclofenac 100 mg bid) received tramadol/APAP add-on (combination with NSAID) for 4 weeks. Thereafter, subjects with significant pain improvement (NRS <4) were randomized to receive either tramadol/APAP or NSAID for 8 weeks. On days 29 and 57, Western Ontario and McMaster Universities (WOMAC) OA index score was measured. Secondary measures included pain intensity (NRS), pain relief score, and subjects' and investigators' overall medication assessments. Of 143 subjects enrolled, 112 completed the 4-week tramadol/APAP and NSAID combination phase and 97 (67.8%) experienced significant pain improvement. Of the 97 subjects randomized, 36 in tramadol/APAP group and 47 in NSAID group completed the 8-week comparator study. On days 29 and 57, WOMAC scores and pain intensities did not increase in both groups compared to measurements immediately after the combination therapy. At these two time points, there were no significant differences in WOMAC scores, pain intensities, and other secondary measures between the two groups. Overall adverse event rates were similar in both groups. Tramadol/APAP add-on significantly improved knee OA pain which had been inadequately controlled by NSAIDs. In those subjects who showed favorable response to tramadol/APAP and NSAID combination therapy, both tramadol/APAP and NSAIDs were effective at maintaining the pain-reduced state and there was no significant difference in efficacy between tramadol/APAP and NSAIDs.

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

PubMed

Long, Georgina V; Hauschild, Axel; Santinami, Mario; Atkinson, Victoria; Mandalà, Mario; Chiarion-Sileni, Vanna; Larkin, James; Nyakas, Marta; Dutriaux, Caroline; Haydon, Andrew; Robert, Caroline; Mortier, Laurent; Schachter, Jacob; Schadendorf, Dirk; Lesimple, Thierry; Plummer, Ruth; Ji, Ran; Zhang, Pingkuan; Mookerjee, Bijoyesh; Legos, Jeff; Kefford, Richard; Dummer, Reinhard; Kirkwood, John M

2017-11-09

Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).

Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

PubMed Central

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-01-01

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

PubMed

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Radiobiological Optimization of Combination Radiopharmaceutical Therapy Applied to Myeloablative Treatment of Non-Hodgkin’s Lymphoma

PubMed Central

Hobbs, Robert F; Wahl, Richard L; Frey, Eric C; Kasamon, Yvette; Song, Hong; Huang, Peng; Jones, Richard J; Sgouros, George

2014-01-01

Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid ‘90s, such treatment strategies have only been implemented clinically recently, and without a rigorous methodology for treatment optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiological normal organ tolerance while optimizing the ratio of two different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-hodgkin’s lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods The range of potential administered activities (AA) is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normal organ constraints as a function of the AAs and calculating tumor biological effective dose (BED) along the normal organ MTBED limits, the optimal combination of activities is obtained. The model was tested using previously acquired patient normal organ and tumor kinetic data and MTBED values taken from the literature. Results The average AA values based solely on normal organ constraints was (19.0 ± 8.2) GBq with a range of 3.9 – 36.9 GBq for 131I-tositumomab, and (2.77 ± 1.64) GBq with a range of 0.42 – 7.54 GBq for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal organ kinetics for the two radiopharmaceuticals. Results included AA ranges which would deliver 95 % of the maximum tumor BED, which allows for informed inclusion of clinical considerations, such as a maximum allowable 131I administration. Conclusions A rational approach for combination radiopharmaceutical treatment has been developed within the framework of a proven 3-dimensional personalized dosimetry software, 3D-RD, and applied to the myeloablative treatment of NHL. We anticipate combined radioisotope therapy will ultimately supplant single radioisotope therapy, much as combination chemotherapy has substantially replaced single agent chemotherapy. PMID:23918734

Changes in Cognitive-Behavioral Constructs Across Treatment Modalities for Seasonal Affective Disorder: Cognitive-Behavioral Therapy, Light Therapy, and their Combination

DTIC Science & Technology

2003-01-01

increased appetite (including cravings for complex carbohydrates and sugars; Kasper et al., 1989). Within the recurrent depressed population...individuals’ rate of engagement in pleasant activities through three interpersonal styles of interaction : assertion, interpersonal style of expressive...degree of change on automatic thoughts. This hypothesized pattern of findings would produce a significant Group X Occasion interaction

[The laser therapy of rheumatoid arthritis].

PubMed

Soroka, N F

1989-01-01

About 300 patients with rheumatoid arthritis (RA) underwent multimodality treatment including laser radiation of varying wavelengths. Use was made of helium-neon, infrared, argon and helium-cadmium lasers. A new method of combined laser therapy by radiation of helium-cadmium and helium-neon lasers is described. A scheme of optimal parameters and types of laser radiation recommended for the treatment of different clinical varieties of RA is provided.

The combination therapy of Ephedra herb and Loxoprofen caused gastric lesions in mice.

PubMed

Cho, Shigefumi; Hong, Tie; Jin, Guang-Bi; Yoshino, Gen; Miura, Myota; Aikawa, Yoshihiro; Yasuno, Fumiko; Cyong, Jong-Chol

2002-01-01

The combination therapy of a Kampo formula and an analgesic-antipyretic agent is often used for the common cold in Japan. We investigated the effect of such a combination therapy, using the Ephedra herb, which is a common ingredient of Kakkon-to and Mao-to, and Loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), on fever induced in an experimental model of mice under strong stress. The combination therapy of Ephedra herb and Loxoprofen caused gastric mucosal lesions and loss of body weight. It is considered that this combination therapy should be avoided because of its adverse effects.

Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects.

PubMed

Brandão, Mariana; Pondé, Noam F; Poggio, Francesca; Kotecki, Nuria; Salis, Mauren; Lambertini, Matteo; de Azambuja, Evandro

2018-05-24

HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.

Recent insights in the therapeutic management of patients with gastric cancer.

PubMed

de Mestier, Louis; Lardière-Deguelte, Sophie; Volet, Julien; Kianmanesh, Reza; Bouché, Olivier

2016-09-01

Gastric cancer remains frequent and one of the most lethal malignancies worldwide. In this article, we aimed to comprehensively review recent insights in the therapeutic management of gastric cancer, with focus on the surgical and perioperative management of resectable forms, and the latest advances regarding advanced diseases. Surgical improvements comprise the use of laparoscopic surgery including staging laparoscopy, a better definition of nodal dissection, and the development of hyperthermic intraperitoneal chemotherapy. The best individualized perioperative management should be assessed before curative-intent surgery for all patients and can consists in perioperative chemotherapy, adjuvant chemo-radiation therapy or adjuvant chemotherapy alone. The optimal timing and sequence of chemotherapy and radiation therapy with respect to surgery should be further explored. Patients with advanced gastric cancer have a poor prognosis. Nevertheless, they can benefit from doublet or triplet chemotherapy combination, including trastuzumab in HER2-positive patients. Upon progression, second-line therapy can be considered in patients with good performance status. Although anti-HER2 (trastuzumab) and anti-VEGFR (ramucirumab) may yield survival benefit, anti-EGFR and anti-HGFR therapies have failed to improve outcomes. Nevertheless, combination regimens containing cytotoxic drugs and targeted therapies should be further evaluated; keeping in mind that gastric cancer biology is different between Asia and the Western countries. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Management of hepatitis C virus infection: the basics.

PubMed

Naggie, Susanna

2012-12-01

Chronic hepatitis C virus (HCV) infection affects some 170 million people worldwide, including 3 to 4 million in the United States who are largely unaware of their infection status. HCV has 6 genotypes; genotype 1 is the most common in the United States and genotypes 1 and 4 are less responsive to interferon alfa-based therapy than the other genotypes. Treatment with available direct-acting antiviral (DAA) drugs has increased sustained virologic response (SVR) rates in genotype 1 infection and shortened duration of therapy in many patients, but at this time these agents must still be administered with peginterferon alfa and ribavirin to prevent rapid emergence of resistance. Baseline predictors of response to therapy continue to play a role with triple-drug combination therapy including the pharmacogenetic IL28B genotype, which differs in prevalence throughout the world. The stopping/futility rules are different for triple-drug combination therapy, allowing for earlier decision-making. Ultimately, SVR is the goal of HCV treatment because it dramatically reduces likelihood of poor long-term outcome, even among patients with histologically advanced disease. This article summarizes a basic review presented by Susanna Naggie, MD, at the IAS-USA live management of HCV continuing medical education program held in Atlanta in October 2012. This article is intended for practitioners who are new to HCV management or who are interested in reviewing the basics of HCV treatments.

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

PubMed

Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

2013-12-01

Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Efficacy of granisetron for preventing chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia treated with a combination of anthracycline and cytarabine].

PubMed

Goto, Takashi; Tanimoto, Kazuki; Ishibashi, Makoto; Okamura, Seiichi

2012-08-01

In Japan, the combination of anthracycline and cytarabine(Ara-C)is a standard therapy for acute myelogenous leukemia(AML). Chemotherapy-induced nausea and vomiting(CINV)are frequently reported as side effects related to the administration of these regimens. In our hospital, patients received prophylactic granisetron at a dose of 3 mg daily during chemotherapy. However, granisetron is known to induce constipation as a side effect. The present study evaluated the efficacy of a single dose of granisetron administered throughout the entire period of chemotherapy in AML patients receiving anthracycline and Ara-C combination therapy, and also examined the incidence of constipation during chemotherapy. From July 2008 to December 2010, all patients with AML treated using anthracycline and Ara-C combination therapy were registered in the study. This retrospective study investigated the patients' background and the incidence of CINV and constipation from the patients' records. The efficacy of granisetron was measured on each day using the complete regression(no vomiting and no rescue medication; CR)rate. A total of 45 patients were included in the study(27 male; 18 female), and received a total 68 courses(56 of induction therapy; 12 of consolidation therapy)of the regimens. The CR rate and the incidence of constipation on the final day of chemotherapy were 61. 8% and 63. 2%, respectively. As the duration of chemotherapy increased, the CR rate tended to decrease, whereas the incidence of constipation tended to increase. The CR rate in this study was 61. 8%, thus indicating that there is still room for improvement. The combination of dexamethasone and a neurokinin-1 receptor antagonist, or the changeover from granisetron to palonosetron could therefore increase the CR rate.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

PubMed Central

GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

PubMed Central

Parra, Karla; Valenzuela, Paloma; Lerma, Natzidielly; Gallegos, Alejandra; Reza, Luis C; Rodriguez, Georgialina; Emmenegger, Urban; Di Desidero, Teresa; Bocci, Guido; Felder, Mitchell S; Manciu, Marian; Kirken, Robert A; Francia, Giulio

2017-01-01

Background: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. Methods: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg−1 day−1), b) bolus (150 mg kg−1) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg−1 every 3 days). Results: EMT-6/P tumours responded to anti-CTLA-4 therapy, but this response was less effective when combined with bolus plus ldCTX. Anti-CTLA-4 could be effectively combined with either ldCTX (without a bolus), or with regimens of either sequential or concomitant gemcitabine, including in orthotopic EMT-6 tumours, and independently of the schedule of drug administration. Tumour responses were confirmed with CT-26 tumours but were less pronounced in drug-resistant EMT-6/CTX or EMT-6/DDP tumour models than in the parent tumour. A number of tumour bearing mice developed spontaneous metastases under continuous therapy. The majority of cured mice rejected tumour re-challenges. Conclusions: Metronomic CTX can be combined with anti-CTLA-4 therapy, but this therapy is impaired by concomitant bolus CTX. Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. PMID:28056464

Combining levodopa and virtual reality-based therapy for rehabilitation of the upper limb after acute stroke: pilot study Part II

PubMed Central

Samuel, Geoffrey Sithamparapillai; Oey, Nicodemus Edrick; Choo, Min; Ju, Han; Chan, Wai Yin; Kok, Stanley; Ge, Yu; Dongen, Antonius M Van; Ng, Yee Sien

2017-01-01

INTRODUCTION This study aimed to evaluate the safety and efficacy of a combination of levodopa and virtual reality (VR)-based therapy for the enhancement of upper limb recovery following acute stroke. METHODS This was a pilot single-blinded case series of acute stroke patients with upper extremity hemiparesis. Patients were randomised to standard care with concomitant administration of either levodopa alone (control group) or combination therapy consisting of VR-based motivational visuomotor feedback training with levodopa neuromodulation (VR group). Main clinical outcome measures were the Fugl-Meyer Upper Extremity (FM-UE) assessment and Action Research Arm Test (ARAT). Kinematic measurements of affected upper limb movement were evaluated as a secondary measure of improvement. RESULTS Of 42 patients screened, four patients were enrolled in each of the two groups. Two patients dropped out from the control group during the trial. Patients receiving combination therapy had clinically significant improvements in FM-UE assessment scores of 16.5 points compared to a 3.0-point improvement among control patients. Similarly, ARAT scores of VR group patients improved by 15.3 points compared to a 10.0-point improvement in the control group. Corresponding improvements were noted in kinematic measures, including hand-path ratio, demonstrating that the quality of upper limb movement improved in the VR group. CONCLUSION Our results suggest that VR-based therapy and pharmacotherapy may be combined for acute stroke rehabilitation. Bedside acquisition of kinematic measurements allows accurate assessment of the quality of limb movement, offering a sensitive clinical tool for quantifying motor recovery during the rehabilitation process after acute stroke. PMID:27311739

Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.

PubMed

Park, Angela; Barrera-Ramirez, Juliana; Ranasinghe, Indee; Pilon, Sophie; Sy, Richmond; Fergusson, Dean; Allan, David S

2016-06-01

Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.

Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes?

PubMed

King, Christopher R; Presti, Joseph C; Gill, Harcharan; Brooks, James; Hancock, Steven L

2004-06-01

The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy. Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS. The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively). Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.

Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis.

PubMed

Zhao, Bing-Cheng; Jiang, Hong-Ye; Ma, Wei-Ying; Jin, Da-Di; Li, Hao-Miao; Lu, Hai; Nakajima, Hideaki; Huang, Tong-Yi; Sun, Kai-Yu; Chen, Shu-Ling; Chen, Ke-Bing

2016-02-01

Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.

Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis

PubMed Central

Nakajima, Hideaki; Huang, Tong-Yi; Sun, Kai-Yu; Chen, Shu-Ling; Chen, Ke-Bing

2016-01-01

Background Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. PMID:26849048

Aspergillus osteomyelitis. Report of a case and review of the literature.

PubMed

Barnwell, P A; Jelsma, L F; Raff, M J

1985-11-01

Aspergillus is a ubiquitous saprophytic fungus seldom pathogenic for normal hosts. Aspergillus osteomyelitis occurs infrequently and is typically limited to patients with predisposing factors, including leukocyte dysfunction, malignancy with neutropenia, steroid or antibiotic therapy, pulmonary aspergillosis, and surgical manipulation. The spine is most frequently affected, and the clinical presentation is nonspecific (50% afebrile). Diagnosis requires demonstration of characteristic, acutely branching, broad, septate hyphae in biopsy material, and culture of Aspergillus. Therapy includes debridement of necrotic bone and loculated purulence combined with amphotericin B and possibly 5-fluorocytosine or rifampin.

Hybrid protocols plus natural treatments for inflammatory conditions.

PubMed

1998-01-01

Hybrid protocols combine one, two, or three pharmaceutical drugs with several nutritional or immune-based therapies. These protocols are not limited solely to FDA-approved drugs or strictly to alternative therapies. The rationale for using a hybrid protocol is to find an effective antiviral regimen that also restores immune function. The goal is to obtain the benefits of protease inhibitors without viral resistance and side effects which include problems with fat metabolism and cholesterol levels. Natural treatments for inflammatory conditions are also described. Options include licorice root, ginger root, and slippery elm.

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

PubMed

Burke, Erin E; Zager, Jonathan S

2018-04-01

Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

Botulinum toxin type A combined with cervical spine manual therapy for masseteric hypertrophy in a patient with Alzheimer-type dementia: a case report.

PubMed

Villafañe, Jorge H; Fernandez-de-Las-Peñas, Cesar; Pillastrini, Paolo

2012-12-01

The purpose of this case study is to present the findings of combining botulinum toxin type A (BoNT-A) and cervical spine manual therapy to address masseter muscle spasticity in a patient with Alzheimer-type dementia. A 78-year-old woman with bilateral spasticity of the masseteric regions for 2 years was referred for physiotherapy. She had trismus and bruxism, and could neither close nor open her mouth normally; thus, she was unable to be fed orally in a normal manner. The patient underwent combined treatment with BoNT-A and cervical spine manual therapy. A medical physician (neurologist) performed the BoNT-A injections into 2 points at the center of the lower third of the masseter muscle. A physical therapist performed manual therapy interventions targeted at the cervical spine. Manual therapy started the day after the BoNT-A injection and continued for 5 sessions per week for a total period of 2 weeks. Clinical outcomes were measured including spasticity (Modified Ashworth Scale), functionality (Barthel Index), and jaw opening. Outcomes were conducted at baseline, 2 weeks after treatment, and at 2-month follow-up session after finishing the treatment. The patient improved in all of the outcomes at the end of treatment, and these results were maintained during the follow-up. After treatment, the patient was able to feed with minimal caregiver dependency because oral feeding was possible. The patient in this study responded positively to a combination of BoNT-A and manual therapy, resulting in decreased masseter muscles spasticity and improved trismus and bruxism.

Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort.

PubMed

Tanner, Zachary; Lachowsky, Nathan; Ding, Erin; Samji, Hasina; Hull, Mark; Cescon, Angela; Patterson, Sophie; Chia, Jason; Leslie, Alia; Raboud, Janet; Loutfy, Mona; Cooper, Curtis; Klein, Marina; Machouf, Nima; Tsoukas, Christos; Montaner, Julio; Hogg, Robert S

2016-10-21

Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada's three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures <50 copies/mL ≥30 days apart) and subsequent rebound (2 measures >200 copies/mL ≥30 days apart). Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1-Q3: 3-7 months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

PubMed Central

Solís García del Pozo, Julián; Solera, Javier

2012-01-01

Background Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. Methods and Findings A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. Conclusions Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice. PMID:22393379

Gene therapy for prostate cancer: where are we now?

PubMed

Steiner, M S; Gingrich, J R

2000-10-01

The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer. We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy. Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.

Update on the management of rosacea

PubMed Central

Weinkle, Allison P; Doktor, Vladyslava; Emer, Jason

2015-01-01

Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Each subtype stands as a unique entity among a spectrum, with characteristic symptoms and physical findings, along with an intricate pathophysiology. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Topical brimonidine tartrate gel and calcineurin inhibitors are at the forefront of topical therapies, alone or in combination with traditional therapies such as topical metronidazole or azelaic acid and oral tetracyclines or isotretinoin. Vascular laser and intense pulsed light therapies are beneficial for the erythema and telangiectasia, as well as the symptoms (itching, burning, pain, stinging, swelling) of rosacea. Injectable botulinum toxin, topical ivermectin, and microsecond long-pulsed neodymium-yttrium aluminum garnet laser are emerging therapies that may prove to be extremely beneficial in the future. Once a debilitating disorder, rosacea has become a well known and manageable entity in the setting of numerous emerging therapeutic options. Herein, we describe the treatments currently available and give our opinions regarding emerging and combination therapies. PMID:25897253

Hybrid Therapy in the Management of Atrial Fibrillation

PubMed Central

Stárek, Zdeněk; Lehar, František; Jež, Jiří; Wolf, Jiří; Novák, Miroslav

2015-01-01

Atrial fibrillation is the most common sustained arrhythmia. Because of the sub-optimal outcomes and associated risks of medical therapy as well as the recent advances in non-pharmacologic strategies, a multitude of combined (hybrid) algorithms have been introduced that improve efficacy of standalone therapies while maintaining a high safety profile. Antiarrhythmic administration enhances success rate of electrical cardioversion. Catheter ablation of antiarrhythmic drug-induced typical atrial flutter may prevent recurrent atrial fibrillation. Through simple ablation in the right atrium, suppression of atrial fibrillation may be achieved in patients with previously ineffective antiarrhythmic therapy. Efficacy of complex catheter ablation in the left atrium is improved with antiarrhythmic drugs. Catheter ablation followed by permanent pacemaker implantation is an effective and safe treatment option for selected patients. Additional strategies include pacing therapies such as atrial pacing with permanent pacemakers, preventive pacing algorithms, and/or implantable dual-chamber defibrillators are available. Modern hybrid strategies combining both epicardial and endocardial approaches in order to create a complex set of radiofrequency lesions in the left atrium have demonstrated a high rate of success and warrant further research. Hybrid therapy for atrial fibrillation reviews history of development of non-pharmacological treatment strategies and outlines avenues of ongoing research in this field. PMID:25028165

Exploiting cancer cell vulnerabilities to develop a combination therapy for Ras-driven tumors

PubMed Central

De Raedt, Thomas; Walton, Zandra; Yecies, Jessica L.; Li, Danan; Chen, Yimei; Malone, Clare F.; Maertens, Ophelia; Jeong, Seung Min; Bronson, Roderick T.; Lebleu, Valerie; Kalluri, Raghu; Normant, Emmanuel; Haigis, Marcia C.; Manning, Brendan D.; Wong, Kwok-Kin; Macleod, Kay F; Cichowski, Karen

2011-01-01

Summary Ras-driven tumors are often refractory to conventional therapies. Here we identify a promising targeted therapeutic strategy for two Ras-driven cancers: Nf1-deficient malignancies and KRas/p53-mutant lung cancer. We show that agents that enhance proteotoxic stress, including the HSP90 inhibitor IPI-504, induce tumor regression in aggressive mouse models, but only when combined with rapamycin. These agents synergize by promoting irresolvable ER stress, resulting in catastrophic ER and mitochondrial damage. This process is fueled by oxidative stress, which is caused by IPI-504-dependent production of reactive oxygen species, and the rapamycin-dependent suppression of glutathione, an important endogenous antioxidant. Notably, the mechanism by which these agents cooperate reveals a therapeutic paradigm that can be expanded to develop additional combinations. PMID:21907929

[Laserotherapy of diabetic angiopathy of the lower extremities].

PubMed

Zolotova, N B; Zolotnitskaia, V P

2009-01-01

Low-intensity laser radiation was included in combined therapy of lower limb angiopathy in patients with diabetes mellitus. The course and results of the treatment were monitored by means of perfusion scintiography.

Breast Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Breast cancer treatment depends on several factors and can include combinations of surgery, chemotherapy, radiation, hormone, and targeted therapy. Learn more about how breast cancer is diagnosed and treated in this expert-reviewed summary.

Management of obesity after spinal cord injury: a systematic review.

PubMed

Shojaei, Mir Hatef; Alavinia, Seyed Mohammad; Craven, B Catharine

2017-11-01

Individuals with chronic spinal cord injury (SCI) are susceptible to central and visceral obesity and it's metabolic consequences; consensus based guidelines for obesity management after SCI have not yet been stablished. To identify and compare effective means of obesity management among SCI individuals. This systematic review included English and non-English articles, published prior to April 2017 found in the PubMed/Medline, Embase, CINAHL Psychinfo and Cochrane databases. Studies evaluating any obesity management strategy, alone or in combination, including: diet therapy, voluntary and involuntary exercise such as neuro-muscular electric stimulation (NMES), pharmacotherapy, and surgery, among individuals with chronic SCI were included. Outcomes of interest were reductions in waist circumference, body weight (BW), body mass index (BMI) and total fat mass (TFM) and increases in total lean body mass (TLBM) from baseline. From 3,553 retrieved titles and abstracts, 34 articles underwent full text review and 23 articles were selected for data abstraction. Articles describing weight loss due to inflammation, cancer or B12 deficiency were excluded. The Downs and Black reported poor to moderate quality of the studies. Bariatric surgery produced the greatest permanent weight reduction and BMI correction followed by combinations of physical exercise and diet therapy. Generally, NMES and pharmacotherapy improved TLBM and reduced TFM but not weight. The greatest weight reduction and BMI correction was produced by bariatric surgery, followed by a combination of physical exercise and diet therapy. NMES and pharmacologic treatment did not reduce weight or TFM but increased in TLBM.

Optimizing topical therapies for treating psoriasis: a consensus conference.

PubMed

Zeichner, Joshua A; Lebwohl, Mark G; Menter, Alan; Bagel, Jerry; Del Rosso, James Q; Elewski, Boni E; Feldman, Steven R; Kircik, Leon H; Koo, John; Gold, Linda Stein; Tanghetti, Emil

2010-09-01

In 2010, an expert committee of physicians and researchers in the field of dermatology working together as the Psoriasis Process of Care Consensus Panel developed consensus guidelines for the treatment of psoriasis. As much as possible, the guidelines were evidence based but also included the extensive clinical experience of the dermatologists. Psoriasis is a lifelong disease that requires long-term treatment and 80% of psoriasis patients have mild to moderate disease. Topical therapies play an important role in the treatment of psoriasis, especially in patients with mild to moderate disease. Patients usually start with monotherapy; however, in more severe cases (> 10% body surface area [BSA], severely impaired quality of life [QOL], or recalcitrant psoriatic lesions), multiple treatment modalities may be used as part of combination, sequential, or rotational therapeutic regimens. Main treatment options include topical steroids, systemic therapies, topical vitamin D treatments such as vitamin D3 ointment, retinoids, phototherapy, and biologic therapies. Other topical therapies include the following steroid-sparing agents: coal tar, anthralin, calcineurin inhibitors, keratolytics, and emollients. Therapeutic considerations also should focus on adherence, improving QOL, and promoting a good patient-physician relationship.

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Response of spinal myoclonus to a combination therapy of autogenic training and biofeedback

PubMed Central

Sugimoto, Koreaki; Theoharides, Theoharis C; Kempuraj, Duraisamy; Conti, Pio

2007-01-01

Introduction Clinical evidence indicates that certain types of movement disorders are due to psychosomatic factors. Patients with myoclonic movements are usually treated by a variety of therapeutic agents. Autogenic training (AT), a recognized form of psychosomatic therapies, is suitable for certain types of neurological diseases. We describe a patient with myoclonus who failed to respond to conventional medical therapy. His symptoms were exaggerated by psychogenic factors, especially anger. Case presentation A 42-year-old man was admitted to our hospital, Preventive Welfare Clinic, for severe paroxysmal axial myoclonus of the left shoulder and abdominal muscles. The initial diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus". The myoclonic movements did not occur during sleep but were aggravated by bathing, alcohol drinking, and anger. Psychological examination indicated hostile attribution. Although considered not to be a case of psychogenic myoclonus, a "psychogenic factor" was definitely involved in the induction of the organic myoclonus. The final diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus accompanied by features of psychosomatic disorders". The patient underwent psychosomatic therapy including AT and surface electromyography (EMG)-biofeedback therapy and treatment with clonazepam and carbamazepine. Results AT and EMG-biofeedback resulted in shortening the duration and reducing the amplitude and frequency of the myoclonic discharges. Conclusion Psychosomatic therapy with AT and surface EMG-biofeedback produced excellent improvement of myoclonic movements and allowed the reduction of the dosage of conventional medications. PMID:17931427

Overview of Thoracic Oncology Trials in Cooperative Groups Around the Globe

PubMed Central

Salahudeen, Ameen Abdulla; Patel, Manali I.; Baas, Paul; Curran, Walter J.; Bradley, Jeffrey D.; Gandara, David R.; Goss, Glenwood D.; Mok, Tony S.; Ramalingam, Suresh S.; Vokes, Everett E.; Malik, Shakun M.; Wakelee, Heather A.

2017-01-01

Survival rates of patients with either early and advanced stage non–small-cell lung cancer (NSCLC) have improved with newer systemic therapy and radiation techniques, including combination regimens, targeted therapies, and immunotherapies. The cancer cooperative groups have historically played a critical role in the advancement of NSCLC therapy. Annually, representatives from cooperative groups worldwide convene at the International Lung Cancer Congress (ILCC). In summer 2015, the ILCC reached its 16th anniversary. This article highlights the NSCLC studies presented by participating groups in 2015. PMID:27473736

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Yuen; Soo, Khee Chee; Olivo, Malini

2009-01-01

Background Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors. PMID:19878607

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

PubMed Central

Quilty, Lena C.; Ravitz, Paula; Rosenbluth, Michael; Pavlova, Barbara; Grigoriadis, Sophie; Velyvis, Vytas; Kennedy, Sidney H.; Lam, Raymond W.; MacQueen, Glenda M.; Milev, Roumen V.; Ravindran, Arun V.; Uher, Rudolf

2016-01-01

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Psychological Treatments” is the second of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy; 4) additional psychological interventions, such as peer interventions and computer- and technology-delivered interventions; and 5) combining and/or sequencing psychological and pharmacological interventions. Conclusions: First-line psychological treatment recommendations for acute MDD include cognitive-behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural activation (BA). Second-line recommendations include computer-based and telephone-delivered psychotherapy. Where feasible, combining psychological treatment (CBT or IPT) with antidepressant treatment is recommended because combined treatment is superior to either treatment alone. First-line psychological treatments for maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient preference, in combination with evidence-based treatments and clinician/system capacity, will yield the optimal treatment strategies for improving individual outcomes in MDD. PMID:27486150

[The fundamental characteristics and application of psychological intervention on acupuncture therapy].

PubMed

Gu, Zhong-yue

2009-06-01

The process of acupuncture therapy is a complete combination of linguistic suggestion, cognitive behavioral therapy and body treatment systems. Differentiation of syndrome and diagnosis play the role of linguistic suggestion, while the magnified phenomenon of bio-information and possible manipulation on the arrival of qi play the role of cognitive behavioral therapy. The objective effectiveness of acupuncture not only includes clinical treatment, but also contains reducing or preventing foreign malignant psychological stimulation, regulating the concentration of 5-hydroxytryptamine and dopamine, and keeping the inter environment stable etc. According to the process of treating patient as followed with "telling his sickness, establishing his confidence, inducing his feeling and relieving his suffering", treatment is carried out with taking the arrival of qi as the key point, combining the steps of characteristics of psychological treatment effectively, and cooperating with psychological and body treatments to obtain effectiveness. It accords with Chinese medical theories of simultaneous treatment of the branch and root as well as effectiveness following arrival of qi.

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

PubMed Central

Katzenstein, D A

1997-01-01

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection. PMID:9217434

Gene Therapy for Infectious Diseases

PubMed Central

Bunnell, Bruce A.; Morgan, Richard A.

1998-01-01

Gene therapy is being investigated as an alternative treatment for a wide range of infectious diseases that are not amenable to standard clinical management. Approaches to gene therapy for infectious diseases can be divided into three broad categories: (i) gene therapies based on nucleic acid moieties, including antisense DNA or RNA, RNA decoys, and catalytic RNA moieties (ribozymes); (ii) protein approaches such as transdominant negative proteins and single-chain antibodies; and (iii) immunotherapeutic approaches involving genetic vaccines or pathogen-specific lymphocytes. It is further possible that combinations of the aforementioned approaches will be used simultaneously to inhibit multiple stages of the life cycle of the infectious agent. PMID:9457428

[Improving wound healing after nose surgery by combined administration of xylometazoline and dexpanthenol].

PubMed

Kehrl, W; Sonnemann, U

2000-03-01

The aim of this study was the examination of efficacy and tolerability of an application-form of the new combination of Xylometazoline with Dexpanthenol (Nasic) versus Xylometazoline alone. Randomized verum controlled parallel-group-comparison of two weeks treatment of a nasal-spray. 61 inpatients with the diagnosis Rhinitis following nasal operation were included in this study and 30 patients were treated with verum and placebo each. The assessment of nasal-breathing-resistance according to scores was defined as target-parameter. Confirmatory statistical analysis was carried out according to Wilcoxon-Mann-Whitney-U two-sided at alpha < or = 0.05. The superiority of the combination of Xylometazoline-Dexpanthenol nasal-spray versus Xylometazoline nasal spray could be proven for the target-parameter as clinically relevant and statistically significant. The clinically proven efficacy is emphasized by good tolerability of both treatments. Due to easy handling of the nasal-spray a good compliance was confirmed. Distinct improvement of symptoms in patients following nasal operations underlines the efficacy of both medications. With respect to the tolerability therapy with the combination is more beneficial in comparison to the alternative therapy. The result of this controlled clinical study confirms that the combination Xylometazoline-Dexpanthenol is an enlargement and improvement of effective medicinal treatment of rhinitis following nasal operation in comparison to therapy with Xylometazoline alone.

Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection.

PubMed

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An; Wang, Li-Fu

2014-01-01

To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/ percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

PubMed

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect.

PubMed

Wairagkar, Maitreyee; McCrindle, Rachel; Robson, Holly; Meteyard, Lotte; Sperrin, Malcom; Smith, Andy; Pugh, Moyra

2017-03-23

The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility presented as graphs plotted from patient game data. Performance indicators include reaction time, accuracy, number of incorrect responses and hand use. The resultant games have also been tested by the PPI with a positive response and further suggestions for future modifications made. MaLT provides a tool that innovatively combines motor and language therapy for high dosage rehabilitation in the home. It has demonstrated that motion sensor technology can be successfully combined with a language therapy task to target both upper limb and linguistic impairment in patients following brain injury. The initial studies on stroke survivors have demonstrated that the combined therapy approach is viable and the outputs of this study will inform planned larger scale future trials.

[Systematic review on conservative treatment options in non-muscle-invasive bladder cancer patients refractory to Bacillus Calmette-Guérin instillation therapy].

PubMed

Martini, Thomas; Wezel, Felix; Löbig, Niklas; Mitterberger, Michael J; Colleselli, Daniela

2017-08-01

Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. Material and Methods We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. Results  This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Conclusions Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed. © Georg Thieme Verlag KG Stuttgart · New York.

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.

PubMed

Che, Huan-Yong; Guo, Hang-Yuan; Si, Xu-Wei; You, Qiao-Ying; Lou, Wei-Ying

2014-01-01

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy.

Combination therapeutic options in the treatment of the luteal phase deficiency.

PubMed

Orazov, M R; Radzinskiy, V E; Nosenko, E N; Khamoshina, M B; Lebedeva, M G; Tokaeva, E S; Barsegyan, L K; Novginov, D S; Zakirova, Y R; Minayeva, A V

2017-01-01

Luteal phase deficiency (LPD) is described as a condition of insufficient progesterone exposure to maintain a regular secretory endometrium and allow for normal embryo implantation and growth. There is evidence that both follicular and luteal phase abnormalities can result in LPD cycles. The aim of this randomized prospective noncomparative study is to evaluate the effectiveness of combination therapy in patients with LPD. This prospective study included 35 women of the reproductive age. They were diagnosed with the LPD with sonographically and laboratory-verified methods. The age of patients was 36 ± 0.46 years. The results of the study sonographically demonstrated an increase in the diameter of the corpus luteum from 1.36 ± 0.32 (initially) to 2.16 ± 0.21 mm after combination therapy. In addition, there was a statistically significant increase in the level of estrogens and progesterone in the corresponding phases of the menstrual cycle. Thus, the combination therapy for patients with LPD contributes to the recovery of cyclic events in the hypothalamic-pituitary-gonadal system, which determines the restoration of the endocrine function of the ovaries and promotes adequate secretory rearrangement of the endometrium in women of reproductive age.

Speech therapy for errors secondary to cleft palate and velopharyngeal dysfunction.

PubMed

Kummer, Ann W

2011-05-01

Individuals with a history of cleft lip/palate or velopharyngeal dysfunction may demonstrate any combination of speech sound errors, hypernasality, and nasal emission. Speech sound distortion can also occur due to other structural anomalies, including malocclusion. Whenever there are structural anomalies, speech can be affected by obligatory distortions or compensatory errors. Obligatory distortions (including hypernasality due to velopharyngeal insufficiency) are caused by abnormal structure and not by abnormal function. Therefore, surgery or other forms of physical management are needed for correction. In contrast, speech therapy is indicated for compensatory articulation productions where articulation placement is changed in response to the abnormal structure. Speech therapy is much more effective if it is done after normalization of the structure. When speech therapy is appropriate, the techniques involve methods to change articulation placement using standard articulation therapy principles. Oral-motor exercises, including the use of blowing and sucking, are never indicated to improve velopharyngeal function. The purpose of this article is to provide information regarding when speech therapy is appropriate for individuals with a history of cleft palate or other structural anomalies and when physical management is needed. In addition, some specific therapy techniques are offered for the elimination of common compensatory articulation productions. © Thieme Medical Publishers.

Helicobacter pylori eradication therapy: A review of current trends.

PubMed

Olokoba, A B; Obateru, O A; Bojuwoye, M O

2013-01-01

Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

PubMed

Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

2012-01-01

The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

Carbon nanotubes as cancer therapeutic carriers and mediators

PubMed Central

Son, Kuk Hui; Hong, Jeong Hee; Lee, Jin Woo

2016-01-01

Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug–CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy. PMID:27785021

An Updated Review of the Efficacy of Cupping Therapy

PubMed Central

Cao, Huijuan; Li, Xun; Liu, Jianping

2012-01-01

Background Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Method Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. Results 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Conclusions Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted. PMID:22389674

Topical Therapies in Psoriasis

PubMed Central

Torsekar, R.; Gautam, Manjyot M.

2017-01-01

Topical therapy as monotherapy is useful in psoriasis patients with mild disease. Topical agents are also used as adjuvant for moderate-to-severe disease who are being concurrently treated with either ultraviolet light or systemic medications. Emollients are useful adjuncts to the treatment of psoriasis. Use of older topical agents such as anthralin and coal tar has declined over the years. However, they are cheaper and can still be used for the treatment of difficult psoriasis refractory to conventional treatment. Salicylic acid can be used in combination with other topical therapies such as topical corticosteroids (TCS) and calcineurin inhibitors for the treatment of thick limited plaques to increase the absorption of the latter into the psoriatic plaques. Low- to mid-potent TCS are used in facial/flexural psoriasis and high potent over palmoplantar/thick psoriasis lesions. The addition of noncorticosteroid treatment can also facilitate the avoidance of long-term daily TCS. Tacrolimus and pimecrolimus can be used for the treatment of facial and intertriginous psoriasis. Tazarotene is indicated for stable plaque psoriasis usually in combination with other therapies such as TCS. Vitamin D analogs alone in combination with TCS are useful in stable plaques over limbs and palmoplantar psoriasis. Topical therapies for scalp psoriasis include TCS, Vitamin D analogs, salicylic acid, coal tar, and anthralin in various formulations such as solutions, foams, and shampoos. TCS, vitamin D analogs, and tazarotene can be used in the treatment of nail psoriasis. PMID:28761838

Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study.

PubMed

Ibrahim, Iman; Zeitouni, Anthony; da Silva, Sabrina Daniela

2018-06-22

Sudden sensorineural hearing loss (SSNHL) is an otological emergency of unknown etiology. Recent reports showed that antioxidant drugs can benefit patients with SSNHL. This study attempted to evaluate the effect of adding antioxidant vitamins as an adjuvant therapy alongside with corticosteroids. To evaluate the effects of the 3 major antioxidant vitamins (A, C, and E) as an adjuvant therapy, administered with corticosteroids, for the treatment of SSNHL in adult patients (≥18 years). MEDLINE, EMBASE, PubMed, Web of Science and Cochrane electronic databases from January 1, 1995, through September 25, 2017. Published studies of adult patients who received antioxidant vitamins (A, C, E, or any combination of these vitamins) as an adjuvant therapy in addition to the regular treatment (corticosteroids) for SSNHL. Quality assessment was performed using the Cochrane Collaboration Tool for Assessing Risk of Bias. Each study had a control group (conventional treatment + placebo) and a trial group (antioxidant vitamin(s) + conventional treatment). From 446 manuscripts identified in the literature, 3 studies were included in the review with 279 patients. The most common vitamins used to treat SSNHL were the 3 major antioxidant vitamins A, C, and E, combined sometimes with other antioxidants such as selenium. The success of the treatment is increased in patients who received antioxidant vitamins in combination with conventional therapy. © 2018 S. Karger AG, Basel.

Effect of combined psycho-physiological stretching and breathing therapy on sexual satisfaction

PubMed Central

2013-01-01

Background During the last few decades, marital tensions and stresses have influenced various dimensions of life. The objective of the current study was to examine the effects of combined psycho-physiological therapy (stretching therapy combined with breathing exercise) on sexual satisfaction among heterosexual men. Methods For this research, we used “convenience sampling” to select 80 males, who were then split equally into two groups, the intervention group and the control group, both groups containing men who had voiced a desire to be in the experimental group. For collection of data, we used an identical quasi-experimental design called the “nonequivalent control group.” Therapy sessions, each lasting 90 to 120 min, were carried out on the same 3 days of the week (Sunday, Tuesday, and Thursday) for a total of 20 sessions. The volunteers were selected from heterosexual men with stable relationships, who had been married a minimum of 6 months and were ages 20 to 55 years of age. Pre-tests, post-tests, and follow-up tests were conducted in a clinic at the Hospital Universiti Sains Malaysia (HUSM [1] ). For assessment, we used the sexual satisfaction subscale of the ENRICH [2] questionnaire. Results The intervention group had better post-test scores than the control group. Also, follow-up test scores for the intervention group were marginally better than those for the control group, but the difference did not reach statistical significance. Conclusions Combined psycho-physiological therapy including stretching and breathing exercise leads to improved sexual satisfaction. PMID:23522405

Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.

PubMed

Konno, Sensuke

2009-07-30

Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.

Recent advances in multidisciplinary management of hepatocellular carcinoma

PubMed Central

Gomaa, Asmaa I; Waked, Imam

2015-01-01

The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

Contemporary Cognitive Behavior Therapy: A Review of Theory, History, and Evidence.

PubMed

Thoma, Nathan; Pilecki, Brian; McKay, Dean

2015-09-01

Cognitive behavior therapy (CBT) has come to be a widely practiced psychotherapy throughout the world. The present article reviews theory, history, and evidence for CBT. It is meant as an effort to summarize the forms and scope of CBT to date for the uninitiated. Elements of CBT such as cognitive therapy, behavior therapy, and so-called "third wave" CBT, such as dialectical behavior therapy (DBT) and acceptance and commitment therapy (ACT) are covered. The evidence for the efficacy of CBT for various disorders is reviewed, including depression, anxiety disorders, personality disorders, eating disorders, substance abuse, schizophrenia, chronic pain, insomnia, and child/adolescent disorders. The relative efficacy of medication and CBT, or their combination, is also briefly considered. Future directions for research and treatment development are proposed.

[Clinical study of cervical spondylotic radiculopathy treated with massage therapy combined with Magnetic sticking therapy at the auricular points and the cost comparison].

PubMed

Wang, Saina; Sheng, Feng; Pan, Yunhua; Xu, Feng; Wang, Zhichao; Cheng, Lei

2015-08-01

To compare the clinical efficacy on cervical spondylotic radiculopathy between the combined therapy of massage and magnetic-sticking at the auricular points and the simple massage therapy, and conduct the health economics evaluation. Seventy-two patients of cervical spondylotic radiculopathy were randomized into a combined therapy group, and a simple massage group, 36 cases in each one. Finally, 35 cases and 34 cases were met the inclusive criteria in the corresponding groups separately. In the combined therapy group, the massage therapy and the magnetic sticking therapy at auricular points were combined in the treatment. Massage therapy was mainly applied to Fengchi (GB 20), Jianjing (GB 21), Jianwaishu (SI 14), Jianyu (LI 15) and Quchi (LI 11). The main auricular points for magnetic sticking pressure were Jingzhui (AH13), Gan (On12) Shen (CO10), Shenmen (TF4), Pizhixia (AT4). In the simple massage group, the simple massage therapy was given, the massage parts and methods were the same as those in the combined therapy group. The treatment was given once every two days, three times a week, for 4 weeks totally. The cervical spondylosis effect scale and the simplified McGill pain questionnaire were adopted to observe the improvements in the clinical symptoms, clinical examination, daily life movement, superficial muscular pain in the neck and the health economics cost in the patients of the two groups. The effect was evaluated in the two groups. The effective rate and the clinical curative rate in the combined therapy group were better than those in the control group [100. 0% (35/35) vs 85. 3% (29/34), 42. 9% (15/35) vs 17. 6% (6/34), both P<0. 05]. The scores of the spontaneous symptoms, clinical examnation, daily life movement and superficialmuscular pain in the neck were improved apparently after treatment as compared with those before treatment in the patients of the two groups (all P<0. 001). In terms of the improvements in the spontaneous symptoms, clinical examination total scores and superficial muscular pain in the' neck were more significant in the combined therapy group as compared with those in the simple massage group (P<0. 05, P<0. 01, P<0. 001). The cost at the unit effect in the combined therapy group was lower than that in the simple massage group (P<0. 05). Compared with the simple massage therapy, the massage therapy combined with magnetic sticking therapy at auricular points achieves the better effect and lower cost in health economics.

Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities.

PubMed

Roumeliotis, M; Long, K; Phan, T; Graham, D; Quirk, S

2018-06-05

The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer. An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques. Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%). The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver Disease: A Systematic Review.

PubMed

Khan, Anam; Tansel, Aylin; White, Donna L; Kayani, Waleed Tallat; Bano, Shah; Lindsay, Jan; El-Serag, Hashem B; Kanwal, Fasiha

2016-02-01

We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), motivational interviewing, supportive therapy, and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and motivational enhancement therapy with comprehensive medical care, delivered during a period of 2 years, produced a significant increase in abstinence (74% increase in intervention group vs 48% increase in control group, P = .02), which was reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group vs 75% in control group, P = .03), which was reported from 1 observational study. However, data were not collected for more than 2 years on outcomes of patients with CLD and AUD. In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical experience in treating hypertension with fixed-dose combination therapy: angiotensin II receptor blocker losartan plus hydrochlorothiazide.

PubMed

Abe, Masanori; Okada, Kazuyoshi; Matsumoto, Koichi

2009-10-01

The goal of antihypertensive treatment is to reduce cardiovascular and cerebrovascular events associated with high blood pressure. A combination therapy with different antihypertensive agents is more successful than monotherapy in most hypertensive patients, with the added advantage of a better safety profile. Therefore, treatment of hypertensive patients with fixed-dose combination therapy consisting of the angiotensin II receptor blocker losartan along with hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with each individual component. It provides more effective blood pressure control, a reduction in the likelihood of adverse effects and facilitation of patient compliance due to a simple once-daily regimen. One of the advantages of the combination of losartan with HCTZ is the potential reduction in HCTZ-induced metabolic disorders; in particular, this combination can have attractive benefits for patients of hyperuricemia. Losartan plus HCTZ fixed-dose combination therapy is frequently recommended for the treatment of hypertension and lowers blood pressure in mild-to-moderate and even severe hypertensive patients to a level comparable with other classes of antihypertensive agents in combination with HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is a logical choice as antihypertensive therapy for patients in whom combination therapy is necessary to achieve additional blood pressure reduction.

[The use of genetic angiogenesis inductors in surgical treatment of chronic lower limb ischemia].

PubMed

Gavrilenko, A V; Voronov, D A; Bochkov, N P

2013-01-01

The efficacy and safety of gene-engineering recombinant constructions with endothelial growth factor gene and angiogenin for the treatment of the chronic lower limb ischemia were studied. 134 patients were included in prospective controlled study. The main group, who received both traditional treatment and genetic therapy, consisted of 74 patients. The rest 60 patients were included into the control group. Of 74 patients from the main group, genetic therapy was used together with conservative means in 39 patients and with reconstructive vascular operations in 35 patients. The gene-engineering angiogenesis stimulation therapy proved to be effective and safe. The combination of angiogenesis genetic stimulation with reconstructive vascular surgery demonstrated significantly better results, then monotherapy.

Difficult to control atopic dermatitis

PubMed Central

2013-01-01

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial / antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. “Eczema school” educational programs have been proven to be helpful. PMID:23663504

Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

PubMed Central

Zhang, Yan; Li, Sainan; He, Lei; Wang, Fan; Chen, Kan; Li, Jingjing; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Xia, Yujing; Zhou, Yingqun; Lu, Jie; Guo, Chuanyong

2015-01-01

Background Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out. Methods A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches. Results Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: −90.44 IU/L; 95% confidence interval [CI]: −119.95 to −60.92; P<0.00001), gamma-glutamyl transferase (MD: −61.58 IU/L; 95% CI: −122.80 to −0.35; P=0.05), immunoglobulin M (MD: −38.45 mg/dL; 95% CI: −64.38 to −12.51; P=0.004), and triglycerides (MD: −0.41 mg/dL; 95% CI: −0.82 to −0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23), total bilirubin (MD: −0.05 mg/dL; 95% CI: −0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: −3.31 IU/L; 95% CI: −14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy. Conclusion In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy. PMID:26045661

A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome (NSTE-ACS): Ezetimibe and rosuvastatin versus high-dose rosuvastatin.

PubMed

Ran, Dan; Nie, Hui-Juan; Gao, Yu-Lin; Deng, Song-Bai; Du, Jian-Lin; Liu, Ya-Jie; Jing, Xiao-Dong; She, Qiang

2017-05-15

Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown. A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up. The primary end point was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal <70mg/dL (1.8mmol/L) at week 12. Secondary end points included changes from baseline in lipids, the occurrence of all cardiovascular events, high-sensitivity C-reactive protein and safety markers. The combination therapy group in the primary end point was significantly higher than rosuvastatin (20mg) and rosuvastatin (10mg) at week 12 (81.0% vs 68.3% vs 33.3%, P<0.001). And the similar change was observed in reducing LDL-C levels at week 12 (67.28% vs 52.80% vs 43.89%, P<0.001). The incidence of drug-related adverse events was much higher in the rosuvastatin 20mg group than the rosuvastatin 10mg group and the combination therapy group (17.0% vs 2.4% vs 4.8%, P<0.05). The combination of rosuvastatin 10mg/ezetimibe 10mg was an effectively alternative therapy superior to rosuvastatin 20mg or 10mg with a greater effect on lowering LDL-C and a lower incidence of drug-related adverse events in Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

NASA Astrophysics Data System (ADS)

Musabaeva, L. I.; Startseva, Zh. A.; Gribova, O. V.; Velikaya, V. V.; Lisin, V. A.

2016-08-01

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

Alternative Medicine and Your Child

MedlinePlus

... TCM practice of acupuncture may be combined with herbal medicine and qi gong. And Ayurveda includes the mind- ... complements to regular medical treatment, some therapies — particularly herbal ... (OTC) medicines, dietary supplements are not rigorously regulated by the ...

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: a randomized controlled trial. 1: clinical effectiveness.

PubMed

Abbott, J H; Robertson, M C; Chapple, C; Pinto, D; Wright, A A; Leon de la Barra, S; Baxter, G D; Theis, J-C; Campbell, A J

2013-04-01

To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0-240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2-47.8) for usual care plus manual therapy, 16.4 (-3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (-5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy (P = 0.027). Physical performance test outcomes favoured the exercise therapy group. Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. Australian New Zealand Clinical Trials Registry ACTRN12608000130369. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors.

PubMed

Interiano, Rodrigo B; McCarville, M Beth; Wu, Jianrong; Davidoff, Andrew M; Sandoval, John; Navid, Fariba

2015-09-01

Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4-31). The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Pneumothorax as a Complication of Combination Antiangiogenic Therapy in Children and Young Adults with Refractory/Recurrent Solid Tumors

PubMed Central

Interiano, Rodrigo B.; McCarville, M. Beth; Wu, Jianrong; Davidoff, Andrew M.; Sandoval, John; Navid, Fariba

2016-01-01

Purpose Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. Patients and Methods Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. Results Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08–24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4–31). Conclusion The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy. PMID:25783402

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score

PubMed Central

Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Ogawa, Osamu; Kitamura, Tadaichi; Suzuki, Kazuhiro; Tsukamoto, Taiji; Naito, Seiji; Namiki, Mikio; Hirao, Yoshihiko; Murai, Masaru

2013-01-01

Purpose: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. Methods: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. Results: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Conclusions: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID:24223407

Enhanced antitumor effect of curcumin liposomes with local hyperthermia in the LL/2 model.

PubMed

Tang, Jian-Cai; Shi, Hua-Shan; Wan, Li-Qiang; Wang, Yong-Sheng; Wei, Yu-Quan

2013-01-01

Curcumin previously was proven to inhibit angiogenesis and display potent antitumor activity in vivo and in vitro. In the present study, we investigated whether a combination curcumin with hyperthermia would have a synergistic antitumor effect in the LL/2 model. The results indicated that combination therapy significantly inhibited cell proliferation of MS-1 and LL/2 in vitro. LL/2 experiment model also demonstrated that the combination therapy inhibited tumor growth and prolonged the life span in vivo. Furthermore, combination therapy reduced angiogenesis and increased tumor apoptosis. Our findings suggest that the combination therapy exerted synergistic antitumor effects, providing a new perspective fpr clinical tumor therapy.

Monitoring the distribution of prompt gamma rays in boron neutron capture therapy using a multiple-scattering Compton camera: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Lee, Taewoong; Lee, Hyounggun; Lee, Wonho

2015-10-01

This study evaluated the use of Compton imaging technology to monitor prompt gamma rays emitted by 10B in boron neutron capture therapy (BNCT) applied to a computerized human phantom. The Monte Carlo method, including particle-tracking techniques, was used for simulation. The distribution of prompt gamma rays emitted by the phantom during irradiation with neutron beams is closely associated with the distribution of the boron in the phantom. Maximum likelihood expectation maximization (MLEM) method was applied to the information obtained from the detected prompt gamma rays to reconstruct the distribution of the tumor including the boron uptake regions (BURs). The reconstructed Compton images of the prompt gamma rays were combined with the cross-sectional images of the human phantom. Quantitative analysis of the intensity curves showed that all combined images matched the predetermined conditions of the simulation. The tumors including the BURs were distinguishable if they were more than 2 cm apart.

Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.

PubMed

Yim, Juwon; Smith, Jordan R; Rybak, Michael J

2017-05-01

Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed. © 2017 Pharmacotherapy Publications, Inc.

PPARγ and Apoptosis in Cancer

PubMed Central

Elrod, Heath A.; Sun, Shi-Yong

2008-01-01

Peroxisome proliferator-activated receptors (PPARs) are ligand binding transcription factors which function in many physiological roles including lipid metabolism, cell growth, differentiation, and apoptosis. PPARs and their ligands have been shown to play a role in cancer. In particular, PPARγ ligands including endogenous prostaglandins and the synthetic thiazolidinediones (TZDs) can induce apoptosis of cancer cells with antitumor activity. Thus, PPARγ ligands have a potential in both chemoprevention and therapy of several types of cancer either as single agents or in combination with other antitumor agents. Accordingly, the involvement of PPARγ and its ligands in regulation of apoptosis of cancer cells have been extensively studied. Depending on cell types or ligands, induction of apoptosis in cancer cells by PPARγ ligands can be either PPARγ-dependent or -independent. Through increasing our understanding of the mechanisms of PPARγ ligand-induced apoptosis, we can develop better strategies which may include combining other antitumor agents for PPARγ-targeted cancer chemoprevention and therapy. This review will highlight recent research advances on PPARγ and apoptosis in cancer. PMID:18615184

Type II diabetes and its therapy in clinical practice - results from the standardised non-interventional registry SIRTA.

PubMed

Gallwitz, B; Kusterer, K; Hildemann, S; Fresenius, K

2014-12-01

Modern antidiabetic therapies should achieve low HbA1c values and avoid hypoglycaemic complications. The registry SIRTA included 1522 patients with type II diabetes mellitus (T2DM) from 306 German medical practices. Patients had an HbA1c > 6.5% under the maximum tolerated metformin dose. If required, they received combination therapy with other antidiabetics according to the guideline of the German Diabetes Society [Deutsche Diabetes Gesellschaft (DDG)] or usual medical practice. Patients were followed up for 6 months. The target criteria included the achievement of HbA1c target values and the emergence of severe hypoglycaemic episodes. Most patients (64.0%) were planned to achieve an HbA1c target < 6.5%, the standard target recommended by the 2009 DDG guideline valid throughout the registry. Primarily to reduce the individual risk for hypoglycaemia, 32.4% of patients had a less strict HbA1c-target of 6.5-7.0%. These targets were achieved by 31.3% and 44.3% of patients, respectively. Combination therapies increased from 45% to 56% over the 6 months registry. Four patients had severe hypoglycaemias (0.26%). The registry confirms results from other epidemiologic studies on the therapy of T2DM in everyday practice. The treatment strategies applied effectively reduced blood glucose and avoided severe hypoglycaemias. An early therapy of insufficiently controlled patients with T2DM is important, as lower baseline values facilitated achieving HbA1c targets. © 2014 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Evidence for the efficacy and safety of tadalafil and finasteride in combination for the treatment of lower urinary tract symptoms and erectile dysfunction in men with benign prostatic hyperplasia

PubMed Central

Olesovsky, Chris; Kapoor, Anil

2016-01-01

Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms (LUTS). These LUTS have a negative impact on an individual’s quality of life, which is why treatment of symptomatic BPH has become a major priority. Although surgical interventions exist for treating BPH, pharmacological therapies are often preferred due to their minimal invasiveness and high degree of effectiveness. The three classes of drugs approved for treating BPH include α-blockers, 5-α-reductase inhibitors (5-ARIs) and phosphodiesterase 5 (PDE-5) inhibitors. Individually, each class of drug has been studied and shown to improve symptom relief through a variety of different mechanisms. A more recent focus has been on the development of combinatorial therapies that combine classes of drugs in order to provide maximal benefit. The mTOPS and CombAT studies were the first of their kind to examine whether the combination of 5-ARIs and α-blockers was more effective than monotherapy alone. Both studies found similar results in that the combinatorial therapy was superior to monotherapy. Over the last decade other combinatorial therapies have been at the forefront of investigation. One in particular is the combination of tadalafil, a PDE-5 inhibitor, with finasteride, a 5-ARI. Studies have shown that the combination of tadalafil and finasteride is a safe, effective, and well tolerated treatment for BPH. Evidence suggests that this combination may be particularly effective in reducing treatment-related sexual adverse events associated with 5-ARI treatments. The following review will explore in detail the current evidence surrounding treatment of BPH LUTS using tadalafil and finasteride. PMID:27928428

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

PubMed

Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study

PubMed Central

Abdul-Ghani, Muhammad; Migahid, Osama; Megahed, Ayman; Adams, John; Triplitt, Curtis; DeFronzo, Ralph A.; Zirie, Mahmoud; Jayyousi, Amin

2017-01-01

OBJECTIVE The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7.0% (53 mmol/mol). RESULTS After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA1c from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA1c independent of sex, ethnicity, BMI, or baseline HbA1c. Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group. CONCLUSIONS Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea. PMID:28096223

A multidisciplinary TBI inpatient rehabilitation programme for active duty service members as part of a randomized clinical trial.

PubMed

Braverman, S E; Spector, J; Warden, D L; Wilson, B C; Ellis, T E; Bamdad, M J; Salazar, A M

1999-06-01

To design and describe an effective rehabilitation programme for use in an ongoing trial on the efficacy of multidisciplinary brain injury rehabilitation for moderately head injury military service members. Treatment arm of a randomized control trial. US military tertiary care hospital inpatient rehabilitation programme. Sixty seven active duty military with moderate to severe TBI who were randomized to the treatment arm of the protocol. Eight week rehabilitation programme combining group and individual therapies with an inpatient milieu-oriented neuropsychological focus. Group therapies included fitness, planning and organization, cognitive skills, work skills, medication, and milieu groups, and community re-entry outings. Individual therapy included neuropsychology, work therapy, occupational therapy, and speech and language pathology. Successful return to work and return to duty. At 1 year follow-up, 64 patients returned to work (96%) and 66% (44/67) returned to duty. The described rehabilitation programme demonstrates one successful effort to rehabilitate active duty military service members with TBI who have the potential to return to duty.

Immune checkpoint therapy in liver cancer.

PubMed

Xu, Feng; Jin, Tianqiang; Zhu, Yuwen; Dai, Chaoliu

2018-05-29

Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.

Putting the genie back in the bottle? Availability and presentation of oral artemisinin compounds at retail pharmacies in urban Dar-es-Salaam

PubMed Central

Kachur, S Patrick; Black, Carolyn; Abdulla, Salim; Goodman, Catherine

2006-01-01

Background Recently global health advocates have called for the introduction of artemisinin-containing antimalarial combination therapies to help curb the impact of drug-resistant malaria in Africa. Retail trade in artemisinin monotherapies could undermine efforts to restrict this class of medicines to more theoretically sound combination treatments. Methods This paper describes a systematic search for artemisinin-containing products at a random sample of licensed pharmacies in Dar-es-Salaam, Tanzania in July 2005. Results Nineteen different artemisinin-containing oral pharmaceutical products, including one co-formulated product, one co-packaged product, and 17 monotherapies were identified. All but one of the products were legally registered and samples of each product were obtained without a prescription. Packaging and labeling of the products seldom included local language or illustrated instructions for low-literate clients. Packaging and inserts compared reasonably well with standards recommended by the national regulatory authority with some important exceptions. Dosing instructions were inconsistent, and most recommended inadequate doses based on international standards. None of the monotherapy products mentioned potential benefits of combining the treatment with another antimalarial drug. Conclusion The findings confirm the widespread availability of artemisinin monotherapies that led the World Health Organization to call for the voluntary withdrawal of these drugs in malaria-endemic countries. As the global public health community gathers resources to deploy artemisinin-containing combination therapies in Africa, planners should be mindful that these drugs will coexist with artemisinin monotherapies in an already well-established market place. In particular, regulatory authorities should be incorporated urgently into the process of planning for rational deployment of artemisinin-containing antimalarial combination therapies. PMID:16569252

New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness

PubMed Central

Corraliza-Gorjón, Isabel; Somovilla-Crespo, Beatriz; Santamaria, Silvia; Garcia-Sanz, Jose A.; Kremer, Leonor

2017-01-01

Antibodies have proven their high value in antitumor therapy over the last two decades. They are currently being used as the first-choice to treat some of the most frequent metastatic cancers, like HER2+ breast cancers or colorectal cancers, currently treated with trastuzumab (Herceptin) and bevacizumab (Avastin), respectively. The impressive therapeutic success of antibodies inhibiting immune checkpoints has extended the use of therapeutic antibodies to previously unanticipated tumor types. These anti-immune checkpoint antibodies allowed the cure of patients devoid of other therapeutic options, through the recovery of the patient’s own immune response against the tumor. In this review, we describe how the antibody-based therapies will evolve, including the use of antibodies in combinations, their main characteristics, advantages, and how they could contribute to significantly increase the chances of success in cancer therapy. Indeed, novel combinations will consist of mixtures of antibodies against either different epitopes of the same molecule or different targets on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding tumor cells, immune cells or extracellular molecules; immunomodulatory antibodies; antibody-based molecules, including fusion proteins between a ligand or a receptor domain and the IgG Fab or Fc fragments; autologous or heterologous cells; and different formats of vaccines. Through complementary mechanisms of action, these combinations could contribute to elude the current limitations of a single antibody which recognizes only one particular epitope. These combinations may allow the simultaneous attack of the cancer cells by using the help of the own immune cells and exerting wider therapeutic effects, based on a more specific, fast, and robust response, trying to mimic the action of the immune system. PMID:29312320

Prognostic utility of gene therapy with herpes simplex virus thymidine kinase for patients with high-grade malignant gliomas: a systematic review and meta analysis.

PubMed

Zhao, Fei; Tian, Jinhui; An, Lifeng; Yang, Kehu

2014-06-01

The aim of this study was to assess the effectiveness of adding viral vector-mediated gene therapy with herpes simplex virus thymidine kinase (HSV-tk) to standard treatment, in comparison with standard treatment alone to treat patients with high-grade gliomas (HGGs). A literature search of the databases PubMed, Embase, the Cochrane Library, Web of Science, and Chinese biomedicine was performed to identify eligible studies. Three randomized controlled trials (involving a total of 532 patients) were included in this systematic review. A meta-analysis of included studies demonstrated a significant increase in median survival time (MST) in patients who were treated with HSV-tk gene therapy (mean deviation 0.59, 95% CI: 0.41-0.76, p < 0.0001). The results of pooled analysis for different patient groups show that overall survival (OS) for all HGG patients was improved by adding gene therapy [hazard ratio (HR) = 0.91, 95% CI: 0.74-1.13, p = 0.42], while a different result was seen for glioblastoma multiforme (GBM) patients (HR = 1.06, 95% CI: 0.80-1.41, p = 0.70). Furthermore, the combined results for tumor progression implied that standard therapy was superior to gene therapy [odds ratio (OR) = 1.31, p = 0.09]; yet differences in HR and OR between experimental groups and control groups had no statistical significance (p > 0.05). Based on the best available evidence, it appears that adding gene therapy with HSV-tk has some effect in treating HGG patients, especially with respect to MST. However, neither the pooled analysis of OS, nor the combined analysis of tumor progress indicates any significant advantage to adding gene therapy compared with standard treatment alone. More prospective studies are needed to draw solid conclusions about whether gene therapy has significant prognostic advantage.

An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

PubMed Central

Stark, Felicity C.; Weeratna, Risini D.; Deschatelets, Lise; Gurnani, Komal; Dudani, Renu; Krishnan, Lakshmi

2017-01-01

Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1) compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18), significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies. PMID:29072624

Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

PubMed

Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

2014-01-01

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

EGFR Gene Amplification and KRAS Mutation Predict Response to Combination Targeted Therapy in Metastatic Colorectal Cancer.

PubMed

Khan, Sajid A; Zeng, Zhaoshi; Shia, Jinru; Paty, Philip B

2017-07-01

Genetic variability in KRAS and EGFR predicts response to cetuximab in irinotecan refractory colorectal cancer. Whether these markers or others remain predictive in combination biologic therapies including bevacizumab is unknown. We identified predictive biomarkers from patients with irinotecan refractory metastatic colorectal cancer treated with cetuximab plus bevacizumab. Patients who received cetuximab plus bevacizumab for irinotecan refractory colorectal cancer in either of two Phase II trials conducted were identified. Tumor tissue was available for 33 patients. Genomic DNA was extracted and used for mutational analysis of KRAS, BRAF, and p53 genes. Fluorescence in situ hybridization was performed to assess EGFR copy number. The status of single genes and various combinations were tested for association with response. Seven of 33 patients responded to treatment. KRAS mutations were found in 14/33 cases, and 0 responded to treatment (p = 0.01). EGFR gene amplification was seen in 3/33 of tumors and in every case was associated with response to treatment (p < 0.001). TP53 and BRAF mutations were found in 18/33 and 0/33 tumors, respectively, and there were no associations with response to either gene. EGFR gene amplification and KRAS mutations are predictive markers for patients receiving combination biologic therapy of cetuximab plus bevacizumab for metastatic colorectal cancer. One marker or the other is present in the tumor of half of all patients allowing treatment response to be predicted with a high degree of certainty. The role for molecular markers in combination biologic therapy seems promising.

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

PubMed Central

Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E. Bart

2014-01-01

The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. PMID:25385098

[Combination drug therapy in patients with BPH].

PubMed

Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

2018-03-01

Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself in a reduced number of complications and thereby contributes to improving the quality of life of patients.

Combining Non-Pharmacological Treatments with Pharmacotherapies for Neurological Disorders: A Unique Interface of the Brain, Drug–Device, and Intellectual Property

PubMed Central

Bulaj, Grzegorz

2014-01-01

Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug–device therapies may be offset by a value proposition of the exclusivity due to the patent–independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries. PMID:25071711

Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection.

PubMed

El Kassas, Mohamed; Elbaz, Tamer; Hafez, Enas; Wifi, Mohamed Naguib; Esmat, Gamal

2017-06-01

Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families. Areas covered: In this review, the authors summarize data from of one of the recently developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333. Herein, the authors discuss the drug discovery data for dasabuvir including data from preclinical, toxicological resistance studies. The authors also review dasabuvir's clinical efficacy across various clinical challenges, in addition to its limitations in clinical practice. Expert opinion: Dasabuvir represents an important medical advance when used as a combination therapy for HCV. Unfortunately, it does present limitations like low genotypic coverage and further research is still required to address some of the lingering issues.

Physical activity, diet and behaviour modification in the treatment of overweight and obese adults: a systematic review.

PubMed

Södlerlund, Anne; Fischer, Annika; Johansson, Titti

2009-05-01

The aim was to extend the body of knowledge through a systematic review that combines the strengths and partly fills the gaps from earlier reviews. The aim is to review randomized controlled trials of the long-term effectiveness of physical exercise/activity with or without diet and/or behaviour modification therapy in terms of training effect, weight loss and improvement of body composition in overweight and obese, healthy adults. Data for systematic review was collected via a search of databases for literature published between 1995 and 2006. The search yielded 12 articles. The studies showed that training intensity should be moderate. The treatment of overweight and obese individuals with training alone cannot be expected to result in any substantial weight loss but should be combined with diet and behaviour modification therapy. However training can be an important factor in preventing further weight gain, or in helping individuals maintain a lowered body weight. According to this systematic review of randomized controlled trials, the treatment that produced the best weight loss results included a combination of training, behaviour therapy and diet.

[Efficacy of initial antiretroviral therapy based on lopinavir/ritonavir plus 2 nucleoside/nucleotide analogs in patients with human immunodeficiency virus type 1 infection].

PubMed

Zamora, Laura; Gatell, José M

2014-11-01

Triple combination regimens consisting of lopinavir/ritonavir (LPV/r) plus 2 nucleoside/nucleotide analogs continue to be a valid option in initial antiretroviral therapy. Other protease inhibitors boosted with ritonavir (and in future with cobicistat) have been introduced, as well as other non-nucleoside analogs (rilpivirin) and 3 integrase inhibitors. None of the new regimens have shown superiority over LPV/r or comparisons are lacking. Therefore, regimens including LPV/r continue to be recommended as initial first-line or alternative strategies in most treatment guidelines. Dual combinations with LPV/r (plus raltegravir or lamivudine) are described in another article and can provide a similar response rate to triple combinations, better tolerance, and an improved cost-efficacy ratio, both for initial therapy and in simplification strategies. In contrast, LPV/r or darunavir/r monotherapy does not seem an acceptable option in treatment-naïve patients and is becoming increasingly less acceptable in simplification strategies. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

PubMed

Wu, Xiang-Dong; Xu, Wei; Liu, Meng-Meng; Hu, Ke-Jia; Sun, Ya-Ying; Yang, Xue-Fei; Zhu, Gui-Qi; Wang, Zi-Wei; Huang, Wei

2018-03-24

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended. © 2018 Wiley Periodicals, Inc.

COMBINATION THERAPY WITH FLUOXETINE AND ALPRAZOLAM TO CONTROL ANXIETY IN A HAND-REARED SNOW LEOPARD (UNCIA UNCIA).

PubMed

Holman, Holly J

2016-09-01

A captive hand-reared adult male snow leopard ( Uncia uncia ) was treated for anxiety associated with taunting from visitors, the presence of large crowds, and introduction to a female for breeding. Behaviors included shaking, chewing on tail, panting, panicking, and bouncing off the viewing glass, pacing, and avoidance of the female. Combination therapy of oral fluoxetine and alprazolam were administered initially to minimize anxious behaviors while the fluoxetine achieved therapeutic levels. The alprazolam was tapered completely and was only used episodically on two occasions. Although a palatability issue with alprazolam initially prevented consistent dosing, anxious behavior was eliminated and successful breeding behavior was achieved for the first time. After 44 mo of therapy, there have been no anxious behaviors requiring additional medications, two additional breeding behaviors observed, and no evidence of adverse side effects with long-term use.

Moxibustion for the treatment of chemotherapy-induced leukopenia: a systematic review of randomized clinical trials.

PubMed

Choi, Tae-Young; Lee, Myeong Soo; Ernst, Edzard

2015-06-01

The purpose of this study is to assess the efficacy of moxibustion as a treatment of chemotherapy-induced leukopenia. Twelve databases were searched from their inception through June 2014, without a language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for leukopenia induced by chemotherapy. Cochrane criteria were used to assess the risk of bias. Six RCTs with a total of 681 patients met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The trials included patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. In four RCTs, moxibustion was more effective than conventional drug therapy. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing white blood cell counts. There is low level of evidence based on these six trials that demonstrates the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia. However, the number of trials, the total sample size, and the methodological quality are too low to draw firm conclusions. Future RCTs appear to be warranted.

Monotherapy versus combination therapy against carbapenem-resistant Gram-negative bacteria: A retrospective observational study.

PubMed

Ghafur, A; Devarajan, V; Raja, T; Easow, J; Raja, M A; Sreenivas, S; Ramakrishnan, B; Raman, S G; Devaprasad, D; Venkatachalam, B; Nimmagadda, R

2016-01-01

Colistin-based combination therapy (CCT) is extensively used to treat infections due to carbapenem-resistant Gram-negative bacteria (CRGNB). There are no data available from India on the usefulness of combination therapy, especially in the oncology setup. The aim of this study was to analyze the clinical effectiveness of CCT over monotherapy in patients with CRGNB. We conducted a retrospective, observational study of patients with CRGNB bloodstream infections in our oncology and bone marrow transplant center. Over a 3-year study period (2011-2014), we could identify 91 patients satisfying study criteria. There was no statistically significant difference in the 28-day mortality between monotherapy and combination therapy arms (mono n = 26, mortality 10 (38.5%); combination n = 65, mortality 28 (40%); P = 0.886). Neutropenic patients with Enterobacteriaceae bloodstream infections performed better with combination therapy (mono n = 7, mortality 6 (85.7%); combination therapy n = 22, mortality 8 (36.4%); P = 0.035). There was no significant difference in the 28-day mortality between the two treatment arms in other subgroups. Our study did not find CCT superior to colistin monotherapy in patients with CRGNB blood stream infections; except in the subgroup of neutropenic patients with Enterobacteriaceae bloodstream infections, where combination therapy performed better.

Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho

Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versusmore » radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.« less

Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

PubMed Central

Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

2015-01-01

Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

PubMed

Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice.

PubMed

Chen, Bin; Kao, Huang-Kai; Dong, Ziqing; Jiang, Zhaohua; Guo, Lifei

2017-01-01

Negative-pressure wound therapy and pulsed radiofrequency energy are two clinical modalities used to treat soft-tissue wounds. They are purported to affect healing differently. The aim of this experimental study was to contrast the two modalities at a mechanistic level and to investigate whether their combined therapy could achieve additive and complementary effects on wound healing. Full-thickness dorsal cutaneous wounds of diabetic, db/db, mice were treated with either negative-pressure wound therapy, pulsed radiofrequency energy, or combined therapies. Macroscopic healing kinetics were examined. Epidermal regeneration (proliferation rate and length of reepithelialization) and neovascularization (blood vessel density) were investigated. Messenger RNA levels indicative of angiogenic (basic fibroblast growth factor), profibrotic (transforming growth factor-β), epidermal proliferative (keratinocyte growth factor), and extracellular matrix remodeling (collagen 1) processes were measured in wound tissues. All three treatment groups displayed faster wound healing. The negative-pressure wound therapy/pulsed radiofrequency energy combined therapy led to significantly faster healing than either the negative-pressure wound therapy or pulsed radiofrequency energy therapy alone. Epidermal regeneration and neovascularization were enhanced in all three groups. The two negative-pressure wound therapy groups (alone and combined with pulsed radiofrequency energy) demonstrated more significant increases in expression of all assayed growth factors than the pulsed radiofrequency energy group. Furthermore, the combined therapy exhibited a more profound elevation in collagen 1 expression than either of the two therapies alone. Combining the negative-pressure wound therapy and pulsed radiofrequency energy modalities can achieve additive benefits in cutaneous healing, and the two therapies can be easily used together to complement each other in clinical wound treatments.

A Feedback Control Model of Comprehensive Therapy for Treating Immunogenic Tumours

NASA Astrophysics Data System (ADS)

Tang, Biao; Xiao, Yanni; Tang, Sanyi; Cheke, Robert A.

Surgery is the traditional method for treating cancers, but it often fails to cure patients for complex reasons so new therapeutic approaches that include both surgery and immunotherapy have recently been proposed. These have been shown to be effective, clinically, in inhibiting cancer cells while allowing retention of immunologic memory. This comprehensive strategy is guided by whether a population of tumour cells has or has not exceeded a threshold density. Conditions for successful control of tumours in an immune tumour system were modeled and the related dynamics were addressed. A mathematical model with state-dependent impulsive interventions is formulated to describe combinations of surgery with immunotherapy. By analyzing the properties of the Poincaré map, we examine the global dynamics of the immune tumour system with state-dependent feedback control, including the existence and stability of the semi-trivial order-1 periodic solution and the positive order-k periodic solution. The main results showed that surgery alone can only control the tumour size below a certain level while there is no immunologic memory. If comprehensive therapy involving combining surgery with immunotherapy is considered, then not only can the cancers be controlled below a certain level, but the immune system can also retain its activity. The existence of positive order-k periodic solutions implies that periodical therapy is needed to control the cancers. However, choosing the treatment frequency and the strength of the therapy remains challenging, and hence a strategy of individual-based therapy is suggested.

Efficacy of Ligustrazine Injection as Adjunctive Therapy for Angina Pectoris: A Systematic Review and Meta-Analysis.

PubMed

Shao, Huikai; Zhao, Lingguo; Chen, Fuchao; Zeng, Shengbo; Liu, Shengquan; Li, Jiajia

2015-11-29

BACKGROUND In the past decades, a large number of randomized controlled trials (RCTs) on the efficacy of ligustrazine injection combined with conventional antianginal drugs for angina pectoris have been reported. However, these RCTs have not been evaluated in accordance with PRISMA systematic review standards. The aim of this study was to evaluate the efficacy of ligustrazine injection as adjunctive therapy for angina pectoris. MATERIAL AND METHODS The databases PubMed, Medline, Cochrane Library, Embase, Sino-Med, Wanfang Databases, Chinese Scientific Journal Database, Google Scholar, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and the Chinese Science Citation Database were searched for published RCTs. Meta-analysis was performed on the primary outcome measures, including the improvements of electrocardiography (ECG) and the reductions in angina symptoms. Sensitivity and subgroup analysis based on the M score (the refined Jadad scores) were also used to evaluate the effect of quality, sample size, and publication year of the included RCTs on the overall effect of ligustrazine injection. RESULTS Eleven RCTs involving 870 patients with angina pectoris were selected in this study. Compared with conventional antianginal drugs alone, ligustrazine injection combined with antianginal drugs significantly increased the efficacy in symptom improvement (odds ratio [OR], 3.59; 95% confidence interval [CI]: 2.39 to 5.40) and in ECG improvement (OR, 3.42; 95% CI: 2.33 to 5.01). Sensitivity and subgroup analysis also confirmed that ligustrazine injection had better effect in the treatment of angina pectoris as adjunctive therapy. CONCLUSIONS The 11 eligible RCTs indicated that ligustrazine injection as adjunctive therapy was more effective than antianginal drugs alone. However, due to the low quality of included RCTs, more rigorously designed RCTs were still needed to verify the effects of ligustrazine injection as adjunctive therapy for angina pectoris.

Efficacy of Ligustrazine Injection as Adjunctive Therapy for Angina Pectoris: A Systematic Review and Meta-Analysis

PubMed Central

Shao, Huikai; Zhao, Lingguo; Chen, Fuchao; Zeng, Shengbo; Liu, Shengquan; Li, Jiajia

2015-01-01

Background In the past decades, a large number of randomized controlled trials (RCTs) on the efficacy of ligustrazine injection combined with conventional antianginal drugs for angina pectoris have been reported. However, these RCTs have not been evaluated in accordance with PRISMA systematic review standards. The aim of this study was to evaluate the efficacy of ligustrazine injection as adjunctive therapy for angina pectoris. Material/Methods The databases PubMed, Medline, Cochrane Library, Embase, Sino-Med, Wanfang Databases, Chinese Scientific Journal Database, Google Scholar, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and the Chinese Science Citation Database were searched for published RCTs. Meta-analysis was performed on the primary outcome measures, including the improvements of electrocardiography (ECG) and the reductions in angina symptoms. Sensitivity and subgroup analysis based on the M score (the refined Jadad scores) were also used to evaluate the effect of quality, sample size, and publication year of the included RCTs on the overall effect of ligustrazine injection. Results Eleven RCTs involving 870 patients with angina pectoris were selected in this study. Compared with conventional antianginal drugs alone, ligustrazine injection combined with antianginal drugs significantly increased the efficacy in symptom improvement (odds ratio [OR], 3.59; 95% confidence interval [CI]: 2.39 to 5.40) and in ECG improvement (OR, 3.42; 95% CI: 2.33 to 5.01). Sensitivity and subgroup analysis also confirmed that ligustrazine injection had better effect in the treatment of angina pectoris as adjunctive therapy. Conclusions The 11 eligible RCTs indicated that ligustrazine injection as adjunctive therapy was more effective than antianginal drugs alone. However, due to the low quality of included RCTs, more rigorously designed RCTs were still needed to verify the effects of ligustrazine injection as adjunctive therapy for angina pectoris. PMID:26615387

Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

PubMed

Zhang, Ming; Tao, Tao; Zhang, Zhao-Bo; Zhu, Xiao; Fan, Wen-Guo; Pu, Li-Jun; Chu, Lei; Yue, Shou-Wei

2016-03-01

To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. Prospective randomized controlled study. Department of physical medicine and rehabilitation. Patients with dysphagia with medullary infarction (N=82). Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction. A sensory approach appears to be better than a motor approach. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

PubMed

Kolter, Donald P

2003-12-01

HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

Comparing Sildenafil alone vs. Sildenafil plus brief couple sex therapy on erectile dysfunction and couples' sexual and marital quality of life: a pilot study.

PubMed

Aubin, Sylvie; Heiman, Julia R; Berger, Richard E; Murallo, A V; Yung-Wen, Liu

2009-01-01

Treatment options for managing erectile dysfunction (ED) include medical and psychological interventions. The present study examined the effectiveness of a drug-only vs. combined treatment approach on erectile function as well as other domains of sexual function and cognition, couple intimacy and adaptation, and treatment satisfaction. Couples with ED were randomly assigned to either Viagra-only (VO) or Viagra plus sex therapy (VST). Sexual and relationship variables were measured at specific time points. Despite limitations, study findings extend previous conclusions and provide empirical support for the effectiveness and satisfaction with the combined treatment approach for treating men with ED of mixed etiology.

[Using dynamic magnetotherapy and transdermal electroneurostimulation in the combined treatment of patients with mandibular fractures and concomitant periodontal inflammatory diseases].

PubMed

Lepilin, A V; Erokina, N L; Rogatina, T V; Khlusov, I Iu

2009-01-01

The objective of this study was to compare results of dynamic magnetotherapy (DMT), transdermal electroneurostimulation (TDENS), and traditional ultrahigh frequency (UHF) therapy in 473 patients with mandibular fractures and concomitant inflammatory diseases of paradontium. The parameters measured in the study included hygienic and paradontal indices, microcirculation patterns (using laser Doppler flowmetry), and the degree of mandibular fragment consolidation. It was shown that combined treatment with DMT and TDENS using an AMO-ATOS-E apparatus permits to eliminate clinical symptoms of paradontal inflammatory diseases twice as fast as traditional ultrahigh frequency therapy and ensures a two-fold reduction in the frequency of complications.

New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin.

PubMed

Frias, Patrick F; Frias, Juan Pablo

2017-08-18

The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity. These properties have translated to significantly reduced risk of hypoglycemia (particularly during the night) compared with previous generation basal insulins. When optimized basal insulin therapy is not sufficient to obtain or maintain glycemic goals, various options exist to improve glycemic control, including intensification of insulin therapy with the addition of prandial insulin or changing to pre-mixed insulin and, more recently, the addition of a GLP-1 receptor agonist, either as a separate injection or as a component of one of the new fixed-ratio combinations of a basal insulin and GLP-1 RA. New safer and often more convenient basal insulins and fixed ratio combinations containing basal insulin (and GLP-1 receptor agonist) are available today for patients with type 2 diabetes not achieving glycemic goals. Head-to-head studies comparing the latest generation basal insulins are underway, and future studies assessing the fixed-ratio combinations will be important to better understand their differentiating features.

[Medical treatment of endometriosis: Hormonal treatment of pain, impact on evolution and future perspectives].

PubMed

Geoffron, Sophie; Legendre, Guillaume; Daraï, Emile; Chabbert-Buffet, Nathalie

2017-12-01

Endometriosis is a chronic painful disease, for which hormone therapy is usually offered as a first line option to women not willing to conceive. To analyse and synthesize the literature, from 2006 onwards, on pain control, and disease evolution in oemn using combined hormonal contraceptives, progestins and GnRH analogs. Data on other current and future treatment perspectives is included as well. Medline (Pubmed), the Cochrane Library, and endometriosis treatment recommendations published by European Society of Human Reproduction and Embryology (ESHRE), National Institute for health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), Royal College of Obstetricians and Gynaecologists (RCOG) and Société des Obstétriciens et Gynécologues du Canada (SOGC). Meta-analysis and clinical trials are included. Study quality is heterogeneous in general. Hormone therapy inconstantly allows pain relief and prevention of endometrioma and rectovaginal wall nodules recurrence. Available molecules and routes of administration as well as risk benefit balance are evaluated. Data on future perspectives are limited to date and do not allow use in routine. Hormonal treatment of endometriosis relies on combined hormonal contraceptives (using different routes of administration), progestins and particularly the levonorgestrel-releasing IUS, and GnRH analogs as a last option, in combination with an add-back therapy. Promising alternatives are currently under preclinical and clinical evaluation. Copyright © 2017. Published by Elsevier Masson SAS.

Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent

PubMed Central

Qi, Guoyan; Liu, Peng; Dong, Huimin; Gu, Shanshan; Yang, Hongxia; Xue, Yinping

2017-01-01

Background Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. Material/Methods MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. Results Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. Conclusions The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma. PMID:28278141

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia.

PubMed

Botzenhardt, Sebastian; Sing, Chor W; Wong, Ian C K; Chan, Godfrey Chi-Fung; Wong, Lisa Y L; Felisi, Mariagrazia; Rascher, Wolfgang; Ceci, Adriana; Neubert, Antje

2016-01-01

There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development.

PubMed

Clark, Amy S; Karasic, Thomas B; DeMichele, Angela; Vaughn, David J; O'Hara, Mark; Perini, Rodolfo; Zhang, Paul; Lal, Priti; Feldman, Michael; Gallagher, Maryann; O'Dwyer, Peter J

2016-02-01

Palbociclib (PD0332991) is a newly developed drug that received breakthrough designation and recent US Food and Drug Administration approval in combination with endocrine therapy in the treatment of hormone receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancer in the first-line metastatic setting. Herein we describe the preclinical and translational data and early- and late-phase clinical trials in which palbociclib has been investigated in a broad array of tumor types. We discuss the pharmacodynamics, pharmacokinetics, toxic effects, and clinical response rates. On March 1, 2015, we conducted a review of the literature describing the development of palbociclib. We used the PubMed search terms "PD0332991," "palbociclib," and "CDK4/6 inhibitor" to find all published articles of interest, without limitation as to publication date. Palbociclib is a potent and specific oral cyclin-dependent kinase (CDK) 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein-expressing tumors. Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect. Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy-naïve and endocrine therapy-resistant metastatic settings. Palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way.

Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections.

PubMed

Tissot, F; Prod'hom, G; Manuel, O; Greub, G

2015-09-01

The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results.

Long-Term Response of Hirsutism and Other Hyperandrogenic Symptoms to Combination Therapy in Polycystic Ovary Syndrome.

PubMed

Ezeh, Uche; Huang, Andy; Landay, Melanie; Azziz, Ricardo

2018-06-07

Polycystic ovary syndrome (PCOS) affects 5%-15% of women and is the most common cause of hirsutism. Data on the time-course of improvement to suppressive therapy and predictors of that response in PCOS are lacking. The objectives of our study are to determine the long-term response and identify predictors of response in PCOS women treated with suppressive therapy, including spironolactone (SPL) + oral contraceptives (OCs). Retrospective cross-sectional analysis of 200 women with PCOS (1990 NIH criteria) treated with suppressive therapy in general, and a subgroup of 138 subjects treated with OCP+SPL who had been prospectively included in a biorepository. Main outcome measure included improvement rate per 100 person-month of follow-up for hirsutism, menstrual irregularity and acne measured qualitatively as "feeling better", and changes in the severity of hirsutism quantified by modified Ferriman-Gallwey [mF-G] score. During a mean follow-up of 34.2 months, 85.1%, 82.7%, and 79.3% of patients reported improvement in hirsutism, menstrual dysfunction, and acne, respectively. The modified Ferriman-Gallwey (mF-G) hirsutism score improved by 59.9%. The net reduction in mF-G score and the percent of patients reporting improvement in hirsutism were greater for OC+SPL than for either drug alone, with no difference in the percent of patients free of adverse effects. Among those treated with OC+SPL (n = 138), the initial mF-G and sex hormone-binding globulin (SHBG) independently predicted successful therapy for hirsutism. There is a high rate of patient satisfaction with suppressive therapy in PCOS. The efficacy of suppressive therapy for hirsutism was greater with OC+SPL than with either drug alone. Successful treatment of hirsutism with combination OC+SPL requires at least 6 months of therapy, with the proportion of satisfied patients continuing to increase with treatment duration. The probability of patient satisfaction with OC+SPL treatment for hirsutism can be predicted by her initial mF-G score or SHBG level.

Integrative and complementary therapies for patients with advanced cancer.

PubMed

Marchand, Lucille

2014-07-01

In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is impossible given the enormous diversity in this area. This review will concentrate on modalities such as nutrition, movement, music, aromatherapy, massage, select supplements, and acupuncture that have been researched in cancer survivors. Many of these modalities are quite effective for a number of symptoms in palliative care and have been studied in non-cancer populations. Resources for further study will also be included.

[Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

PubMed

Yamane, T; Tanaka, K; Hasuike, T; Hirai, M; Misu, K; Ota, K; Ohira, H; Nakao, Y; Yasui, Y; Inoue, T

1992-08-01

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: a cost-effectiveness analysis.

PubMed

Saito, Shota; Shimizu, Utako; Nan, Zhang; Mandai, Nozomu; Yokoyama, Junji; Terajima, Kenshi; Akazawa, Kouhei

2013-03-01

Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease. To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD. A decision analysis model is constructed to compare, over a time horizon of 1year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-α therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results. The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750. Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects.

PubMed

Huang, Zhangjian; Fu, Junjie; Zhang, Yihua

2017-09-28

The increasing understanding of the role of nitric oxide (NO) in cancer biology has generated significant progress in the use of NO donor-based therapy to fight cancer. These advances strongly suggest the potential adoption of NO donor-based therapy in clinical practice, and this has been supported by several clinical studies in the past decade. In this review, we first highlight several types of important NO donors, including recently developed NO donors bearing a dinitroazetidine skeleton, represented by RRx-001, with potential utility in cancer therapy. Special emphasis is then given to the combination of NO donor(s) with other therapies to achieve synergy and to the hybridization of NO donor(s) with an anticancer drug/agent/fragment to enhance the activity or specificity or to reduce toxicity. In addition, we briefly describe inducible NO synthase gene therapy and nanotechnology, which have recently entered the field of NO donor therapy.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

PubMed

Somaraju, Usha Rani; Solis-Moya, Arturo

2014-10-13

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 14 August 2014.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 12 May 2014. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 11 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 426 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67, P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, abdominal pain and fecal fat excretion. Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency. There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

PubMed

Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

2018-06-08

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER.

Imaging in conjunction with physical therapy in management of a patient with history of thoracic tumour

PubMed Central

Rendeiro, Daniel G.; Deyle, Gail D.; Boissonnault, William G.

2015-01-01

Background: Physical therapy care for musculoskeletal conditions includes an ongoing process that systematically considers and prioritises diagnostic hypotheses. These diagnostic hypotheses include those that are typical for common musculoskeletal conditions, and must also include more rare conditions that would require care outside the scope of practice of the physical therapist. When additional screening is required, physical therapists collaborate with other providers or directly order the appropriate tests to rule out suspected pathology. Case Description: This article illustrates the use of musculoskeletal imaging ordered by a physical therapist to guide ongoing management of a patient with back pain and a history of cancer. Outcomes: The patient successfully returned to moderate-intensity sport activities after a course of physical therapy. Discussion: This case provides an example of how clinical diagnostic reasoning combined with clinical privileges to order musculoskeletal imaging can facilitate diagnostic accuracy in a timely and cost-efficient manner. PMID:26309382

Enhancing Approaches to the Identification and Management of Pseudobulbar Affect.

PubMed

Crumpacker, David W

2016-09-01

Pseudobulbar affect (PBA) is a socially debilitating condition that primarily affects people with neurologic diseases, such as Alzheimer's disease or multiple sclerosis. This condition is characterized by uncontrolled, exaggerated expressions of laughing or crying-often when the situation does not warrant this behavior. Although the true prevalence of PBA is surprisingly high, this condition remains widely misdiagnosed and underdiagnosed. While its exact etiology is unknown, PBA likely results from disruptions in the brain structures and/or neurotransmitters that regulate emotions. Differential diagnosis of PBA includes ruling out depression or other psychiatric conditions. Treatment of PBA has traditionally centered on antidepressant therapies, but newer therapeutic options include combination agents employing multiple modalities. Therapy should include patient counseling to reassure patients and families that PBA is not the fault of the individual. Counseling should also emphasize safety precautions to minimize adverse events and maximize appropriate adherence to the selected therapies. © Copyright 2016 Physicians Postgraduate Press, Inc.

Update on the medical treatment of juvenile idiopathic arthritis.

PubMed

Hashkes, Philip J; Laxer, Ronald M

2006-12-01

Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.

Non-viral gene therapy for bone tissue engineering.

PubMed

Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

2013-01-01

The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

The Next Wave of Influenza Drugs.

PubMed

Shaw, Megan L

2017-10-13

Options for influenza therapy are currently limited to one class of drug, the neuraminidase inhibitors. Amidst concerns about drug resistance, much effort has been placed on the discovery of new drugs with distinct targets and mechanisms of action, with great success. There are now several candidates in late stage development which include small molecules targeting the three subunits of the viral polymerase complex and monoclonal antibodies targeting the hemagglutinin, as well as host-directed therapies. The availability of drugs with diverse mechanisms now opens the door to exploring combination therapies for influenza, and the range of administration routes presents more opportunities for treating hospitalized patients.

ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

PubMed Central

Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

2017-01-01

Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with each drug individually in a preclinical model for pulmonary infection with MDR P. aeruginosa. These data strongly support further evaluation of ZTI-01 in combination with other antibiotics as potential therapies against pulmonary infections with MDR bacteria. Disclosures E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary

Intensive treatment of speech disorders in robin sequence: a case report.

PubMed

Pinto, Maria Daniela Borro; Pegoraro-Krook, Maria Inês; Andrade, Laura Katarine Félix de; Correa, Ana Paula Carvalho; Rosa-Lugo, Linda Iris; Dutka, Jeniffer de Cássia Rillo

2017-10-23

To describe the speech of a patient with Pierre Robin Sequence (PRS) and severe speech disorders before and after participating in an Intensive Speech Therapy Program (ISTP). The ISTP consisted of two daily sessions of therapy over a 36-week period, resulting in a total of 360 therapy sessions. The sessions included the phases of establishment, generalization, and maintenance. A combination of strategies, such as modified contrast therapy and speech sound perception training, were used to elicit adequate place of articulation. The ISTP addressed correction of place of production of oral consonants and maximization of movement of the pharyngeal walls with a speech bulb reduction program. Therapy targets were addressed at the phonetic level with a gradual increase in the complexity of the productions hierarchically (e.g., syllables, words, phrases, conversation) while simultaneously addressing the velopharyngeal hypodynamism with speech bulb reductions. Re-evaluation after the ISTP revealed normal speech resonance and articulation with the speech bulb. Nasoendoscopic assessment indicated consistent velopharyngeal closure for all oral sounds with the speech bulb in place. Intensive speech therapy, combined with the use of the speech bulb, yielded positive outcomes in the rehabilitation of a clinical case with severe speech disorders associated with velopharyngeal dysfunction in Pierre Robin Sequence.

Immune mediated neuropathy following checkpoint immunotherapy.

PubMed

Gu, Yufan; Menzies, Alexander M; Long, Georgina V; Fernando, S L; Herkes, G

2017-11-01

Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Exercise on Motor and Nonmotor Symptoms of Parkinson's Disease

PubMed Central

Dashtipour, Khashayar; Johnson, Eric; Kani, Camellia; Kani, Kayvan; Hadi, Ehsan; Ghamsary, Mark; Pezeshkian, Shant; Chen, Jack J.

2015-01-01

Background. Novel rehabilitation strategies have demonstrated potential benefits for motor and non-motor symptoms of Parkinson's disease (PD). Objective. To compare the effects of Lee Silverman Voice Therapy BIG (LSVT BIG therapy) versus a general exercise program (combined treadmill plus seated trunk and limb exercises) on motor and non-motor symptoms of PD. Methods. Eleven patients with early-mid stage PD participated in the prospective, double-blinded, randomized clinical trial. Both groups received 16 one-hour supervised training sessions over 4 weeks. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Modified Fatigue Impact Scale (MFIS). Five patients performed general exercise and six patients performed LSVT BIG therapy. Post-intervention evaluations were conducted at weeks 4, 12 and 24. Results. The combined cohort made improvements at all follow-up evaluations with statistical significance for UPDRS total and motor, BDI, and MFIS (P < 0.05). Conclusion. This study demonstrated positive effects of general exercise and LSVT BIG therapy on motor and non-motor symptoms of patients with PD. Our results suggest that general exercise may be as effective as LSVT BIG therapy on symptoms of PD for patients not able to readily access outpatient LSVT BIG therapy. PMID:25722915

Emerging biological therapies for the treatment of myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Stahl, Maximilian; Komrokji, Rami

2016-09-01

No drug has resulted in a survival advantage in patients with lower-risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have revolutionized treatment options for patients with higher-risk MDS, the prognosis remains dismal after HMA treatment failure. Novel effective therapies are urgently needed especially after HMA failure. This review covers the current approach to disease prognostication and risk-adaptive therapy, as well as novel therapeutic approaches. We discuss the recent advancements in the understanding of MDS disease biology as a basis of targeted drug development. Several classes of novel agents are reviewed including drugs targeting dysregulated epigenetic control mechanisms, signaling pathways, abnormal splicing, as well as agents that target the immune system and the MDS bone marrow niche. Significant advancements in the understanding of the underlying biology of MDS are only starting to be translated into novel treatment options for MDS. Epigenetic therapy has shown significant clinical activity with HMA but the results of clinical trials combining HMAs with histone deacetylase inhibitors (HDACi) have been disappointing to date. Similarly, targeting several aberrant pathways in MDS has not resulted in significant improvements in therapy. Future therapies will focus both on synergic combination of existing drugs as well as novel agents targeting dysregulated immune responses and abnormal RNA splicing in MDS.

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

PubMed

Price, David B; Colice, Gene; Israel, Elliot; Roche, Nicolas; Postma, Dirkje S; Guilbert, Theresa W; van Aalderen, Willem M C; Grigg, Jonathan; Hillyer, Elizabeth V; Thomas, Victoria; Martin, Richard J

2016-04-01

Asthma management guidelines recommend adding a long-acting β 2 -agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.

Tramadol prescription patterns in patients followed by general practitioners and orthopedists in Germany in the year 2015.

PubMed

Kostev, Karel; Von Vultée, Christian; Usinger, Diethard M; Reese, Jens-Peter

2018-01-01

The aim of this study was to analyze tramadol prescription patterns in acute pain patients followed by general practitioners and orthopedists in Germany. This study included patients ≥18 years diagnosed with acute pain who received at least one tramadol prescription each in one of 1,129 general or 179 orthopedic practices in Germany between January and December 2015 (index date). Patients were excluded if they had received a prescription for another analgesic in the year prior to the index date, had a follow-up of less than 15 months after the index date, or were prescribed tramadol for a period of more than three months. The main outcome of this retrospective study was the share of patients receiving tramadol in combination therapy. Combination therapy was defined as the prescription of tramadol in conjunction with at least one other analgesic during the same medical visit. The present study included a total of 8,766 individuals. Overall, 1,492 (22.0%) of tramadol patients seen by general practitioners and 370 (18.7%) of those seen by orthopedists received tramadol in combination with other analgesics. Although this proportion was similar throughout the different subgroups in orthopedic practices, it was considerably higher in patients >80 years and in those with private health insurance coverage in general practices. Approximately one of five tramadol patients was prescribed tramadol in combination therapy. Further research is needed to gain a better understanding of the demographic and clinical factors that have an effect on tramadol prescription patterns in Germany.

Bipolar affective disorder and psychoeducation.

PubMed

Prasko, Jan; Ociskova, Marie; Kamaradova, Dana; Sedlackova, Zuzana; Cerna, Monika; Mainerova, Barbora; Sandoval, Aneta

2013-01-01

Bipolar affective disorder runs a natural course of frequent relapses and recurrences. Despite significant strides in the pharmacological treatment of bipolar disorder, most bipolar patients cannot be treated only by drugs. The limitations of using medication alone in symptomatic, relapse prevention, and satisfaction/quality of life terms have long prompted interest in wider forms of management. One of the promising way how to enhance remission seems to be combination of pharmacotherapy and psychoeducation. Studies were identified through PUBMED, Web of Science and Scopus databases as well as existing reviews. The search terms included "bipolar disorder", "psychoeducation", "psychotherapy", "psychosocial treatment", "family therapy", "individual therapy", "group therapy", and "psychoeducation". The search was performed by repeated use of the words in different combinations with no language or time limitations. This article is a review with conclusions concerned with psychoeducation in bipolar disorder. Randomized controlled trials of cognitive behavioral therapy, interpersonal and social rhythm therapy, individual, group and family psychoeducation show that these approaches augment stabilizing effect of pharmacotherapy. Patients and their families should be educated about bipolar disorder, triggers, warning signs, mood relapse, suicidal ideation, and the effectiveness of early intervention to reduce complications. Psychosocial approaches are important therapeutic strategies for reducing relapse and rehospitalization in bipolar disorder.

Case report of exercise and statin-fibrate combination therapy-caused myopathy in a patient with metabolic syndrome: contradictions between the two main therapeutic pathways.

PubMed

László, Andrea; Kalabay, László; Nemcsik, János

2013-02-06

Lifestyle modifications including exercise are beneficial and fundamentally part of the therapy of metabolic syndrome, although in most of the cases medical interventions are also required to reach the target values in the laboratory parameters. Statin and fibrate combination therapy is considered to be safe and effective in dyslipidaemia and metabolic syndrome. However, increased physical activity can enhance the statin and fibrate-associated myopathy. Myositis and the rare but life-threatening rhabdomyolysis are causing a conflict between exercise and statin-fibrate therapy, which is yet to be resolved. We present a case of a 43-year-old Caucasian man with metabolic syndrome who had the side-effect of exercise and drug-associated myositis. The patient had only transient moderate complaints and rhabdomyolysis could be avoided with the one-month creatine kinase control, a test which is not recommended routinely by the new guidelines. We would like to turn the spotlight on the possible complications of statin-fibrate therapy and exercise, when strict follow-up is recommended. In this condition high number of patients can be affected and the responsibility of general practitioners is accentuated.

Management of cutaneous rosacea: emphasis on new medical therapies.

PubMed

Del Rosso, James Q

2014-10-01

Over the past decade, both basic science and clinical research have provided new information on pathophysiology and therapy that has led to advances in the management of rosacea. As rosacea is a very common facial skin disorder in adults of both genders and essentially all races and ethnicities, these advances can provide therapeutic benefit to many affected individuals around the world. This article provides a collective review of more recent information on the pathophysiology and clinical manifestations of rosacea, and discusses individual medical therapies based on PubMed literature searches on 'rosacea', 'rosacea therapies' and each therapy that are included in this article. The perspectives of the author on management of rosacea are also included. Newer therapies and treatment concepts received greater emphasis. Management of cutaneous rosacea involves patient education, integration of proper skin care, differentiation of visible manifestations and symptoms, selecting therapies that correlate with the manifestations that are to be treated, setting realistic patient expectations on anticipated degree and time course of response and designing an overall management plan that addresses needs of the individual patient. In many cases, a combination approach is needed, and due to the chronicity of the disease long-term management is often warranted.

Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients with Chronic Liver Disease – A Systematic Review

PubMed Central

Khan, Anam; Tansel, Aylin; White, Donna L.; Kayani, Waleed Tallat; Bano, Shah; Lindsay, Jan; El-Serag, Hashem B.; Kanwal, Fasiha

2016-01-01

Background & Aims We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). Methods We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles, published from January 1983 through November 2014, that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. Results We identified 13 eligible studies, comprising 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy (MET), cognitive behavioral therapy (CBT), motivational interviewing (MI), supportive therapy and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and MET with comprehensive medical care, delivered over 2 years, produced a significant increase in abstinence (74% increase in intervention group versus 48% increase in control group; P=.02), reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group versus 75% decrease in control group, P=.03), reported from 1 observational study. However, data were not collected for more than 2 y on outcomes of patients with CLD and AUD. Conclusion In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism. PMID:26256464

Efficacy of rasagiline for the treatment of Parkinson's disease: an updated meta-analysis.

PubMed

Chang, Ying; Wang, Li-Bo; Li, Dan; Lei, Ke; Liu, Song-Yan

2017-08-01

Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson's disease rating scale (UPDRS) and the three subscales. Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores. Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols. KEY MESSAGES Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales. Both monotherapy and combination therapy significantly improved total UPDRS scores. Effect of rasagiline on total UPDRS scores was not dose-dependent.

Effectiveness of Physical Therapy in Patients with Tension-type Headache: Literature Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Arbós-Berenguer, Teresa; González, Ángel Arturo López; Vicente-Herrero, Teófila

2014-01-01

Tension-type headache (TTH) is a disease with a great incidence on quality of life and with a significant socioeconomic impact. The aim of this review is to determine the effectiveness of physical therapy by using manual therapy (MT) for the relief of TTH. A review was done identifying randomized controlled trials through searches in MEDLINE, PEDro, Cochrane and CINAHL (January 2002 - April 2012). English-language studies, with adult patients and number of subjects not under 11, diagnosed with episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) were included. Initial search was undertaken with the words Effectiveness, Tension-type headache, and Manual therapy (39 studies). In addition, a search which included terms related to treatments such as physiotherapy, physical therapy, spinal manipulation was performed (25 studies). From the two searches 9 studies met the inclusion criteria and were analysed finding statistically significant results: 1) myofascial release, cervical traction, neck muscles trigger points in cervical thoracic muscles and stretching; 2) Superficial heat and massage, connective tissue manipulation and vertebral Cyriax mobilization; 3) cervical or thoracic spinal manipulation and cervical chin-occipital manual traction; 4) massage, progressive relaxation and gentle stretching, program of active exercises of shoulder, neck and pericranial muscles; 5) massage, passive rhythmic mobilization techniques, cervical, thoracic and lumbopelvic postural correction and cranio-cervical exercises; 6) progressive muscular relaxation combined with joint mobilization, functional, muscle energy, and strain/counterstrain techniques, and cranial osteopathic treatment; 7) massage focused on relieving myofascial trigger point activity; 8) pressure release and muscle energy in suboccipital muscles; 9) combination of mobilizations of the cervical and thoracic spine, exercises and postural correction. All studies used a combination of different techniques and none analyzed treatments separately, also all the studies have assessed aspects related to TTH beyond frequency and intensity of pain. The findings from these studies showed evidence that physiotherapy with articulatory MT, combined with cervical muscle stretching and massage are effective for this disease in different aspects related with TTH. No evidence was found of the effectiveness of the techniques applied separately.

Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits.

PubMed

Hamamoto, Shinichi; Okuma, Tomohisa; Yamamoto, Akira; Kageyama, Ken; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

2013-05-01

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity. © RSNA, 2013.

New targeted therapies in pancreatic cancer.

PubMed

Seicean, Andrada; Petrusel, Livia; Seicean, Radu

2015-05-28

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours: therapeutic efficacy and histological changes.

PubMed

Mukaratirwa, S; Chitanga, S; Chimatira, T; Makuleke, C; Sayi, S T; Bhebhe, E

2009-06-01

Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was assessed. Tumour biopsies were taken weekly to evaluate histological changes. Complete tumour regression was observed in all the dogs treated with BCG, vincristine and BCG/vincristine combination therapy. BCG/vincristine combination therapy had a statistically significantly shorter regression time than BCG or vincristine therapy. No tumour regression was observed in the control group. Intratumoral BCG treatment resulted in the appearance of macrophages and increased numbers of tumour infiltrating lymphocytes (TILs) followed by tumour cell apoptosis and necrosis. Treatment with vincristine resulted in increased tumour cell apoptosis, reduction in the mitotic index and a decrease in the number of TILs. Tumours from dogs on BCG/vincristine combination were characterised by reduction in the mitotic index, and appearance of numerous TILs and macrophages followed by marked tumour cell apoptosis and necrosis. This study indicates that combined BCG and vincristine therapy is more effective than vincristine in treating CTVT, suggesting that the clinical course of this disease may be altered by immunochemotherapy.

A Military-Centered Approach to Neuroprotection for Traumatic Brain Injury

PubMed Central

Shear, Deborah A.; Tortella, Frank C.

2013-01-01

Studies in animals show that many compounds and therapeutics have the potential to greatly reduce the morbidity and post-injury clinical sequela for soldiers experiencing TBI. However, to date there are no FDA approved drugs for the treatment of TBI. In fact, expert opinion suggests that combination therapies will be necessary to treat any stage of TBI recovery. Our approach to this research effort is to conduct comprehensive pre-clinical neuroprotection studies in military-relevant animal models of TBI using the most promising neuroprotective agents. In addition, emerging efforts incorporating novel treatment strategies such as stem cell based therapies and alternative therapeutic approaches will be discussed. The development of a non-surgical, non-invasive brain injury therapeutic clearly addresses a major, unresolved medical problem for the Combat Casualty Care Research Program. Since drug discovery is too expensive to be pursued by DOD in the TBI arena, this effort capitalizes on partnerships with the Private Sector (Pharmaceutical Companies) and academic collaborations (Operation Brain Trauma Therapy Consortium) to study therapies already under advanced development. Candidate therapies selected for research include drugs that are aimed at reducing the acute and delayed effects of the traumatic incident, stem cell therapies aimed at brain repair, and selective brain cooling to stabilize cerebral metabolism. Each of these efforts can also focus on combination therapies targeting multiple mechanisms of neuronal injury. PMID:23781213

Effects of the addition of transcranial direct current stimulation to virtual reality therapy after stroke: a pilot randomized controlled trial.

PubMed

Viana, R T; Laurentino, G E C; Souza, R J P; Fonseca, J B; Silva Filho, E M; Dias, S N; Teixeira-Salmela, L F; Monte-Silva, K K

2014-01-01

Upper limb (UL) impairment is the most common disabling deficit following a stroke. Previous studies have suggested that transcranial direct current stimulation (tDCS) enhances the effect of conventional therapies. This pilot double-blind randomized control trial aimed to determine whether or not tDCS, combined with Wii virtual reality therapy (VRT), would be superior to Wii therapy alone in improving upper limb function and quality of life in chronic stroke individuals. Twenty participants were randomly assigned either to an experimental group that received VRT and tDCS, or a control group that received VRT and sham tDCS. The therapy was delivered over 15 sessions with 13 minutes of active or sham anodal tDCS, and one hour of virtual reality therapy. The outcomes included were determined using the Fugl-Meyer scale, the Wolf motor function test, the modified Ashworth scale (MAS), grip strength, and the stroke specific quality of life scale (SSQOL). Minimal clinically important differences (MCID) were observed when assessing outcome data. Both groups demonstrated gains in all evaluated areas, except for the SSQOL-UL domain. Differences between groups were only observed in wrist spasticity levels in the experimental group, where more than 50% of the participants achieved the MCID. These findings support that tDCS, combined with VRT therapy, should be investigated and clarified further.

A treatment for a chronic stroke patient with a plegic hand combining CI therapy with conventional rehabilitation procedures: case report.

PubMed

Bowman, Mary H; Taub, Edward; Uswatte, Gitendra; Delgado, Adriana; Bryson, Camille; Morris, David M; McKay, Staci; Mark, Victor W

2006-01-01

Constraint-Induced Movement therapy (CI therapy) is a recognized rehabilitation approach for persons having stroke with mild to moderately severe motor upper extremity deficits. To date, no rehabilitation treatment protocol has been proven effective that addresses both motor performance and spontaneous upper extremity use in the life situation for chronic stroke participants having severe upper extremity impairment with no active finger extension or thumb abduction. This case report describes treatment of a chronic stroke participant with a plegic hand using a CI therapy protocol that combines CI therapy with selected occupational and physical therapy techniques. Treatment consisted of six sessions of adaptive equipment and upper extremity orthotics training followed by a three-week, six-hour daily intervention of CI therapy plus neurodevelopmental treatment. Outcome measures included the Motor Activity Log for very low functioning patients (Grade 5 MAL), upper extremity portion of the Fugl-Meyer Motor Assessment, Graded Wolf Motor Function Test - for very low functioning patients (gWMFT- Grade 5), and Modified Ashworth Scale. The participant showed improvement on each outcome measure with the largest improvement on the Grade 5 MAL. In follow-up, the participant had good retention of his gains in motor performance and use of his more affected arm for real world activities after 3 months; after a one-week brush-up at 3 months, and at one year post-treatment.

[The National Database of the Regional Collaborative Rheumatic Centers as a tool for clinical epidemiology and quality assessment in rheumatology].

PubMed

Zink, Angela; Huscher, Dörte; Listing, Joachim

2003-01-01

The national database of the German Collaborative Arthritis Centres is a well-established tool for the observation and assessment of health care delivery to patients with rheumatic diseases in Germany. The discussion of variations in treatment practices contributes to the internal quality assessment in the participating arthritis centres. This documentation has shown deficits in primary health care including late referral to a rheumatologist, undertreatment with disease-modifying drugs and complementary therapies. In rheumatology, there is a trend towards early, intensive medical treatment including combination therapy. The frequency and length of inpatient hospital and rehabilitation treatments is decreasing, while active physiotherapy in outpatient care has been increased. Specific deficits have been identified concerning the provision of occupational therapy services and patient education.

Management of hepatitis C infection in the era of direct-acting antiviral therapy

NASA Astrophysics Data System (ADS)

Zain, L. H.; Sungkar, T.

2018-03-01

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.

PubMed

Alhamadi, Wisam; Al-Saigh, Rafal J; Al-Dabagh, Nebras N; Al-Humadi, Hussam W

2017-01-01

Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA. Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis. According to bliss independent interaction, the synergistic interactions depended on Δ E values that showed the best for CIP was with AMB (Δ E = 55.14) followed with KET (Δ E = 41.23) and lastly ITR (Δ E = 39.67) at CIP = 150 mg/L. DOX was optimal with KET (Δ E = 42.11) followed with AMB (Δ E = 40.77) and the lowest with ITR (Δ E = 9.12) at DOX = 75 mg/L. MET is the best with AMB (Δ E = 40.95) and then with ITR (Δ E = 35.45) and finally KET (Δ E = 15.15) at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects. This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.

PubMed

Claxton, Lindsay; Jenks, Michelle; Taylor, Matthew; Wallenstein, Gene; Mendelsohn, Alan M; Bourret, Jeffrey A; Singh, Amitabh; Moynagh, Dermot; Gerber, Robert A

2016-09-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib is approved in the United States for use in adults with moderately to severely active RA and an inadequate response or intolerance to methotrexate. To (a) evaluate, using an economic model, the treatment costs of an RA strategy including tofacitinib, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic RA treatment strategies, which are commonly prescribed in the United States, and (b) assess the economic impact of monotherapy and combination therapy in patients who had an inadequate response to methotrexate therapy (MTX-IR analysis) and to combination therapy in patients who had an inadequate response to a tumor necrosis factor inhibitor (TNF-IR analysis). A transparent, Excel-based economic model with a decision-tree approach was developed to evaluate costs over a 1- and 2-year time horizon. The model compared tofacitinib 5 mg twice a day (BID) either as monotherapy or in combination with MTX with similarly labeled biologic therapies. Response to treatment was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR20 represented clinical response and determined whether patients continued therapy. ACR response rates at 6-month intervals were sourced from prescribing information and safety event rates from a published meta-analysis. Following an adverse event or a lack of response to treatment, it was assumed that 75% of patients switched to the next line of treatment (first to abatacept and then to rituximab). The perspective was that of a U.S. payer. Costs were reported in 2015 U.S. dollars and included drug wholesale acquisition costs, monitoring, drug administration, and treatment for minor and serious adverse events. The patient population eligible for treatment was based on the total number of members (i.e., RA and non-RA) in a payer organization; members with RA treated with biologic therapies were estimated using epidemiological data. Sensitivity analyses were conducted to explore the impact of varying key parameters, including treatment-switching probability, product rebate, major rates of adverse drug reaction, and ACR20 rates, on the model outcomes. Tofacitinib combination therapy after MTX failure was associated with the lowest cost per member per month (PMPM) over a 2-year time frame at $5.53, compared with $6.49 for adalimumab, $6.43 for etanercept, $5.95 for certolizumab, and $5.89 for tocilizumab. Similar savings were observed when all biologics were administered as monotherapy. Tofacitinib combination therapy was also associated with the lower PMPM cost compared with adalimumab combination therapy in the TNF-IR analysis. Tofacitinib was also among the lowest cost per ACR20 responder in each analysis. Sensitivity analyses demonstrated that tofacitinib would potentially be cost saving even in the least optimistic scenarios. This analysis suggests that tofacitinib 5 mg BID following MTX failure is a lower cost per patient treatment option when used either as monotherapy or combination therapy, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic regimens. Tofacitinib + MTX in TNF-IR patients was also predicted to be a lower-cost treatment option compared with adalimumab+MTX and was associated with the lowest cost per ACR 20/50/70 responder. This study was funded by Pfizer, which determined the research topic and paid York Health Economics Consortium to develop the analysis and conduct the research. York Health Economics Consortium has received consultancy fees from Pfizer. Gerber, Wallenstein, Mendelsohn, Bourret, Singh, and Moynagh are employees and shareholders of Pfizer. Editorial support was funded by Pfizer and was provided by Claxton, Jenks, and Taylor, who are employees of York Health Economics Consortium. Study concept and design were contributed primarily by Taylor, Jenks, Gerber, and Singh, along with the other authors. Gerber, Moynagh, and Singh collected the data, assisted by Bouret and Mendelsohn; data interpretation was performed by Claxton, Gerber, Bouret, and Mendelsohn. The manuscript was written primarily by Claxton, with assistance from the other authors, and revised by Claxton, Gerber, Bouret, and Mendelsohn, with assistance from the other authors.

Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases.

PubMed

Bulaj, Grzegorz; Ahern, Margaret M; Kuhn, Alexis; Judkins, Zachary S; Bowen, Randy C; Chen, Yizhe

2016-01-01

Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies.

Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers.

PubMed

Lipshultz, Steven E; Williams, Paige L; Zeldow, Bret; Wilkinson, James D; Rich, Kenneth C; van Dyke, Russell B; Seage, George R; Dooley, Laurie B; Kaltman, Jonathan R; Siberry, George K; Mofenson, Lynne M; Shearer, William T; Colan, Steven D

2015-01-02

We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.

Upregulation of mucin4 in ER-positive/HER2-overexpressing breast cancer xenografts with acquired resistance to endocrine and HER2-targeted therapies.

PubMed

Chen, Albert C; Migliaccio, Ilenia; Rimawi, Mothaffar; Lopez-Tarruella, Sara; Creighton, Chad J; Massarweh, Suleiman; Huang, Catherine; Wang, Yen-Chao; Batra, Surinder K; Gutierrez, M Carolina; Osborne, C Kent; Schiff, Rachel

2012-07-01

We studied resistance to endocrine and HER2-targeted therapies using a xenograft model of estrogen receptor positive (ER)/HER2-overexpressing breast cancer. Here, we report a novel phenotype of drug resistance in this model. MCF7/HER2-18 xenografts were treated with endocrine therapy alone or in combination with lapatinib and trastuzumab (LT) to inhibit HER2. Archival tumor tissues were stained with hematoxylin and eosin and with mucicarmine. RNA extracted from tumors at early time points and late after acquired resistance were analyzed for mucin4 (MUC4) expression by microarray and quantitative reverse transcriptase-PCR. Protein expression of the MUC4, ER, and HER2 signaling pathways was measured by immunohistochemistry and western blotting. The combination of the potent anti-HER2 regimen LT with either tamoxifen (Tam + LT) or estrogen deprivation (ED + LT) can cause complete eradication of ER-positive/HER2-overexpressing tumors in mice. Tumors developing resistance to this combination, as well as those acquiring resistance to endocrine therapy alone, exhibited a distinct histological and molecular phenotype-a striking increase in mucin-filled vacuoles and upregulation of several mucins including MUC4. At the onset of resistance, MUC4 mRNA and protein were increased. These tumors also showed upregulation and reactivation of HER2 signaling, while losing ER protein and the estrogen-regulated gene progesterone receptor. Mucins are upregulated in a preclinical model of ER-positive/HER2-overexpressing breast cancer as resistance develops to the combination of endocrine and anti-HER2 therapy. These mucin-rich tumors reactivate the HER2 pathway and shift their molecular phenotype to become more ER-negative/HER2-positive.

Upregulation of Mucin4 in ER-positive/HER2-Overexpressing Breast Cancer Xenografts with Acquired Resistance to Endocrine and HER2-Targeted Therapies

PubMed Central

Chen, Albert C.; Migliaccio, Ilenia; Rimawi, Mothaffar; Lopez-Tarruella, Sara; Creighton, Chad J.; Massarweh, Suleiman; Huang, Catherine; Wang, Yen-Chao; Batra, Surinder K.; Gutierrez, M. Carolina; Osborne, C. Kent; Schiff, Rachel

2012-01-01

Background We studied resistance to endocrine and HER2-targeted therapies using a xenograft model of estrogen receptor positive (ER)/HER2-overexpressing breast cancer. Here, we report a novel phenotype of drug resistance in this model. Methods MCF7/HER2-18 xenografts were treated with endocrine therapy alone or in combination with lapatinib and trastuzumab (LT) to inhibit HER2. Archival tumor tissues were stained with hematoxylin & eosin and mucicarmine. RNA extracted from tumors at early time points and late after acquired resistance were analyzed for mucin4 (MUC4) expression by microarray and quantitative reverse transcriptase-PCR. Protein expression of the MUC4, ER and HER2 signaling pathways was measured by immunohistochemistry and Western blotting. Results The combination of the potent anti-HER2 regimen LT with either tamoxifen (Tam+LT) or estrogen deprivation (ED+LT) can cause complete eradication of ER-positive/HER2-overexpressing tumors in mice. Tumors developing resistance to this combination, as well as those acquiring resistance to endocrine therapy alone, exhibited a distinct histological and molecular phenotype—a striking increase in mucin-filled vacuoles and upregulation of several mucins including MUC4. At the onset of resistance, MUC4 mRNA and protein were increased. These tumors also showed upregulation and reactivation of HER2 signaling, while losing ER protein and the estrogen-regulated gene, progesterone receptor. Conclusions Mucins are upregulated in a preclinical model of ER-positive/HER2-overexpressing breast cancer as resistance develops to the combination of endocrine and anti-HER2 therapy. These mucin-rich tumors reactivate the HER2 pathway and shift their molecular phenotype to become more ER-negative/HER2-positive. PMID:22644656

Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.

PubMed

Haffmans, P M; Sival, R C; Lucius, S A; Cats, Q; van Gelder, L

2001-01-01

The purpose of this study was to evaluate the effects of bright light therapy combined with melatonin on motor restless behaviour in dementia. Double-blind, placebo-controlled, cross-over trial consisting of four periods. One week wash-out was followed by a 2-week period of light therapy in combination with placebo or melatonin. The second wash-out period of 1 week was followed by 2 weeks of treatment (cross-over). Twenty-four bed medium-stay psychogeriatric ward at a Dutch psychiatric teaching hospital. Ten patients, who met the criteria for dementia (DSM-IV) and motor restless behaviour (subscale 10 of the GIP), were included. Informed consent was obtained by proxy. All subjects were exposed during 2x5 consecutive days for 30 minutes to 10,000 lux bright light and randomly administered 2.5 mg melatonin or placebo at 22.00 h. Clinical Global Impression (CGI), Dutch version of the geriatric behavioural observation scale (GIP), Social Dysfunction and Aggression Scale (SDAS) were assessed after each wash-out and treatment period. Outcome criteria were CGI, assessing motor restless behaviour, the SDAS, measuring extrovert aggression and the GIP, assessing social, psychomotor and emotional behaviour. Six demented inpatients completed the trial. Positive effects were found for the treatment combined with placebo. Patients were less restless and more co-operative. The condition with melatonin showed no additional positive effects, additionally, patients became more aggressive and showed the same or more disturbed behaviour. Bright light therapy has a positive effect on motor restless behaviour. Light therapy in combination with melatonin has no positive effects. The results might be explained by a possible overshoot of chronobiological synchronisation or the timing of the melatonin intake. Copyright 2001 John Wiley & Sons, Ltd.

The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.

PubMed

Trauner, Andrej; Liu, Qingyun; Via, Laura E; Liu, Xin; Ruan, Xianglin; Liang, Lili; Shi, Huimin; Chen, Ying; Wang, Ziling; Liang, Ruixia; Zhang, Wei; Wei, Wang; Gao, Jingcai; Sun, Gang; Brites, Daniela; England, Kathleen; Zhang, Guolong; Gagneux, Sebastien; Barry, Clifton E; Gao, Qian

2017-04-19

Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics. By combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance. Our findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.

Genetics and molecular pathology of gastric malignancy: Development of targeted therapies in the era of personalized medicine

PubMed Central

Van Ness, Michael; Gregg, Jeffrey; Wang, Jun

2012-01-01

Gastric malignancy constitutes a major cause of cancer deaths worldwide. Despite recent advances in surgical techniques combined with neoadjuvant chemotherapy and radiotherapy approaches, patients with advanced disease still have poor outcomes. An emerging understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis, invasion and metastasis has provided novel targets in gastric cancer therapy. In this review, recent advances in the understanding of molecular tumorigenesis for common gastric malignancies are discussed. We also briefly review the current targeted therapies in the treatment of gastric malignancies. Practical insights are highlighted including HER2 testing and target therapy in gastric adenocarcinoma, morphologic features and molecular signatures of imatinib-resistance GISTs, and recent investigations aimed at tumor-specific therapy for neuroendocrine tumors. PMID:22943015

Effectiveness of topical silicone gel and pressure garment therapy for burn scar prevention and management in children: study protocol for a randomised controlled trial.

PubMed

Wiseman, Jodie; Simons, Megan; Kimble, Roy; Ware, Robert; McPhail, Steven; Tyack, Zephanie

2017-02-16

Abnormal scar development following burn injury can cause substantial physical and psychological distress to children and their families. Common burn scar prevention and management techniques include silicone therapy, pressure garment therapy, or a combination of both. Currently, no definitive, high-quality evidence is available for the effectiveness of topical silicone gel or pressure garment therapy for the prevention and management of burn scars in the paediatric population. Thus, this study aims to determine the effectiveness of these treatments in children. A randomised controlled trial will be conducted at a large tertiary metropolitan children's hospital in Australia. Participants will be randomised to one of three groups: Strataderm® topical silicone gel only, pressure garment therapy only, or combined Strataderm® topical silicone gel and pressure garment therapy. Participants will include 135 children (45 per group) up to 16 years of age who are referred for scar management for a new burn. Children up to 18 years of age will also be recruited following surgery for burn scar reconstruction. Primary outcomes are scar itch intensity and scar thickness. Secondary outcomes include scar characteristics (e.g. colour, pigmentation, pliability, pain), the patient's, caregiver's and therapist's overall opinion of the scar, health service costs, adherence, health-related quality of life, treatment satisfaction and adverse effects. Measures will be completed on up to two sites per person at baseline and 1 week post scar management commencement, 3 months and 6 months post burn, or post burn scar reconstruction. Data will be analysed using descriptive statistics and univariate and multivariate regression analyses. Results of this study will determine the effectiveness of three noninvasive scar interventions in children at risk of, and with, scarring post burn or post reconstruction. Australian New Zealand Clinical Trials Registry, ACTRN12616001100482 . Registered on 5 August 2016.

Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models.

PubMed

Xu, Chunxiao; Zhang, Yanping; Rolfe, P Alexander; Hernández, Vivian M; Guzman, Wilson; Kradjian, Giorgio; Marelli, Bo; Qin, Guozhong; Qi, Jin; Wang, Hong; Yu, Huakui; Tighe, Robert; Lo, Kin-Ming; English, Jessie M; Radvanyi, Laszlo; Lan, Yan

2017-10-01

Purpose: To determine whether combination therapy with NHS-muIL12 and the anti-programmed death ligand 1 (PD-L1) antibody avelumab can enhance antitumor efficacy in preclinical models relative to monotherapies. Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt - mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice. Immune cell populations within spleen and tumors were evaluated by FACS and IHC. Immune gene expression in tumor tissue was profiled by NanoString® assay and plasma cytokine levels were determined by multiplex cytokine assay. The frequency of tumor antigen-reactive IFNγ-producing CD8 + T cells was evaluated by ELISpot assay. Results: NHS-muIL12 and avelumab combination therapy enhanced antitumor efficacy relative to either monotherapy in both tumor models. Most EMT-6 tumor-bearing mice treated with combination therapy had complete tumor regression. Combination therapy also induced the generation of tumor-specific immune memory, as demonstrated by protection against tumor rechallenge and induction of effector and memory T cells. Combination therapy enhanced cytotoxic NK and CD8 + T-cell proliferation and T-bet expression, whereas NHS-muIL12 monotherapy induced CD8 + T-cell infiltration into the tumor. Combination therapy also enhanced plasma cytokine levels and stimulated expression of a greater number of innate and adaptive immune genes compared with either monotherapy. Conclusions: These data indicate that combination therapy with NHS-muIL12 and avelumab increased antitumor efficacy in preclinical models, and suggest that combining NHS-IL12 and avelumab may be a promising approach to treating patients with solid tumors. Clin Cancer Res; 23(19); 5869-80. ©2017 AACR . ©2017 American Association for Cancer Research.

The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome.

PubMed

Minozzi, Massimo; Costantino, Demetrio; Guaraldi, Claudia; Unfer, Vittorio

2011-11-01

Compare the effects of a combined contraceptive pill (OCP) in combination with myo-inositol (MI) on endocrine, metabolic, and clinical parameters in patients with polycystic ovary syndrome (PCOS). One hundred fifty-five patients with PCOS were enrolled in this prospective, open-label clinical study. Patients were assigned to receive oral treatment with OCP alone (estradiol (EE) 30 μg/gestodene 75 μg) or in combination with myo-inositol 4 g/die, for 12 months. OCP plus MI therapy resulted in a higher reduction of FG score compared with OCP alone therapy. The combined therapy (OCP plus MI) significantly decreased hyperinsulinaemia, by positively affecting the fasting insulin and glucose levels and homeostasis model assessment-insulin resistance parameters, while no significant changes were observed in the OCP group. Androgens serum levels decreased in both groups, but significantly more in the combined therapy group. The lipid profile was improved in the combined therapy group, by reducing low-density lipoprotein cholesterol levels and enhancing high-density lipoprotein cholesterol levels. Our data show that a combination of combined contraceptive pill and MI may be more effective in controlling endocrine, metabolic, and clinical profile in patients with PCOS than OCP alone, and may reduce insulin levels and insulin resistance. Hence, combined treatment may become a more effective long-term therapeutic choice for controlling PCOS symptoms.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.