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Sample records for long-term chloroquine therapy

  1. Delayed Onset Chloroquine Retinopathy Presenting 10 Years after Long-Term Usage of Chloroquine

    PubMed Central

    Kazi, Mohmmad Salman; Saurabh, Kumar; Rishi, Pukhraj; Rishi, Ekta

    2013-01-01

    Chloroquine retinopathy is a known complication of long-term use of chloroquine. This retinopathy can appear even after usage of chloroquine has stopped. The present case report describes the history and clinical features of chloroquine retinopathy developing a decade after discontinuing the drug. PMID:23580861

  2. Ocular Complications of Chloroquine Therapy

    PubMed Central

    Tamler, Edward

    1965-01-01

    Long-term therapy with chloroquine can lead to irreversible retinal damage and serious loss of visual acuity and visual field. Not only are the retinal changes irreversible but they may continue to progress after discontinuance of the drug. Work is proceeding on the development of electrophysiological techniques for early detection of toxic effect before significant retinal damage occurs. Another possibility for minimizing the toxic effect of chloroquine is the use of other drugs which increase the excretion of chloroquine from the body. ImagesFigure 1. PMID:14336789

  3. Ocular Complications of Chloroquine Therapy

    PubMed Central

    Lloyd, Lois A.; Hiltz, John W.

    1965-01-01

    Ocular complications of long-term chloroquine therapy were observed in 18 of 45 patients so treated. This therapy was used in patients with rheumatoid arthritis, lupus erythematosus, sarcoidosis, discoid lupus and other chronic “collagen disease”. Thirteen patients had reversible corneal opacifications, and seven had irreversible retinal changes, with visual loss and visual field defects. Pathological evidence of chloroquine retinopathy was obtained in one patient. Physicians are therefore warned to use this drug only after careful consideration. If it is used, repeated ocular examinations should include assessment of visual acuity, visual fields on a tangent screen and fundus examination through a dilated pupil. ImagesFig. 4Fig. 7Fig. 8 PMID:14275038

  4. Long-term safety of retinoid therapy.

    PubMed

    Vahlquist, A

    1992-12-01

    The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy. PMID:1460122

  5. Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice.

    PubMed

    Ramadan, Azza; Wheatcroft, Mark D; Quan, Adrian; Singh, Krishna K; Lovren, Fina; Dhingra, Natasha; Teoh, Hwee; Al-Omran, Mohammed; Leong-Poi, Howard; Verma, Subodh

    2015-08-01

    Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE(-/-) mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation. PMID:26099030

  6. Are Long-Term Chloroquine or Hydroxychloroquine Users Being Checked Regularly for Toxic Maculopathy?

    PubMed Central

    Nika, Melisa; Blachley, Taylor S.; Edwards, Paul; Lee, Paul P.; Stein, Joshua D.

    2014-01-01

    Importance According to evidence-based, expert recommendations, long-term users of chloroquine (CQ) or hydroxychloroquine (HCQ) should undergo regular visits to eye-care providers and diagnostic testing to check for maculopathy. Objective To determine whether patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) taking CQ or HCQ are regularly visiting eye-care providers and being screened for maculopathy. Setting, Design and Participants Patients with RA or SLE who were continuously enrolled in a particular managed-care network for ≥5 years during 2001-2011 were studied. Patients' amount of CQ/HCQ use in the 5 years since initial RA/SLE diagnosis was calculated, along with their number of eye-care visits and diagnostic tests for maculopathy. Those at high risk for maculopathy were identified. Visits to eye providers and diagnostic testing for maculopathy were assessed for each enrollee over the study period. Logistic regression was performed to assess potential factors associated with regular eye-care-provider visits (≥3 in 5 years) among CQ/HCQ users, including those at greatest risk for maculopathy. Main Outcome Measures Among CQ/HCQ users and those at high risk for toxic maculopathy, the proportions with regular eye-care visits and diagnostic testing, and the likelihood of regular eye-care visits (odds ratios [ORs] with 95% confidence intervals [CI]). Results Among 18,051 beneficiaries with RA or SLE, 6,339 (35.1%) had ≥1 record of HCQ/CQ use and 1,409 (7.8%) used HCQ/CQ for ≥4 years. Among those at high risk for maculopathy, 27.9% lacked regular eye-provider visits, 6.1% had no visits to eye providers, and 34.5% had no diagnostic testing for maculopathy during the 5-year period. Among high-risk patients, each additional month of HCQ/CQ use was associated with a 2.0%-increased likelihood of regular eye care (adjusted OR=1.02, CI=1.01-1.03). High-risk patients whose SLE/RA were managed by rheumatologists had a 77%-increased

  7. Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

    PubMed Central

    Ehmann, Laura Maximiliane

    2012-01-01

    Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized. PMID:22879707

  8. The use of long-term acid-suppression therapy.

    PubMed

    Rubin, G P; Contractor, B; Bramble, M G

    1995-01-01

    Drug therapy to suppress gastric acid secretion is commonly used in the management of dyspepsia, many patients taking such therapy over long periods of time. An audit of patients on long-term (> 12 months) acid-suppression therapy was carried out in the two practices providing primary healthcare to a town in Northeast England. Patients on continuous therapy (> 10 months' supply in the previous year) and intermittent therapy (6-10 months' supply in the previous year) were identified through computerised prescribing records. Their written and computer records were scrutinised to determine diagnosis, duration of therapy, use of NSAIDs and other features. A total of 365 patients were identified (208 men, 157 women): 132 were on intermittent and 233 on continuous therapy. Of the total, 83% were over 45 years and one-fifth were taking NSAIDs. Of the 310 patients investigated for their dyspepsia, only 250 had a positive diagnosis, of which duodenal ulcer (154) was the most common. PMID:7779658

  9. Long-term oxygen therapy--state of the art.

    PubMed

    Flenley, D C

    1983-07-01

    Long-term oxygen therapy prolongs life in adults with chronic hypoxia caused by chronic bronchitis and emphysema who have cor pulmonale, pulmonary hypertension, and secondary polycythemia ('blue bloaters'). Good results require oxygen therapy for more than 15 hours and preferably 20-24 hours per day. The oxygen concentrator, delivering 1 to 3 l/min of oxygen by nasal prongs, is probably the most cost-effective method of providing this therapy. Dangers of the therapy include fires and burning of patients who smoke, and this is a contraindication to treatment. Excessive CO2 retention during sleep should not result from controlled low-dose oxygen therapy unless the patient also has an obstructive sleep apnea syndrome. Oxygen therapy during sleep may prevent hypoxemic episodes in blue bloaters, and it may thus reverse their pulmonary hypertension, which probably potentiates the risk of right-heart failure and cor pulmonale. PMID:10315396

  10. Long-term management of gout: nonpharmacologic and pharmacologic therapies.

    PubMed

    Chaichian, Yashaar; Chohan, Saima; Becker, Michael A

    2014-05-01

    Gout is a common disorder with clinical signs and symptoms resulting from inflammatory responses to monosodium urate crystals deposited in tissues from extracellular fluids saturated for urate. Long-term management of gout focuses on nonpharmacologic and pharmacologic means to achieve and maintain serum urate levels in a subsaturating range. Despite a firm understanding of gout pathophysiology, means to achieve certain diagnosis, and a variety of effective therapies, treatment outcomes remain suboptimal. In this review, available nonpharmacologic and pharmacologic therapies for chronic gout are discussed and a framework is provided for successful achievement and maintenance of goal-range serum urate levels. PMID:24703352

  11. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    PubMed

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. PMID:26450442

  12. Long-term maintenance therapy with calcineurin inhibitors: an update.

    PubMed

    Campistol, J M

    2010-11-01

    Combination therapy with mammalian target of rapamycin (mTOR)-inhibitors and calcineurin inhibitors (CNIs) provides significant immunosuppressive efficacy. If the combination of these agents is not properly optimized, however, important risks for synergistic toxicity and long-term complications may result. The combination of a CNI and an mTOR-inhibitor is a potent immunosuppressive therapy that effectively prevents the incidence of acute rejection, although the potential nephrotoxic impact must be considered in the longer term. The trend has therefore been to use a low-dose CNI in combination with the mTOR-inhibitor sirolimus in order to reduce the risk of nephrotoxicity. Recent studies show that an mTOR-inhibitor/low-dose CNI combination is effective in the short term following transplantation, and over time, consideration should be given to the elimination of the CNI in order to preserve renal function. In the medium to long term, it is also possible to consider the elimination of steroids from such a protocol. Considering CNI dose minimization or elimination is an essential component of this approach, as is the optimal dose and level of both drugs when used in combination. PMID:21095445

  13. Malignant external otitis: long-term (months) antimicrobial therapy

    SciTech Connect

    Strauss, M.; Aber, R.C.; Conner, G.H.; Baum, S.

    1982-04-01

    Since Chandler's initial report in 1968 on malignant external otitis (MEO), this entity has been recognized in its earlier stages with increasing frequency. As a result of this, the availability of new antimicrobial agents, and the judicious use of surgery, there has been an improvement in the results of therapy. There remains, however, a subgroup of patients who continue to experience a significant mortality from this infection. A review and selected discussion of our experience with MEO from 1976 to 1979 is presented. Six patients have been diagnosed and successfully treated for MEO. They presented with problems ranging from severe otalgia to multiple cranial neuropathy. For the most part, therapy consisted of the now standard aminoglycoside and carbenicillin combination. Two of the patients were in the high mortality risk group. One of these patients developed an osteomyelitis which extended across the skull base resulting in bilateral cranial neuropathies. His therapy included surgery as well as long-term (months) outpatient treatment with tobramycin and carbenicillin with an excellent result. The second patient was treated similarly. The efficacy of this approach is discussed as well as the usefulness of radionuclide bone scanning in assessing the course and therapy of patients with MEO.

  14. Chloroquine and hydroxychloroquine for cancer therapy

    PubMed Central

    Manic, Gwenola; Obrist, Florine; Kroemer, Guido; Vitale, Ilio; Galluzzi, Lorenzo

    2014-01-01

    Macroautophagy (herein referred to as autophagy) is a highly conserved mechanism for the lysosomal degradation of cytoplasmic components. Autophagy is critical for the maintenance of intracellular homeostasis, both in baseline conditions and in the context of adaptive responses to stress. In line with this notion, defects in the autophagic machinery have been etiologically associated with various human disorders including infectious, inflammatory and neoplastic conditions. Once tumors are established, however, autophagy sustains the survival of malignant cells, hence representing an appealing target for the design of novel anticancer regimens. Accordingly, inhibitors of autophagy including chloroquine and hydroxychloroquine have been shown to mediate substantial antineoplastic effects in preclinical models, especially when combined with chemo- or radiotherapeutic interventions. The pharmacological profile of chloroquine and hydroxychloroquine, however, appear to involve mechanisms other than autophagy inhibition. Here, we discuss the dual role of autophagy in oncogenesis and tumor progression, and summarize the results or design of clinical studies recently completed or initiated to evaluate the therapeutic activity of chloroquine derivatives in cancer patients. PMID:27308318

  15. Keratopathy with low dose chloroquine therapy.

    PubMed

    Cullen, A P; Chou, B R

    1986-05-01

    Antimalarial drugs (4-aminoguinolines) are often used as non-steroidal anti-inflammatories and remission inducers in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this paper we report on ocular signs of aminoquinolinic toxicity among 39 patients, 31 with RA and 8 with SLE. These patients received either chloroquine 250 mg q.h.s. or hydroxychloroquine 200 mg b.i.d. No maculopathy was detected, however 75% of the patients showed various degrees of keratopathy ranging from epithelial haze to dense "whorl" deposits. No correlation was found between severity of the keratopathy and the estimated total amount of aminoquinoline administered. PMID:3711574

  16. Long term differential consequences of miglustat therapy on intestinal disaccharidases.

    PubMed

    Amiri, Mahdi; Naim, Hassan Y

    2014-11-01

    Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50 μM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect. PMID:24863482

  17. A Case Report of Long-Term Bisphosphonate Therapy and Atypical Stress Fracture of Bilateral Femur

    PubMed Central

    Jo, Yil Ryun; Kim, Hye Won; Moon, Seock Ho

    2013-01-01

    Bisphosphonates are potent inhibitors of bone resorption and considered as a gold standard and are generally recommended as first-line therapy in patients with osteoporosis. Though bisphosphonates are shown to significantly reduce the risk of vertebral, non-vertebral and hip fractures, recent reports suggest a possible correlation between long-term bisphosphonate therapy and the occurrence of insufficiency fractures owing to prolonged bone turnover suppression. We report a patient with non-traumatic stress fractures of bilateral femoral shafts related to long-term bisphosphonate therapy indicating the need for a critical evaluation of patients with long-term bisphosphonate therapy. PMID:23869343

  18. Current and long-term technologies of laser therapy

    NASA Astrophysics Data System (ADS)

    Ulashcyk, Vladimir S.; Volotovskaya, Anna V.

    2007-06-01

    Laser therapy, using low-energy laser radiation, is being more and more applied. The most applied technology is transcutaneous radiation of tissues by laser radiation. Originally, a direct action on a pathological site was mostly used, but recently more attention is given to reflexogenic areas, acupuncture points, and endocrine organ projection sites. The development of light-conductive engineering made it possible to practically apply intraorgan laser therapy. This technology is widely spread in gynecology, otorhinolaryngology, urology, gastroenterology, etc. Close to it are different versions of intratissue laser therapy (intraosteal, periosteal, myofascial). A special kind of laser therapy is laser hemotherapy. Depending on the techniques and protocol of its application, there are extracorporeal, intravascular, and supravenous ways of action. According to our comparative investigations, supravenous hemotherapy by its therapeutic efficacy and major medicinal effects can be well compared with intravascular laser hemotherapy. With good prospects and efficiency is laser therapy as a combination of laser and other physical factors. Magnetolaser therapy has been scientifically substantiated and practically applied so far. Theoretically and experimentally substantiated is a combined application of laser radiation and physical factors such as ultrasound, direct current field, vacuum, cryotherapy, etc. Experimental research and few so far clinical observations are indicative of prospects of a complex application of laser radiation and drugs. To improve light absorption, laser radiation is combined with different dyes. Photodynamic therapy, originally used in oncology, is applied today in treating different diseases. We showed a possibility of using a number of drugs possessing simultaneously photosensitizing properties to this end. Laser radiation significantly influences pharmacokinetics and pharmacodynamics of drugs, which gives reason to practically implement laser

  19. Long term responses with cetuximab therapy in glioblastoma multiforme.

    PubMed

    Belda-Iniesta, Cristóbal; Carpeño, Javier de Castro; Saenz, Enrique Casado; Gutiérrez, Manuel; Perona, Rosario; Barón, Manuel González

    2006-08-01

    Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab. PMID:16929166

  20. Drug interactions and long-term antidiabetic therapy

    PubMed Central

    Logie, A. W.; Galloway, D. B.; Petrie, J. C.

    1976-01-01

    1 A study has been carried out on a representative sample (709 patients) of the Aberdeen Diabetic Clinic. The aims were to measure the occurrence and attempt to assess the clinical significance of drug interactions involving antidiabetic agents. 2 In the month before interview, 63% of the patients were taking between one and nine additional prescribed medicines. Fifty-one per cent of the patients had been exposed to one to five drugs with a potential to interact with their anti-diabetic therapy. Only 22% of the patients had taken no drugs other than their anti-diabetic medication. 3 The degree of control of diabetes, based on arbitrary criteria on data from seven consecutive out-patient visits, was significantly worse for sulphonylurea-treated patients exposed to drugs with the potential to interact compared to patients not taking such drugs. In particular, control was adversely affected in older patients taking concurrent barbiturate or diuretic therapy. No such influence of interacting drugs on control was evident in patients on insulin or biguanide therapy. 4 A system designed to prevent the unintentional initiation of drug interactions in patients on hypoglycaemic agents is described. PMID:22216525

  1. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  2. [Long-term toxicity after therapy for testicular cancer with special focus on sexual disorders].

    PubMed

    Oldenburg, J; Fosså, S D

    2009-04-01

    Due to cisplatin-based chemotherapy, the survival rate of testicular cancer patients approaches 90%. Chemo- or radiotherapy may cause long-term complications, e.g. cardiovascular disease, secondary cancers and reduced fertility. Sperm cryopreservation is recommended depending on the extent of therapy and should be performed before orchiectomy. Furthermore, patients should be informed about long-term complications and their possible reduction by optimizing the risk factor profile. PMID:19234684

  3. 75 FR 53976 - Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy Products; Public Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... Therapy Products; Public Workshop; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION... risks and benefits associated with the long- term use of nicotine replacement therapy (NRT)...

  4. Medical and Psychological Risks and Consequences of Long-Term Opioid Therapy in Women

    PubMed Central

    Darnall, Beth D.; Stacey, Brett R.; Chou, Roger

    2016-01-01

    Background Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. Purpose To review the medical and psychological risks and consequences of long-term opioid therapy in women. Method Scientific literature containing relevant keywords and content were reviewed. Results and Conclusions Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted. PMID:22905834

  5. Generalised stunting of roots in an epileptic child: is long-term phenytoin therapy the cause?

    PubMed Central

    Jindal, Garima; Pandey, Ramesh K; Kumar, Dipanshu

    2012-01-01

    Long-term phenytoin therapy is known to cause disturbance in calcium and bone homeostasis. Dental tissues being calcified tissues can also be affected by this derangement of mineral metabolism, especially during developmental phases. This report describes a case of an epileptic child who presented with short roots, enlarged pulp chambers, blunt apices and delayed eruption of permanent dentition, which might be attributed to long-term phenytoin therapy. The purpose of this case report is to increase awareness among the clinicians about its possible dental implications and emphasise upon the need of regular dental check-ups in epileptic children. PMID:22761220

  6. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    ClinicalTrials.gov

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  7. Comparison of Long-Term Outcomes in Adolescents with Anorexia Nervosa Treated with Family Therapy

    ERIC Educational Resources Information Center

    Lock, James; Couturier, Jennifer; Agras, W. Stewart

    2006-01-01

    Objective: To describe the relative effectiveness of a short versus long course of family-based therapy (FBT) for adolescent anorexia nervosa at long-term follow-up. Method: This study used clinical and structured interviews to assess psychological and psychosocial outcomes of adolescents (ages 12-18 years at baseline) who were previously treated…

  8. Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

    ERIC Educational Resources Information Center

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-01-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

  9. Regarding long-term statin therapy: are we trading stronger hearts for weaker brains?

    PubMed

    Goldstein, Mark R; Mascitelli, Luca

    2014-09-01

    Ideally, the benefits of long-term statin therapy should outweigh the risks in all populations. However, some data suggest that long-term statin therapy might promote cerebral small vessel disease and impair myelination, perhaps resulting from cholesterol depletion and pleiotropic effects on amyloid-β metabolism and oligodendrocyte function. The clinical ramifications can be problematic and have a negative impact on the quality of life. Questions are proposed and the answers should be found by analysis of randomized prospective trials specifically investigating the effects of statin therapy on brain structure and function. Those trials should not be funded by drug companies and the investigators should not have financial ties to the pharmaceutical industry. The relevance of the aforementioned is amplified in light of the new cardiovascular guidelines that might culminate in more than a billion people receiving statin therapy worldwide. PMID:24986644

  10. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26-3.23), age >70 years (OR 1.15, 95% CI 1.06-1.24), immobility (OR 2.06, 95% CI 1.93-2.19), renal insufficiency (OR 2.42, 95% CI 2.15-2.71) and anemia (OR 1.75, 95% CI 1.65-1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64-2.06), immobility (OR 1.51, 95% CI 1.30-1.76) and metastases (OR 3.22, 95% CI 2.87-3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

  11. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed Central

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

  12. Predictors of atypical femoral fractures during long term bisphosphonate therapy: A case series & review of literature

    PubMed Central

    Bhadada, Sanjay Kumar; Sridhar, Subbiah; Muthukrishnan, Jeyaram; Mithal, Ambrish; Sharma, Dinesh C.; Bhansali, Anil; Dhiman, Vandana

    2014-01-01

    Background & objectives: Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison's disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases. PMID:25222777

  13. Right atrial indwelling catheter for patients requiring long-term intravenous therapy.

    PubMed

    Ivey, M F; Adam, S M; Hickman, R O; Gibson, D L

    1978-12-01

    The use of a central venous catheter for long-term intravenous therapy is described. The catheter's history, physical description, and uses are discussed. Also reviewed are complications from use of the catheter, the pharmacist's role in patient teaching, and the procedure for administering medications through the catheter. A listing of drugs administered through the catheter, incompatibility data and patient teaching instructions are also included. PMID:717409

  14. Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy

    PubMed Central

    Yu, Xiaobo; Li, Mengwei; Wen, Wen; Sun, Xinghuai

    2016-01-01

    Objective To compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST), in untreated primary open angle glaucoma (POAG) patients, POAG patients with long-term topical prostaglandin analog (PGA) therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics. Methods In this case-control study, 35 consecutive medication naïve eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters, including deformation amplitude (DA), applanation time (AT1 and AT2), applanation length (AL1 and AL2), applanation velocity (AV1 and AV2), and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany). General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed. Results AT1 (p<0.0001), AV1 (p<0.0001), AT2 (p = 0.0001), AV2 (p<0.0001) and DA (p = 0.0004) in newly diagnosed glaucoma patients were significantly different from those in normal subjects and in patients underwent at least 2 years topical PGA therapy after adjusting for age and gender. After adjusting for age, gender, IOP, CCT, axial length and corneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387). Furthermore, there were no statistical significant differences in all of the corneal

  15. Stereotactic Radiation Therapy for Benign Meningioma: Long-Term Outcome in 318 Patients

    SciTech Connect

    Fokas, Emmanouil; Henzel, Martin; Surber, Gunar; Hamm, Klaus; Engenhart-Cabillic, Rita

    2014-07-01

    Purpose: To investigate the long-term outcome of stereotactic-based radiation therapy in a large cohort of patients with benign intracranial meningiomas. Methods and Materials: Between 1997 and 2010, 318 patients with histologically confirmed (44.7%; previous surgery) or imaging-defined (55.3%) benign meningiomas were treated with either fractionated stereotactic radiation therapy (79.6%), hypofractionated stereotactic radiation therapy (15.4%), or stereotactic radiosurgery (5.0%), depending on tumor size and location. Local control (LC), overall survival (OS), cause-specific survival (CSS), prognostic factors, and toxicity were analyzed. Results: The median follow-up was 50 months (range, 12-167 months). Local control, OS, and CSS at 5 years were 92.9%, 88.7%, and 97.2%, and at 10 years they were 87.5%, 74.1%, and 97.2%, respectively. In the multivariate analysis, tumor location (P=.029) and age >66 years (P=.031) were predictors of LC and OS, respectively. Worsening of pre-existing neurologic symptoms immediately after radiation therapy occurred in up to 2%. Clinically significant acute toxicity (grade 3°) occurred in 3%. Only grade 1-2 late toxicity was observed in 12%, whereas no new neurologic deficits or treatment-related mortality were encountered. Conclusions: Patients with benign meningiomas predominantly treated with standard fractionated stereotactic radiation therapy with narrow margins enjoy excellent LC and CSS, with minimal long-term morbidity.

  16. Specific Therapy Regimes Could Lead to Long-Term Immunological Control of HIV

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik; Nowak, Martin A.

    1999-12-01

    We use mathematical models to study the relationship between HIV and the immune system during the natural course of infection and in the context of different antiviral treatment regimes. The models suggest that an efficient cytotoxic T lymphocyte (CTL) memory response is required to control the virus. We define CTL memory as long-term persistence of CTL precursors in the absence of antigen. Infection and depletion of CD4+ T helper cells interfere with CTL memory generation, resulting in persistent viral replication and disease progression. We find that antiviral drug therapy during primary infection can enable the development of CTL memory. In chronically infected patients, specific treatment schedules, either including deliberate drug holidays or antigenic boosts of the immune system, can lead to a re-establishment of CTL memory. Whether such treatment regimes would lead to long-term immunologic control deserves investigation under carefully controlled conditions.

  17. [Long-term oxygen therapy in chronic respiratory insufficiency. Usefulness, indications, modes of administration].

    PubMed

    Weitzenblum, E

    1992-03-01

    Long-term oxygen therapy improves the life expectancy of hypoxaemic patients with chronic obstructive pulmonary disease (COPD), provided the hypoxaemia is sufficiently pronounced under stable conditions (PaO2 less than 55 mmHg) and oxygen is given for more than 16 out of 24 hours. By extension, the same indications are applicable to hypoxaemia due to other causes (diffuse fibrosis, pneumoconiosis, cystic fibrosis, etc.). Long-term oxygen therapy improves the patients' quality of life and also has favourable effects on oxygen transport, neuropsychological status, polycythaemia and pulmonary hypertension. It is usually delivered by means of O2 extractors, to which may be added small flasks of O2 gas for walking and moving about. Liquid O2 is a good solution for subjects who are motivated and are obliged to do a great deal of walking. The O2 flow rate administered must be such that it rises the PaO2 level above 60 mmHg. Oxygen therapy is only a symptomatic treatment and cannot replace other types of therapy, such as bronchodilators, physiotherapy, etc. It gives satisfactory results but it has not transformed the prognosis of severe hypoxaemic COPD. PMID:1533036

  18. Long-term effects of music therapy on elderly with moderate/severe dementia.

    PubMed

    Takahashi, Takiko; Matsushita, Hiroko

    2006-01-01

    Over a period of 2 years we assessed the long-term effects of group music therapy carried out once weekly on the elderly (mean age: 83 years) suffering from moderate or severe dementia by observing changes in the cortisol level in saliva and in blood pressure and by an intelligence assessment. Systolic blood pressure determined 1 and 2 years after the start of therapy increased significantly in the nonmusic therapy group compared with that in music therapy group (p < .05). Systolic blood pressure increases with aging; the systolic blood pressure was significantly lower in participants who received music therapy. No significant differences in cortisol level in saliva or intelligence assessment score were observed, but the music therapy group maintained their physical and mental states during the 2-year period better than the nonmusic therapy group. This result indicates the lasting effect of once-a-week continuous music therapy. Even the elderly with moderate or severe dementia were able to participate in the group music therapy, and results suggest that enjoying singing and playing musical instruments in a concert was effective in preventing cardiac and cerebral diseases. PMID:17348758

  19. A novel conceptual framework for understanding the mechanism of adherence to long term therapies

    PubMed Central

    Reach, Gérard

    2008-01-01

    The World Health Organization claimed recently that improving patient adherence to long term therapies would be more beneficial than any biomedical progress. First, however, we must understand its mechanisms. In this paper I propose a novel approach using concepts elaborated in a field rarely explored in medicine, the philosophy of mind. While conventional psychological models (eg, the Health Belief Model) provide explanations and predictions which have only a statistical value, the philosophical assumption that mental states (eg, beliefs) are causally efficient (mental causation) can provide the basis for a causal theory of health behaviors. This paper shows that nonadherence to long term therapies can be described as the medical expression of a philosophical concept, that is, weakness of will. I use philosophical explanations of this concept to suggest a mechanistic explanation of nonadherence. I propose that it results from the failure of two principles of rationality. First, a principle of continence, described by the philosopher Donald Davidson in his explanation of weakness of will. This principle exhorts us to act after having considered all available arguments and according to which option we consider best. However, patients conforming to this principle of continence should rationally be nonadherent. Indeed, when patients face a choice between adherence and nonadherence, they must decide, in general, between a large, but delayed reward (eg, health) and a small, but immediate reward (eg, smoking a cigarette). According to concepts elaborated by George Ainslie and Jon Elster, the force of our desires is strongly influenced by the proximity of reward. This inter-temporal choice theory on one hand, and the mere principle of continence on the other, should therefore lead to nonadherence. Nevertheless, adherence to long term therapies is possible, as a result of the intervention of an additional principle, the principle of foresight, which tells us to give

  20. A Chronic Respiratory Pasteurella multocida Infection Is Well-Controlled by Long-Term Macrolide Therapy.

    PubMed

    Seki, Masafumi; Sakata, Tomomi; Toyokawa, Masahiro; Nishi, Isao; Tomono, Kazunori

    2016-01-01

    A 57-year-old woman with severe bronchiectasis frequently received antibiotics, including penicillin, for acute exacerbations due to Pasteurella multocida. Although the bacteria showed a decrease in antibiotic susceptibility, her symptoms and X-ray findings became stable, and severe exacerbations were not observed for the last few years after a low-dose erythromycin treatment was started. The development of a respiratory infection with Pasteurella multocida is relatively uncommon, but it can be controlled by immunomodulation which is associated with long-term macrolide therapy. PMID:26831030

  1. The long-term effects of radiation therapy on patients with ovarian dysgerminoma

    SciTech Connect

    Mitchell, M.F.; Gershenson, D.M.; Soeters, R.P.; Eifel, P.J.; Delclos, L.; Wharton, J.T. )

    1991-02-15

    A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.

  2. Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54.

    PubMed

    Parker, William A E; Storey, Robert F

    2016-05-15

    Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndromes (ACS), typically comprising the use of aspirin with either an irreversible thienopyridine P2Y12 inhibitor, clopidogrel or prasugrel, or reversibly binding ticagrelor. Pivotal studies led to guidelines recommending DAPT for up to 12 months post-ACS. Despite this, there remains a significant burden of coronary artery disease (CAD)-related events up to and after this period. Recent meta-analyses, including both patients with ACS and patients with stable CAD treated with DAPT following percutaneous coronary intervention, have suggested that long-term thienopyridine-based DAPT reduces the risks of myocardial infarction (MI) and stent thrombosis but may paradoxically increase all-cause mortality risk. The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) study examined the effects of long-term DAPT with aspirin and ticagrelor, compared with aspirin alone, on major adverse cardiovascular events (MACE) and complications, including bleeding in patients with prior history of MI. It showed that, over a 3-year period, ticagrelor reduced the risk of MACE but increased non-fatal bleeding risk. Overall, the PEGASUS-TIMI 54 results demonstrate that patients with a history of ACS deemed to be at high risk of further ischaemic events, particularly those in whom the risks of ischaemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based DAPT. Guidelines are emerging which reflect this. The relationship between aspirin and ticagrelor, particularly with regard to aspirin dosing, remains to be fully elucidated and attention has recently been turned to the option of ticagrelor monotherapy. Future studies will explore optimal individualised strategies for long-term

  3. Inosine monophosphate dehydrogenase variability in renal transplant patients on long-term mycophenolate mofetil therapy

    PubMed Central

    Chiarelli, Laurent R; Molinaro, Mariadelfina; Libetta, Carmelo; Tinelli, Carmine; Cosmai, Laura; Valentini, Giovanna; Canton, Antonio Dal; Regazzi, Mario

    2010-01-01

    AIMS Long-term mycophenolate mofetil (MMF) therapy may induce inosine 5′-monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells (PBMCs), thus decreasing MMF immunosuppressive properties. Pharmacodynamic monitoring was used to investigate whether biological activity is altered after long-term therapy. METHODS IMPDH activity was measured in PBMC samples from 54 stable kidney transplant patients, already on MMF (for at least 3 months), before (t0) and 2 h after (t2) MMF morning dose administration; levels were monitored for up to 15 months, together with total mycophenolic acid (MPA) and free MPA concentrations. RESULTS During the 15 months' monitoring, t0 IMPDH activity in transplant recipients increased from 5.9 ± 3.7 nmol h−1 mg−1[95% confidence interval (CI) 4.9, 6.9] to 9.0 ± 3.9 nmol h−1 mg−1 (95% CI 7.2, 10.8), with an intra- and interpatient variability of 28% and 42%. Five patients experienced acute rejection during the follow-up: t0 IMPDH activity was increased during rejection vs. nonrejection, and the trend was significantly higher in rejecting than in nonrejecting subjects for the whole monitoring period. CONCLUSIONS Even though a correlation has been found between IMPDH activity and rejection, its efficacy as a predictive tool in long-term transplant outcomes may be affected by high interpatient variability; on the other hand, continuous monitoring of the IMPDH trend could make an effective prognostic parameter of rejection. Other trials also including pre-transplant data on both IMPDH expression and activity are warranted to better assess their role as biomarkers for MPA effect in clinical practice. PMID:20078611

  4. Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy.

    PubMed

    Koido, Shigeo; Ohkusa, Toshifumi; Kajiura, Takayuki; Shinozaki, Junko; Suzuki, Manabu; Saito, Keisuke; Takakura, Kazuki; Tsukinaga, Shintaro; Odahara, Shunichi; Yukawa, Toyokazu; Mitobe, Jimi; Kajihara, Mikio; Uchiyama, Kan; Arakawa, Hiroshi; Tajiri, Hisao

    2014-01-01

    Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy. PMID:24489770

  5. Long-Term Follow-Up After Gene Therapy for Canavan Disease

    PubMed Central

    Leone, Paola; Shera, David; McPhee, Scott W.J.; Francis, Jeremy S.; Kolodny, Edwin H.; Bilaniuk, Larissa T.; Wang, Dah-Jyuu; Assadi, Mitra; Goldfarb, Olga; Goldman, H. Warren; Freese, Andrew; Young, Deborah; During, Matthew J.; Samulski, R. Jude; Janson, Christopher G.

    2013-01-01

    Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetylaspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 1011 vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status. PMID:23253610

  6. Percutaneous Therapy of Ureteral Obstructions and Leak After Renal Transplantation: Long-Term Results

    SciTech Connect

    Aytekin, Cueneyt Boyvat, Fatih; Harman, Ali; Ozyer, Umut; Colak, Turan; Haberal, Mehmet

    2007-11-15

    The purpose of this study was to evaluate the long-term outcome of percutaneous therapy of ureteral complications after renal transplantation. Between January 2000 and June 2006 we percutaneously treated 26 renal transplant patients with ureteral obstruction (n=19) and leak (n=7). Obstructions were classified as early (<2 months after transplantation) or late (>2 months). Patients with leak were treated with nephro-ureteral catheter placement and subsequent double-J stenting. Balloon dilatation, stent placement, and basket extraction were used to treat ureteral obstructions. Patients were followed with ultrasonography. No major procedure-related complication occurred. The mean follow-up time was 34.3 months (range: 6 to 74 months). Initial clinical success was achieved in all 19 patients with obstruction and 6 of 7 patients with leak. Four of 9 early obstructions and 4 of 10 late obstructions recurred during the follow-up. All recurrences were initially managed again with percutaneous methods, including cutting balloon technique and metallic stent placement. Although there was no recurrence in patients with successfully treated leak, stricture was seen at the previous leak site in two patients. These strictures were also successfully managed percutaneously. We conclude that in the treatment of ureteral obstruction and leak following renal transplantation, percutaneous therapy is an effective alternative to surgery. However, further interventions are usually needed to maintain long-term patency.

  7. Long-term subcutaneous recombinant interleukin-2 as maintenance therapy: biological effects and clinical implications.

    PubMed

    Guida, M; Abbate, I; Casamassima, A; Musci, M D; Latorre, A; Lorusso, V; Correale, M; De Lena, M

    1995-01-01

    Several trials have evaluated the therapeutic efficacy of rIL-2 combined with more traditional treatments such as chemotherapy and radiotherapy, but the use of IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical response obtained with other standard treatments has yet to be investigated. The aim of the present trial was to study the biological effects of maintenance long-term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with different neoplasms previously treated with chemo-immuno therapeutic regimens or with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility and therapeutic implications are also discussed. The IL-2 schedule was as follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients completed therapy without requiring dose modifications and are free of progression after a median duration of 8+ months (range: 7+ to 34+) while two patients progressed during therapy (one inflammatory breast cancer and one renal cancer). Important and persistent hemato-immunostimulating effects in both soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes, eosinophils) parameters were noted during the entire treatment. The IL-2 related toxicity was quite low. Moreover, this long-term IL-2 therapy could control neoplastic growth and thus prolong clinical response obtained with standard treatments. Prospective randomized studies regarding the clinical efficacy have been initiated. PMID:8547958

  8. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

    PubMed Central

    Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

  9. Value of Inhaled Corticosteroid Therapy In Long-Term Asthma Management

    PubMed Central

    Beam, Donald S.

    2010-01-01

    Asthma, which affects more than 22 million people in the U.S. every year, poses a significant clinical and economic burden to our health care system. Patients, health care practitioners, and payers require a variety of resources to ensure optimal disease management and positive clinical outcomes while also managing costs. In addition, decision makers in health care must determine the most appropriate and cost-efficient therapy or class of agents to achieve asthma control. As such, payers rely on evidence-based medicine, including guidelines to determine the right therapy for the right patient. Inhaled corticosteroid (ICS) therapy plays a critical role in the management of mild-to-moderate persistent asthma. Despite national treatment guidelines that cite ICS therapy as the most effective and safest long-term treatment option for persistent asthma, ICS monotherapy continues to be underused. One retrospective claims study found that 55.2% of children with mild-to-moderate asthma received prescriptions for combination therapy (ICS and long-acting beta-agonists) as initial controller treatment. This practice is contrary to national treatment guidelines, which recommend a step-therapy approach. These prescribing patterns result in higher pharmacy costs, do not always ensure control of symptoms, and sometimes expose patients to potential safety risks. This article addresses the importance of ICS therapy in the treatment of mild-to-moderate asthma, as advocated by the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 guidelines; the role of small airway disease in asthma pathophysiology; and the clinical and economic benefits of ICS therapy. PMID:20689625

  10. Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

    PubMed

    Aizawa, Kazunori; Hanaoka, Takeshi; Kasai, Hiroki; Kogashi, Kaoru; Kumazaki, Setsuo; Koyama, Jun; Tsutsui, Hiroshi; Yazaki, Yoshikazu; Watanabe, Noboru; Kinoshita, Osamu; Ikeda, Uichi

    2006-02-01

    The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH. PMID:16755146

  11. Bupivacaine for intercostal nerve blockade in patients on long-term beta-receptor blocking therapy.

    PubMed

    Pontén, J; Biber, B; Henriksson, B A; Jonsteg, C

    1982-01-01

    Possible cardiovascular side effects of a local anaesthetic in patients on long-term beta-receptor blocking therapy were studied in 26 patients given postoperative intercostal nerve blockades (ICB) with 18-28 ml of plain bupivacaine 0.5% (1.30-1.82 mg kg-1). The patients had a history of hypertension and/or ischaemic heart disease and were scheduled for gall bladder surgery. Thirteen patients were randomized to a gradual preoperative withdrawal of the beta-receptor blockers and the other 13 continued the beta-receptor blockade until surgery. Cardiovascular changes were measured noninvasively and 11 patients were also monitored with pulmonary artery catheters. Blood pressure and heart rate (HR) were stable in all patients although those in whom the beta-receptor blockade was withdrawn had the highest HR and most frequent arrhythmias both before and after ICB. The ICB was associated with a decrease in the overall postoperative arrhythmia incidence, but seemed most efficient (P less than 0.02) concerning the ventricular arrhythmias in the beta-receptor-blocked patients (even including idionodal rhythm). The bupivacaine blood levels did not modify other cardiovascular changes except in one beta-receptor-blocked patient with cardiac failure in whom signs of a slight transient cardiodepression were observed. It is concluded that bupivacaine does not negatively affect cardiovascular stability in long-term beta-receptor-blocked patients. In the presence of cardiac failure, however, an additive cardiodepression may be elicited. PMID:6152885

  12. Short-term and long-term effects of osteoporosis therapies.

    PubMed

    Reid, Ian R

    2015-07-01

    Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <-2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies. PMID:25963272

  13. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  14. Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

    PubMed Central

    Chapman, Jason E.; Schoenwald, Sonja K.

    2014-01-01

    The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were found, independently, and in the presence of ethnic similarity, between adherence and reductions in youth Externalizing and Internalizing behavior problems 1-year post-treatment and youth criminal charges 4 years post-treatment. Relations between ethnic similarity and outcomes were found only for reductions in youth Externalizing behavior problems and not when adherence was included in the model. Adherence ratings were higher, however, in ethnically similar caregiver-therapist pairs, and evidence was found that this increased adherence predicted slightly better outcomes for youth. Implications for future research and clinical practice are considered. PMID:24999302

  15. The Efficacy of Short- and Long-Term Therapy in the Treatment of Childhood Sexual Abuse: A Review of the Literature.

    ERIC Educational Resources Information Center

    Aoto-Sullivan, Stacey Y.

    This paper presents a review of the short- and long-term treatments for children who have been sexually abused. Short-term group therapy, long-term group therapy, short-term individual, and long-term individual therapy were each evaluated in terms of efficacy in alleviating symptoms associated with sexual abuse. The paper also evaluates the…

  16. Long-term Efficacy of Intravenous Immunoglobulin Therapy for Moderate to Severe Childhood Atopic Dermatitis

    PubMed Central

    Jee, Sue-Jung; Kim, Joo-Hwa; Baek, Hey-Sung; Lee, Ha-Baik

    2011-01-01

    Purpose The present study investigates the long-term effects of intravenous immunoglobulin (IVIg) therapy for the treatment of moderate to severe childhood atopic dermatitis (AD). Previous research indicates that IVIg can treat severe AD; however, the effectiveness of IVIg has not been confirmed in prospective, blinded clinical trials. Methods Forty eligible children with moderate to severe AD, as defined by the criteria of Hanifin and Rajka, were enrolled in a randomized, placebo-controlled study. After the completion of an initial screening visit (V0), the patients were randomly allocated into therapy (n=30) and control (n=10) groups (V1). Thirty children were each treated with three injections of 2.0 g/kg IVIg at 1-month intervals over a 12-week period. Ten children were treated with placebo. Assessments were conducted after each injection (V2, V3, and V4) and at 3 (V5) and 6 months (V6) after completed treatment. Results The disease severity index was significantly decreased at V5 compared with the value at V1 (P<0.05). There were no significant changes in the total IgE level or total eosinophil count in peripheral blood at the last injection (V4) compared with the value at V1. The interleukin (IL)-5/interferon (IFN)-γ ratio was assessed in T-helper 1 (Th1) and Th2 cells. The ratio significantly decreased between V1 and V5, after which it increased, such that the ratio at V6 was not significantly different from that at V1. Compared with the level at V1, the intercellular cell adhesion molecule-1 level at V4 did not differ significantly, but the level at V5 was lower. Conclusions This study suggests that IVIg therapy may clinically improve AD in patients after 3 months of therapy, but the improvement may decline by 6 months after therapy. PMID:21461247

  17. Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery

    PubMed Central

    Zhang, Heng; Yuan, Xin; Zhang, Haibo; Chen, Sipeng; Zhao, Yan; Hua, Kun; Rao, Chenfei; Wang, Wei; Sun, Hansong; Hu, Shengshou

    2015-01-01

    Background— Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain. Methods and Results— The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50–2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01–2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10–1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17–2.48) in inconsistent users and 1.23 (95% CI, 0.76–1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43–3.20) and for never users (HR, 1.59; 95% CI, 1.07–2.63). Consistent results were obtained in equivalent sensitivity analyses. Conclusions— In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence. PMID:25908770

  18. Inflammatory activation following interruption of long-term cardiac resynchronization therapy.

    PubMed

    Rubaj, Andrzej; Ruciński, Piotr; Oleszczak, Krzysztof; Trojnar, Michał K; Wójcik, Maciej; Wysokiński, Andrzej; Kutarski, Andrzej

    2013-09-01

    Previous observations suggest that cardiac resynchronization therapy (CRT) may exert an anti-inflammatory effect. The objective of this study was to evaluate the effect of temporary interruption of long-term CRT on plasma concentrations of proinflammatory cytokines and brain natriuretic peptide (BNP). The study group consisted of 54 patients (32 male and 22 female, mean age 64 years) with chronic heart failure (HF) treated with CRT. BNP, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and neopterin were measured three times: after 26-28 weeks of continuous CRT (CRT-on), 48 h after its cessation (CRT-off), and 48 h after switching the CRT-on again. CRT interruption resulted in a significant worsening of left ventricular systolic function: reduction of cardiac output (CO), dP/dt, and left ventricular ejection fraction (LVEF), as well as deterioration of mitral regurgitation in the CRT responder group. A significant increase in serum concentrations of hs-CRP, neopterin, IL-6, and BNP was noted in this subpopulation. In CRT nonresponders, no significant changes were observed. In responders the changes in serum concentrations of hs-CRP, IL-6, neopterin, and BNP, following CRT interruption, significantly correlated with the respective changes in thoracic fluid content (TFC) and inversely correlated with LVEF changes. Even short (48 h) interruption of long-term CRT led to a significant increase of proinflammatory cytokines and BNP concentrations in responders. The changes in hs-CRP, IL-6, neopterin, and BNP concentrations correlated with the change in TFC-marker of pulmonary congestion and inversely correlated with the change in LVEF. PMID:23242167

  19. Long term effects of high intensity laser therapy in lateral epicondylitis patients.

    PubMed

    Akkurt, Ekrem; Kucuksen, Sami; Yılmaz, Halim; Parlak, Selman; Sallı, Ali; Karaca, Gülten

    2016-02-01

    The objective of this study is to investigate short- and long-term effects of high-intensity laser therapy (HILT) in lateral epicondylitis (LE) patients. Thirty patients with LE diagnosis (23 unilateral and 7 bilateral in total 37 elbows) were treated using HILT. LE patients were evaluated before, right after, and 6 months following HILT intervention post-treatment using visual analogue scale for pain (VAS) during activity and resting. Disabilities of the Arm, Shoulder, and Hand (DASH) Score and hand grip strength test (HGST) were used. The participants of the present study were also evaluated using Short-Form 36 (SF-36) before and 6 months after the treatment. Out of the 30 patients, 8 were male and 22 female with a mean age of 47.2 ± 9.7. The activity and resting VAS, DASH, and HGST scores revealed statistically significant improvement (p = 0.001) following treatment. Whereas VAS activity, DASH, and HGST scores increased after treatment until post-treatment 6 months significantly (p = 0.001), VAS resting scores remained stable (p = 0.476). A statistically significant improvement was also evident in the physical and mental components of SF-36 scores following treatment until post-treatment 6 months compared to pre-treatment scores (p = 0.001). In conclusion, the results of the present study suggest that HILT is a reliable, safe, and effective treatment option in LE patients in the short and long term considering pain, functional status, and quality of life. PMID:26714978

  20. The Relationship of Echocardiographic Dyssynchrony to Long-Term Survival Following Cardiac Resynchronization Therapy

    PubMed Central

    Gorcsan, John; Oyenuga, Olusegun; Habib, Phillip J.; Tanaka, Hidekazu; Adelstein, Evan C.; Hara, Hideyuki; McNamara, Dennis M.; Saba, Samir

    2010-01-01

    Background The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear. Methods and Results A prospective, longitudinal study was designed with pre-defined dyssynchrony indices and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long term survival following CRT. We studied 229 consecutive Class III–IV heart failure patients, with ejection fraction (EF) ≤35%, and QRS duration ≥120ms for CRT. Dyssynchrony before CRT was defined as: tissue Doppler velocity opposing wall delay ≥ 65 ms, 12-site standard deviation (Yu Index) ≥32ms; speckle tracking radial strain anteroseptal to posterior wall delay ≥130ms; or pulsed Doppler interventricular mechanical delay (IVMD) ≥ 40 ms. Outcome was defined as freedom from death, heart transplant or left ventricular assist device (LVAD). Of 210 patients (89%) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplants, and 6 LVADs over 4 years. Event-free survival was associated with: Yu Index (p=0.003), speckle tracking radial strain (p=0.003), and IVMD (p=0.019). When adjusted for confounding baseline variables of ischemic etiology and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (p<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration 120–150 ms (p=0.002). Conclusions The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival following CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long term outcome. These observations support the relationship of dyssynchrony to CRT response. PMID:20975000

  1. Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series

    PubMed Central

    Lin, Hsiang-Yu; Chuang, Chih-Kuang; Wang, Chung-Hsing; Chien, Yin-Hsiu; Wang, Yu-Mei; Tsai, Fuu-Jen; Chou, Yen-Yin; Lin, Shio Jean; Pan, Hui-Ping; Niu, Dau-Ming; Hwu, Wuh-Liang; Ke, Yu-Yuan; Lin, Shuan-Pei

    2016-01-01

    Background Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited. Methods Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed. A set of biochemical and clinical assessments were evaluated annually. Results After 6.2 to 11.2 years of galsulfase treatment, 6 patients experienced improvement over baseline in the 6-minute walk test by a mean of 150 m (59% change over time), and 3 patients also increased the 3-minute stair climb test by a mean of 60 steps (46%). In a manual dexterity test, 3 patients decreased the time required to pick up 10 coins and put the coins into a cup by 15 s (33%). Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%). Four patients showed improved pulmonary function. Five patients had positive effects on cardiac-wall diameters. Four patients had improved cardiac diastolic function. Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients. However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT. A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response. Conclusions Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. This treatment reduced urinary GAG and had positive effects on a wide range of clinical functional assessments including endurance, mobility, joint function, pulmonary function, liver and spleen size, cardiac hypertrophy and diastolic dysfunction. PMID:27134829

  2. Sequential Therapy with Minocycline and Candesartan Improves Long Term Recovery after Experimental Stroke

    PubMed Central

    Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y.; Patel, Ami; Pillai, Bindu; Fagan, Susan C.

    2015-01-01

    Background Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. Objective In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. Methods In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-minute middle cerebral artery occlusion (MCAO) were randomized into 4 groups: saline, candesartan, minocycline and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7 and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Results Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome and reduced infarct size. Conclusion Sequential combination therapy with minocycline and candesartan improves long term recovery and maintains candesartan’s proangiogenic potential. PMID:26004281

  3. Long-term effects of electrotactile sensory substitution therapy on balance disorders.

    PubMed

    Yamanaka, Toshiaki; Sawai, Yachiyo; Murai, Takayuki; Nishimura, Tadashi; Kitahara, Tadashi

    2016-07-01

    This clinical research investigated whether a new type of rehabilitation therapy involving the use of a vestibular substitution tongue device (VSTD) is effective for severe balance disorders caused by unilateral vestibular loss. Sixteen patients with postural imbalances because of unilateral vestibular loss underwent training with VSTD. The VSTD transmits information on the head position to the brain through the tongue as substitutes for the lost vestibular information. The device's electrode array was placed on the tongue and participants were trained to maintain a centered body position by ensuring the electrical signals in the center of their tongue. All participants completed 10 min training sessions 2-3 times per day for 8 weeks. Functional gait assessments and the dizziness handicap inventory were, respectively, used to the evaluate participants' dynamic gait function and their severity of balance problems before and after the training period. All examined parameters improved after the 8-week training period. These changes were maintained for up to 2 years after the termination of the training program. Short-term training with VSTD had beneficial carry-over effects. VSTD training might represent a useful rehabilitation therapy in individuals with persistent balance disorders and might lead to long-term improvements in their balance performance and ability to perform daily and social activities. PMID:27213931

  4. Long-Term Follow-Up to a Randomized Clinical Trial of Multisystemic Therapy with Serious and Violent Juvenile Offenders

    ERIC Educational Resources Information Center

    Schaeffer, Cindy M.; Borduin, Charles M.

    2005-01-01

    In this study, the authors examined the long-term criminal activity of 176 youths who had participated in either multisystemic therapy (MST) or individual therapy (IT) in a randomized clinical trial (C. M. Borduin et al., 1995). Arrest and incarceration data were obtained on average 13.7 (range = 10.2-15.9) years later when participants were on…

  5. Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy

    PubMed Central

    Chico, R Matthew; Chandramohan, Daniel

    2011-01-01

    Introduction: The first-line therapy for the intermittent preventive treatment of malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an urgent need to identify safe, well-tolerated and efficacious alternatives to SP due to widespread Plasmodium falciparum resistance. Combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-Saharan Africa and where IPTp is a government policy in 33 countries. Areas covered: Key safety, tolerability and efficacy data are presented for azithromycin and chloroquine, alone and/or in combination, when used to prevent and/or treat P. falciparum, P. vivax, and several curable sexually transmitted and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from pregnant women is also summarized for both compounds. Expert opinion: The azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non-pregnant adults has been a 3-day course containing daily doses of 1 g of azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of these compounds individually suggests that dose adjustments may not be necessary when used in combination for treatment efficacy against P. falciparum, P. vivax, as well as several curable STI/ RTI among pregnant women, although clinical confirmation will be necessary. Mass trachoma-treatment campaigns have shown that azithromycin selects for macrolide resistance in the pneumococcus, which reverses following the completion of therapy. Most importantly, no evidence to date suggests that azithromycin induces pneumococcal resistance to penicillin. PMID:21736423

  6. Chemotherapy for patients with advanced lung cancer receiving long-term oxygen therapy

    PubMed Central

    Suzuki, Hidekazu; Shiroyama, Takayuki; Tamiya, Motohiro; Okamoto, Norio; Tanaka, Ayako; Morishita, Naoko; Nishida, Takuji; Nishihara, Takashi; Hirashima, Tomonori

    2016-01-01

    Background Long-term oxygen therapy (LTOT) is sometimes prescribed for patients with advanced lung cancer who are potential candidates for chemotherapy. The aim of this study was to assess the usefulness of chemotherapy for patients with this disease who require LTOT. Methods The medical records of 40 patients with advanced lung cancer who received LTOT while undergoing systemic chemotherapy at our institution between January 2009 and December 2014 were retrospectively reviewed. Chemotherapy consisted of cytotoxic or molecular-targeted agents. Results Twenty-four patients had adenocarcinoma, 6 had squamous cell carcinoma, and 10 had small cell lung cancer (SCLC). The median survival time from the date of the first chemotherapy cycle performed in conjunction with LTOT was 194 days. In a multivariate analysis, the only factor significantly associated with better prognosis was the line (first or second) of the first chemotherapy with LTOT (hazard ratio =0.42; 95% confidence interval, 0.18 to 0.94). Among the 40 patients, 10 (25%) received chemotherapy during the last 30 days of their lives, 2 of whom died of chemotherapy-related adverse events. Conclusions Chemotherapy for patients with advanced lung cancer who receive LTOT may be acceptable if it is the first- or second-line treatment. However, we should be mindful of the potential overuse of chemotherapy and its negative impact on quality of life. PMID:26904219

  7. Long-term efficacy of microbiology-driven periodontal laser-assisted therapy.

    PubMed

    Martelli, F S; Fanti, E; Rosati, C; Martelli, M; Bacci, G; Martelli, M L; Medico, E

    2016-03-01

    Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease. PMID:26740323

  8. Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes

    SciTech Connect

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Gonzalez, Carmen; Desco, Manuel; Martinez-Monge, Rafael

    2015-08-01

    Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

  9. Effects of long-term FK 506 therapy on the alveolar bone and cementum of rats.

    PubMed

    Nassar, C A; Nassar, P O; Andia, D C; Guimarães, M R; Spolidorio, L C

    2009-06-01

    Cyclosporine (CsA) and tacrolimus (FK 506) exert complex, incompletely understood actions on bone. The objective of the study was to evaluate the effects of long-term tacrolimus therapy on the periodontium. Rats were treated for 60, 120, 180, and 240 days with daily subcutaneous injections of 1 mg/kg body weight of FK 506. After the experimental period, we obtained serum levels of calcium and alkaline phosphatase (ALP). After histological processing, the alveolar bone and cementum, as well as volume densities of bone (V(b)) and osteoclasts (V(o)), were assessed at the regions of the lower first molar. There was a tendency toward a statistically significant decrease in ALP levels with FK 506; however, serum calcium levels increased during the long periods. At 60, 180, and 240 days of treatment with FK 506, we did not observe V(b) and V(o) alterations. At 120 days of treatment, there was an evident decrease in V(b), but it did not show alveolar bone loss. We did not observe any alterations of cementum among rats treated with FK 506. It may be concluded that FK 506 administration did not induce side effects on the periodontium. PMID:19545747

  10. Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas

    SciTech Connect

    Chen, Allen M. . E-mail: achen@radonc17.ucsf.edu; Bucci, M. Kara; Quivey, Jeanne M.; Garcia, Joaquin; Eisele, David W.; Fu, Karen K.

    2006-11-15

    Purpose: To review a single-institution experience with the management of salivary gland cancers treated by radiation alone. Methods and Materials: Between 1960 and 2004, 45 patients with newly diagnosed salivary gland carcinomas were treated with definitive radiation to a median dose of 66 Gy (range, 57-74 Gy). Distribution of T-stage was: 24% T1, 18% T2, 31% T3, and 27% T4. Histology was: 14 mucoepidermoid (31%), 10 adenocarcinoma (22%), 8 adenoid cystic (18%), 4 undifferentiated (9%), 4 acinic (9%), 2 malignant mixed (4%), 2 squamous (4%), and 1 salivary duct carcinoma (2%). No patient had clinical or pathologic evidence of lymph node disease. Median follow-up was 101 months (range, 3-285 months). Results: The 5-year and 10-year rate estimates of local control were 70% and 57%, respectively. A Cox proportional hazard model identified T3-4 disease (p = 0.004) and radiation dose lower than 66 Gy (p = 0.001) as independent predictors of local recurrence. The 10-year overall survival and distant metastasis-free rates were 46% and 67%, respectively. Conclusion: Radiation therapy alone is a reasonable alternative to surgery in the definitive management of salivary gland cancers and results in long-term survival in a significant proportion of patients. Radiation dose in excess of 66 Gy is recommended.

  11. Long-Term Results After Intraoperative Radiation Therapy for Gastric Cancer

    SciTech Connect

    Drognitz, Oliver Henne, Karl; Weissenberger, Christian; Bruggmoser, Gregor; Goebel, Heike; Hopt, Ulrich Theodor; Frommhold, Herrmann; Ruf, Guenther

    2008-03-01

    Purpose: We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. Methods and Materials: From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT{sup +}] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT{sup -}] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). Results: Mean follow-up was 4.8 years in the IORT{sup +} group and 5.0 years in the IORT{sup -} group. The overall 5-year patient survival rate was 58% in the IORT{sup +} group vs. 59% in the IORT{sup -} group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT{sup +} vs. IORT{sup -} group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT{sup +} vs. IORT{sup -} group. Total surgical complications were more common in the IORT{sup +} than IORT{sup -} group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT{sup +} group. Conclusions: Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.

  12. Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients.

    PubMed

    Rudick, R A; Cutter, G R; Baier, M; Weinstock-Guttman, B; Mass, M K; Fisher, E; Miller, D M; Sandrock, A W

    2005-12-01

    Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNbeta-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of < or = 3.5 at entry, disability progression at follow-up was defined as EDSS > or = 6.0. Two methods were used to estimate the expected proportions that reached EDSS > or = 6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNbeta-1a patients reached an EDSS > or = 6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNbeta-1a patients should have reached an EDSS > or = 6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNbeta-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term

  13. Long-term Cardiac Mortality After Hypofractionated Radiation Therapy in Breast Cancer

    SciTech Connect

    Tjessem, Kristin Holm; Johansen, Safora; Reinertsen, Kristin V.; Danielsen, Turi; Fosså, Sophie D.; Fosså, Alexander

    2013-10-01

    Purpose: To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables. Methods and Materials: Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and with age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model. Results: Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation. Conclusions: The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades.

  14. National study of discontinuation of long-term opioid therapy among veterans.

    PubMed

    Vanderlip, Erik R; Sullivan, Mark D; Edlund, Mark J; Martin, Bradley C; Fortney, John; Austen, Mark; Williams, James S; Hudson, Teresa

    2014-12-01

    Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence among this population. All veterans with at least 90 days of opioid use within a 180-day period were identified using national Veteran's Health Affairs (VHA) data between 2009 and 2011. Discontinuation was defined as 6 months with no opioid prescriptions. We used Cox proportional hazards analysis to determine clinical and demographic correlates for discontinuation. A total of 550,616 veterans met criteria for LTOT. The sample was primarily male (93%) and white (74%), with a mean age of 57.8 years. The median daily morphine equivalent dose was 26 mg, and 7% received high-dose (>100mg MED) therapy. At 1 year after initiation, 7.5% (n=41,197) of the LTOT sample had discontinued opioids. Among those who discontinued (20%, n=108,601), the median time to discontinuation was 317 days. Factors significantly associated with discontinuation included both younger and older age, lower average dosage, and having received less than 90 days of opioids in the previous year. Although tobacco use disorders decreased the likelihood of discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in veterans with mental health and substance use disorders. Further research is needed to delineate causes and consequences of opioid discontinuation. PMID:25277462

  15. Pigmented lichenoid drug eruption secondary to chloroquine therapy: an unusual presentation in lower lip.

    PubMed

    Moraes, P C; Noce, C W; Thomaz, L A; Cintra, M L; Correa, M E P

    2011-06-01

    Antimalarial drugs, like chloroquine, may produce hyperpigmentation of the oral mucosa, affecting most commonly the palate. Its pathogenesis is not clear; an increased production of melanin is currently believed to be the cause of this oral manifestation. The purpose of this study was to report a case of atypical oral mucosal hyperpigmentation secondary to antimalarial therapy. A 66-year-old, dark skinned woman was evaluated for oral pigmentation. The patient had a history of chloroquine therapy, and presented a diffuse blue-gray pigmentation in the hard palate and, mainly, in the lower lip. Diagnostic hypothesis were of physiologic pigmentation, drug-induced pigmentation, pigmentation associated with systemic diseases, smoker's melanosis and post-inflammatory pigmentation. Incisional biopsy was conducted and histopathological examination revealed lichenoid dermatitis and pigment incontinence. Fontana-Masson staining was positive for melanin, but Perl's iron staining was negative. The histopathological diagnosis was consistent with melanin incontinence related to drug-induced lichenoid reaction secondary to chloroquine therapy. Adequate correlation of clinical and microscopic aspects was essential for the definitive diagnosis, especially in atypical cases. This diagnosis is of great relevance for the patient, since the oral manifestation might be an early sign of ocular complications due to antimalarial therapy. Therefore, the identification of these oral manifestations indicates regular evaluations by an ophtalmologist, preventing greater complications of antimalarial therapy for the patient. PMID:21666569

  16. Evidence for Long-term Efficacy and Safety of Gene Therapy for Wiskott–Aldrich Syndrome in Preclinical Models

    PubMed Central

    Marangoni, Francesco; Bosticardo, Marita; Charrier, Sabine; Draghici, Elena; Locci, Michela; Scaramuzza, Samantha; Panaroni, Cristina; Ponzoni, Maurilio; Sanvito, Francesca; Doglioni, Claudio; Liabeuf, Marie; Gjata, Bernard; Montus, Marie; Siminovitch, Katherine; Aiuti, Alessandro; Naldini, Luigi; Dupré, Loïc; Roncarolo, Maria Grazia; Galy, Anne; Villa, Anna

    2009-01-01

    Wiskott–Aldrich Syndrome (WAS) is a life-threatening X-linked disease characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancies. Gene therapy could represent a therapeutic option for patients lacking a suitable bone marrow (BM) donor. In this study, we analyzed the long-term outcome of WAS gene therapy mediated by a clinically compatible lentiviral vector (LV) in a large cohort of wasnull mice. We demonstrated stable and full donor engraftment and Wiskott–Aldrich Syndrome protein (WASP) expression in various hematopoietic lineages, up to 12 months after gene therapy. Importantly, we observed a selective advantage for T and B lymphocytes expressing transgenic WASP. T-cell receptor (TCR)-driven T-cell activation, as well as B-cell's ability to migrate in response to CXCL13, was fully restored. Safety was evaluated throughout the long-term follow-up of primary and secondary recipients of WAS gene therapy. WAS gene therapy did not affect the lifespan of treated animals. Both hematopoietic and nonhematopoietic tumors arose, but we excluded the association with gene therapy in all cases. Demonstration of long-term efficacy and safety of WAS gene therapy mediated by a clinically applicable LV is a key step toward the implementation of a gene therapy clinical trial for WAS. PMID:19259069

  17. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy

    PubMed Central

    Ford, Ian; Murray, Heather; Packard, Chris J.

    2016-01-01

    Background— Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. Methods and Results— The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80–0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. Conclusion— Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. PMID:26864092

  18. The importance of knowing the home conditions of patients receiving long-term oxygen therapy

    PubMed Central

    Godoy, Ilda; Tanni, Suzana Erico; Hernández, Carme; Godoy, Irma

    2012-01-01

    Purpose Long-term oxygen therapy (LTOT) is one of the main treatments for patients with chronic obstructive pulmonary disease. Patients receiving LTOT may have less than optimal home conditions and this may interfere with treatment. The objective of this study was, through home visits, to identify the characteristics of patients receiving LTOT and to develop knowledge regarding the home environments of these patients. Methods Ninety-seven patients with a mean age of 69 plus or minus 10.5 years were evaluated. This study was a cross-sectional descriptive analysis. Data were collected during an initial home visit, using a questionnaire standardized for the study. The results were analyzed retrospectively. Results Seventy-five percent of the patients had chronic obstructive pulmonary disease, and 11% were active smokers. The patients’ mean pulse oximetry values were 85.9% plus or minus 4.7% on room air and 92% plus or minus 3.9% on the prescribed flow of oxygen. Most of the patients did not use the treatment as prescribed and most used a humidifier. The extension hose had a mean length of 5 plus or minus 3.9 m (range, 1.5–16 m). In the year prior to the visit, 26% of the patients received emergency medical care because of respiratory problems. Few patients reported engaging in leisure activities. Conclusion The home visit allowed us to identify problems and interventions that could improve the way LTOT is used. The most common interventions related to smoking cessation, concentrator maintenance and cleaning, use of a humidifier, and adjustments of the length of the connector hose. Therefore, the home visit is a very important tool in providing comprehensive care to patients receiving LTOT, especially those who show lack of adequate progress and those who show uncertainty about the treatment method. PMID:22848155

  19. Long-term effect of a short interprofessional education interaction between medical and physical therapy students.

    PubMed

    Sytsma, Terin T; Haller, Elizabeth P; Youdas, James W; Krause, David A; Hellyer, Nathan J; Pawlina, Wojciech; Lachman, Nirusha

    2015-01-01

    Medicine is increasingly focused on team-based practice as interprofessional cooperation leads to better patient care. Thus, it is necessary to teach teamwork and collaboration with other health care professionals in undergraduate medical education to ensure that trainees entering the workforce are prepared to work in teams. Gross anatomy provides an opportunity to expose students to interprofessional education (IPE) early in their training. The purpose of this study is to describe an IPE experience and report if the experience has lasting influence on the participating students. The Readiness for Interprofessional Learning Scale (RIPLS) questionnaire was administered to first year medical (MD) and physical therapy (PT) students at Mayo Medical School and Mayo School of Health Sciences. Results demonstrated an openness on the part of the students to IPE. Interprofessional education experiences were incorporated into gross anatomy courses in both medical and PT curricula. The IPE experiences included a social event, peer-teaching, and collaborative clinical problem-solving sessions. These sessions enhanced gross anatomy education by reinforcing previous material and providing the opportunity to work on clinical cases from the perspective of two healthcare disciplines. After course completion, students again completed the RIPLS. Finally, one year after course completion, students were asked to provide feedback on their experience. The post-curricular RIPLS, similar to the pre-curricular RIPLS, illustrated openness to IPE from both MD and PT students. There were however, significant differences in MD and PT perceptions of roles and responsibilities. One-year follow-up indicated long-term retention of lessons learned during IPE. PMID:26040635

  20. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  1. Long-Term Outcomes for Desmoid Tumors Treated With Radiation Therapy

    SciTech Connect

    Guadagnolo, B. Ashleigh Zagars, Gunar K.; Ballo, Matthew T.

    2008-06-01

    Purpose: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery. Methods and Materials: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy). Results: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size ({<=}5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age ({<=} 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age {<=}30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01). Conclusions: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.

  2. Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

    PubMed

    Chen, G; Crispin, P; Cherian, M; Dahlstrom, J E; Sethna, F F; Kaye, G; Pavli, P; Subramaniam, K

    2016-01-01

    We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death. PMID:26813900

  3. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    ERIC Educational Resources Information Center

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  4. Pentoxifylline as adjunct therapy to long-term clinical management of a right-to-left patent ductus arteriosus.

    PubMed

    Turner, Elizabeth

    2016-06-01

    Management of a right-to-left ("reversed") patent ductus arteriosus (PDA) focuses on control of clinical signs associated with hyperviscosity due to erythrocytosis. Pentoxifylline therapy is presented as an adjunct to routine phlebotomies for the long-term clinical management of reversed PDA in a 10-year-old Chihuahua. PMID:27247468

  5. Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

    PubMed Central

    Duong, Trinh; Judd, Ali; Collins, Intira Jeannie; Doerholt, Katja; Lyall, Hermione; Foster, Caroline; Butler, Karina; Tookey, Pat; Shingadia, Delane; Menson, Esse; Dunn, David T.; Gibb, Di M.

    2014-01-01

    Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI + 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirty-nine (34%) children experienced virological failure. Although progression to failure varied by regimen (P < 0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI + 3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9–8.9%) NVP, 8.3% (95% CI 5.6–11.6) EFV, and 9.8% (95% CI 5.7–15.3%) protease inhibitor-based regimens (P = 0.48). Conclusion: Viral load suppression by 12 months was high with

  6. Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis

    PubMed Central

    Namba, Sayaka; Yamaoka-Tojo, Minako; Hashikata, Takehiro; Ikeda, Yuki; Kitasato, Lisa; Hashimoto, Takuya; Shimohama, Takao; Tojo, Taiki; Takahira, Naonobu; Masuda, Takashi; Ako, Junya

    2015-01-01

    Background Stroke prevention by warfarin, a vitamin K antagonist, has been an integral part in the management of atrial fibrillation. Vitamin K-dependent matrix Gla protein (MGP) has been known as a potent inhibitor of arterial calcification and osteoporosis. Therefore, we hypothesized that warfarin therapy affects bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. Methods We studied 42 atrial fibrillation patients at high-risk for atherosclerosis having one or more coronary risk factors. Twenty-four patients had been treated with warfarin for at least 12 months (WF group), and 18 patients without warfarin (non-WF group). Bone alkaline phosphatase (BAP) and under carboxylated osteocalcin (ucOC) and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured as bone metabolism markers. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) index measured by Endo-PAT2000 was used as an indicator of vascular endothelial function. Results There were no significant differences in patient background characteristics and other clinical indicators between the two groups. In WF group, the ucOC levels were significantly higher than those in the non-WF group (10.3 ± 0.8 vs. 3.4 ± 0.9 ng/mL; P < 0.01), similarly, the RANKL levels in the WF group were higher than those in the non-WF group (0.60 ± 0.06 vs. 0.37 ± 0.05 ng/mL; P = 0.007). Moreover, RH-PAT index was significantly lower in the WF group compared to those in the non-WF group (1.48 ± 0.11 vs. 1.88 ± 0.12; P = 0.017). Conclusions Long-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60–80 year old hypertensive patients. PMID:26674156

  7. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  8. Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion.

    PubMed

    Shuai, Yi; Liao, Li; Su, Xiaoxia; Yu, Yang; Shao, Bingyi; Jing, Huan; Zhang, Xinjing; Deng, Zhihong; Jin, Yan

    2016-01-01

    Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy. PMID:27570559

  9. Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

    PubMed Central

    Shuai, Yi; Liao, Li; Su, Xiaoxia; Yu, Yang; Shao, Bingyi; Jing, Huan; Zhang, Xinjing; Deng, Zhihong; Jin, Yan

    2016-01-01

    Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy. PMID:27570559

  10. The Mediating Role of Insight for Long-Term Improvements in Psychodynamic Therapy

    ERIC Educational Resources Information Center

    Johansson, Paul; Hoglend, Per; Ulberg, Randi; Amlo, Svein; Marble, Alice; Bogwald, Kjell-Petter; Sorbye, Oystein; Sjaastad, Mary Cosgrove; Heyerdahl, Oscar

    2010-01-01

    Objective: According to psychoanalytic theory, interpretation of transference leads to increased insight that again leads to improved interpersonal functioning over time. In this study, we performed a full mediational analysis to test whether insight gained during treatment mediates the long-term effects of transference interpretation in dynamic…

  11. Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

    PubMed Central

    Davila, G. Willy

    2011-01-01

    Objective. To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence (SUI) through a review of the literature. Methods. PubMed was searched for reports on prospective clinical trials with at least 12-month follow-up of minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in women with SUI. Each report was examined for long-term rates of effectiveness and safety. Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery. PMID:21738529

  12. Linking Estrogen-Induced Apoptosis With Decreases in Mortality Following Long-term Adjuvant Tamoxifen Therapy

    PubMed Central

    2014-01-01

    The impressive first results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and the adjuvant Tamoxifen To offer more (aTTom) trials both demonstrate that 10 years of tamoxifen is superior to five years of treatment. Tamoxifen is a nonsteroidal antiestrogen that blocks estrogen-stimulated tumor growth. Paradoxically, mortality decreases dramatically only in the decade after long-term tamoxifen is stopped. It is proposed that the evolution and clonal selection of micrometastases that acquire tamoxifen resistance now become increasingly vulnerable to endogenous estrogen-induced apoptosis. Laboratory and clinical studies confirm the concept, and supporting clinical evidence from the estrogen-alone trial in the Women’s Health Initiative (WHI), demonstrate that long-term estrogen-deprived women given exogenous physiologic estrogen have a decreased incidence of breast cancer and decreased mortality. It is proposed that a natural process of apoptosis is recruited to execute the long-term survival benefit of stopping ten years of adjuvant tamoxifen, but only after clonal selection of vulnerable breast cancer cells in an estrogen-deprived environment. PMID:25269699

  13. The long-term effectiveness of cognitive behavior therapy for psychosis within a routine psychological therapies service

    PubMed Central

    Peters, Emmanuelle; Crombie, Tessa; Agbedjro, Deborah; Johns, Louise C.; Stahl, Daniel; Greenwood, Kathryn; Keen, Nadine; Onwumere, Juliana; Hunter, Elaine; Smith, Laura; Kuipers, Elizabeth

    2015-01-01

    Randomised controlled trials (RCTs) have shown the efficacy of CBTp, however, few studies have considered its long-term effectiveness in routine services. This study reports the outcomes of clients seen in a psychological therapies clinic, set up following positive results obtained from an RCT (Peters et al., 2010). The aims were to evaluate the effectiveness of CBTp, using data from the service’s routine assessments for consecutive referrals over a 12 years period, and assess whether gains were maintained at a 6+ months’ follow-up. Of the 476 consenting referrals, all clients (N = 358) who received ≥5 therapy sessions were offered an assessment at four time points (baseline, pre-, mid-, and end of therapy) on measures assessing current psychosis symptoms, emotional problems, general well-being and life satisfaction. A sub-set (N = 113) was assessed at a median of 12 months after finishing therapy. Following the waiting list (median of 3 months) clients received individualized, formulation-based CBTp for a median number of 19 sessions from 121 therapists with a range of experience receiving regular supervision. Clients showed no meaningful change on any measure while on the waiting list (Cohen’s d <= 0.23). In contrast, highly significant improvements following therapy, all of which were significantly greater than changes during the waiting list, were found on all domains assessed (Cohen’s d: 0.44–0.75). All gains were maintained at follow-up (Cohen’s d: 0.29–0.82), with little change between end of therapy and follow-up (Cohen’s d <= 0.18). Drop-out rate from therapy was low (13%). These results demonstrate the positive and potentially enduring impact of psychological therapy on a range of meaningful outcomes for clients with psychosis. The follow-up assessments were conducted on only a sub-set, which may not generalize to the full sample. Nevertheless this study is the largest of its kind in psychosis, and has important implications for the

  14. Patients’ perspectives regarding long-term warfarin therapy and the potential transition to new oral anticoagulant therapy

    PubMed Central

    Gebler-Hughes, Elizabeth S.; Kemp, Linda

    2014-01-01

    Objectives: To examine patients’ perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions. Design, setting and participants: Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July–September 2013. Main outcome measures: Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought. Results: Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (±4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (±4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001). Conclusion: When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area. PMID:25436104

  15. Label-free proteomic analysis of PBMCs reveals gender differences in response to long-term antiretroviral therapy of HIV.

    PubMed

    Zhang, Lu; Wang, Zhuoran; Chen, Yulong; Zhang, Chi; Xie, Shiping; Cui, Yinglin; Wang, Zhao

    2015-08-01

    The association of gender with the treatment outcome during long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients has been controversial. Here, we performed a comparative proteomic analysis of peripheral blood mononuclear cells (PBMC) by using a label-free shotgun method with nano-LC-MS/MS to investigate the gender differences in responses to long-term ART. This analysis enrolled 30 HIV-infected patients (16 males and 14 females), as well as 20 healthy adults (10 males and 10 females) as control. Quantitative real-time RT-PCR and immunoblotting were used to validate the results of proteomic approach. A total of 53 proteins showing differential expression (± 1.5 fold, p < 0.05) were identified in HIV-infected patients versus healthy adults. Of these proteins, 22 proteins showed identical regulation patterns in both men and women, while 31 proteins were gender-specific (21 men-specific and 10 women-specific proteins). Bioinformatics analysis indicated that long-term ART causes up-regulation of apoptosis, oxidative phosphorylation and mitochondrial dysfunction while down-regulation of oxidative stress and immune system process in men compared to women. These findings point to a concept that gender has a significant influence on the outcomes of ART at protein level and women present a potential favorable immunological pattern and recovery during long-term ART. PMID:26045010

  16. A systematic review of the use of Acceptance and Commitment Therapy (ACT) in chronic disease and long-term conditions.

    PubMed

    Graham, Christopher D; Gouick, Joanna; Krahé, Charlotte; Gillanders, David

    2016-06-01

    Many have proposed that Acceptance and Commitment Therapy (ACT) may be particularly effective for improving outcomes in chronic disease/long-term conditions, and ACT techniques are now being used clinically. However, reviews of ACT in this context are lacking, and the state of evidence is unclear. This systematic review aimed to: collate all ACT interventions with chronic disease/long-term conditions, evaluate their quality, and comment on efficacy. Ovid MEDLINE, EMBASE and Psych Info were searched. Studies with solely mental health or chronic pain populations were excluded. Study quality was then rated, with a proportion re-rated by a second researcher. Eighteen studies were included: eight were randomised controlled trials (RCTs), four used pre-post designs, and six were case studies. A broad range of applications was observed (e.g. improving quality of life and symptom control, reducing distress) across many diseases/conditions (e.g. HIV, cancer, epilepsy). However, study quality was generally low, and many interventions were of low intensity. The small number of RCTs per application and lower study quality emphasise that ACT is not yet a well-established intervention for chronic disease/long-term conditions. However, there was some promising data supporting certain applications: parenting of children with long-term conditions, seizure-control in epilepsy, psychological flexibility, and possibly disease self-management. PMID:27176925

  17. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era

    PubMed Central

    Toth, Peter P

    2016-01-01

    Background Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Methods Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. Conclusion NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism. PMID:26929637

  18. Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?

    PubMed Central

    2010-01-01

    Background Pulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients. Methods We performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH) Registry to estimate long-term survival with each therapy. Results Ten RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD) age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH), 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%. Conclusion When applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH therapy. PMID:20170553

  19. Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis.

    PubMed Central

    Ching, G. W.; Franklyn, J. A.; Stallard, T. J.; Daykin, J.; Sheppard, M. C.; Gammage, M. D.

    1996-01-01

    OBJECTIVES: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. DESIGN: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). METHODS: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. RESULTS: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs. CONCLUSIONS: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence

  20. Autologous Immunoglobulin Therapy in Patients With Severe Recalcitrant Atopic Dermatitis: Long-Term Changes of Clinical Severity and Laboratory Parameters.

    PubMed

    Nahm, Dong Ho; Ahn, Areum; Kim, Myoung Eun; Cho, Su Mi; Park, Mi Jung

    2016-07-01

    This report evaluated long-term changes in clinical severity and laboratory parameters in 3 adult patients with severe recalcitrant atopic dermatitis (AD) who were treated with intramuscular injections of 50 mg of autologous immunoglobulin G (IgG) twice a week for 4 weeks (autologous immunoglobulin therapy, AIGT) and followed up for more than 2 years after the treatment. We observed the following 4 major findings in these 3 patients during the long-term follow-up after AIGT. (1) Two of the 3 patients showed a long-term clinical improvement for more than 36 weeks after AIGT with a maximum decrease in clinical severity score greater than 80% from baseline. (2) These 2 patients also showed long-term decreases in serum total IgE concentrations and peripheral blood eosinophil count for more than 36 weeks after AIGT with a maximum decrease in the two laboratory parameters of allergic inflammatory greater than 70% from baseline. (3) No significant side effect was observed during the 2 years of follow-up period after the AIGT in all 3 patients. (4) Serum levels of IgG anti-idiotype antibodies to the F(ab')₂ fragment of autologous IgG administered for the treatment were not significantly changed after AIGT in all 3 patients. These findings suggest that AIGT has long-term favorable effects on both clinical severity and laboratory parameters in selected patients with severe recalcitrant AD. Further studies are required to evaluate the clinical usefulness and therapeutic mechanism of AIGT for AD. PMID:27126731

  1. Establishment of intravenous lines for long-term intravenous therapy and monitoring.

    PubMed

    Parsa, M H; Tabora, F

    1985-08-01

    Our experience at this institution indicates that the greater the individual and the institutional experience, the lower the complications of central venous lines. The techniques of double catheter insertions in one vein or region, as described, are safe, cost-effective, and useful. These catheters can remain in place for up to 8 weeks. Insertion of double catheters is ideal for intravenous feeding to avoid premixing amino acids and glucose, thus minimizing the hazards of contamination as well as saving time and cost for mixing. Special unconventional techniques for vascular access when indicated in patients who have limited accessible sites may be lifesaving. Except for fibrinous clots around the catheters, the complications in our series have diminished as our experience has grown. Vascular access techniques and long-term care should be formally taught to committed individuals. Well-trained, concerned, experienced personnel available 24 hours a day, 7 days a week is the most important factor in the reduction of complications of vascular access technique and the long-term maintenance of intravenous lines. PMID:3931265

  2. Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

    PubMed Central

    Honda, Koichi; Seike, Masataka; Oribe, Junya; Endo, Mizuki; Arakawa, Mie; Syo, Hiroki; Iwao, Masao; Tokoro, Masanori; Nishimura, Junko; Mori, Tetsu; Yamashita, Tsutomu; Fukuchi, Satoshi; Muro, Toyokichi; Murakami, Kazunari

    2016-01-01

    AIM: To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS: A total of 123 patients with hepatitis B virus- or hepatitis C virus-related hepatocellular car-cinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS: CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as signi-ficant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION: Long-term liver function following RFA was dependent on liver functional reserve, the degree of fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. PMID:27168872

  3. Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy: follow up study

    PubMed Central

    Wells, Michael; Sturdee, David W; Barlow, David H; Ulrich, Lian G; O'Brien, Karen; Campbell, Michael J; Vessey, Martin P; Bragg, Anthony J

    2002-01-01

    Objective To determine effects of five years of treatment with an oral continuous combined regimen of 2 mg 17β-oestradiol and 1 mg norethisterone acetate on endometrial histology in postmenopausal women. Design Follow up study in postmenopausal women. Setting 31 menopause clinics in the United Kingdom. Participants 534 postmenopausal women, all with an intact uterus, who had completed nine months of treatment with oral continuous combined 2 mg 17β-oestradiol and 1 mg norethisterone acetate agreed to take part in a long term follow up study. Women were assigned to different groups on the basis of the treatment status immediately before entering the original study: 360 women had taken sequential oestrogen-progestogen hormone replacement therapy, 164 had taken no hormone replacement therapy, and 10 had taken unopposed oestrogen therapy. Methods Endometrial aspiration specimens were taken before the women started the continuous combined regimen, after 9 and 24-36 months, and at the end of the five year treatment period or on withdrawal from the study. Main outcome measure Results of endometrial histology. Results The duration of treatment with continuous combined hormone replacement therapy was 4.4 (range 1.1-5.9) years. Data on endometrial specimens were available for 526 women after nine months of treatment, 465 women after 24-36 months of treatment, and 398 women who completed the five years treatment (345 women) or were withdrawn between the two latter visits for biopsies (53 women). No cases of endometrial hyperplasia or malignancy were detected at biopsy; 69% of women had an endometrium classified as atrophic or unassessable on completion of the study or withdrawal from it. Before the continuous combined therapy was started, complex hyperplasia was detected in 21 women who had taken sequential hormone replacement therapy before the study and in one who had taken unopposed oestrogen. All of these women had normal results on histological examination of

  4. The opioid epidemic and the long-term opioid therapy for chronic noncancer pain revisited: a transatlantic perspective.

    PubMed

    Häuser, Winfried; Petzke, Frank; Radbruch, Lukas; Tölle, Thomas R

    2016-05-01

    The rise of opioid prescriptions and associated deaths ('opioid epidemic') in North America has evoked worldwide discussions on the long-term efficacy and safety of long-term opioid therapy (LtOT) for chronic noncancer pain (CNCP). We discuss if the opioid epidemic is a real worldwide or a more North American phenomenon. We consider reasons of the opioid epidemic. We highlight differences in the appraisal of the evidence of recent systematic reviews on LtOT for CNCP of US and European authors. We discuss similarities and differences of recent North American and European guidelines on LtOT for chronic CNCP. We point out potential indications and contraindications of LtOT in CNCP syndromes. PMID:26988312

  5. Short and long-term effects of high-dose intravenous methylprednisolone pulse therapy on thyroid-associated ophthalmopathy

    PubMed Central

    Liu, Xiaomei; Wang, Shu; Qin, Li; Qiang, Wei; Dahal, Mahesh; Fan, Ping; Gao, Shan; Shi, Bingyin

    2016-01-01

    The majority of previous studies on high-dose intravenous methylprednisolone pulse (IVMP) therapy have observed the clinical conditions of patients prior to and following treatment without any long-term follow-up, and these studies have predominantly focused on combined treatment. The present prospective clinical study aimed to assess the long-term effects and safety of high-dose IVMP therapy in thyroid-associated ophthalmopathy (TAO), as well as the significance of thyrotropin receptor antibody (TRAb) and soluble intercellular adhesion molecule-l (sICAM-1) during IVMP therapy. A total of 58 patients with TAO were treated with high-dose IVMP therapy, and their clinical characteristics and indices were recorded before, during and after therapy, with a 12–57 month (mean, 28.4 months) follow-up. Before treatment and on the second day after each IVMP therapy, serum TRAb and sICAM-1 levels were evaluated in 23 patients with TAO via a competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The results of the present study demonstrated that the symptoms of eyelid swelling, ophthalmodynia, photophobia, lacrimation and diplopia, and visual acuity, ocular motility, proptosis and clinical activity score (CAS) indices were all significantly improved after IVMP therapy. In addition, analysis of covariance demonstrated that alterations in the levels of serum TRAb during the course of treatment were associated with CAS of TAO, whereas the change in serum sICAM-1 was not. In conclusion, high-dose IVMP therapy is an effective, safe, stable and well-tolerated treatment for TAO, which is associated with rare, minor adverse effects. Furthermore, serum TRAb levels are correlated with the CAS of TAO and may serve as a predictor of the response to methylprednisolone therapy. PMID:27446294

  6. Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy

    SciTech Connect

    Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.; Singleton, R.T.; Wesley, M.N.; Wiernik, P.H.

    1982-04-01

    The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

  7. Long-term non-invasive ventilation therapies in children: a scoping review protocol

    PubMed Central

    Castro Codesal, Maria L; Featherstone, Robin; Martinez Carrasco, Carmen; Katz, Sherri L; Chan, Elaine Y; Bendiak, Glenda N; Almeida, Fernanda R; Young, Rochelle; Olmstead, Deborah; Waters, Karen A; Sullivan, Collin; Woolf, Vicki; Hartling, Lisa; MacLean, Joanna E

    2015-01-01

    Introduction Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children. Methods and analysis We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups. Ethics and dissemination This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses. PMID:26270951

  8. Intraperitoneal gene therapy by rAAV provides long-term survival against epithelial ovarian cancer independently of survivin pathway.

    PubMed

    Isayeva, T; Ren, C; Ponnazhagan, S

    2007-01-01

    Epithelial ovarian carcinoma is the leading cause of death from gynecological malignancies. Owing to the lack of an effective screening method, insidious onset, and non-specific symptoms, a majority of women present with advanced stage disease. Despite improvements from cytoreductive surgery and chemotherapy, recurrent disease remains a formidable challenge. In the present study, we demonstrate for the first time that stable intra-abdominal genetic transfer of endostatin and angiostatin (E+A) by recombinant adeno-associated virus (rAAV) provides sustained antitumor effects on the growth and dissemination of epithelial ovarian cancer in a mouse model. Further, when combined with paclitaxel (taxol), the effect of this therapy was dramatically increased and resulted in long-term tumor-free survival overcoming prior limitations of chemotherapy and gene therapy. The combined effects of angiosuppressive therapy and chemotherapy were found to be independently of survivin pathway. Evidence for the superior effects of the combination therapy was indicated by significantly lower ascites volume with less hemorrhage and tumor conglomerates, lower ascites vascular endothelial growth factor, higher tumor cell apoptosis and decreased blood vasculature, and long-term disease-free survival. Histopathology of visceral organs and liver enzyme assays indicated no toxicity or pathology. PMID:16943851

  9. Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism.

    PubMed

    Krampe, Henning; Stawicki, Sabina; Hoehe, Margret R; Ehrenreich, Hannelore

    2007-01-01

    Alcohol dependence is a frequent, chronic, relapsing, and incurable disease with enormous societal costs. Thus, alcoholism therapy and research into its outcome are of major importance for public health. The present article will: (i) give a brief overview of the epidemiology, pathogenesis, and treatment outcomes of alcohol dependence; (ii) introduce the basic principles of outpatient long-term therapy of alcohol-dependent patients; and (iii) discuss in detail process-outcome research on Outpatient Long-term Intensive Therapy for Alcoholics (OLITA). This successful biopsychosocial approach to the treatment of alcoholism shows a 9-year abstinence rate of over 50%, a re-employment rate of 60%, and a dramatic recovery from comorbid depression, anxiety disorders, and physical sequelae. The outcome data are empirically based on treatment processes that have proven high predictive validity and give concrete information about where to focus the therapeutic efforts. Thus, process-outcome research on OLITA can serve for the development of new therapeutic guidelines on adapting individual relapse prevention strategies. PMID:18286800

  10. Treatment Response and Long-Term Outcome of Peginterferon α and Ribavirin Therapy in Korean Patients with Chronic Hepatitis C

    PubMed Central

    Jung, Chang Ho; Um, Soon Ho; Kim, Tae Hyung; Yim, Sun Young; Suh, Sang Jun; Yim, Hyung Joon; Seo, Yeon Seok; Choi, Hyuk Soon; Chun, Hoon Jai

    2016-01-01

    Background/Aims Peginterferon plus ribavirin remains a standard therapy for patients with chronic hepatitis C (CHC) in Korea. We investigated the efficacy and long-term outcome of peginterferon and ribavirin therapy in Korean patients with CHC, particularly in relation to the stage of liver fibrosis. Methods The incidence of sustained virological response (SVR), hepatic decompensation, hepatocellular carcinoma, and liver-related death was analyzed in 304 patients with CHC; the patients were followed up for a median of 54 months. Results Among patients with HCV genotype 1, the SVR rate was 36.7% (18/49) and 67% (69/103) for patients with and without cirrhosis, respectively (p<0.001). For patients with non-1 HCV genotypes, the SVR rates were 86.0% (37/43) in cirrhotic patients and 86.2% (94/109) in noncirrhotic patients. SVR significantly reduced the risk of liver-related death, hepatic decompensation, and hepatocellular carcinoma, which had hazard ratios of 0.27, 0.16, and 0.22, respectively (all p<0.05). However, despite the SVR rate, patients with advanced fibrosis were still at risk of developing liver-related complications. Conclusions A relatively high SVR rate was achieved by peginterferon plus ribavirin therapy in Korean patients with CHC, which improved their long-term outcomes. However, all CHC patients with advanced hepatic fibrosis should receive close follow-up observations, even after successful antiviral treatment. PMID:27114417

  11. Long-term results of forward intensity-modulated radiation therapy for patients with early-stage breast cancer

    PubMed Central

    Ha, Boram; Lee, Jihae; Lee, Kyung-Ja; Lee, Rena; Moon, Byung In

    2013-01-01

    Purpose To observe long-term clinical outcomes for patients with early-stage breast cancer treated with forward intensity-modulated radiation therapy (IMRT), including local control and clinical toxicities. Materials and Methods We retrospectively analyzed a total of 214 patients with stage I-II breast cancer who were treated with breast conserving surgery followed by adjuvant breast radiation therapy between 2001 and 2008. All patients were treated using forward IMRT. The whole breast was irradiated to a dose of 50 to 50.4 Gy followed by an 8 to 12 Gy electron boost to the surgical bed. Results The median age was 46 years (range, 21 to 82 years) and the medial follow-up time was 7.3 years (range, 2.4 to 11.7 years). Stage T1 was 139 (65%) and T2 was 75 (35%), respectively. Ipsilateral breast recurrence was observed in 3 patients. The 5- and 10-year local control rates were 99.1% and 97.8%, respectively. The cosmetic outcome was evaluated according to the Harvard scale and 89.4% of patients were scored as excellent or good. Conclusion The whole breast radiation therapy as an adjuvant treatment using a forward IMRT technique showed excellent long-term local control as well as favorable outcomes of toxicity and cosmesis. PMID:24501706

  12. Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism

    PubMed Central

    Krampe, Henning; Stawicki, Sabina; Hoehe, Margret R.; Ehrenreich, Hannelore

    2007-01-01

    Alcohol dependence is a frequent, chronic, relapsing, and incurable disease with enormous societal costs. Thus, alcoholism therapy and research into its outcome are of major importance for public health. The present article will: (i) give a brief overview of the epidemiology, pathogenesis, and treatment outcomes of alcohol dependence; (ii) introduce the basic principles of outpatient long-term therapy of alcohol-dependent patients; and (iii) discuss in detail process-outcome research on Outpatient Long-term intensive Therapy for Alcoholics (OLITA). This successful biopsychosocial approach to the treatment of alcoholisms shows a 9-year abstinence rate of over 50%, a re-employment rate of 60%, and a dramatic recovery from comorbid depression, anxiety disorders, and physical sequelae. The outcome data are empirically based on treatment processes that have proven high predictive validity and give concrete information about where to focus the therapeutic efforts. Thus, process-outcome research on OLITA can serve for the development of new therapeutic guidelines on adapting individual relapse prevention strategies. PMID:18286800

  13. The long-term safety and efficacy of intrathecal therapy using sufentanil in chronic intractable non-malignant pain.

    PubMed

    Monsivais, Jose Jesus; Monsivais, Diane Burn

    2014-07-01

    This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome. PMID:25031819

  14. Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

    PubMed Central

    Talat, Mohamed A.; Ahmed, Anwar; Mohammed, Lamia

    2015-01-01

    Objective: To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. Methods: A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. Results: The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001). Conclusion: Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients. PMID:26492112

  15. Major Long-Term Benefits of Intensive Therapy for Type 1 Diabetes

    MedlinePlus

    ... Benefits of Intensive Therapy for Type 1 Diabetes: Study Reports Near-Normal Glucose Levels Lead to Large ... the latest results from a landmark government-sponsored study, reported at a special symposium held at the ...

  16. Estrogen Therapy Has No Long-Term Effect on Cognition in Younger Postmenopausal Women

    MedlinePlus

    ... risk to cognitive function years after treatment. A randomized clinical trial of estrogen therapy in younger postmenopausal ... 1998 at 40 academic research centers. Participants were randomized to one of two groups: women who had ...

  17. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    PubMed

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

  18. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    PubMed Central

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5-years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of “longer is better” for adjuvant therapy in pre-menopausal patients. One-year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five-years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten-years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective nor-epinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical

  19. [Significance of intermittent CDDP therapy for improving long-term prognosis in patients with advanced ovarian cancer].

    PubMed

    Umesaki, N; Yamamoto, A; Nakano, M; Matsumoto, Y; Tsuda, K; Kawabata, M; Sugawa, T

    1991-12-01

    In cases of advanced ovarian cancer, intermittent CDDP therapy (ICDDPT) was applied after the first operation and induction chemotherapy, and its efficacy and limit were studied. One cycle of this therapy involved consecutive 5 day CDDP treatment (25-30mg/body/day). The therapy was repeated at intervals of 3 months. In many cases, ovarian cancer was histologically rated as epithelial adenocarcinoma. The study included 18 cases in total. ICDDPT was applied to 13 cases in which no tumor mass was detected by second look operation (SLO) or which showed clinical remission after operation. Only 3 of these 13 cases showed recurrence, and all these 13 are still living. Of the 5 cases in which SLO disclosed a tumor mass or which did not show remission after the first operation, 2 died. When the survival rate after ICDDPT was compared by the Kaplan-Meier method with that of controls without CDDP therapy, the effectiveness of ICDDPT was demonstrated. The survival rate could therefore be improved by ICDDPT. The therapy particularly improved the long term prognosis of SLO negative cases and cases in clinical remission. It seems necessary to repeat this therapy for a long period to achieve satisfactory results. In SLO positive cases and cases without clinical remission, the therapy had only a limited effect. PMID:1744459

  20. Combining garden therapy and supported employment - a method for preparing women on long-term sick leave for working life.

    PubMed

    Lidén, Eva; Alstersjö, Karin; Gurné, Frida L; Fransson, Sandra; Bergbom, Ingegerd

    2016-06-01

    Women are overrepresented among the group people suffering from long-term illness. In addition to their illness, suffering long-term sick leave leads to economical restraints as well social distress. There are gaps in our understanding of the challenges these women face. There is also lack of knowledge about how these challenges can be effectively addressed in rehabilitation. This deficiency is problematic from an ethical, justice and a caring perspective. In this study, changes in health-related quality of life (HRQoL) among women on long-term sick leave were investigated during and after participating in a rehabilitation programme combining two validated methods, Garden Therapy and Supported Employment (SE). The study also discusses difficulties in realising research related to vulnerable under-privileged people. From a population of 329 women who had reported their interest to participate, 245 were randomised to the programme. Of these 144 accepted participation in the research project and of these 123 women accepted to answer the SF-36 questionnaire. The participants were between 21 and 62 years with poor physical and mental health. They had received public financial support from <1 year to >10 years. The SF-36 measurement was carried out at baseline, after completion of Garden Therapy and after completion of SE. The results are based on data of respondents who participated at all the three occasions (n = 52). When comparing HRQoL baseline with the following occasions, the participants' General Health (GH), Vitality (VT), Social Functioning (SF) and mental health had improved significantly. The Four Leaf Clover (FLC) programme could be an appropriate method for reducing socially induced suffering. However, to conduct intervention studies where vulnerable persons are involved, it is off vital importance to consider whether the participants have the strength to complete the intervention. PMID:26346293

  1. [Topical therapy of balanitis xerotica obliterans in childhood. Long-term clinical results and an overview].

    PubMed

    Ebert, A-K; Vogt, T; Rösch, W H

    2007-12-01

    Balanitis xerotica obliterans (BXO) is a chronic and progressive dermatitis of unknown aetiology and incidence. Its management in childhood is controversial. Although in most cases only the prepuce is affected, meatal and urethral involvement may lead to major surgical reconstruction. Therefore complete surgical excision of the affected skin is considered to be mandatory. In case of involvement, incidental histological evidence or a relapse, or when complete removal of the affected skin is not possible, a topical therapy should be implemented. In a retrospective analysis of our study population (13 children) with BXO, relapse rate was lower after topical therapy with tacrolimus (Protopic), a highly selective immune modulator, than after the standard anti-inflammatory therapy with betamethasone. The use of tacrolimus ointment is a safe therapy with no severe side effects. Due to the fact that there are no predictive factors for progression or relapse of BXO, we consider a topical anti-inflammatory therapy is always indicated after any type of surgery for BXO. Follow-up monitoring should be close, so that any relapse can be detected and treated as early as possible. PMID:17994212

  2. Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences

    PubMed Central

    Li, Qianhong; Guo, Yiru; Tan, Wei; Stein, Adam B.; Dawn, Buddhadeb; Wu, Wen-Jian; Zhu, Xiaoping; Lu, Xiaoqin; Xu, Xiaoming; Siddiqui, Tariq; Tiwari, Sumit; Bolli, Roberto

    2013-01-01

    Previous studies have shown that gene therapy with inducible nitric oxide synthase (iNOS) protects against myocardial infarction at 3 days after gene transfer. However, the long-term effects of iNOS gene therapy on myocardial ischemic injury and cardiac function are unknown. To address this issue, we used a recombinant adenovirus 5 (Ad5) vector (Av3) with deletions of the E1, E2a, and E3 regions, which enables long-lasting recombinant gene expression for at least 2 mo due to lack of inflammation. Mice received intramyocardial injections in the left ventricular (LV) anterior wall of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 1 or 2 mo later, they were subjected to myocardial infarction (30-min coronary occlusion followed by 4 h of reperfusion). Cardiac iNOS gene expression was confirmed by immunoblotting and activity assays at 1 and 2 mo after gene transfer. In the iNOS group, infarct size (percentage of risk region) was significantly reduced (P < 0.05) both at 1 mo (24.2 ± 3.4%, n = 6, vs. 48.0 ± 3.6%, n = 8, in the LacZ group) and at 2 mo (23.4 ± 3.1%, n = 8, vs. 36.6 ± 2.4%, n = 7). The infarct-sparing effects of iNOS gene therapy were as powerful as those observed 24 h after ischemic preconditioning (23.1 ± 3.4%, n = 10). iNOS gene transfer had no effect on LV function or dimensions up to 8 wk later (echocardiography). These data demonstrate that iNOS gene therapy mediated by the Av3 vector affords long-term (2 mo) cardioprotection without inflammation or adverse functional consequences, a finding that provides a rationale for further preclinical testing of this therapy. PMID:16172153

  3. Association of β-blocker therapy with long-term clinical outcomes in patients with coronary chronic total occlusion.

    PubMed

    Hwang, Jin Kyung; Yang, Jeong Hoon; Hwang, Ji-Won; Jang, Woo Jin; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Lee, Sang Hoon; Gwon, Hyeon-Cheol; Choi, Seung-Hyuk

    2016-07-01

    There are limited data regarding the efficacy of β-blockers for secondary prevention in patients with coronary chronic total occlusion (CTO). Therefore, we investigated the association of β-blocker therapy with long-term clinical outcomes in CTO patients. From March 2003 to February 2012, a total of 2024 CTO patients treated with either medical therapy alone or revascularization were enrolled in the study. We assessed 1596 patients with stable ischemic heart disease and divided them into the β-blocker group (n = 932) and the no-β-blocker group (n = 664). The primary outcome was all-cause death. The median follow-up duration was 3.9 (interquartile range: 2.0-6.2) years. All-cause death occurred in 11.6% patients in the β-blocker group and 13.6% patients in the no-β-blocker group (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.61-1.08; P = 0.15). In the propensity score-matched population (570 pairs), all-cause death occurred in 12.3% patients in the β-blocker group and 12.8% patients in the no-β-blocker group (HR: 0.93, 95% CI: 0.67-1.29; P = 0.66). In subgroup analysis, β-blocker therapy was associated with better outcome, in terms of all-cause death, in patients with CTO of the left anterior descending coronary artery and Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score ≥23 (P for interaction = 0.01 and 0.02, respectively). In conclusion, β-blocker therapy was not associated with favorable long-term clinical outcomes in stable CTO patients, regardless of treatment strategy. However, β-blocker therapy might be beneficial in a highly selective group of CTO patients with a high ischemic burden. PMID:27472704

  4. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    PubMed

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future. PMID:27576727

  5. Comparison of the long-term effectiveness of progressive neuromuscular facilitation and continuous passive motion therapies after total knee arthroplasty.

    PubMed

    Alaca, Nuray; Atalay, Ayçe; Güven, Zeynep

    2015-11-01

    [Purpose] The aim of this longitudinal study was to examine the long term functional effectiveness of proprioceptive neuromuscular facilitation (PNF) after total knee arthroplasty. [Subjects and Methods] We included 30 patients and they were randomly assigned to two groups. In addition to the standard rehabilitation program the PNF group received proprioceptive neuromuscular facilitation therapy and the CPM group received continuous passive motion therapy. The outcome measures included range of motion using a goniometer, pain scores using a numeric pain rating scale, days to reach functional benchmarks, the Beck depression scale and isokinetic torque and isometric strength measurements. [Results] There were no significant differences between the two groups in terms of baseline demographic data, clinical findings and length of stay. Days to reach range of motion benchmarks were similar in the two groups. Pain at the 8th week was slightly higher in the PNF group. With the exception of walking with a walker, days to reach functional benchmarks were statistically significantly fewer in patients of the PNF group despite similar isokinetic measurements. Administration of PNF resulted in earlier functional gains in patients after total knee arthroplasty. These functional accomplishments were more pronounced in the PNF group despite it having isokinetic torque measurements similar to those of the CPM group. [Conclusion] PNF techniques can positively affect functional outcomes over the long term. PMID:26696702

  6. Comparison of the long-term effectiveness of progressive neuromuscular facilitation and continuous passive motion therapies after total knee arthroplasty

    PubMed Central

    Alaca, Nuray; Atalay, Ayçe; Güven, Zeynep

    2015-01-01

    [Purpose] The aim of this longitudinal study was to examine the long term functional effectiveness of proprioceptive neuromuscular facilitation (PNF) after total knee arthroplasty. [Subjects and Methods] We included 30 patients and they were randomly assigned to two groups. In addition to the standard rehabilitation program the PNF group received proprioceptive neuromuscular facilitation therapy and the CPM group received continuous passive motion therapy. The outcome measures included range of motion using a goniometer, pain scores using a numeric pain rating scale, days to reach functional benchmarks, the Beck depression scale and isokinetic torque and isometric strength measurements. [Results] There were no significant differences between the two groups in terms of baseline demographic data, clinical findings and length of stay. Days to reach range of motion benchmarks were similar in the two groups. Pain at the 8th week was slightly higher in the PNF group. With the exception of walking with a walker, days to reach functional benchmarks were statistically significantly fewer in patients of the PNF group despite similar isokinetic measurements. Administration of PNF resulted in earlier functional gains in patients after total knee arthroplasty. These functional accomplishments were more pronounced in the PNF group despite it having isokinetic torque measurements similar to those of the CPM group. [Conclusion] PNF techniques can positively affect functional outcomes over the long term. PMID:26696702

  7. AAV-based Neonatal Gene Therapy for Hemophilia A: Long-Term Correction and Avoidance of Immune Responses in Mice

    PubMed Central

    Hu, Chuhong; Lipshutz, Gerald S.

    2012-01-01

    Hemophilia A gene therapy has been hampered by immune responses to vector-associated antigens and by neutralizing antibodies or inhibitors to the factor VIII (FVIII) protein; these ‘inhibitors’ more commonly effect hemophilia A patients than those with hemophilia B. A gene replacement strategy beginning in the neonatal period may avoid the development of these immune responses and lead to prolonged expression with correction of phenotype thereby avoiding long-term consequences. Serotype rh10 AAV was developed splitting the FVIII coding sequence into heavy and light chains with the chicken β-actin promoter/CMV enhancer for dual recombinant AAV vector delivery. Coinjection of virions of each FVIII chain intravenously to mice on the second day of life was performed. Mice express sustained FVIII antigen levels of ≥5% to 22 months of life without the development of antibodies to FVIII. Phenotypic correction was manifest in all AAV-FVIII-treated mice as demonstrated by functional assay and reduction in bleeding time. This study demonstrates the use of AAV in a gene replacement strategy in neonatal mice that establishes both long-term phenotypic correction of hemophilia A and lack of antibody development to FVIII in this disease model where AAV is administered shortly after birth. These studies support consideration of gene replacement therapy for diseases that are diagnosed in utero or in the early neonatal period. PMID:22241178

  8. A Comparison of Short- And Long-Term Family Therapy for Adolescent Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Lock, James; Agras, W. Stewart; Bryson, Susan; Kraemer, Helena C.

    2005-01-01

    Objective: Research suggests that family treatment for adolescents with anorexia nervosa may be effective. This study was designed to determine the optimal length of such family therapy. Method: Eighty-six adolescents (12-18 years of age) diagnosed with anorexia nervosa were allocated at random to either a short-term (10 sessions over 6 months) or…

  9. Long-Term Effects of Brief Acceptance and Commitment Therapy for Psychosis

    ERIC Educational Resources Information Center

    Bach, Patricia; Hayes, Steven C.; Gallop, Robert

    2012-01-01

    A previous report explored the impact of a brief (four session) acceptance and commitment therapy (ACT) intervention as compared with treatment as usual (TAU) on rehospitalization over 4 months in a sample of 80 inpatients with psychosis. The present study extended the follow-up period to 1 year and used a more sophisticated survival analysis to…

  10. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

    PubMed Central

    Garcia-Chavez, Jaime; Montiel-Cervantes, Laura; Esparza, Miriam García-Ruiz; Vela-Ojeda, Jorge

    2007-01-01

    The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 × 109/l, partial remission (PR) if platelets were >50 × 109/l, minimal response (MR) if the platelet count was >30 × 109/l and <50 × 109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 × 109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. PMID:17874322

  11. Renal osteopenia - an assessment of long-term therapy with vitamin D analogues.

    PubMed

    Catto, G R; Junor, B J; Fraser, R A; Smith, F W; Ettinger, K V; Edward, N; MacLeod, M

    1979-01-01

    Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone. PMID:232916

  12. Long-term risks of psoralen and UV-A therapy for psoriasis

    SciTech Connect

    Farber, E.M.; Abel, E.A.; Cox, A.J.

    1983-05-01

    It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.

  13. Sustained Long-term Antiviral Maintenance Therapy in HCV/HIV Coinfected Patients (SLAM-C)

    PubMed Central

    Sherman, Kenneth E; Andersen, Janet W; Butt, Adeel A; Umbleja, Triin; Alston, Beverly; Koziel, Margaret J; Peters, Marion G; Sulkowski, Mark; Goodman, Zachary D; Chung, Raymond T

    2010-01-01

    Background HCV/HIV coinfection treatment is suboptimal with low SVR rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated-interferon maintenance therapy was performed by the NIH-funded ACTG network. Methods HCV treatment naïve and non-responding interferon-experienced subjects with confirmed HCV and HIV, CD4>200 cells/mm3, and at least Stage 1 fibrosis were enrolled, and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg/week (PEG) + weight-based ribavirin to determine response status. Non-responder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist. Results 330 subjects were enrolled; median age was 48 years; 43% White, 37% Black, non-Hispanic; 83% male; CD4+ 498 cells/mm3; 32% were interferon experienced; 74% had entry HIV RNA<50 cp/ml. EVR was observed in 55.9% and 42.5% achieved cEVR. A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm. Conclusion Lack of fibrotic progression in the control arm was unexpected, and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression and use of antiretroviral regimens that may be less toxic than prior generations of therapy. PMID:20921898

  14. Dermatofibrosarcoma Protuberans: Long-term Outcomes of 53 Patients Treated With Conservative Surgery and Radiation Therapy

    SciTech Connect

    Castle, Katherine O.; Guadagnolo, B. Ashleigh; Tsai, C. Jillian; Feig, Barry W.; Zagars, Gunar K.

    2013-07-01

    Purpose: To evaluate outcomes of conservative surgery and radiation therapy (RT) treatment in patients with dermatofibrosarcoma protuberans. Methods and Materials: We retrospectively reviewed the medical records of 53 consecutive dermatofibrosarcoma protuberans patients treated with surgery and preoperative or postoperative radiation therapy between 1972 and 2010. Median tumor size was 4 cm (range, 1-25 cm). Seven patients (13%) were treated with preoperative RT (50-50.4 Gy) and 46 patients (87%) with postoperative RT (60-66 Gy). Of the 46 patients receiving postoperative radiation, 3 (7%) had gross disease, 14 (30%) positive margins, 26 (57%) negative margins, and 3 (7%) uncertain margin status. Radiation dose ranged from 50 to 66 Gy (median dose, 60 Gy). Results: At a median follow-up time of 6.5 years (range, 0.5 months-23.5 years), 2 patients (4%) had disease recurrence, and 3 patients (6%) had died. Actuarial overall survival was 98% at both 5 and 10 years. Local control was 98% and 93% at 5 and 10 years, respectively. Disease-free survival was 98% and 93% at 5 and 10 years, respectively. The presence of fibrosarcomatous change was not associated with increased risk of local or distant relapse (P=.43). One of the patients with a local recurrence had gross residual disease at the time of RT and despite RT to 65 Gy developed both an in-field recurrence and a nodal and distant recurrence 3 months after RT. The other patient with local recurrence was found to have in-field recurrence 10 years after initial treatment. Thirteen percent of patients had an RT complication at 5 and 10 years, and 9% had a moderate or severe complication at 5 and 10 years. Conclusions: Dermatofibrosarcoma protuberans is a radioresponsive disease with excellent local control after conservative surgery and radiation therapy. Adjuvant RT should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins would result in significant morbidity.

  15. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study.

    PubMed

    Carrel, Aaron L; Myers, Susan E; Whitman, Barbara Y; Allen, David B

    2002-04-01

    Obesity, poor growth, and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a GH-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While short-term benefits of treatment with GH have been shown, whether these beneficial effects are dose dependent and persist or wane with prolonged therapy remains uncertain. Effects of 24 additional months of GH treatment at varying doses (0.3, 1.0, and 1.5 mg/m(2).d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 46 children with PWS, who had previously been treated with GH therapy (1 mg/m(2).d) for 12-24 months. Percent body fat, lean muscle mass, and bone mineral density (BMD) were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotient. A modified Bruininks-Oseretski test of physical performance evaluated strength and agility. During months 24-48 of GH therapy, continued beneficial effects on body composition (decrease in fat mass and increase in lean body mass), growth velocity, and REE occurred with GH therapy doses of 1.0 and 1.5 mg/m(2).d (P < 0.05), but not with 0.3 mg/m(2).d. BMD continued to improve at all doses of GH (P < 0.05). Prior improvements in strength and agility that occurred during the initial 24 months were sustained but did not improve further during the additional 24 months regardless of dose. Salutary and sustained GH-induced changes in growth, body composition, BMD, and physical function in children with PWS can be achieved with daily administration of GH doses > or =1 mg/m(2). Lower doses of GH, (0.3 mg/m(2).d) effective in improving body composition in GHD adults, do not appear to be effective in children with PWS at sustaining improvement in body composition. PMID:11932286

  16. Long-term captopril therapy in severe refractory congestive heart failure

    PubMed Central

    Steingo, L.; Pocock, W. A.; Flax, H.; Stein, M.; Barlow, J. B.

    1982-01-01

    1 The favourable haemodynamic effects of captopril in patients with congestive heart failure have been reported. 2 We have treated 25 patients with severe chronic congestive heart failure with captopril in doses of 75-450 mg daily. Before entering the study all patients remained in New York Heart Association functional class IV despite high-dose diuretic and vasodilator therapy. 3 Mean cardiothoracic ratio was 60%, and all patients had a shortening fraction of 18% or less on echocardiography (normal 25 to 40%). 4 Five patients died within one month of captopril and five between four and seven months, three of whom had improved to class IIM and one to IIS before death. 5 Of the 15 survivors one was referred for a heart transplant when he had improved to class IIM. The remaining 14 patients were followed for 8-16 months. Ten improved to New York Heart Association class I or IIS and four to class IIM or III. Diuretic requirements were decreased considerably in all 14. Side effects were common but captopril did not have to be withdrawn. Captopril is a highly effective drug in the treatment of patients with congestive heart failure refractory to currently accepted therapy. PMID:6753902

  17. Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

    PubMed Central

    Jordan, V. Craig

    2014-01-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

  18. Retrospective Long-Term Comparison of Naturopathic Fasting Therapy and Weight Reduction Diet in Overweight Patients

    PubMed Central

    Ismar, Lena Elisabeth; Wessely, Dominik Karl; Pötschke, Tanja; Weidner, Beate; Wiebelitz, Karl Rüdiger

    2014-01-01

    In a follow-up study overweight and obese patients fasting according to Buchinger (modified) and a control group treated by a weight reduction diet in the context of an inpatient naturopathic complex treatment were compared using a questionnaire developed for a standardized phone interview 6.8 ± 1.1 years after inpatient treatment. During the inpatient treatment the fasting patients significantly more body weight, but at the time of the interview significantly more weight was gained again. 10.7% of the fasting patients and 31.9% of the control group lowered their weight at least 5% of their initial weight up to the interview. 42% of the fasting and 74% of the control group persistently changed their diet. The control group followed a significantly higher number of trained nutritional aspects. 21% of the fasting and 40% of the control group increased their leisure activity permanently. Continued improvement in quality of life was achieved by 16% of the fasting patients and 28% of the control group. The fasting therapy, carried out as part of the inpatient naturopathic complex treatment, turned out to be less suitable for the treatment of overweight and obesity compared to standard therapy. One likely determinant is the minor poststationary lifestyle modification. PMID:25126098

  19. Acute and long-term effects of radioiodine therapy on serum levels of calcitonin

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

    The purpose of this study is to establish data on the radiosensitivity of thyroid C cells and medullary carcinoma of the thyroid (MCT) as reflected by the alterations in serum concentrations of calcitonin (Ct) after radioiodine therapy. Serum levels of Ct were measured by radioimmunoassay in 1437 patients subjected to diagnostic and therapeutic procedures for thyroid diseases. The effect of low dose and of high dose radioiodine therapy (RLO, RHI) was studied in 158 patients with hyperthyroidism and in 84 patients with thyroid cancer, respectively. RLO and RHI were followed by significant alterations in the distribution of Ct values. RLO decreased the occurrence of high values. RHI was followed by the absence of high concentrations and a substantial reduction in normal levels. The effect of RLO was confirmed in 47 patients by comparing their individual levels before and 8 weeks after RLO, the means +- SD being 24.3+-8.3 and 12.6+-5.7 pmol/l, respectively (p<0.001). In 30 patients followed up for late onset hypothyroidism who had been treated by RLO 10-25 years ago, the concentrations of Ct were almost normal (mean +- SD 16.6 +- 5.7 pmol/l).

  20. Long-term follow-up after coronary stenting and intravascular red laser therapy.

    PubMed

    De Scheerder, I; Wang, K; Nikolaychik, V; Kaul, U; Singh, B; Sahota, H; Keelan, M H; Kipshidze, N

    2000-11-01

    A high restenosis rate remains a limiting factor for coronary angioplasty and stenting. Recently, use of intravascular red light therapy (IRLT) has been shown to be effective in different animal models and in humans in reducing the restenosis rate. Sixty-eight patients were treated with IRLT in conjunction with coronary stenting procedures. Mean age was 64 +/- 9 years. Treated lesions were type A (11), type B (42), and type C (18) with a mean lesion length of 16.5 +/- 2.4 mm. Reference vessel diameter and minimal lumen diameter (MLD) before therapy were 2.90 +/- 0.15 and 1.12 +/- 0.36 mm, respectively. After stenting and laser irradiation, MLD was 2.76 +/- 0.39 mm. No procedural complications or in-hospital adverse events occurred. All patients were followed up as depicted in the protocol. Sixty-one patients underwent angiographic restudy, which revealed restenosis in 9 patients (14.7%). Observed restenosis rate by artery size was > 3 mm (n = 21, 0%), 2.5 to 3.0 mm (n = 28, 14.2%), and <2.5 mm (n = 12, 41.6%). We conclude that IRLT is safe and feasible and reduces the expected restenosis rate in patients after coronary stenting in arteries of >2.5 mm. PMID:11053701

  1. The Impact of Transarterial Therapy in Hepatitis C Related Hepatocellular Carcinoma on Long Term Outcomes after Liver Transplantation

    PubMed Central

    Cabrera, Roniel; Dhanasekaran, Renu; Caridi, James; Clark, Virgina; Morelli, Giuseppe; Soldevila-Pico, Consuelo; Magglioca, Joseph; Nelson, David; Firpi, Roberto Jose

    2011-01-01

    Objectives To evaluate the impact for long term outcomes of transarterial embolization (TAE) therapy in patients with HCV-related hepatocellular carcinoma (HCC) on the waiting list for liver transplantation (LT). Methods We retrospectively evaluated the post-LT patients with HCV-related HCC who received TAE intervention (n=33) and those who had no treatment (n=47) while on the waiting list to determine long term outcomes. Results Over a ten year period, of the 424 patients transplanted with HCV, 80 patients had HCC with a tumor burden within Milan criteria. For the entire study cohort the mean duration of post-LT follow-up was 3.5 yrs; mean time on transplant waiting list was 120 days; and median post-LT survival was 8.9 yrs. The survival rates at 1, 3, 5 and 10 yrs were 82%, 70%, 55% and 35%, respectively. From the study cohort, 33 patients received TAE and 47 patients did not while on the waiting list. The two groups were well matched, except, that the intervention subjects received post-LT interferon more often and had a shorter time on the waiting list (56.2 days) when compared to the no treatment group (164.6 days, p<0.001). Median survival in the TAE group was 4.8 yrs and 8.9 yrs in the no treatment group. The recurrence rate was 15.6% in the treatment group and 6.9% in the no therapy group (p=0.275). Conclusion Pre-LT transarterial therapy has no benefit on post-LT survival and tumor recurrence in patients with HCV related HCC who underwent a mean waiting period less than 3 months to transplant. PMID:21552101

  2. Long term therapy with a new liquid L-thyroxine preparation: bioequivalence with L-T4 tablets.

    PubMed

    Carpi, A; Toni, M G; Maccheroni, M; De Gaudio, C

    1992-12-01

    Seventy-four euthyroid patients with nodular goiter (55) or primary hypothyroidism (19) were selected for long term treatment with a new preparation containing L-T4 in solution (Tiroxen, Laboratori Baldacci, Pisa, Italy). Each patient underwent, before or after receiving the L-T4 in solution, long term treatment with L-T4 in tablet form at the same dose. The serum concentrations of TSH, TT4, TT3, FT4 and FT3 were measured basally and during therapy with each of the two L-T4 preparations (liquid and tablet). In the golter group, mean serum TSH concentration was 1.4 microUI/ml basally, while it was 0.47 microUI/ml following both L-T4 tablet therapy and L-T4 solution administration. Mean basal TSH value was significantly different from the two values on the therapy (p < 0.001 in each instance). Mean basal serum TT4 concentration was 8.2 +/- 0.25 microgram/dl basally while it was 9.9 +/- 0.28 microgram/dl (p < 0.001) on L-T4 tablet therapy and 9.7 +/- 0.26 (p < 0.001) on L-T4 solution administration. Mean basal serum concentration of TT3, FT4, FT3 was not significantly different from the value on the therapy, either with L-T4 tablet or with L-T4 solution. In the hypothyroid patients the high mean basal serum TSH concentration (23.6 microUI/ml) returned to normal similar values on L-T4 tablet therapy (0.96 microUI/ml; p < 0.01) and on L-T4 solution administration (1.24 microUI/ml; p < 0.01). The serum TSH concentration value during L-T4 therapy varied from unmeasurable level to 3.5 microUI/ml during the tablet administration and to 4.8 microUI/ml during the solution administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1285037

  3. [Combined arterial bypass operation and coumarin therapy--a concept for long-term management and its conditions].

    PubMed

    Kühnel, L; Heinrichs, C; Wache, I; Neugebauer, J

    1991-01-01

    Antithrombotics of cumarin type or with antiplatelet effect are preferred to obtain results from vascular surgical interventions in arterial occlusion disease. In our experience the combination with cumarin long term therapy seems to be the better method, especially if the following conditions can be achieved: very good compliance of patients respectively strict consideration of absolute and relative contraindications, a sufficient number of patients who are treated and a long enough experience of therapeutists followed by using the recommendations of the WHO expert committee for the worldwide application of standardization in measuring the anticoagulation effect, using reagents and calibration materials, and the expression of results in INR. Further in our anticoagulation behaviour we are used influencing risk factors, having a good cooperation between patients and doctors during secondary diseases and new drug intake. For dental surgery we prefer a Quick test between 30 and 35% activity or 1, 9 and 2, 1 INR. With Phenprocoumon (Falithrom, Markumar) we use the long term anticoagulation effect without several daily applications. Since September 1987 there has been the possibility of a computer assisted programme for dose prediction. PMID:1771568

  4. Preliminary long-term follow-up of Mindfulness-based cognitive therapy-induced remission of depression.

    PubMed

    Munshi, Krishna; Eisendrath, Stuart; Delucchi, Kevin

    2013-12-01

    Major depressive disorder (MDD) is often chronic and characterized by relapse and recurrence despite successful treatments to induce remission. Mindfulness-based cognitive therapy (MBCT) was developed as a means of preventing relapse for individuals in remission using cognitive interventions. In addition, MBCT has preliminarily been found to be useful in treating active depression. This current investigation is unique in evaluating the long-term outcome of individuals with active depression who achieved remission with MBCT. 18 participants who achieved remission after an 8-week MBCT group were seen for evaluation at a mean follow-up interval of 48.7 months (SD=10.2) after completing treatment. The current study shows that in these participants, the gains achieved after the initial treatment including remission of depression, decreased rumination, decreased anxiety, and increased mindfulness continued for up to 58.9 months of follow-up. The data suggests that all levels of depression from less recurrent and mild to more recurrent and severe were responsive to MBCT. The average number of minutes per week of continued practice in our cohort was 210, but the number of minutes of practice did not correlate with depression outcomes. MBCT's effects may be more related to regularity of practice than specific quantity. This study provides a preliminary exploration of MBCT's long-term effects, which can aid in future research with a typically chronic illness. PMID:24443660

  5. Ultrasound aspects in therapy-naive CIDP compared to long-term treated CIDP.

    PubMed

    Grimm, Alexander; Vittore, Debora; Schubert, Victoria; Rasenack, Maria; Décard, Bernhard F; Heiling, Bianka; Hammer, Nadin; Axer, Hubertus

    2016-06-01

    To investigate the use of nerve ultrasound (NUS) along with the European Federation of Neurological Societies (EFNS) guidelines and clinical scores in untreated, recently diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) vs. long-lasting treated CIDP. NUS and nerve conduction studies (NCS) of predefined nerves/cervical roots were performed in CIDP on diagnostic onset and "chronic-CIDP" (diagnosis and therapy >6 months), compared to controls. Nerve morphology was quantified using the modified ultrasound pattern sum score mUPSS, which is the sum of 3 ultrasound scores derived at 12 predefined measurement points and the homogeneity score (HS) in ulnar, median, and tibial nerve. 21 onset-CIDP, 21 "chronic-CIDP", and 21 age-matched controls were included. No differences in clinical scores or in the number of electrophysiologically affected nerves existed between the groups. Significantly enlarged cross-sectional areas of the nerves and diameters of the roots ensued already in onset-CIDP; however, with proximal predominance, whilst in chronic-CIDP, nerve enlargement was more prominent and ubiquitous. Increased UPS scores were shown in both patient groups compared to the controls. Significant differences between the patient groups were found particularly in the peripheral nerve score UPSA. Evaluation by means of HS revealed that the nerves in onset-CIDP were mostly regionally enlarged (often sparing distal segments) whereas in chronic-CIDP, nerves were more generalized enlarged. Onset- and chronic-CIDP show enlarged nerves and therefore increased mUPSS, however, nerve enlargement shows a more generalized pattern in chronic-CIDP compared to disease onset and correlates with disease duration and delayed therapy start, but not with disability. PMID:27017343

  6. Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy.

    PubMed

    Binley, Katie; Askham, Zoe; Iqball, Sharifah; Spearman, Hayley; Martin, Leigh; de Alwis, Mahesh; Thrasher, Adrian J; Ali, Robin R; Maxwell, Patrick H; Kingsman, Susan; Naylor, Stuart

    2002-10-01

    Anemia is a common clinical problem, and there is much interest in its role in promoting left ventricular hypertrophy through increasing cardiac workload. Normally, red blood cell production is adjusted through the regulation of erythropoietin (Epo) production by the kidney. One important cause of anemia is relative deficiency of Epo, which occurs in most types of renal disease. Clinically, this can be corrected by supplementation with recombinant Epo. Here we describe an oxygen-regulated gene therapy approach to treating homozygous erythropoietin-SV40 T antigen (Epo-TAg(h)) mice with relative erythropoietin deficiency. We used vectors in which murine Epo expression was directed by an Oxford Biomedica hypoxia response element (OBHRE) or a constitutive cytomegalovirus (CMV) promoter. Both corrected anemia, but CMV-Epo-treated mice acquired fatal polycythemia. In contrast, OBHRE-Epo corrected the hematocrit level in anemic mice to a normal physiologic level that stabilized without resulting in polycythemia. Importantly, the OBHRE-Epo vector had no significant effect on the hematocrit of control mice. Homozygous Epo-TAg(h) mice display cardiac hypertrophy, a common adaptive response in patients with chronic anemia. In the OBHRE-Epo-treated Epo-TAg(h) mice, we observed a significant reversal of cardiac hypertrophy. We conclude that the OBHRE promoter gives rise to physiologically regulated Epo secretion such that the hematocrit level is corrected to healthy in anemic Epo-TAg(h) mice. This establishes that a hypoxia regulatory mechanism similar to the natural mechanism can be achieved, and it makes EPO gene therapy more attractive and safer in clinical settings. We envisage that this control system will allow regulated delivery of therapeutic gene products in other ischemic settings. PMID:12239150

  7. Factors determining long-term outcomes of hepatocellular carcinoma within the Milan criteria: liver transplantation versus locoregional therapy

    PubMed Central

    Kim, Jung Hee; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Gyu-Seong; Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Ki Yeon; Kim, Kyunga; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    Abstract Patients with hepatocellular carcinoma (HCC) satisfying the Milan criteria are candidates for liver transplantation (LT), but locoregional therapies could be another options for them. A total of 1859 treatment-naïve HCC patients fulfilling the Milan criteria were analyzed. Survival tree analysis was performed to generate survival nodes with similar survival risks in 1729 non-LT group, and compared with the survival of 130 patients who received LT. Among patients who did not receive LT, survival tree analysis classified patients into 6 nodes according to Child-Pugh (CP) score, serum alphafetoprotein (AFP) levels, tumor size, and age, with different mortality risks (5-year survival rate of 87.3%, 77.5%, 65.8%, 64.7%, 44.0%, and 28.7% for nodes 1–6, respectively; P < 0.001). The overall survival of patients in nodes 1 (CP score 5 with AFP levels <5 ng/mL) and 2 (CP score 5 with maximal tumor size <2.5 cm) were comparable with that of patients who received LT (both P > 0.05), but the survival rates of patients in nodes 3 to 6 were worse than that of LT (P < 0.05 for all). In each survival node, survival differed slightly according to initial treatment modality for patients who did not receive LT. For patients who received LT, tumor stage at the time of LT was associated with long-term outcome. Certain groups of non-LT patients showed survival rates that were similar to the survival rates of LT patients. CP score, AFP levels, tumor size, and age were baseline factors that can help estimate the long-term outcomes of non-LT treatment. In addition, tumor stage at the time of LT and specific initial treatment modality in non-LT patients affected the long-term outcomes. These factors can help estimate the long-term outcomes of HCC patients diagnosed within the Milan criteria. PMID:27583916

  8. Recurrent pleomorphic adenoma of the parotid gland: Long-term outcome of patients treated with radiation therapy

    SciTech Connect

    Chen, Allen M. . E-mail: achen@radonc17.ucsf.edu; Garcia, Joaquin; Bucci, M. Kara; Quivey, Jeanne M.; Eisele, David W.

    2006-11-15

    Purpose: To evaluate the role of radiation therapy in the management of recurrent pleomorphic adenoma of the parotid gland. Methods and Materials: Between 1960 and 2004, 34 patients were treated with postoperative radiation therapy for recurrent pleomorphic adenoma of the parotid gland to a median dose of 5000 cGy (range, 4,500-6,000 cGy). Median age was 48 years (range, 24-72 years). Gross total resection at the time of surgery before radiation was achieved in 30 patients (88%), and histologic analysis demonstrated multifocal disease in 16 patients (47%). Radiation was delivered for a first, second, third, fourth, fifth, and sixth local recurrence in 24%, 21%, 24%, 24%, 6%, and 3% of patients, respectively. Results: With a median follow-up of 17.4 years (range, 2.3-28.9 years), 2 patients had local recurrences at a median of 3.4 years after completion of radiation. The 20-year actuarial local control rate was 94%. One patient developed a second malignancy at approximately 14 years after completion of therapy. Conclusion: The use of postoperative radiation therapy leads to excellent long-term local control for the treatment of recurrent pleomorphic adenoma with acceptable late toxicity. Although the incidence of second malignancy was low in this population, continued follow-up is warranted.

  9. Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine.

    PubMed

    Peura, David A; Freston, James W; Haber, Marian M; Kovacs, Thomas O; Hunt, Barbara; Atkinson, Stuart

    2009-05-01

    In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P<0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P<0.001). Symptom status correlated with healing (P=0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief. PMID:18726153

  10. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodeling in chronic asthma. PMID:25220646

  11. Cognitive-behavioral therapy for obsessive–compulsive disorder: access to treatment, prediction of long-term outcome with neuroimaging

    PubMed Central

    O’Neill, Joseph; Feusner, Jamie D

    2015-01-01

    This article reviews issues related to a major challenge to the field for obsessive–compulsive disorder (OCD): improving access to cognitive-behavioral therapy (CBT). Patient-related barriers to access include the stigma of OCD and reluctance to take on the demands of CBT. Patient-external factors include the shortage of trained CBT therapists and the high costs of CBT. The second half of the review focuses on one partial, yet plausible aid to improve access – prediction of long-term response to CBT, particularly using neuroimaging methods. Recent pilot data are presented revealing a potential for pretreatment resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy of the brain to forecast OCD symptom severity up to 1 year after completing CBT. PMID:26229514

  12. [Long-term oxygen therapy (LTOT)--what should physicians, homecare-providers and health insurance companies know?].

    PubMed

    Koehler, U; Hildebrandt, O; Jerrentrup, L; Koehler, K-I; Kianinejad, P; Sohrabi, K; Schäfer, H; Kenn, K

    2014-03-01

    Long-term oxygen treatment (LTOT) has been demonstrated to improve prognosis in patients with chronic respiratory insufficiency. In terms of pathogenesis, improved oxygenation, reduction of pulmonary artery pressure as well as reduction of respiratory work are important. Since there are considerable differences between the LTOT systems, individually tailored therapy is needed. In particular, the mobility aspects of the patients must be taken into consideration. It is important to distinguish between stationary/mobile devices with a liquid oxygen system and stationary/mobile devices with oxygen concentrator. Oxygen titration should be performed in relation to rest and activity phases (e. g. 6 minute walk test) as well as in relation to the sleep phase. Employing devices with demand-controlled valves should be critically examined. This can be undertaken only under physician orders and requires continuous monitoring. PMID:24595853

  13. Comparison of an oxygen concentrator and wall oxygen in the assessment of patients undergoing long term oxygen therapy assessment.

    PubMed

    Bolton, C E; Annandale, J A; Ebden, P

    2006-01-01

    Long term oxygen therapy (LTOT) is a recognised management option for hypoxaemic patients with chronic respiratory disease. Formal assessment is required which is usually conducted in the hospital and performed on piped oxygen to ensure correction of the hypoxaemia. However, an oxygen concentrator is the standard oxygen source for the patient at home who requires LTOT. The oxygen concentration delivered is lower from a concentrator than piped oxygen. Here, we present a study of ten hypoxaemic patients using both delivery sources in a cross-over design. The partial pressure of oxygen was lower in patients when receiving oxygen from a concentrator, p < 0.05. This encourages the Clinician to consider formal assessments on an oxygen concentrator in order to ensure that the hypoxaemia will be corrected when they are prescribed a concentrator for home use. PMID:16509177

  14. Cognitive-behavioral therapy for obsessive-compulsive disorder: access to treatment, prediction of long-term outcome with neuroimaging.

    PubMed

    O'Neill, Joseph; Feusner, Jamie D

    2015-01-01

    This article reviews issues related to a major challenge to the field for obsessive-compulsive disorder (OCD): improving access to cognitive-behavioral therapy (CBT). Patient-related barriers to access include the stigma of OCD and reluctance to take on the demands of CBT. Patient-external factors include the shortage of trained CBT therapists and the high costs of CBT. The second half of the review focuses on one partial, yet plausible aid to improve access - prediction of long-term response to CBT, particularly using neuroimaging methods. Recent pilot data are presented revealing a potential for pretreatment resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy of the brain to forecast OCD symptom severity up to 1 year after completing CBT. PMID:26229514

  15. [Is primary or secondary prevention of diabetes mellitus in hyperliporoteinemia possible under long-term clofibrate therapy?].

    PubMed

    Haller, H; Michaelis, D; Hanefeld, M; Leonhardt, W; Schulze, J

    1976-07-01

    The investigations of metabolism explained speak for an improved condition of the carbohydrate metabolism during the first months of the therapy. However, they are not sufficient to prove a preventive effect of clofibrat per se during long-term treatment. Our examinations by means of the glucose infusion test show that on certain defined conditions with intensive general treatment positive effects may be registered, which, however, cannot be reproduced in a large collective during outpatient care. On the contrary, it is to be assumed that the whole therapeutic regime has an influence. Nevertheless, one may establish that the incidence portion of the diabetes manifestation in patients with hyperlipoproteinaemia treated with regadrin corresponds nearly to that one of the average population of Dresden. It is puzzling that the death rate in patients with hyperlipoproteinaemia and diabetic condition of metabolism is significantly higher than in hyperlipoproteinaemia without disturbance of the carbohydrate metabolism. PMID:822610

  16. Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris.

    PubMed

    Tan, Jerry; Stein Gold, Linda; Schlessinger, Joel; Brodell, Robert; Jones, Terry; Cruz, Alma; Kerrouche, Nabil; Jarratt, Michael

    2012-02-01

    Few long-term treatment regimens for severe acne vulgaris have been investigated in clinical trials. Data were combined from two consecutive, randomized, double-blind, controlled studies to evaluate the efficacy, safety and subject satisfaction of four nine-month regimens in severe acne vulgaris treatment. Subjects were first randomized to receive doxycycline (DCN) and adapalene 0.1% - benzoyl peroxide 2.5% (A/BPO) or vehicle once daily for 12 weeks. Subjects who had at least 50% global improvement were subsequently randomized to receive A/BPO or its vehicle once daily for 24 weeks. Over nine months, there were four regimens: A/BPO and DCN followed by A/BPO, vehicle and DCN followed by A/BPO, A/BPO and DCN followed by vehicle, and vehicle and DCN followed by vehicle. Among the four regimens, A/BPO and DCN followed by A/BPO led to the highest percentage of subjects rated "clear" or "almost clear" (50.0% vs. 40.4%, 26.2% and 25.0%, respectively), biggest reduction in total lesion counts (76% vs. 70%, 51% and 47%, respectively) and greatest subject satisfaction (85.0% vs. 75.5%, 63.3% and 52.4%, respectively) at week 36. It provided a faster onset of action compared to groups started with vehicle and DCN (P<.05 at week 2). Subjects receiving A/BPO and DCN followed by vehicle experienced deterioration once the active treatment was discontinued. All regimens were safe and well-tolerated. In conclusion, efficacious initial therapy and long-term treatment are both important. An initial combination therapy with adapalene-BPO and DCN followed by longer-term adapalene-BPO treatment is an efficacious and satisfactory new regimen for severe acne subjects. PMID:22270198

  17. Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

    PubMed Central

    Hovi, Sirpa-Liisa; Veerus, Piret; Rahu, Mati; Hemminki, Elina

    2008-01-01

    Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a

  18. [Critical study of the indications for long-term oxygen therapy. Chronic obstructive bronchopneumopathies].

    PubMed

    Sadoul, P; Duwoos, H; Pretet, S

    1988-01-01

    Numerous studies have shown that longterm oxygen therapy in hypoxaemic patients with chronic airflow obstruction (BPCO) is capable of improving the prognosis and decreasing the risk of cardio-respiratory decompensation; in addition sometimes physical capacity and intellectual capacity is improved. Another result often noted is a reduction in the mean hospital stay which corresponds to an improvement in the quality of life. A PaO2 constantly below 55 mmHg (7.3 kPa) is defined by the majority of authors as a precarious state. At this level even a small change in alveolar ventilation or disturbance of distribution would lead to an important fall in the oxygen content of the arterial blood. The stability of the PaO2 during the weeks of respiratory reeducation with specially controlled medical treatment, as well as the willing consent of the patient and his family, are indispensable conditions for the prescription of OLT. When hypoxaemia is of moderate severity (PaO2 between 50 and 60 mmHg (6.6-8 kPa), prolonged medical treatment (with abstention from tobacco) for at least two months is advised and a study of complementary criteria to further validate the indications for oxygen. Such features would include a worsening of the hypoxaemia during exercise of 30 to 40 watts (PaO2 less than 50 mmHg, 6.6 kPa), an elevated haematocrit (greater than 55%), a rise of the P (A-a)O2 (greater than 30 mmHg or 4 kPa), a nocturnal desaturation even in the absence of apnoea (oxyhaemoglobin saturation (SaO2) of less than 80% for more than 50% of the time asleep). Added to these criteria are the radiological, echographic and clinical signs of the effect of hypoxaemia on the pulmonary circulation. Frank pulmonary arterial hypertension observed in hypoxaemia of moderate severity when the PaO2 is in the region of 55 mmHg and is an argument for the prescription of OLT. Amongst the developing criteria, exacerbations of respiratory encephalopathy, intellectual deterioration, progressive wasting

  19. Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of antiviral therapy.

    PubMed

    Ljungman, P; Locasciulli, A; de Soria, V G; Békássy, A N; Brinch, L; Espigado, I; Ferrant, A; Franklin, I M; O'Riordan, J; Rovira, M; Shaw, P; Einsele, H

    2012-09-01

    This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications. PMID:22158388

  20. Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases

    PubMed Central

    Thomas, Clare E.; Schiedner, Gudrun; Kochanek, Stefan; Castro, Maria G.; Löwenstein, Pedro R.

    2000-01-01

    Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity adenoviral (HC-Ad) vectors succeed in maintaining long-term transgene expression in the brain, even in the presence of an active peripheral immunization with adenovirus that completely eliminates expression from first-generation vectors within 60 days. Importantly, even 60 days after the peripheral infection, brains injected with first-generation vectors exhibited evidence of a chronic infiltration of CD8+ cells, macrophage/microglial activation, and up-regulation of brain MHC-I expression. No inflammation was observed in the brains injected with the HC-Ad vector. Thus, these results demonstrate that HC-Ad vectors will allow safe, stable, and long-term transgene expression in the brain, even in the presence of peripheral infection with adenovirus. This markedly improves the prospects for the use of adenoviral vectors for long-term gene therapy of neurological disorders. PMID:10840055

  1. Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

    SciTech Connect

    Ha Vu-Nishino; Tavassoli, Fattaneh A.; Ahrens, Willam A.; Haffty, Bruce G. . E-mail: hafftybg@umdnj.edu

    2005-07-15

    Purpose: The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up. Methods and Materials: Chart records of patients with invasive breast cancer managed with breast-conserving therapy (BCT) at the therapeutic radiology facilities of Yale University School of Medicine before 2001 were reviewed. Forty-six cases (1971-2001) were identified with medullary histology; 1,444 patients with infiltrating ductal carcinoma served as a control group. Results: The medullary cohort presented at a younger age with a higher percentage of patients in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve patients with medullary histology underwent genetic screening, and 6 patients were identified with deleterious mutations. This group showed greater association with BRCA1/2 mutations compared with screened patients in the control group (50.0% vs. 15.8%, p 0.0035). The medullary cohort was also significantly associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2 vs. 2.5 cm, p 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001) and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow-up times for the medullary and control groups were 13.9 and 14.0 years, respectively. Although breast relapse-free rates were not significantly different (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028). Conclusions: Despite poor clinicopathologic features, patients with medullary histology demonstrate favorable long-term distant relapse-free survival. Local control rates of patients with medullary and infiltrating ductal carcinoma are comparable. These findings suggest that patients diagnosed with medullary carcinoma are appropriate candidates for

  2. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    SciTech Connect

    Fujita, Tetsuo; Teh, Bin S.; Mai, W.-Y.; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-05-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR{sup +}CD8{sup +} T cells were increased at all timepoints up to 8 months. The mean percentages of DR{sup +}CD4{sup +} T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.

  3. Mitochondrial DNA mutations in blood samples from HIV-1-infected children undergoing long-term antiretroviral therapy.

    PubMed

    Ouyang, Yabo; Qiao, Luxin; Liu, Kai; Zang, Yunjin; Sun, Yu; Dong, Yaowu; Liu, Daojie; Guo, Xianghua; Wei, Feili; Lin, Minghua; Zhang, Fujie; Chen, Dexi

    2016-07-01

    We have analyzed mutations in whole mitochondrial (mt) genomes of blood samples from HIV-1-infected children treated with long-term antiretroviral therapy (ART), who had an excellent virological response. HIV-1-infected children who have undergone ART for 4 y with an excellent virological response (group A; 15 children) and ten healthy children (controls) without HIV-1 infection were enrolled retrospectively. Peripheral blood mononuclear cells (PBMCs) were obtained and mt DNA mutations were studied. The total number of mtDNA mutations in group A was 3 H more than in the controls (59 vs. 19, P<0.001) and the same trend was seen in all mtDNA regions. Among these mtDNA mutations, 140 and 28 mutations were detected in group A and the controls, respectively. The D-loop, CYTB and 12s rRNA were the three most common mutation regions in both groups, with significant differences between the groups observed at nucleotide positions C309CC, T489C CA514deletion, T16249C and G16474GG (D-loop); T14783C, G15043A, G15301A, and A15662G (CYTB); and G709A (12s rRNA). G15043A and A15662G had been associated with mitochondrial diseases. Our findings suggest that mtDNA mutations occur frequently in long-term ART-treated, HIV-1-infected children who have an excellent virological response, although they did not have obvious current symptoms. The CYTB region may play an important role in mtDNA mutation during ART, which might contribute to the development of subsequent mitochondrial diseases. PMID:27402477

  4. Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

    SciTech Connect

    Kim, Julian O.; Ma, Roy; Akagami, Ryojo; McKenzie, Michael; Johnson, Michelle; Gete, Ermias; Nichol, Alan

    2013-11-01

    Purpose: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. Methods and Materials: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. Results: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. Conclusion: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.

  5. Immediate results and long-term cardiovascular outcomes of endovascular therapy in octogenarians and nonoctogenarians with peripheral arterial diseases

    PubMed Central

    Huang, Hsuan-Li; Jimmy Juang, Jyh-Ming; Chou, Hsin-Hua; Hsieh, Chien-An; Jang, Shih-Jung; Cheng, Shih-Tsung; Ko, Yu-Lin

    2016-01-01

    Purpose To investigate the clinical outcomes of endovascular therapy (EVT) in octogenarians and nonoctogenarians with peripheral arterial disease. Methods A retrospective analysis of 511 patients (654 affected legs) who underwent EVT between July 2005 and December 2013 was conducted in a prospectively maintained database. Immediate results and long-term vascular outcomes were analyzed and compared between octogenarians and nonoctogenarians. Results Octogenarians were more likely to be female and have atrial fibrillation (AF), whereas nonoctogenarians had higher rates of obesity, claudication, and medical comorbidities. There were no differences in the rates of EVT success, 30-day major adverse vascular events, and 6-month functional improvement between groups. Over the 10-year follow-up period, the rates of 3-year limb salvage, sustained clinical success, freedom from major cerebrovascular and cardiovascular events, and composite vascular events were similar between groups, but the survival rate was better in nonoctogenarians than in octogenarians (73% vs 63%, respectively, P=0.004). In Cox regression analysis, dependence on dialysis and AF were significant predictors of death (odds ratio [OR] 4.44 in dialyzed and 2.83 in AF patients), major cerebrovascular and cardiovascular events (OR 3.49 and 2.45), and composite vascular events (OR 3.14 and 2.25). Conclusion EVT in octogenarians was feasible, without an increased risk of periprocedural complications. The rates of limb salvage, sustained clinical success, and long-term vascular events were comparable between groups. Dialysis dependence and AF are independent predictors for poor prognosis in patients with peripheral arterial disease. However, these observations require further confirmation in larger scale studies. PMID:27217735

  6. Bone mineral density, microarchitectural and mechanical alterations of osteoporotic rat bone under long-term whole-body vibration therapy.

    PubMed

    Xie, Pengfei; Tang, Zhurong; Qing, Fangzhu; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

    2016-01-01

    Low-magnitude, high-frequency whole body vibration (WBV) is receiving increasing interest as a non-pharmacological anti-osteoporosis approach. However, the long-term effect of WBV therapy is seldom studied. In this study, the efficacy of 16-week WBV (0.3g, 30 Hz) on bone mineral density (BMD), microarchitectural parameters and mechanical properties of ovariectomized rat femur were examined by in vivo peripheral quantitative computed tomography (pQCT), ex vivo micro-computed tomography (µCT), dynamic mechanical analysis (DMA) and fracture test. To the best of our knowledge, 16 weeks of WBV administration (20 min/day) is currently the longest duration on rodent. The longitudinal BMD change showed that positive effect of WBV on ovariectomized rat femoral neck diminished with prolonged administration duration. In addition, 16-week of WBV treatment was found to cause significantly reduction in the mean BMD, trabecular BMD (Tb.BMD), trabecular bone volume ration (BV/TV), trabecular number (Tb.N) and maximum load in femoral neck of ovariectomized rat. Metaphyseal Tb.BMD and BV/TV were also significantly decreased in WBV treated ovariectomized group than non-treated controls. Whole-femur DMA was demonstrated as a sensitive tool in distinguishing osteoporotic femur from healthy aged-matched controls, in terms of decreased storage modulus (E') and loss factor (tan δ). However, E' and tan δ are not enhanced by 16-week WBV treatment. Together, these findings indicate that administration duration played an important role in the effect of WBV. 16-week WBV may exacerbate trabecular bone loss in ovariectomized rat femur, especially in trabecular-rich femoral neck region. An optimal WBV protocol including administration duration should be established prior to long-term clinical practice. PMID:26398779

  7. Continuing Risk of Ipsilateral Breast Relapse After Breast-Conserving Therapy at Long-Term Follow-up

    SciTech Connect

    Kreike, Bas; Hart, Augustinus A.M.; Velde, Tony van de; Borger, Jacques; Peterse, Hans; Rutgers, Emiel; Bartelink, Harry; Vijver, Marc J. van de

    2008-07-15

    Purpose: Currently, the local treatment of most patients with early invasive breast cancer consists of breast-conserving therapy (BCT). We have previously reported on the risk factors for ipsilateral breast relapse (IBR) in 1,026 patients treated with BCT after a median follow-up of 5.5 years. In the present study, we evaluated the IBR incidence and the risk factors for IBR after prolonged follow-up. Methods and Materials: We updated the disease outcome for all 1,026 patients using the clinical information collected from the medical registration of The Netherlands Cancer Institute and performed step-wise proportional hazard Cox regression analysis to identify the risk factors associated with an increased risk of IBR after BCT at long-term follow-up. Results: After a median follow-up of 13.3 years, 114 patients had developed an IBR as the first event. The IBR rate was 9.3% and 13.8%, respectively, at 10 and 15 years. Also, the increase in IBR was continuous without reaching a plateau, even after 15 years. Univariate analysis showed that involved surgical resection margins, young age, vascular invasion, and the presence and quantity of an in situ component are risk factors for IBR. Multivariate analysis showed that tumor-positive surgical resection margins (hazard ratio, 2.9; 95% confidence interval, 1.7-5.2, p = 0.0002) or the presence of vascular invasion (hazard ratio, 2.0; 95% confidence interval, 1.2-3.2, p = 0.004) is the major independent risk factor for IBR. Conclusions: The data from long-term follow-up showed a constant increase in IBR among patients treated by BCT, even after 15 years, without reaching a plateau. Involved surgical resection margins and vascular invasion were the most important risk factors for IBR.

  8. Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy

    PubMed Central

    Bicanic, Iva; de Roos, Carlijn; van Wesel, Floryt; Sinnema, Gerben; van de Putte, Elise

    2014-01-01

    Background Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. Aim The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents’ group on rape-related symptomatology in female adolescents (13–18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Methods Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Results Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. Conclusions The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own. PMID:24936285

  9. Mechanisms of Fibroblast Cell Therapy for Dystrophic Epidermolysis Bullosa: High Stability of Collagen VII Favors Long-term Skin Integrity

    PubMed Central

    Kern, Johannes S; Loeckermann, Stefan; Fritsch, Anja; Hausser, Ingrid; Roth, Wera; Magin, Thomas M; Mack, Claudia; Müller, Marcel L; Paul, Oliver; Ruther, Patrick; Bruckner-Tuderman, Leena

    2009-01-01

    Here, we report on the first systematic long-term study of fibroblast therapy in a mouse model for recessive dystrophic epidermolysis bullosa (RDEB), a severe skin-blistering disorder caused by loss-of-function of collagen VII. Intradermal injection of wild-type (WT) fibroblasts in >50 mice increased the collagen VII content at the dermal–epidermal junction 3.5- to 4.7-fold. Although the active biosynthesis lasted <28 days, collagen VII remained stable and dramatically improved skin integrity and resistance to mechanical forces for at least 100 days, as measured with a digital 3D-skin sensor for shear forces. Experiments using species-specific antibodies, collagen VII–deficient fibroblasts, gene expression analyses, and cytokine arrays demonstrated that the injected fibroblasts are the major source of newly deposited collagen VII. Apart from transitory mild inflammation, no adverse effects were observed. The cells remained within an area ≤10 mm of the injection site, and did not proliferate, form tumors, or cause fibrosis. Instead, they became gradually apoptotic within 28 days. These data on partial restoration of collagen VII in the skin demonstrate the excellent ratio of clinical effects to biological parameters, support suitability of fibroblast-based therapy approaches for RDEB, and, as a preclinical test, pave way to human clinical trials. PMID:19568221

  10. Long-term follow-up study of compensated low-dose /sup 131/I therapy for Graves' disease

    SciTech Connect

    Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

    1984-08-16

    We treated 187 patients who had Graves' disease with low-dose radioactive iodide (/sup 131/I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after /sup 131/I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose /sup 131/I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with /sup 131/I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism.

  11. The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

    SciTech Connect

    Orman, Amber; Koru-Sengul, Tulay; Miao, Feng; Markoe, Arnold; Panoff, Joseph E.

    2014-12-01

    Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

  12. Protective Effect of Long-Term CPAP Therapy on Cognitive Performance in Elderly Patients with Severe OSA: The PROOF Study

    PubMed Central

    Crawford-Achour, Emilie; Dauphinot, Virginie; Saint Martin, Magali; Tardy, Magali; Gonthier, Régis; Barthelemy, Jean Claude; Roche, Frédéric

    2015-01-01

    Objective: Obstructive sleep apnea syndrome (OSA) leads to a deterioration in cognitive functions, with regard to memory and executive functions. However, few studies have investigated the impact of treatment on these cognitive functions in elderly subjects. Methods: The study was conducted in a large cohort of subjects aged 65 years or older (the PROOF cohort). Subjects were not diagnosed or treated for OSA. Subjects underwent a polygraphic recording. Cognitive performance was assessed in all OSA subjects at baseline and 10 years later, whether or not they were receiving continuous positive airway pressure (CPAP) therapy. Results: A group of 126 patients were analyzed. Only 26% of them were treated, with therapy initiated at the discretion of the primary care physician. Among treated subjects, self-reported compliance with therapy was good (> 6 h/night on average), and 66% of them reported an improvement in their quality of life. Patients receiving CPAP treatment had a higher apneahypopnea index (p = 0.006), a higher oxygen desaturation index (p < 0.001), and experienced more pronounced daytime repercussions (p = 0.004). These patients showed a statistically significant improvement in mental agility (similarities test; p < 0.0001) and memory performance (Grober and Buschke delayed free recall; p = 0.02). Conclusion: CPAP treatment is associated with the maintenance of memory performance over time. Citation: Crawford-Achour E, Dauphinot V, Saint Martin M, Tardy M, Gonthier R, Barthelemy JC, Roche F. Protective effect of long-term CPAP therapy on cognitive performance in elderly patients with severe OSA: the PROOF study. J Clin Sleep Med 2015;11(5):519–524. PMID:25700873

  13. Chloroquine: Ophthalmological Safety, and Clinical Assessment in Rheumatoid Arthritis

    PubMed Central

    Percival, S. P. B.; Meanock, I.

    1968-01-01

    272 patients on long-term chloroquine therapy were assessed with respect to ocular toxicity and clinical benefit. A simple scheme for rendering patients ophthalmologically safe is presented, employing the recording of central fields to red targets. Under this it was possible to diagnose a state of premaculopathy, which was reversible on stopping treatment. The incidence of premaculopathy was 41% in 143 patients who otherwise displayed no abnormality of the fundus oculi and who had received a mean total dose of 410 g. of chloroquine phosphate or the hydroxychloroquine sulphate equivalent. Under this joint ophthalmological and rheumatological supervision it was considered that the minor side-effects that may be caused by chloroquine are outweighed by its therapeutic value. ImagesFig. 3 PMID:4875645

  14. Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

    PubMed Central

    Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

    2014-01-01

    Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

  15. Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors

    PubMed Central

    Kitano, Hisataka; Mamiya, Atsushi; Ishikawa, Tomomi; Egoshi, Kayo; Kokubun, Shinichiro; Hidai, Chiaki

    2016-01-01

    Cancer gene therapy using nonviral vectors is useful for long periods of treatment because such vectors are both safe and inexpensive, and thus can be used repeatedly. It has been reported that gene therapy with an E3C1 fragment of Del1 in a mouse explanted tumor model improved prognosis. The present study aimed to analyze the long-term effects of repeated non-viral gene transfer of E3C1. Mice with explanted tumors of SCCKN cells, a human squamous carcinoma, were treated with a plasmid encoding E3C1. Plasmids were injected locally every week using a transfection reagent. Control mice treated with mock DNA started to be euthanized on day 18, because the tumors had grown to over 15% of the body weight, and all of them had died by day 43. On the other hand, the tumors in two of ten mice treated with E3C1 had disappeared. The other eight mice started to be euthanized on day 46 and eight of ten mice had been euthanized by day 197. After 18 days of therapy, the tumor volume of control mice was 2,804±829 mm3 and that of the E3C1 mice was 197±159 mm3. Histochemical studies showed enhanced apoptosis in the E3C1-treated tumors, as compared with controls. Changes in cell morphology and decreased polymerized actin induced by E3C1 indicated disturbed cell adhesion to the matrix. In in vitro studies of SCCKN cells, prolonged administration of an E3C1 recombinant protein to cultured cells reduced adhesion-independent growth of cancer cells, as compared with control cells. These data suggest that E3C1 treatment induces anoikis. PMID:26889088

  16. Long-Term Continuous Positive Airway Pressure Therapy Normalizes High Exhaled Nitric Oxide Levels in Obstructive Sleep Apnea

    PubMed Central

    Chua, Ai-Ping; Aboussouan, Loutfi S.; Minai, Omar A.; Paschke, Kelly; Laskowski, Daniel; Dweik, Raed A.

    2013-01-01

    Study Objectives: Upper airway inflammation and oxidative stress have been implicated in the pathogenesis of obstructive sleep apnea (OSA) and may be linked to cardiovascular consequences. We prospectively examined fraction of exhaled nitric oxide (FENO), a surrogate marker of upper airway inflammation using a portable nitric oxide analyzer (NIOX MINO). Design: In consecutive adult nonsmokers with suspected OSA, FENO was measured immediately before and after polysomnographic studies, and within 1-3 months following continuous positive airway pressure (CPAP) therapy. Measurement and Results: FENO levels were increased in the 75 patients with OSA compared to the 29 controls, both before sleep (13.4 ± 6.5 ppb vs. 6.5 ± 3.5; p < 0.001) and after sleep (19.0 ± 7.7 ppb vs. 6.9 ± 3.7; p < 0.001). Furthermore, in patients with OSA, FENO levels were significantly higher post-sleep than pre-sleep (19.0 ± 7.7 ppb vs. 13.4 ± 6.5; p < 0.001), while there was no significant overnight change in patients without OSA. The rise in FENO correlated with the apnea-hypopnea index (r = 0.65, p < 0.001), nadir oxygen saturation (r = 0.54, p < 0.001), and arousal index (r = 0.52, p < 0.001). Thirty-seven of these patients underwent CPAP titration and treatment. Successful titration was associated with a lower overnight increase in FENO (7.2 ± 3.3 vs. 11.0 ± 4.3, p = 0.02). FENO levels declined after 1-3 months of CPAP therapy (11.7 ± 4.4 ppb, p < 0.001). Conclusions: FENO levels are elevated in OSA, correlate with severity, and decrease after positive pressure therapy. This study supports the role of upper airway inflammation in OSA pathogenesis and a possible role for FENO in monitoring CPAP therapy. Citation: Chua AP; Aboussouan LS; Minai OA; Paschke K; Laskowski D; Dweik RA. Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea. J Clin Sleep Med 2013;9(6):529-535. PMID:23772184

  17. Stepped care model of pain management and quality of pain care in long-term opioid therapy.

    PubMed

    Moore, Brent A; Anderson, Daren; Dorflinger, Lindsey; Zlateva, Ianita; Lee, Allison; Gilliam, Wesley; Tian, Terrence; Khatri, Khushbu; Ruser, Christopher B; Kerns, Robert D

    2016-01-01

    Successful organizational improvement processes depend on application of reliable metrics to establish targets and to monitor progress. This study examined the utility of the Pain Care Quality (PCQ) extraction tool in evaluating implementation of the Stepped Care Model for Pain Management at one Veterans Health Administration (VHA) healthcare system over 4 yr and in a non-VHA Federally qualified health center (FQHC) over 2 yr. Two hundred progress notes per year from VHA and 150 notes per year from FQHC primary care prescribers of long-term opioid therapy (>90 consecutive days) were randomly sampled. Each note was coded for the presence or absence of key dimensions of PCQ (i.e., pain assessment, treatment plans, pain reassessment/outcomes, patient education). General estimating equations controlling for provider and facility were used to examine changes in PCQ items over time. Improvements in the VHA were noted in pain reassessment and patient education, with trends in positive directions for all dimensions. Results suggest that the PCQ extraction tool is feasible and may be responsive to efforts to promote organizational improvements in pain care. Future research is indicated to improve the reliability of the PCQ extraction tool and enhance its usability. PMID:27006068

  18. Expression of oral cytokines in HIV-infected subjects with long-term use of antiretroviral therapy

    PubMed Central

    Nittayananta, Wipawee; Amornthatree, Korntip; Kemapunmanus, Marisa; Talungchit, Sineepat; Sriplung, Hutcha

    2013-01-01

    Objectives The objectives of this study were to determine 1) the expression of oral pro-inflammatory cytokines in HIV-infected subjects compared with non-HIV individuals, 2) the cytokine expression in the subjects with antiretroviral therapy (ART) compared with those without ART, and 3) factors associated with the expression of the cytokines. Materials and methods Oral examination was performed and saliva samples were collected and analyzed for the expression of pro-inflammatory cytokines using ELISA. Logistic regression analysis was performed to determine the association between HIV/ART status and the cytokine expression. Results One hundred and fifty-seven HIV-infected subjects with and without ART, and 50 non-HIV individuals were enrolled. TNF-α and IL-6 in saliva were significantly decreased, while IL-8 was significantly increased in HIV infection (p< 0.05). Changes in the expression of IL-8 was also observed between HIV-infected subjects who were and were not on ART (p< 0.05). Duration of HIV infection and smoking were significantly associated with the expression of pro-inflammatory cytokines in saliva (p< 0.05). Conclusion Oral innate immunity is affected by HIV infection and use of ART. IL-8 may be the useful biomarker to identify subjects at risk of infection and malignant transformation due to HIV infection and long-term use of ART. PMID:23718561

  19. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  20. The adequacy of oxygenation in COPD patients undergoing long-term oxygen therapy assessed by pulse oximetry at home.

    PubMed

    Sliwiński, P; Lagosz, M; Górecka, D; Zieliński, J

    1994-02-01

    It is probable that some daily activities may cause marked falls in arterial oxygen saturation (SaO2) in patients undergoing long-term oxygen therapy (LTOT), despite good oxygenation at rest. We estimated the adequacy of LTOT in 34 randomly selected chronic obstructive pulmonary disease (COPD) patients at home by monitoring SaO2 continuously over 24 h. The subjects were also asked to complete a questionnaire listing frequent daily activities. Despite almost normal mean SaO2 (94%) at the beginning of recording (O2 2 l.min-1, at rest) the subjects studied spent 6.9 h below an SaO2 of 90%, with minimum SaO2 of 61%. On average we observed 10 episodes of desaturation in each patient over 24 h, both while breathing air and oxygen. The comparison of SaO2 recordings and questionnaires revealed the highest number of desaturations during sleep, followed by naps, watching the television, eating, washing and talking. The oxygen flow rate prescribed, based on blood gas measurements at rest, did not protect 85% of the patients studied from deep falls in SaO2 during daily life. An increase oxygen flow during some activities and during sleep is suggested. PMID:8162980

  1. Implementation of a telehealth programme for patients with severe chronic obstructive pulmonary disease treated with long-term oxygen therapy.

    PubMed

    Jódar-Sánchez, Francisco; Ortega, Francisco; Parra, Carlos; Gómez-Suárez, Cristina; Jordán, Ana; Pérez, Pablo; Bonachela, Patricia; Leal, Sandra; Barrot, Emilia

    2013-01-01

    We conducted a pilot study of the effectiveness of home telehealth for patients with advanced chronic obstructive pulmonary disease treated with long-term oxygen therapy. Patients were randomized into a telehealth group (n = 24) and a control group (n = 21) who received usual care. Patients in the telehealth group measured their vital signs on weekdays and performed spirometry on two days per week. The data were transmitted automatically to a clinical call centre. After four months of monitoring the mean number of accident and emergency department visits in the telehealth group was slightly lower than in the control group (0.29 versus 0.43, P = 0.25). The mean number of hospital admissions was 0.38 in the telehealth group and 0.14 in the control group (P = 0.47). During the study a total of 40 alerts were detected. The clinical triage process detected eight clinical exacerbations which were escalated by the case manager for a specialist consultation. There were clinically important differences in health-related quality of life in both groups. The mean score on the SGRQ was 10.9 versus 4.5 in the control group (P = 0.53). The EuroQol-5D score improved by 0.036 in the telehealth group and by 0.003 in the control group (P = 0.68). Both patients and healthcare professionals showed a high level of satisfaction with the telehealth programme. PMID:23393057

  2. A cytogenic evaluation of long-term colchicine therapy in the treatment of Familial Mediterranean fever (FMF).

    PubMed

    Cohen, M M; Levy, M; Eliakim, M

    1977-01-01

    Thirty-eight patients suffering from Famlial Mediterranean Fever (FMF) and undergoing colchicine therapy for periods varying from one week to three years were examined cytogenetically. Preparations were derived from short-term lymphocyte cultures; mitotic rate, percent tetraploidy, and chromosome breakage rates were determined. Twenty-one patients were examined prior to treatment, 22 during treatment and 5 both before and during treatment and 5 both before and during treatment. No statistically significant differences were observed in the parameters studied between ten controls and the patient groups. An in vitro experiment indicated a direct correlation between increased colchicine concentration and mitotic rate. However, tetrapoloidy or chromosome damage showed no such association with colchicine concentration. Among the patient group, pregnancy occurred in four patients while under treatment; three pregnancies resulted in the birth of normal children while the fourth has not yet been completed. In one preganancy, cultured fetal amniotic fluid cells demonstrated no effect of colchicine on the cytogenetic parameters invetigated. These results indicate no untoward effects on long-term colchicine treatment in FMF with respect to fertility, teratogenicity and chromosomal damage. PMID:602955

  3. Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy--Long-Term Outcome of a Phase II Pilot Study.

    PubMed

    Wagner, Andrej; Wiedmann, Marcus; Tannapfel, Andrea; Mayr, Christian; Kiesslich, Tobias; Wolkersdörfer, Gernot W; Berr, Frieder; Hauss, Johann; Witzigmann, Helmut

    2015-01-01

    Hilar cholangiocarcinoma (CC) is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0) recurrence can be as high as 70%. Photodynamic therapy (PDT) is an established palliative local tumor ablative treatment for non-resectable hilar CC. We report the long-term outcome of curative resection (R0) performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years) with initially non-resectable hilar CC. Photofrin(®) was injected intravenously 24-48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0) resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments--however, this concept needs to be validated in a larger trial. PMID:26561801

  4. Long-Term Clinical Remission in Biologically Naïve Crohn's Disease Patients with Adalimumab Therapy, Including Analyses of Switch from Adalimumab to Infliximab

    PubMed Central

    Mizoshita, Tsutomu; Tanida, Satoshi; Ozeki, Keiji; Katano, Takahito; Shimura, Takaya; Mori, Yoshinori; Kubota, Eiji; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

    2016-01-01

    There is little evidence regarding the maintenance of long-term clinical remission by adalimumab (ADA) therapy in Crohn's disease (CD) patients naïve to anti-tumor necrosis factor treatment (naïve CD patients), since most CD patients are treated with ADA after infliximab (IFX) therapy. The long-term clinical response to ADA was retrospectively analyzed in 17 naïve CD patients for at least 24 months, and the serum trough IFX levels were evaluated in patients switching from ADA to IFX. Of the 17 naïve CD patients, 14 (82.4%) maintained long-term clinical remission with ADA therapy for at least 24 months, without serious adverse events. The clinical condition of 7 patients was observed for more than 36 months, and 3, 1, 1, and 2 cases maintained remission at months 42, 48, 54, and 60 after ADA therapy, respectively. Three patients (17.6%) switched from ADA to IFX less than 24 months after the start of ADA therapy, and they had remission, retaining trough levels of IFX higher than 1 μg/ml, occasionally by dose escalation. In conclusion, maintenance ADA therapy achieves long-term clinical remission in naïve CD patients. Switching from ADA to IFX is an important therapeutic option in CD patients showing loss of response to ADA, occasionally with dose escalation, based on the analysis of serum IFX trough levels.

  5. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

    PubMed Central

    Mansur, Adel H.; Pertseva, Tetyana; Kaiser, Kirsten; McIver, Tammy; Grothe, Birgit; Dissanayake, Sanjeeva

    2016-01-01

    Abstract Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively. Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be

  6. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.

    PubMed

    Harrison, C N; Vannucchi, A M; Kiladjian, J-J; Al-Ali, H K; Gisslinger, H; Knoops, L; Cervantes, F; Jones, M M; Sun, K; McQuitty, M; Stalbovskaya, V; Gopalakrishna, P; Barbui, T

    2016-08-01

    Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35-0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44-1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18-1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits. PMID:27211272

  7. Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection

    PubMed Central

    Lok, Judith J; Bosch, Ronald J; Benson, Constance A; Collier, Ann C; Robbins, Gregory K; Shafer, Robert W; Hughes, Michael D

    2010-01-01

    Objective To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4+ T-cell counts (CD4 counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 count trajectory accounting for losses-to-follow-up and treatment discontinuations. Design The study population included 898 U.S. patients first initiating ART in a randomized trial (ACTG 384); 575 were subsequently prospectively followed in an observational study (ALLRT). Methods Inverse probability of censoring weighting statistical methods were used to estimate the CD4 count trajectory accounting for losses-to-follow-up and ART-discontinuations, overall and for pre-treatment CD4 count categories ≤ 200, 201–350, 351–500, and >500 cells/mm3. Results Median CD4 count increased from 270 cells/mm3 pre-ART to an estimated 556 at three and 532 cells/mm3 at seven years after starting ART in analyses ignoring treatment discontinuations; and to 570 and 640 cells/mm3, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25%, 9%, 3% and 2% of patients with pre-treatment CD4 counts of ≤ 200, 201–350, 351–500, and >500 cells/mm3 would have had CD4 counts ≤350 cells/mm3 after seven years. Conclusions If patients remain on ART, CD4 counts increase in most patients for at least seven years. However, the substantial percentage of patients starting therapy at low CD4 counts who still had low CD4 counts after seven years provides support for ART initiation at higher CD4 counts. PMID:20467286

  8. Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

    SciTech Connect

    Canyilmaz, Emine; Yavuz, Melek Nur; Serdar, Lasif; Uslu, Gonca Hanedan; Zengin, Ahmet Yasar; Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan

    2014-11-01

    Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

  9. Long-term follow up Helicobacter Pylori reinfection rate after second-line treatment: bismuth-containing quadruple therapy versus moxifloxacin-based triple therapy

    PubMed Central

    2013-01-01

    Background The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy. Methods A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed. Results The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection. Conclusions The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment. Trial registration Clinical Trial Registration Number NCT01792700 PMID:24050512

  10. Management of problematic behaviours among individuals on long-term opioid therapy: protocol for a Delphi study

    PubMed Central

    Merlin, Jessica S; Young, Sarah R; Azari, Soraya; Becker, William C; Liebschutz, Jane M; Pomeranz, Jamie; Roy, Payel; Saini, Shalini; Starrels, Joanna L; Edelman, E Jennifer

    2016-01-01

    Introduction Given the sharp rise in opioid prescribing and heightened recognition of opioid addiction and overdose, opioid safety has become a priority. Clinical guidelines on long-term opioid therapy (LTOT) for chronic pain consistently recommend routine monitoring and screening for problematic behaviours. Yet, there is no consensus definition regarding what constitutes a problematic behaviour, and recommendations for appropriate management to inform front-line providers, researchers and policymakers are lacking. This creates a barrier to effective guideline implementation. Thus, our objective is to present the protocol for a Delphi study designed to: (1) elicit expert opinion to identify the most important problematic behaviours seen in clinical practice and (2) develop consensus on how these behaviours should be managed in the context of routine clinical care. Methods/analysis We will include clinical experts, defined as individuals who provide direct patient care to adults with chronic pain who are on LTOT in an ambulatory setting, and for whom opioid prescribing for chronic non-malignant pain is an area of expertise. The Delphi study will be conducted online in 4 consecutive rounds. Participants will be asked to list problematic behaviours and identify which behaviours are most common and challenging. They will then describe how they would manage the most frequently occurring common and challenging behaviours, rating the importance of each management strategy. Qualitative analysis will be used to categorise behaviours and management strategies, and consensus will be based on a definition established a priori. Ethics/dissemination This study has been approved by the Institutional Review Board (IRB) of the University of Alabama at Birmingham (UAB). This study will generate Delphi-based expert consensus on the management of problematic behaviours that arise in individuals on LTOT, which we will publish and disseminate to appropriate professional societies

  11. Immune recovery in HIV-infected patients after Candida esophagitis is impaired despite long-term antiretroviral therapy

    PubMed Central

    Stuehler, Claudia; Bernardini, Claudia; Elzi, Luigia; Stoeckle, Marcel; Zimmerli, Stefan; Furrer, Hansjakob; Günthard, Huldrych F.; Leibundgut-Landmann, Salomé; Battegay, Manuel; Khanna, Nina

    2016-01-01

    Objective: Candida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking. Design: We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4+ cell counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4+ cell counts higher than 500 cells/μl, CD4+ cell nadirs higher than 350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group) and 20 healthy individuals. Methods: We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and enzyme-linked immunosorbent spot. Results: We found that patients with Candida esophagitis had nearly abolished CD4+ cell proliferation in response to Candida albicans, significantly increased percentages of dysfunctional CD4+ cells, significantly decreased cytotoxic natural killer cell counts and peripheral innate lymphoid cell counts and significantly reduced IFN-γ and IL-17 production compared with the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery. Conclusion: Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects. PMID:27149086

  12. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

    SciTech Connect

    Prabhu, Roshan S.; Kandula, Shravan; Liebman, Lang; Wojno, Ted H.; Hayek, Brent; Hall, William A.; Shu, Hui-Kuo; Crocker, Ian

    2013-03-01

    Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

  13. Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

    SciTech Connect

    Weber, Damien C.; Schneider, Ralf; Goitein, Gudrun; Koch, Tamara; Ares, Carmen; Geismar, Jan H.; Schertler, Andreas; Bolsi, Alessandra; Hug, Eugen B.

    2012-07-01

    Background: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. Patients and Methods: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 {+-} 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm{sup 3} (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. Results: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade {>=}3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). Conclusions: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

  14. The risk of burn injury during long-term oxygen therapy: a 17-year longitudinal national study in Sweden

    PubMed Central

    Tanash, Hanan A; Huss, Fredrik; Ekström, Magnus

    2015-01-01

    Background Long-term oxygen therapy (LTOT) improves the survival time in hypoxemic chronic obstructive pulmonary disease. Despite warnings about potential dangers, a considerable number of patients continue to smoke while on LTOT. The incidence of burn injuries related to LTOT is unknown. The aim of this study was to estimate the rate of burn injury requiring health care contact during LTOT. Methods Prospective, population-based, consecutive cohort study of people starting LTOT from any cause between January 1, 1992 and December 31, 2009 in the Swedish National Register of Respiratory Failure (Swedevox). Results In total, 12,497 patients (53% women) were included. The mean (standard deviation) age was 72±9 years. The main reasons for starting LTOT were chronic obstructive pulmonary disease (75%) and pulmonary fibrosis (15%). Only 269 (2%) were active smokers when LTOT was initiated. The median follow-up time to event was 1.5 years (interquartile range, 0.55–3.1). In total, 17 patients had a diagnosed burn injury during 27,890 person-years of LTOT. The rate of burn injury was 61 (95% confidence interval, 36–98) per 100,000 person-years. There was no statistically significant difference in the rate of burn injury between ever-smokers and never-smokers, or between men and women. Conclusion The rate of burn injuries in patients on LTOT seems to be low in Sweden. The strict requirements in Sweden for smoking cessation before LTOT initiation may contribute to this finding. PMID:26622175

  15. Stereotactic body radiotherapy for chronic obstructive pulmonary disease patients undergoing or eligible for long-term domiciliary oxygen therapy

    PubMed Central

    Hara, Yu; Takeda, Atsuya; Eriguchi, Takahisa; Sanuki, Naoko; Aoki, Yousuke; Nishimura, Shuichi; Enomoto, Tatsuji; Shinkai, Masaharu; Kawana, Akihiko; Kaneko, Takeshi

    2016-01-01

    A major cause of death in patients undergoing long-term domiciliary oxygen therapy (LTOT) is lung cancer progression. In our institution, we actively perform stereotactic body radiotherapy (SBRT) on patients with early-stage non–small-cell lung cancer undergoing LTOT. In this study, we retrospectively analyzed the treatment efficacy and safety of SBRT for patients with T1-3N0M0 non–small-cell lung cancer who had been prescribed LTOT for treatment of chronic obstructive pulmonary disease (COPD). A total of 24 patients were studied. Their median age was 74 years (range, 63–87 years). The median duration from the start of LTOT to SBRT was 23 months (range, 0–85 months). Four of the 24 patients underwent lobectomy due to lung cancer. The median follow-up duration was 29 months (range, 5–79 months). One patient had a local recurrence. The median survival time was 30 months. The 3-year overall survival was 49%. In 6 of the 24 patients (25%), COPD presented with interstitial pneumonia. The 3-year overall survival for patients with COPD without interstitial pneumonia was significantly better than that for patients with both COPD and interstitial pneumonia (67% and 0%, respectively; P < 0.0001). Grade 5 radiation pneumonitis occurred in one patient (4%) with COPD with interstitial pneumonia. SBRT was tolerated by patients with early-stage non–small-cell lung cancer undergoing LTOT. SBRT should be considered for patients undergoing LTOT. However, clinicians should consider the risk of severe radiation pneumonitis in patients with interstitial pneumonia. PMID:26487713

  16. The appearance of newly identified intraocular lesions in Gaucher disease type 3 despite long-term glucocerebrosidase replacement therapy

    PubMed Central

    Sawicka-Gutaj, Nadia; Machaczka, Maciej; Kulińska-Niedziela, Izabela; Bernardczyk-Meller, Jadwiga; Gutaj, Paweł; Sowiński, Jerzy; Ruchała, Marek

    2016-01-01

    Background Gaucher disease (GD) is an autosomal recessive lipid storage disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase. The presence of central nervous system disease is a hallmark of the neuronopathic forms of GD (types 2 and 3). Intraocular lesions (e.g. corneal clouding, retinal lesions, and vitreous opacities) have been infrequently reported in GD type 3 (GD3). Moreover, there are virtually no published data on the occurrence and natural course of intraocular lesions in GD3 patients treated with enzyme replacement therapy (ERT). Case presentation We describe the case of a 26-year-old Polish male with L444P homozygous GD3 (mutation c.1448T > C in the GBA1 gene) who developed fundus lesions despite 10 years of ERT. At the age of 23 years, a spectral domain optical coherence tomography (OCT) examination was performed which disclosed the presence of discrete lesions located preretinally, intraretinally in the nerve fiber layer, and in the vitreous body. A 3-year follow-up OCT examination has not shown any significant progression of the fundus lesions. Conclusions To the best of our knowledge, this is the first published report describing the occurrence of newly identified retinal and preretinal lesions occurring during long-term ERT in GD3. We recommend that a careful ophthalmic assessment, including a dilated fundus examination, should be included as part of annual follow-up in patients with GD3. Further studies are needed to understand the nature and clinical course of these changes and whether or not these intraocular findings have any predictive value in the context of neurologic and skeletal progression in GD3. PMID:27064303

  17. Response to Nadler's Commentary on Arch and Craske's (2011) "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes"

    ERIC Educational Resources Information Center

    Arch, Joanna J.; Craske, Michelle G.

    2012-01-01

    Nadler (this issue), in his commentary of our article, "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes" (Arch & Craske, 2011), argues that we misrepresent the role of panic attacks within learning theory and overlook cognitive treatment targets. He presents several case…

  18. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  19. [Chloroquine and hydroxychloroquine: side effect profile of important therapeutic drugs].

    PubMed

    Ochsendorf, F R; Runne, U

    1991-03-01

    Precise knowledge of the undesirable effects of chloroquine and hydroxychloroquine allows better exploitation of their therapeutic effects. Retinopathy can be avoided by observing a maximum daily dosage of 3.5-4 mg/kg ideal body weight for chloroquine and 6-6.5 mg/kg for hydroxychloroquine. In this way, both can be used for long-term therapy. The pharmacokinetics of chloroquine (storage in deep compartments with long plasma half-life) means that it can cumulate, especially with higher dosages and in the presence of renal or hepatic insufficiency. A high plasma concentration reinforces the side-effects without reinforcing the therapeutic effects. Besides subjective symptoms (e.g. anorexia, diarrhoea, nausea), the following undesirable reactions are significant. On the skin exanthema, hyperpigmentation and photodynamic reactions can develop. The hair can become white in blonde and red-haired men. In the eye, chloroquine deposits in the cornea and disturbances of accommodation can occur, besides retinopathy. Neuromyopathy and central nervous system disturbances (e.g. psychosis) are rare, as is impairment of auditory function or blood cells. During pregnancy there is a risk of potential fetal damage (hearing loss, abortion). An acute overdose is extremely dangerous: the lethal dose is 1 g for children and 4 g for adults. As death occurs rapidly, chloroquine has to be stored where it is absolutely inaccessible to children. PMID:2055762

  20. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

    PubMed Central

    Tamirou, Farah; D'Cruz, David; Sangle, Shirish; Remy, Philippe; Vasconcelos, Carlos; Fiehn, Christoph; Ayala Guttierez, Maria del Mar; Gilboe, Inge-Magrethe; Tektonidou, Maria; Blockmans, Daniel; Ravelingien, Isabelle; le Guern, Véronique; Depresseux, Geneviève; Guillevin, Loïc; Cervera, Ricard; Houssiau, Frédéric A

    2016-01-01

    Objective To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. Methods In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Results Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. Conclusions The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. Trial registration number NCT00204022. PMID:25757867

  1. Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients

    PubMed Central

    Nagy, Vivien Klaudia; Széplaki, Gábor; Apor, Astrid; Kutyifa, Valentina; Kovács, Attila; Kosztin, Annamária; Becker, Dávid; Boros, András Mihály; Gellér, László; Merkely, Béla

    2015-01-01

    Background Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT. Design We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months. Results RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0–12.8) vs. 19.5 (15.0–23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0–19.3) vs. 17.4 (10.5–22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15–0.90), p = 0.02 and HR = 0.42 (0.19–0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32–0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40–1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60–0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76–15.48), p = 0.003]. Conclusions Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation. PMID:26700308

  2. Long-Term Cognitive and Behavioral Therapies, Combined with Augmentative Communication, Are Related to Uncinate Fasciculus Integrity in Autism

    ERIC Educational Resources Information Center

    Pardini, Matteo; Elia, Maurizio; Garaci, Francesco G.; Guida, Silvia; Coniglione, Filadelfo; Krueger, Frank; Benassi, Francesca; Gialloreti, Leonardo Emberti

    2012-01-01

    Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive…

  3. Impact of Long-Term Tiotropium Bromide Therapy on Annual Lung Function Decline in Adult Patients with Cystic Fibrosis

    PubMed Central

    Brandt, Claudia; Thronicke, Anja; Roehmel, Jobst F.; Krannich, Alexander; Staab, Doris; Schwarz, Carsten

    2016-01-01

    Background Chronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function. Methods This retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1). Results A total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50–69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898). Conclusion This study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity. PMID:27351829

  4. Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: A possible late effect of therapy

    SciTech Connect

    Allen, J.C.; Miller, D.C.; Budzilovich, G.N.; Epstein, F.J. )

    1991-01-01

    Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.

  5. Long-Term Outcome of Cognitive Behavior Therapy for Body Dysmorphic Disorder: A Naturalistic Case Series of 1 to 4 Years After a Controlled Trial.

    PubMed

    Veale, David; Miles, Sarah; Anson, Martin

    2015-11-01

    There is some evidence for the efficacy of cognitive behavior therapy (CBT) for body dysmorphic disorder (BDD) after 1 to 6months but none in the long term. The aim of this study was to follow up the participants in a randomized controlled trial of CBT versus anxiety management to determine whether or not the treatment gains were maintained over time. Thirty of the original 39 participants who had CBT were followed up over 1 to 4years and assessed using a number of clinician and self-report measures, which included the primary outcome measure of the Yale-Brown Obsessive Compulsive Scale modified for BDD. Outcome scores generally maintained over time from end of treatment to long-term follow-up. There was a slight deterioration from n=20 (51.3%) to n=18 (46.2%) who met improvement criteria at long-term follow-up. Eleven (28.2%) were in full remission and 22 (56.4%) were in partial remission. The gains made were generally maintained at long-term follow-up. However, there were a significant number of participants who maintained chronic symptoms after treatment and may need a longer-term or more complex intervention and active medication management. PMID:26520220

  6. Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate.

    PubMed

    Armanini, D; Scaroni, C; Mattarello, M J; Fiore, C; Albiger, N; Sartorato, P

    2005-03-01

    We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis. PMID:15952408

  7. Initial and Long-Term Results of Endovascular Therapy for Chronic Total Occlusion of the Subclavian Artery

    SciTech Connect

    Babic, Srdjan; Sagic, Dragan; Radak, Djordje; Antonic, Zelimir; Otasevic, Petar; Kovacevic, Vladimir; Tanaskovic, Slobodan; Ruzicic, Dusan; Aleksic, Nikola; Vucurevic, Goran

    2012-04-15

    Purpose: To study the initial and long-term results of angioplasty and primary stenting for the treatment of chronic total occlusion (CTO) of the subclavian artery (SA). Materials and Methods: From January 1999 to February 2010, 56 patients (25 men with a mean age of 58 {+-} 8 years) underwent endovascular treatment for CTO of the SA. Duplex scans and arteriograms confirmed occlusion in all cases. Indications for recanalization were subclavian steal syndrome in 33 patients (58.1%), arm claudication in 13 patients (23.2%), and coronary ischemia in 7 patients (12.5%) who had a history of previous coronary artery bypass grafting that included left internal thoracic artery graft. Three patients (5.4%) were treated before the scheduled coronary artery bypass surgery, which included left internal thoracic artery graft. After successful recanalization, all arteries were stented, and all of the patients were followed-up at 1, 3, 6, and 12 months after surgery and annually thereafter. Results: Successful recanalization of the SA was achieved in 46 patients (82.1%), and the complication rate was 7.1%. During follow-up (mean 40 {+-} 26 months; range 2 to 125), the primary patency rates after 1 and 3 years were 97.9% and 82.7%, respectively. At the end of follow-up, 76% of the arteries showed no evidence of restenosis. Univariate analysis failed to identify any variable predictive of long-term patency of successfully recanalized SA. Conclusion: Percutaneous transluminal angioplasty with stenting of the complete total occlusion of the SA is a safe and effective procedure associated with low risks and good long-term results.

  8. Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients

    PubMed Central

    Kim, Byung Kook; Ko, Soon Young; Kwon, So Young; Park, Eugene; Kim, Jeong Han; Choe, Won Hyeok; Lee, Chang Hong

    2013-01-01

    Background Recently, several reports issued clevudine induced myopathy in the long term use. Objectives The aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB). Patients and Methods The subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period. Results In HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy. Conclusions Long-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine. PMID:23805155

  9. Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

    SciTech Connect

    Thoma, Clemens; Bachy, Veronique; Seaton, Patricia; Green, Nicola K.; Greaves, David R.; Klavinskis, Linda; Seymour, Leonard W.; Morrison, Joanne

    2013-12-15

    In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.

  10. Examining the Influence of Occupational Therapy and Its Effectiveness in Long-Term Care on Dementia Patients Through Ontology-Based Clustering

    NASA Astrophysics Data System (ADS)

    Fang, Kwoting; Change, Chingwei; Yuliao, Miao; Chi, Yenping

    Over the past decade, the number of long-term care (LTC) residents has increased, and many have accepted treatments such as medication, rehabilitation and occupational therapy. This study discusses the effectiveness of occupational therapy when given to dementia patients of different contexts. The results of this study showed that patients of a good condition in the first stage present a more positive attitude towards participation in the occupational therapy designed by the institution; therefore, they have a greater chance of their condition improving or remaining the same. However, patients of an average condition have a more passive attitude towards taking part in any therapy; therefore, they have a greater chance of their condition deteriorating. In conclusion, occupational therapy has an effect on all kinds of patients.

  11. Chloroquine Phosphate Oral

    MedlinePlus

    ... allergic to chloroquine phosphate, chloroquine hydrochloride (Aralen HCl), hydroxychloroquine (Plaquenil), or any other drugs.tell your doctor ... taking chloroquine phosphate, chloroquine hydrochloride (Aralen HCl), or hydroxychloroquine (Plaquenil).tell your doctor if you are pregnant ...

  12. Chloroquine Phosphate Oral

    MedlinePlus

    ... allergic to chloroquine phosphate, chloroquine hydrochloride (Aralen HCl), hydroxychloroquine (Plaquenil), or any other drugs.tell your doctor and ... taking chloroquine phosphate, chloroquine hydrochloride (Aralen HCl), or hydroxychloroquine (Plaquenil).tell your doctor if you are pregnant ...

  13. The long-term benefits of genotypic resistance testing in patients with extensive prior antiretroviral therapy: a model-based approach

    PubMed Central

    Yazdanpanah, Y; Vray, M; Meynard, J; Losina, E; Weinstein, MC; Morand-Joubert, L; Goldie, SJ; Hsu, HE; Walensky, RP; Dalban, C; Sax, PE; Girard, PM; Freedberg, KA

    2008-01-01

    Objectives Resistance testing in HIV disease may provide long-term benefits that are not evident from short-term data. Our objectives were to estimate the long-term effectiveness, cost and cost-effectiveness of genotype testing in patients with extensive antiretroviral exposure. Methods We used an HIV simulation model to estimate the long-term effectiveness and cost-effectiveness of genotype testing. Clinical data incorporated into the model were from NARVAL, a randomized trial of resistance testing in patients with extensive antiretroviral exposure, and other randomized trials. Each simulated patient was eligible for up to three sequential regimens of antiretroviral therapy (i.e. two additional regimens beyond the trial-based regimen) using drugs not available at the time of the study, such as lopinavir/ritonavir, darunavir/ritonavir and enfuvirtide. Results In the long term, projected undiscounted life expectancy increased from 132.2 months with clinical judgement alone to 147.9 months with genotype testing. Median survival was estimated at 11.9 years in the resistance testing arm vs 10.4 years in the clinical judgement alone arm. Because of increased survival, the projected lifetime discounted cost of genotype testing was greater than for clinical judgement alone (€313 900 vs €263100; US$399 000 vs US$334 400). Genotype testing cost €69 600 (US$88 500) per quality-adjusted life year gained compared with clinical judgement alone. Conclusions In patients with extensive prior antiretroviral exposure, genotype testing is likely to increase life expectancy in the long term as a result of the increased likelihood of receiving two active new drugs. Genotype testing is associated with cost-effectiveness comparable to that of strategies accepted in patients with advanced HIV disease, such as enfuvirtide use. PMID:17760736

  14. Combined-Modality Therapy With Gemcitabine and Radiation Therapy as a Bladder Preservation Strategy: Long-Term Results of a Phase I Trial

    SciTech Connect

    Oh, Kevin S. M.D.; Soto, Daniel E.; Smith, David C.; Sandler, Howard M.

    2009-06-01

    Purpose: A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy (RT) was performed in patients with muscle-invasive bladder cancer. We present the final analysis of bladder-intact survival (BIS), disease-specific survival (DSS), and overall survival (OS). Methods and Materials: Eligible patients had muscle-invasive transitional cell carcinoma (cT2-3) and were candidates for cystectomy. Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder (total of 60 Gy over 6 weeks). Gemcitabine doses ranged from 10 to 33 mg/m{sup 2}. Results: Median follow-up was 5.6 years (range, 0.6-9.5 years). Twenty-three of 24 patients were evaluable for response. All patients were clinical stage T2. Locoregional failure occurred in seven patients (30%), which were successfully salvaged by radical cystectomy (n = 5) or intravesical therapy (n = 2). Four local failures occurred > 5 years after therapy. Most local failures were noninvasive tumors (Ta or Tis, n = 6). Ten patients (43%) experienced optimal outcome (no failures and bladder intact). The 5-year actuarial estimates of survival are BIS 62%, OS 76%, and DSS 82%. Conclusion: Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature. All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy. Given the high proportion of late local failures, we recommend long-term monitoring when using this regimen. Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocols are pending.

  15. Long-Term Quality of Life After Swallowing and Salivary-Sparing Chemo–Intensity Modulated Radiation Therapy in Survivors of Human Papillomavirus–Related Oropharyngeal Cancer

    SciTech Connect

    Vainshtein, Jeffrey M.; Moon, Dominic H.; Feng, Felix Y.; Chepeha, Douglas B.; Eisbruch, Avraham; Stenmark, Matthew H.

    2015-04-01

    Purpose: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo–intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). Methods and Materials: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. Results: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus–positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. “Moderate” or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported “moderate” or “severe” long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. Conclusions: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was

  16. Long-term IL-2 therapy after transplantation of T cell depleted stem cells from alternative donors in children.

    PubMed

    Schlegel, Patrick; Teltschik, Heiko-Manuel; Pfeiffer, Matthias; Handgretinger, Rupert; Schumm, Michael; Koscielniak, Ewa; Feuchtinger, Tobias; Klingebiel, Thomas; Bader, Peter; Schlegel, Paul-Gerhard; Greil, Johann; Lang, Peter

    2011-09-01

    The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias / myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; ≥CR 2, n = 2) and relapsed or progressive Ewing's sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 administration occurred. IL-2 administration was started at median day 57 (range 13-154) post-transplant for a mean duration of 28 days (range 15-250). IL-2 administration clearly increased NK cell activity. 3 of 11 patients (ALL, AML, multifocal Ewings sarcoma) survived with a follow-up of ten years. In conclusion, long-term low-dose IL-2 subcutaneous application is feasible in children due to a low side effect profile even after HLA mismatched transplantation and may be a strategy to prevent relapse in pediatric malignancies with extremely high risk of relapse. PMID:21925097

  17. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy

    PubMed Central

    Rocheteau, P.; Chatre, L.; Briand, D.; Mebarki, M.; Jouvion, G.; Bardon, J.; Crochemore, C.; Serrani, P.; Lecci, P. P.; Latil, M.; Matot, B.; Carlier, P. G.; Latronico, N.; Huchet, C.; Lafoux, A.; Sharshar, T.; Ricchetti, M.; Chrétien, F.

    2015-01-01

    Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity. PMID:26666572

  18. Bilateral atypical insufficiency fractures of the proximal tibia and a unilateral distal femoral fracture associated with long-term intravenous bisphosphonate therapy: a case report

    PubMed Central

    2012-01-01

    Introduction Atypical insufficiency fractures of the femur in patients on long-term bisphosphonate therapy have been well described in recent literature. The majority of cases are associated with minimal or no trauma and occur in the subtrochanteric or diaphyseal region. Case presentation We describe the case of a 76-year-old British Caucasian woman who presented initially to an emergency department and then to her primary care physician with a long-standing history of bilateral knee pain after minor trauma. Plain radiographs showed subtle linear areas of sclerosis bilaterally in her proximal tibiae. Magnetic resonance imaging confirmed the presence of insufficiency fractures in these areas along with her left distal femur. There are very few reports of atypical insufficiency fractures involving the tibia in patients on long-term bisphosphonate therapy and this appears to be the only documented bilateral case involving the metaphyseal regions of the proximal tibia and distal femur. Conclusion In addition to existing literature describing atypical fractures in the proximal femur and femoral shaft, there is a need for increased awareness that these fractures can also occur in other weight-bearing areas of the skeleton. All clinicians involved in the care of patients taking long-term bisphosphonates need to be aware of the growing association between new onset lower limb pain and atypical insufficiency fractures. PMID:22309438

  19. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: Results of the REVERSE study

    PubMed Central

    Gold, Michael R.; Daubert, Claude; Abraham, William T.; Ghio, Stefano; Sutton, Martin St. John; Hudnall, John Harrison; Cerkvenik, Jeffrey; Linde, Cecilia

    2015-01-01

    BACKGROUND Cardiac resynchronization therapy (CRT) reduces mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure (HF). The magnitude of reverse remodeling predicts survival with many HF medical therapies. However, there are few studies assessing the effect of remodeling on long-term survival with CRT. OBJECTIVE The purpose of this study was to assess the effect of CRT-induced reverse remodeling on long-term survival in patients with mildly symptomatic heart failure. METHODS The REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial was a multicenter, double-blind, randomized trial of CRT in patients with mild HF. Long-term follow-up of 5 years was preplanned. The present analysis was restricted to the 353 patients who were randomized to the CRT ON group with paired echocardiographic studies at baseline and 6 months post-implantation. The left ventricular end-systolic volume index (LVESVi) was measured in the core laboratory and was an independently powered end point of the REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial. RESULTS A 68% reduction in mortality was observed in patients with ≥15% decrease in LVESVi compared to the rest of the patients (P = .0004). Multivariable analysis showed that the change in LVESVi was a strong independent predictor (P = .0002), with a 14% reduction in mortality for every 10% decrease in LVESVi. Other remodeling parameters such as left ventricular enddiastolic volume index and ejection fraction had a similar association with mortality. CONCLUSION The change in left ventricular end-systolic volume after 6 months of CRT is a strong independent predictor of long-term survival in mild HF. PMID:25460860

  20. Long-term care characteristics that influence the utility and effectiveness of nonpharmacological therapies for people with dementia.

    PubMed

    Chenoweth, Lynn

    2015-01-01

    Political, economic and organizational factors shape requirements for long-term aged care (LTC) serving people with chronic conditions, including dementia. Organization size, ownership and human resources need to be considered when examining the use and effectiveness of nonpharmacological modalities for people with dementia in LTC. Since LTC facility size, ownership, managerial leadership and staff-to-resident ratio appear to consistently influence staff capability to give quality care, these structural factors will also likely enhance, or limit, the therapeutic benefits of nonpharmacological approaches in dementia care. This issues paper recommends further debate in establishing consensus on the necessary criteria for successful implementation and realistic evaluation of nonpharmacological approaches when caring for the person with dementia in LTC. PMID:25894875

  1. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.

    PubMed

    Greenspan, S L; Parker, R A; Ferguson, L; Rosen, H N; Maitland-Ramsey, L; Karpf, D B

    1998-09-01

    Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary

  2. The Beneficial Effects of Postinfarct Cytokine Combination Therapy are Sustained During Long-Term Follow-Up

    PubMed Central

    Sanganalmath, Santosh K.; Stein, Adam B.; Guo, Yiru; Tiwari, Sumit; Hunt, Greg; Vincent, Robert J.; Huang, Yiming; Rezazadeh, Arash; Ildstad, Suzanne T.; Dawn, Buddhadeb; Bolli, Roberto

    2009-01-01

    We have previously reported that administration of granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL) or G-CSF+stem cell factor (SCF) improves left ventricular (LV) function and halts LV remodeling at 35 days after myocardial infarction (MI). In the current study, we investigated whether these beneficial effects are sustained in the long term - an issue of fundamental importance for clinical translation. Mice undergoing a 30-min coronary occlusion followed by reperfusion received vehicle (group I), G-CSF+FL (group II), G-CSF+SCF (group III), or G-CSF alone (group IV) starting 4 h after reperfusion and were euthanized 48 weeks later. LV structure and function were assessed by serial echocardiography before and at 48 h and 4, 8, 16, 32, and 48 wk after MI. During follow-up, mice in group I exhibited worsening of LV function and progressive LV remodeling. Compared with group I, both groups II and III exhibited improved LV EF at 4 wk after MI; however, only in group II was this improvement sustained at 48 wk. Group II was also the only group in which the decrease in infarct wall thickening fraction, the LV dilatation, and the increase in LV mass were attenuated vs. group I. We conclude that the beneficial effect of G-CSF+FL on postinfarction LV dysfunction and remodeling is sustained for at least 11 months, and thus is likely to be permanent. In contrast, the effect of G-CSF+SCF was not sustained beyond the first few weeks, and G-CSF alone is ineffective. To our knowledge, this is the first long-term study of cytokines in postinfarction LV remodeling. The results reveal heretofore unknown differential actions of cytokines and have important translational implications. PMID:19616005

  3. Adeno-associated virus 2-mediated antiangiogenic cancer gene therapy: long-term efficacy of a vector encoding angiostatin and endostatin over vectors encoding a single factor.

    PubMed

    Ponnazhagan, Selvarangan; Mahendra, Gandham; Kumar, Sanjay; Shaw, Denise R; Stockard, Cecil R; Grizzle, William E; Meleth, Sreelatha

    2004-03-01

    Angiogenesis is characteristic of solid tumor growth and a surrogate marker for metastasis in many human cancers. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. However, for long-term tumor-free survival by antiangiogenic therapy, the factors controlling tumor neovasculature need to be systemically maintained at stable therapeutic levels. Here we show sustained expression of the antiangiogenic factors angiostatin and endostatin as secretory proteins by recombinant adeno-associated virus 2 (rAAV)-mediated gene transfer. Both vectors provided significant protective efficacy in a mouse tumor xenograft model. Stable transgene persistence and systemic levels of both angiostatin and endostatin were confirmed by in situ hybridization of the vector-injected tissues and by serum ELISA measurements, respectively. Whereas treatment with rAAV containing either endostatin or angiostatin alone resulted in moderate to significant protection, the combination of endostatin and angiostatin gene transfer from a single vector resulted in a complete protection. These data suggest that AAV-mediated long-term expression of both endostatin and angiostatin may have clinical utility against recurrence of cancers after primary therapies and may represent rational adjuvant therapies in combination with radiation or chemotherapy. PMID:14996740

  4. Predictors of Appropriate ICD Therapy in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy: Long Term Experience of a Tertiary Care Center

    PubMed Central

    Saguner, Ardan M.; Wolber, Thomas; Tanner, Felix C.; Jenni, Rolf; Corti, Natascia; Lüscher, Thomas F.; Brunckhorst, Corinna; Duru, Firat

    2012-01-01

    Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically transmitted disease prone to ventricular arrhythmias. We therefore investigated the clinical, echocardiographical and electrophysiological predictors of appropriate implantable cardioverter defibrillator (ICD) therapy in patients with ARVC. Methods A retrospective analysis was performed in 26 patients (median age of 40 years at diagnosis, 21 males and 5 females) with ARVC who underwent ICD implantation. Results Over a median (range) follow-up period of 10 (2.7, 37) years, appropriate ICD therapy for ventricular arrhythmias was documented in 12 (46%) out of 26 patients. In all patients with appropriate ICD therapy the ICD was originally inserted for secondary prevention. Median time from ICD implantation to ICD therapy was 9 months (range 3.6, 54 months). History of heart failure was a significant predictor of appropriate ICD therapy (p = 0.033). Left ventricular disease involvement (p = 0.059) and age at implantation (p = 0.063) were borderline significant predictors. Patients with syncope at time of diagnosis were significantly less likely to receive ICD therapy (p = 0.02). Invasive electrophysiological testing was not significantly associated with appropriate ICD therapy. Conclusion In our cohort of patients with ARVC, history of heart failure was a significant predictor of appropriate ICD therapy, whereas left ventricular involvement and age at time of ICD implantation were of borderline significance. These predictors should be tested in larger prospective cohorts to optimize ICD therapy in this rare cardiomyopathy. PMID:23028419

  5. Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer.

    PubMed

    Jin, Chuan; Fotaki, Grammatiki; Ramachandran, Mohanraj; Nilsson, Berith; Essand, Magnus; Yu, Di

    2016-01-01

    Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity. PMID:27189167

  6. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center.

    PubMed

    Chin, Kelly Marie; Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando

    2015-09-01

    Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = -0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose. PMID:26401252

  7. Crown lengthening procedure following intentional endodontic therapy for correction of supra-erupted posterior teeth: Case series with long-term follow-up

    PubMed Central

    Patil, Shruti Arun; Kulkarni, Sudhindra; Thakur, Srinath; Naik, Balaram

    2016-01-01

    Context: The crown lengthening procedure (CLP) is routinely carried out to correct gingival levels and achieve esthetic contours and adequate crown lengths for restorative purposes. Though the short-term outcomes have been found to be stable, long-term results are not much reported. Aims: To evaluate the long-term stability of the marginal bone levels, gingival levels, and the status of the teeth, which underwent endodontic therapy, followed by CLP and final restorations. Settings and Design: Institutional setting, long-term case series. Materials and Methods: Case records of the patients who underwent CLP and endodontic therapy for corrections of the supra-erupted teeth to regain the lost interocclusal spaces were retrieved, and the cases with complete set of the clinical and radiographs were taken. All the cases were recalled and bone levels on the radiographs, bleeding on probing, probing pocket depths, and changes in the soft tissue margins were evaluated. Statistical Analysis Used: Descriptive analysis. Results: A total of 25 teeth had undergone CLP and endodontic therapy and final restorations for a minimum of 24 months. The mean post-restorative duration was 50.8 ± 22.48 months (range 24–96 months). All the teeth were functional and asymptomatic with 100% survival. Interdental bone loss of 1 mm, probing pockets of 5 mm, and 1 mm buccal recession were observed in 16% of the sites. The amount of interocclusal space regained was adequate to restore the missing teeth in the opposing arch. Conclusions: The CLP is a predictive procedure for correction of supra-erupted teeth. The survival of the teeth that underwent the procedure in the present study was 100% over 24–96 months. PMID:27041850

  8. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center

    PubMed Central

    Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando

    2015-01-01

    Abstract Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = −0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose. PMID:26401252

  9. Change in healthcare utilization and costs following initiation of benzodiazepine therapy for long-term treatment of generalized anxiety disorder: a retrospective cohort study

    PubMed Central

    2012-01-01

    Background Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD). While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. Methods Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02) who began a long-term course of treatment (≥90 days) with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation (“pretreatment” and “post-treatment”, respectively), and focused attention on accident-related encounters (e.g., for treatment of fractures) and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness). Results A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine), while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p<0.01); costs of accident-related encounters and other care that was possibly related to use of benzodiazepines increased by an average of $1099 ($1757 [$7656] vs $2856 [$14,836]; p=0.03). Conclusions Healthcare costs increase in patients with GAD beginning long-term (≥90 days) treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use. PMID:23088742

  10. Combined oral pulse and topical corticosteroid therapy for severe alopecia areata in children: a long-term follow-up study.

    PubMed

    Lalosevic, Jovan; Gajic-Veljic, Mirjana; Bonaci-Nikolic, Branka; Nikolic, Milos

    2015-01-01

    There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty-three percent of patients had AA plurifocalis (AAP). Fifty-seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long-term follow-up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0-100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long-term follow-up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long-lasting results, without serious side effects. PMID:26179196

  11. A Case of Long-term Survival of Advanced Paratesticular Rhabdomyosarcoma Treated With a Multimodal Therapy Including a Combination of Cyclophosphamide, Vincristine, Doxorubicin and Dacarbazine.

    PubMed

    Isono, Makoto; Sato, Akinori; Asano, Tomohiko

    2016-07-01

    There is no established treatment for advanced rhabdomyosarcoma (RMS) with metastases at the time of diagnosis. A 17-year-old male was referred to our hospital because of a right scrotal mass. Computed tomography showed multiple lung metastases with pleural effusion and retroperitoneal lymph node metastasis, and bone scintigraphy revealed multiple bone metastases. Right high orchiectomy was performed and the tumor was diagnosed as paratesticular embryonal RMS. He was treated with a multimodal therapy including 17 cycles of combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dacarbazine (CYVADIC) and achieved a long-term survival of 4 years. PMID:27335778

  12. Long-term anti-FVIII antibody response in Bethesda-negative haemophilia A patients receiving continuous replacement therapy.

    PubMed

    Klintman, Jenny; Hillarp, Andreas; Berntorp, Erik; Astermark, Jan

    2013-11-01

    It has previously been shown that patients with haemophilia A may develop non-neutralizing anti-factor VIII (FVIII) antibodies (NNA) that escape detection by the Bethesda assay, but are detected using immune-based assays. We and others found NNAs to be directed not only towards non-functional parts of the protein, but towards all regions of the FVIII protein. We also showed a heterogeneous antibody response towards different FVIII products. However, the clinical relevance and the natural history of NNA remain unclear. Therefore, we followed a cohort of unrelated subjects with haemophilia A for 4 years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12·8%) exhibited an immune response that was transient and heterogeneous, and none of the subjects developed an FVIII inhibitor. The result of the ELISA was examined in relation to clinical variables and no significant associations between a positive ELISA and age, F8 mutation, port-à-cath implantation and HCV infection were shown. Interestingly, patients with NNA had significantly fewer bleeding episodes (P = 0·048) compared with NNA-negative subjects. The results indicate that the immune response to FVIII products within an individual may vary over time. However, the clinical impact of NNA remains unclear. PMID:24032553

  13. The Impact of a 35-Week Long-Term Exercise Therapy on Psychosocial Health of Children With Benign Epilepsy.

    PubMed

    Eom, Soyong; Lee, Mi Kyung; Park, Ji-Hye; Lee, Dongpyo; Kang, Hoon-Chul; Lee, Joon Soo; Jeon, Justin Y; Kim, Heung Dong

    2016-07-01

    The purpose of this study was to evaluate the feasibility of a 35-week exercise program and its efficacy on neurocognitive and psychological variables in children with benign epilepsy with centrotemporal spikes. Ten children with benign epilepsy with centrotemporal spikes (aged 8 to 12 years) completed a 35-week exercise program consisting of supervised sport activities for 5 weeks and home-based exercise program for 30 weeks. The children and their parents participated in neurocognitive and psychological evaluations including measures of attention, executive function, behaviors, and quality of life at baseline and postexercise follow-up at the 35th week. At postintervention evaluation, significant improvements were seen relative to baseline in neurocognitive domains such as psychomotor speed, sustained attention, divided attention, and inhibition-disinhibition ability, and in psychological domains including internalizing behavior problems, general health, and general quality of life. Long-term exercise intervention may have benefits for some aspects of neurocognitive and psychological function in children with benign epilepsy. PMID:26961267

  14. Long-term intermittent pharmacological therapy of uterine fibroids – a possibility to avoid hysterectomy and its negative consequences

    PubMed Central

    Olszak-Wąsik, Katarzyna; Czerwinska-Bednarska, Anna

    2016-01-01

    Uterine fibroids are found in almost 20-40% of women of reproductive age. For each woman an individualised treatment method should be applied because the hysterectomy procedure is not a good option in every case. The uterus is an organ necessary not only in reproduction. Its removal may result in: pelvic floor dysfunction and stress urinary incontinence, negative impair on life quality, depressive disorders, increased risk of cardiovascular and neurodegenerative diseases, and higher incidence of neoplastic disease. According to the last scientific reports, selective progesterone receptor modulators are the effective therapeutic option in uterine fibroids in women of reproductive age because progesterone is an important factor in their pathogenesis. Ulipristal acetate (UPA) is a progesterone receptor antagonist. It inhibits cell proliferation and angiogenesis in uterine fibroids and also reduces collagen deposits in extracellular matrix. Significant data concerning ulipristal acetate efficacy have been provided by scientific research, especially from the consecutive PEARL studies. Oral ulipristal acetate effectively and safely controls bleeding and pain in patients with symptomatic fibroids. It reduces fibroid volume and restores quality of life. The results of UPA long-term intermittent treatment are largely maintained during the off-treatment periods. PMID:27095959

  15. Long-term intermittent pharmacological therapy of uterine fibroids - a possibility to avoid hysterectomy and its negative consequences.

    PubMed

    Olejek, Anita; Olszak-Wąsik, Katarzyna; Czerwinska-Bednarska, Anna

    2016-03-01

    Uterine fibroids are found in almost 20-40% of women of reproductive age. For each woman an individualised treatment method should be applied because the hysterectomy procedure is not a good option in every case. The uterus is an organ necessary not only in reproduction. Its removal may result in: pelvic floor dysfunction and stress urinary incontinence, negative impair on life quality, depressive disorders, increased risk of cardiovascular and neurodegenerative diseases, and higher incidence of neoplastic disease. According to the last scientific reports, selective progesterone receptor modulators are the effective therapeutic option in uterine fibroids in women of reproductive age because progesterone is an important factor in their pathogenesis. Ulipristal acetate (UPA) is a progesterone receptor antagonist. It inhibits cell proliferation and angiogenesis in uterine fibroids and also reduces collagen deposits in extracellular matrix. Significant data concerning ulipristal acetate efficacy have been provided by scientific research, especially from the consecutive PEARL studies. Oral ulipristal acetate effectively and safely controls bleeding and pain in patients with symptomatic fibroids. It reduces fibroid volume and restores quality of life. The results of UPA long-term intermittent treatment are largely maintained during the off-treatment periods. PMID:27095959

  16. Interfacial Cohesion and Assembly of Bioadhesive Molecules for Design of Long-Term Stable Hydrophobic Nanodrugs toward Effective Anticancer Therapy.

    PubMed

    Shen, Guizhi; Xing, Ruirui; Zhang, Ning; Chen, Chengjun; Ma, Guanghui; Yan, Xuehai

    2016-06-28

    The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly. PMID:27223166

  17. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials.

    PubMed

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-07-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2-4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; www.clinicaltrials.gov identifier NCT00635427. PMID:25801797

  18. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials

    PubMed Central

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-01-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc. PMID:25801797

  19. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe.

    PubMed

    Aggarwal, Bharat B; Vijayalekshmi, R V; Sung, Bokyung

    2009-01-15

    Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. Although acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducers and activators of transcription 3 (STAT3), two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-kappaB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-kappaB; fifth, chemotherapeutic agents and gamma-irradiation activate NF-kappaB and lead to chemoresistance and radioresistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NF-kappaB and STAT3; seventh, suppression of NF-kappaB and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemopreventive agents mediate their effects through inhibition of NF-kappaB and STAT3 activation pathways. Thus, suppression of these proinflammatory pathways may provide opportunities for both prevention and treatment of cancer. PMID:19147746

  20. An Economic Analysis of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke

    PubMed Central

    Wagner, Todd H.; Lo, Albert C.; Peduzzi, Peter; Bravata, Dawn M.; Huang, Grant D.; Krebs, Hermano I.; Ringer, Robert J.; Federman, Daniel G.; Richards, Lorie G.; Haselkorn, Jodie K.; Wittenberg, George F.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Siroka, Andrew; Guarino, Peter D.

    2015-01-01

    Background and Purpose Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. Methods We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. Results A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. Conclusions The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00372411. PMID:21757677

  1. Expression of oral secretory leukocyte protease inhibitor in HIV-infected subjects with long-term use of antiretroviral therapy

    PubMed Central

    Nittayananta, Wipawee; Kemapunmanus, Marisa; Yangngam, Supaporn; Talungchit, Sineepat; Sriplung, Hutcha

    2012-01-01

    BACKGROUND The objectives of this study were to determine 1) expression of oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects compared to non-HIV controls, 2) the oral SLPI expression in HIV-infected subjects with ART compared to those without ART, and 3) factors associated with the expression of oral SLPI. METHODS Oral tissues and samples of both un-stimulated and stimulated saliva were collected from HIV-infected subjects with and without ART, and non-HIV individuals. The expression of SLPI mRNA in the tissue was determined by quantitative real-time PCR. Salivary SLPI protein was detected using ELISA. Chi-square test and logistic regression analysis were performed to determine the association between HIV/ART status and the expression of oral SLPI. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled; 99 on ART (age range 23–57 yr, mean 39 yr), 58 not on ART (age range 20–59 yr, mean 34 yr), and 50 non-HIV controls (age range 19–59 yr, mean 36 yr). The most common ART regimen was 2 NRTIs+1 NNRTI. The expression of oral SLPI in stimulated saliva was significantly decreased with HIV infection (p< 0.001). The expression was also significantly different with respect to ART use (p=0.007). Smoking, CD4+ cell count, and HIV viral load were the factors associated with the oral SLPI expression. CONCLUSION The expression of oral SLPI is altered by HIV infection and use of ART. Thus, oral SLPI may be the useful biomarker to identify subjects at risk of infections and malignant transformation due to HIV infection and long-term ART. PMID:23126266

  2. Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma.

    PubMed

    Reverter, J L; Holgado, S; Alonso, N; Salinas, I; Granada, M L; Sanmartí, A

    2005-12-01

    The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean +/- SD age: 51 +/- 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 +/- 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 +/- 0.148 gr/cm(2) vs 0.956 +/- 0.130 gr/cm(2) in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 +/- 0.329 gr/cm(2) vs 1.155 +/- 0.224 gr/cm(2) respectively, P < 0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma. PMID:16322336

  3. Motor learning curve and long-term effectiveness of modified constraint-induced movement therapy in children with unilateral cerebral palsy: a randomized controlled trial.

    PubMed

    Geerdink, Yvonne; Aarts, Pauline; Geurts, Alexander C

    2013-03-01

    The goal of this study was to determine the progression of manual dexterity during 6 weeks (54h) (modified) constraint-induced movement therapy ((m)CIMT) followed by 2 weeks (18h) bimanual training (BiT) in children with unilateral spastic cerebral palsy (CP), to establish whether and when a maximal training effect was reached and which factors might influence the motor learning curve. In addition, long-term retention of effects was determined. In a randomized controlled trial of 52 children with CP, aged 2.5-8 years, comparing mCIMT-BiT to conventional therapy, 28 children were allocated to the mCIMT-BiT group. This group was assessed weekly with the Box and Block test. Long-term effectiveness was determined by collecting follow-up data of the primary (Assisting Hand Assessment, ABILHAND-Kids) and secondary (Melbourne, COPM) outcomes at six months and one year after intervention. Fifteen children (53.6%) reached a maximum training effect within the mCIMT period. This group differed from others with respect to age, but not gender, affected side or manual ability. Children younger than five years had a greater chance to reach a maximum score within 6 weeks mCIMT (OR=6.67, 95%CI=1.24-35.71) that stabilized already after four weeks; older children showed a longer progression and tended to decline afterwards. In both age groups, beneficial effects were retained in the long term. The findings suggest that children of 5 years and older might profit from a longer period of mCIMT than 54h to reach their maximum unimanual capacity and to retain this capacity during subsequent bimanual training. PMID:23291509

  4. Clinical Relevance of Minimal Residual Viremia during Long-Term Therapy with Nucleos(t)ide Analogues in Patients with Chronic Hepatitis B

    PubMed Central

    Maier, Melanie; Liebert, Uwe G.; Wittekind, Christian; Kaiser, Thorsten; Berg, Thomas; Wiegand, Johannes

    2013-01-01

    Background Successful therapy of chronic hepatitis B with nucleos(t)ide analogues (NUCs) has been defined by undetectable HBV-DNA determined with conventional PCR (lower limit of detection (LLD) 60–80 IU/mL) in clinical registration trials. However, current EASL guidelines recommend highly sensitive real-time PCR (LLD<10–20 IU/mL) and define treatment response by HBV-DNA<10 IU/mL. Aim We evaluated frequency and relevance of minimal residual viremia (MRV) during long-term NUC-treatment in a real-life setting. Methods Frozen serum samples (HBV-DNA negative by in-house PCR, LLD <73 IU/mL) were re-analyzed by real-time PCR (LLD<10 IU/mL, Abbott, Germany). MRV was defined by real time PCR positivity and conventional PCR negativity. Results 237 samples of six HBsAg carriers and 27 NUC-treated CHB patients were analyzed (treatment period 28 (11–111) months, different treatment regimens with mono- or combination therapy). MRV was detected in 31/33 individuals (n = 160/237 serum samples) and more frequent in HBsAg carriers (95%) and HBeAg positive (87%) compared to HBeAg negative patients (53%) (p<0.0001, respectively). Five HBsAg carriers, five HBeAg positive, and four HBeAg negative individuals were continuously HBV-DNA positive. MRV was not significantly more often observed during NUC-monotherapies compared to combination therapies. Concomitant immunosuppressive therapy was present in nine cases and did not influence the results. Viral resistance occurred in three immunocompetent patients with adefovir or lamivudine monotherapy. Conclusions MRV is frequently observed during long-term NUC-therapy. Adjustment of treatment with highly potent NUCs does not seem to be necessary in case of minimal residual viremia in a real-life setting. PMID:23826307

  5. How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long-term study.

    PubMed

    Kawabe, Kazuki; Homma, Yukio; Kubota, Kiyoshi; Sozu, Takashi

    2006-02-01

    Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an alpha1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0+/-3.3 years (mean+/-SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I-PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I-PSS, QOL index, and Qmax, in accordance with the 'Severity Criteria for BPH' issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin. PMID:16563136

  6. Post-Extinction Conditional Stimulus Valence Predicts Reinstatement Fear: Relevance for Long Term Outcomes of Exposure Therapy

    PubMed Central

    Zbozinek, Tomislav D.; Hermans, Dirk; Prenoveau, Jason M.; Liao, Betty; Craske, Michelle G.

    2014-01-01

    Exposure therapy for anxiety disorders is translated from fear conditioning and extinction. While exposure therapy is effective in treating anxiety, fear sometimes returns after exposure. One pathway for return of fear is reinstatement: unsignaled unconditional stimuli following completion of extinction. The present study investigated the extent to which valence of the conditional stimulus (CS+) after extinction predicts return of CS+ fear after reinstatement. Participants (N = 84) engaged in a differential fear conditioning paradigm and were randomized to reinstatement or non-reinstatement. We hypothesized that more negative post-extinction CS+ valence would predict higher CS+ fear after reinstatement relative to non-reinstatement and relative to extinction retest. Results supported the hypotheses and suggest that strategies designed to decrease negative valence of the CS+ may reduce the return of fear via reinstatement following exposure therapy. PMID:24957680

  7. Long Term Effects on Cognitive Function of Postmenopausal Hormone Therapy Prescribed to Women Aged 50–55 Years

    PubMed Central

    Espeland, Mark A.; Shumaker, Sally A.; Leng, Iris; Manson, JoAnn E.; Brown, Candice M.; LeBlanc, Erin S.; Vaughan, Leslie; Robinson, Jennifer; Rapp, Stephen R.; Goveas, Joseph S.; Lane, Dorothy; Wactawski-Wende, Jean; Stefanick, Marcia L.; Li, Wenjun; Resnick, Susan M.

    2013-01-01

    Background Postmenopausal hormone therapy with conjugated equine estrogens (CEE) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women. Methods 1,326 postmenopausal women, who had begun treatment in two randomized placebo-controlled clinical trials of hormone therapy when aged 50–55 years, were assessed with an annual telephone-administered cognitive battery that included measures of global (primary outcome) and domain-specific cognitive functions (verbal memory, attention, executive function, verbal fluency, and working memory). The clinical trials in which they participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate (MPA) over an average of 7.0 years. Cognitive testing was conducted an average of 7.2 years following the end of the trials, when women had mean age 67.2 years, and repeated one year later. Results Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean [95% confidence interval] intervention effect of 0.02 [−0.08,0.12]standard deviation units (p=0.66). Similarly, no overall differences were found for any individual cognitive domain (all p>0.15). Pre-specified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 [−0.33, −0.02] and −0.25 [−0.42, −0.08], respectively, however this may be a chance finding. We are not able to address whether initiating hormone therapy during the menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. Conclusions CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50–55 years. PMID:23797469

  8. Neuropsychological results of long-term therapy with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia in comparison with a control group.

    PubMed

    Parnetti, L; Mecocci, P; Petrini, A; Longo, A; Buccolieri, A; Senin, U

    1989-01-01

    The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia. PMID:2518332

  9. Impact of long-term use of eHealth systems in adolescents with type 1 diabetes treated with sensor-augmented pump therapy.

    PubMed

    Schiaffini, R; Tagliente, I; Carducci, C; Ullmann, N; Ciampalini, P; Lorubbio, A; Cappa, M

    2016-07-01

    Telemedicine in diabetes includes telemonitoring and transmission of important data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.) from the patient s home to the diabetic unit, with a real-time health feedback. Moreover, an eHealth approach is thought to facilitate diabetes management and to improve compliance to CSII/SAP treatment in adolescents, but to date, limited literature related to this topic is available and long-term studies are still lacking. The main aim of this study was to compare the long-term effect on glycometabolic control of eHealth intervention and traditional care in T1DM SAP-treated adolescents. In our study we demonstrated a favorable impact of monthly teleassistance on treatment compliance. Adolescents receiving frequent feedback provided by the medicalmultidisciplinary team, due to the telemonitoring, resulted more compliant in self-management of diabetes. In particular, the medical team feedback resulted in interventions on behavioral errors and insulin therapy adjustments, leading to an improved glycometabolic control. PMID:26289613

  10. Economic Aspects of a Therapy and Support Service for People with Long-Term Stroke and Aphasia

    ERIC Educational Resources Information Center

    van der Gaag, Anna; Brooks, Richard

    2008-01-01

    Background: This paper considers some economic aspects of a therapy and support service for people with stroke and aphasia. This material was part of a broader evaluation of the service, which is reported elsewhere (van der Gaag et al. 2005, van der Gaag and Mowles 2005). Aims: The purpose of this part of the study was to investigate the…