A Predictive Algorithm to Detect Opioid Use Disorder

PubMed Central

Lee, Chee; Sharma, Maneesh; Kantorovich, Svetlana

2018-01-01

Purpose: The purpose of this study was to determine the clinical utility of an algorithm-based decision tool designed to assess risk associated with opioid use in the primary care setting. Methods: A prospective, longitudinal study was conducted to assess the utility of precision medicine testing in 1822 patients across 18 family medicine/primary care clinics in the United States. Using the profile, patients were categorized into low, moderate, and high risk for opioid use. Physicians who ordered testing were asked to complete patient evaluations and document their actions, decisions, and perceptions regarding the utility of the precision medicine tests. Results: Approximately 47% of primary care physicians surveyed used the profile to guide clinical decision-making. These physicians rated the benefit of the profile on patient care an average of 3.6 on a 5-point scale (1 indicating no benefit and 5 indicating significant benefit). Eighty-eight percent of all clinicians surveyed felt the test exhibited some benefit to their patient care. The most frequent utilization for the profile was to guide a change in opioid prescribed. Physicians reported greater benefit of profile utilization for minority patients. Patients whose treatment was guided by the profile had pain levels that were reduced, on average, 2.7 levels on the numeric rating scale. Conclusions: The profile provided primary care physicians with a useful tool to stratify the risk of opioid use disorder and was rated as beneficial for decision-making and patient improvement by the majority of physicians surveyed. Physicians reported the profile resulted in greater clinical improvement for minorities, highlighting the objective use of this profile to guide judicial use of opioids in high-risk patients. Significantly, when physicians used the profile to guide treatment decisions, patient-reported pain was greatly reduced. PMID:29383324

A Predictive Algorithm to Detect Opioid Use Disorder: What Is the Utility in a Primary Care Setting?

PubMed

Lee, Chee; Sharma, Maneesh; Kantorovich, Svetlana; Brenton, Ashley

2018-01-01

The purpose of this study was to determine the clinical utility of an algorithm-based decision tool designed to assess risk associated with opioid use in the primary care setting. A prospective, longitudinal study was conducted to assess the utility of precision medicine testing in 1822 patients across 18 family medicine/primary care clinics in the United States. Using the profile, patients were categorized into low, moderate, and high risk for opioid use. Physicians who ordered testing were asked to complete patient evaluations and document their actions, decisions, and perceptions regarding the utility of the precision medicine tests. Approximately 47% of primary care physicians surveyed used the profile to guide clinical decision-making. These physicians rated the benefit of the profile on patient care an average of 3.6 on a 5-point scale (1 indicating no benefit and 5 indicating significant benefit). Eighty-eight percent of all clinicians surveyed felt the test exhibited some benefit to their patient care. The most frequent utilization for the profile was to guide a change in opioid prescribed. Physicians reported greater benefit of profile utilization for minority patients. Patients whose treatment was guided by the profile had pain levels that were reduced, on average, 2.7 levels on the numeric rating scale. The profile provided primary care physicians with a useful tool to stratify the risk of opioid use disorder and was rated as beneficial for decision-making and patient improvement by the majority of physicians surveyed. Physicians reported the profile resulted in greater clinical improvement for minorities, highlighting the objective use of this profile to guide judicial use of opioids in high-risk patients. Significantly, when physicians used the profile to guide treatment decisions, patient-reported pain was greatly reduced.

Surgical treatment of comminuted mandibular fractures using a low-profile locking mandibular reconstruction plate system

PubMed Central

Kanno, Takahiro; Sukegawa, Shintaro; Nariai, Yoshiki; Tatsumi, Hiroto; Ishibashi, Hiroaki; Furuki, Yoshihiko; Sekine, Joji

2014-01-01

Objective: The treatment of comminuted mandibular fractures is challenging due to the severity of associated injuries and the need for a careful diagnosis with adequate treatment planning. Recently, open reduction and stable internal fixation (OR-IF) with a load-bearing reconstruction plate have been advocated for reliable clinical outcomes with minimal complications. This clinical prospective study evaluated OR-IF in the surgical management of comminuted mandibular fractures with a new low-profile, thin, mandibular locking reconstruction plate. Materials and Methods: We prospectively assessed OR-IF of comminuted mandibular fractures with a low-profile locking mandibular reconstruction plate in 12 patients (nine men, three women; mean age 32.2 [range 16-71] years) between April 2010 and December 2011. The clinical characteristics and associated clinical parameters of patients were evaluated over a minimum follow-up period of 12 months. Results: Traffic accidents caused 50% of the fractures, followed by falls (25%). Four patients (33.3%) had associated midfacial maxillofacial fractures, while five patients had other mandibular fractures. Seven patients (58.3%) needed emergency surgery, mostly for airway management. Anatomical reduction of the comminuted segments re-established the mandibular skeleton in stable occlusion with rigid IF via extraoral (33.3%), intraoral (50%), or combined (16.7%) approaches. Immediate functional recovery was achieved. Sound bone healing was confirmed in all patients, with no complications such as malocclusion, surgical site infection, or malunion with a mean follow-up of 16.3 (range 12-24) months. Conclusions: OR-IF using a low-profile reconstruction plate system is a reliable treatment for comminuted mandibular fractures, enabling immediate functional recovery with good clinical results. PMID:25593862

Surgery for vertigo: 10-year audit from a contemporary vertigo clinic.

PubMed

Patnaik, U; Srivastava, A; Sikka, K; Thakar, A

2015-12-01

To present the profile of patients undergoing surgical treatment for vertigo at a contemporary institutional vertigo clinic. A retrospective analysis of clinical charts. The charts of 1060 patients, referred to an institutional vertigo clinic from January 2003 to December 2012, were studied. The clinical profile and long-term outcomes of patients who underwent surgery were analysed. Of 1060 patients, 12 (1.13 per cent) were managed surgically. Of these, disease-modifying surgical procedures included perilymphatic fistula repair (n = 7) and microvascular decompression of the vestibular nerve (n = 1). Labyrinth destructive procedures included transmastoid labyrinthectomy (n = 2) and labyrinthectomy with vestibular nerve section (n = 1). One patient with vestibular schwannoma underwent both a disease-modifying and destructive procedure (translabyrinthine excision). All patients achieved excellent vertigo control, classified as per the American Academy of Otolaryngology - Head and Neck Surgery 1995 criteria. With the advent of intratympanic treatments, surgical treatments for vertigo have become further limited. However, surgery with directed intent, in select patients, can give excellent results.

Clinical Profiles of Children with Disruptive Behaviors Based on the Severity of Their Conduct Problems, Callous-Unemotional Traits and Emotional Difficulties.

PubMed

Andrade, Brendan F; Sorge, Geoff B; Na, Jennifer Jiwon; Wharton-Shukster, Erika

2015-08-01

This study identified clinical profiles of referred children based on the severity of callous-unemotional (CU) traits, emotional difficulties, and conduct problems. Parents of 166 children (132 males) aged 6-12 years referred to a hospital clinic because of disruptive behavior completed measures to assess these key indicators, and person-centered analysis was used to identify profiles. Four distinct profiles were identified that include: (1) Children low in severity on the three domains, (2) Children high in severity on the three domains, (3) Children high in severity in conduct problems and CU traits with minimal emotional difficulties, and (4) Children high in severity in conduct problems and emotional difficulties with minimal CU traits. Profiles differed in degree of aggression and behavioral impairment. Findings show that clinic-referred children with disruptive behaviors can be grouped based on these important indicators into profiles that have important implications for assessment and treatment selection.

Clinically Applicable Inhibitors Impacting Genome Stability.

PubMed

Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

2018-05-13

Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

Use of betahistine in the treatment of peripheral vertigo.

PubMed

Ramos Alcocer, Rubén; Ledezma Rodríguez, José Gregorio; Navas Romero, Antonio; Cardenas Nuñez, José Luis; Rodríguez Montoya, Vicente; Deschamps, Jose Junior; Liviac Ticse, Jorge Anibal

2015-01-01

Clinical studies and meta-analyses demonstrated that betahistine is effective and safe in the treatment of Ménière's disease, BPPV (benign paroxysmal positional vertigo), vestibular neuronitis, and other types of peripheral vertigo. The goal of this paper is to review the pharmacological profile of betahistine and the evidence for its effectiveness and safety in the treatment of peripheral vertigo. Selection criteria for the publications on betahistine included randomized clinical trials that evaluated the effectiveness and safety of betahistine vs placebo or active control in the treatment of peripheral vertigo. Recent meta-analyses were also included. Databases searched included PubMed, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, and ICTRP. The review also presents an update on the mechanisms of action, pharmacodynamics, and pharmacokinetics of betahistine. Efficacy and safety of betahistine has been demonstrated in numerous clinical trials. The precise mechanism of action of betahistine is still not completely understood, but the clinical experience demonstrated the benefit of betahistine in different types of peripheral vertigo. In more than 40 years of clinical use, betahistine has shown an excellent safety profile with the usual dose range from 8-48 mg daily. According to clinical studies, betahistine 48 mg daily during 3 months is an effective and safe option for the treatment of peripheral vertigo.

Analysis of pain behavior profiles and functional disability in outpatient physical therapy clinics.

PubMed

Hankin, H A; Spencer, T; Kegerreis, S; Worrell, T; Rice, J M

2001-02-01

Descriptive, ex post facto. To determine the proportion of physical therapy outpatients with pain who exhibit various pain behavior profiles, and to determine whether there are differences in functional disability across the profiles. Physical therapists treat many patients who have chronic pain. Research suggests that early identification and multidisciplinary treatment are effective and economical for these patients. The Multidimensional Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening tools that could be used in physical therapy clinics to determine which patients should be referred for multidisciplinary treatment. MPI and PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5 years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was used to analyze differences in mean PDI scores across the MPI profiles. Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile. There were significant differences in PDI scores among profile groups. Post hoc analysis showed that the PDI scores of the Adaptive Coper and Interpersonally Distressed groups were different from the Dysfunctional group, but that there was no difference between the Adaptive Coper and Interpersonally Distressed groups. Many patients in outpatient physical therapy settings exhibit behavioral, affective, and cognitive characteristics associated with chronic pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed and dysfunctional) that suggest they might benefit from multidisciplinary treatment.

A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

PubMed Central

Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

2015-01-01

Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different toxicity profiles. Patient’s predisposition to toxicities may govern the selection of a particular regime. PMID:26870703

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

Computer-Based Intepretation of the Marital Satisfaction Inventory: Use in Treatment Planning.

ERIC Educational Resources Information Center

Snyder, Douglas K.; And Others

1988-01-01

Describes computer-based interpretive system for Marital Satisfaction Inventory (MSI) and application in initial phases of clinical assessment and treatment planning. Provides case study. Compares clinical findings at intake with MSI profiles for one couple obtained at termination and follow-up. Considers strengths and limitations of self-report…

Management of schizophrenia: clinical experience with asenapine.

PubMed

Cortese, Leonardo; Bressan, Rodrigo A; Castle, David J; Mosolov, Sergey N

2013-04-01

Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety). The management of schizophrenia requires effective short- and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term. Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults. It has a unique receptor-binding profile and a broad range of therapeutic effects. Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent's efficacy and tolerability under 'real-world' clinical practice conditions is also required. As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention. It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia. Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters. As such, asenapine is valuable option for the treatment of schizophrenia in adults.

Expanding choices in intranasal steroid therapy: summary of a roundtable meeting.

PubMed

Blaiss, Michael S; Benninger, Michael S; Fromer, Len; Gross, Gary; Mabry, Richard; Mahr, Todd; Marple, Bradley; Stoloff, Stuart

2006-01-01

Intranasal steroids (INSs) are recommended as first-line treatment for allergic rhinitis (AR) and a wealth of data exist supporting them as safe and effective. Our goal was to develop a consensus to help physicians choose between INSs by focusing on clinical profiles and patient preferences and providing expert advice on choosing the appropriate INS for each patient. Experts from specialties that manage patients with AR attended a roundtable meeting to discuss INS therapy. Besides comparisons with other pharmacologic agents, they examined the effects of INS on nasal anatomy, patient preferences for INS, and benefits of product selection based on patient profile. The literature on INSs in AR was reviewed, examining properties of the various drugs, delivery devices, formulations, and patient preference data. Nasal anatomy and physiology must be considered to optimize INS deposition in the nose. Teaching patients proper technique for using INS devices is important to prevent nasal injury and may help concentrate drug effect on affected tissues. INS therapies differ somewhat in biological properties and specific formulation; however, all are considered safe and effective treatment for AR. Patients exhibit different clinical profiles, which play a role in INS selection. Patients can clearly identify sensory characteristics of INS and therefore establish product preference. Patient preference also can guide physicians in choosing the appropriate agent for each patient. Control of AR requires a systematic approach to treatment selection and follow-up. Treatment selection should be matched with clinical profile and patient preferences.

Profiling the clinical presentation of diagnostic characteristics of a sample of symptomatic TMD patients.

PubMed

Pimenta e Silva Machado, Luciana; de Macedo Nery, Marianita Batista; de Góis Nery, Cláudio; Leles, Cláudio Rodrigues

2012-08-02

Temporomandibular disorder (TMD) patients might present a number of concurrent clinical diagnoses that may be clustered according to their similarity. Profiling patients' clinical presentations can be useful for better understanding the behavior of TMD and for providing appropriate treatment planning. The aim of this study was to simultaneously classify symptomatic patients diagnosed with a variety of subtypes of TMD into homogenous groups based on their clinical presentation and occurrence of comorbidities. Clinical records of 357 consecutive TMD patients seeking treatment in a private specialized clinic were included in the study sample. Patients presenting multiple subtypes of TMD diagnosed simultaneously were categorized according to the AAOP criteria. Descriptive statistics and two-step cluster analysis were used to characterize the clinical presentation of these patients based on the primary and secondary clinical diagnoses. The most common diagnoses were localized masticatory muscle pain (n = 125) and disc displacement without reduction (n = 104). Comorbidity was identified in 288 patients. The automatic selection of an optimal number of clusters included 100% of cases, generating an initial 6-cluster solution and a final 4-cluster solution. The interpretation of within-group ranking of the importance of variables in the clustering solutions resulted in the following characterization of clusters: chronic facial pain (n = 36), acute muscle pain (n = 125), acute articular pain (n = 75) and chronic articular impairment (n = 121). Subgroups of acute and chronic TMD patients seeking treatment can be identified using clustering methods to provide a better understanding of the clinical presentation of TMD when multiple diagnosis are present. Classifying patients into identifiable symptomatic profiles would help clinicians to estimate how common a disorder is within a population of TMD patients and understand the probability of certain pattern of clinical complaints.

Understanding compliance issues for daily self-injectable treatment in ambulatory care settings

PubMed Central

Brod, Meryl; Rousculp, Matthew; Cameron, Ann

2008-01-01

Background The challenge of understanding factors influencing compliance with injectable treatments is critical as injectable biologics/medications become more common. Objective Understanding compliance issues for long term self-injectable treatments, using a chronic condition (osteoporosis) as a model. Research design A qualitative study to generate hypotheses regarding compliance issues for self-injectable treatments. Semi-structured interview guides were developed and data collected from patients and clinical experts. Findings were analyzed for common themes and a conceptual model of the compliance impact of self-injectable treatments generated. Subjects Six physicians (Rheumatology, Internal Medicine, and Endocrinology) and 22 patients (14% never began treatment, 23% had filled at least one prescription but discontinued treatment, and 63% were currently on treatment) were interviewed. Results Physician and patient factors influenced the compliance process at four distinct time-points: pre-treatment, time treatment recommended, short-term, and long-term. Physician factors that influenced patients’ persistence were knowledge about treatment, patient-training resources, and clinical profile/efficacy evaluations. For patients, motivation level, physician message, and clinical profile were key. Logistical issues, minor side effects and injection site issues influenced adherence but not persistence. Conclusions Compliance is a multifactorial, dynamic process. Both physician and patient factors influence compliance at different points in the process. PMID:19920953

Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

PubMed Central

Khanna, Ish K; Pillarisetti, Sivaram

2015-01-01

Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed μ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other μ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain. PMID:26672499

Brexpiprazole: A Partial Dopamine Agonist for the Treatment of Schizophrenia.

PubMed

Ekinci, Asli; Ekinci, Okan

2018-01-31

Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is challenging to treat, despite there being a large antipsychotic armamentarium. Brexpiprazole acts both as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at the serotonin 5- HT2A and noradrenaline alpha1B and alpha2C receptors, all with similar potency. This balanced receptor profile may produce promising antipsychotic effects on positive, negative and cognitive symptoms in schizophrenia with minimal adverse effects. This review summarizes the pharmacodynamics and pharmacokinetic profile of brexpiprazole and the clinical trial information pertaining to its effectiveness and safety and tolerability, discusses its best clinical use, and compares its clinical profile to those of other widely used antipsychotic agents. Brexpiprazole demonstrated significant clinical efficacy and had good safety and tolerability in well-designed trials with patients with schizophrenia. This agent may be a useful treatment alternative. However, it will be valuable to consider a long-term observational study that includes an active comparator, especially other second-generation antipsychotics (SGAs), to further evaluate the efficacy and safety of brexpiprazole in the treatment of schizophrenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optoacoustic imaging of tissue blanching during photodynamic therapy of esophageal cancer

NASA Astrophysics Data System (ADS)

Jacques, Steven L.; Viator, John A.; Paltauf, Guenther

2000-05-01

Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

A Latent Profile Analysis of Aggression and Victimization Across Relationship Types Among Veterans Who Use Substances.

PubMed

Anderson, RaeAnn E; Bonar, Erin E; Walton, Maureen A; Goldstick, Jason E; Rauch, Sheila A M; Epstein-Ngo, Quyen M; Chermack, Stephen T

2017-07-01

This study examined patterns of violence victimization and aggression in both intimate partner and nonpartner relationships among U.S. military veterans using latent profile analysis to identify subtypes of violence involvement. Participants were 839 substance use treatment-seeking veterans (93% male) from a large Veterans Affairs Medical Center who completed screening measures for a randomized controlled trial. Past-year violence involvement, including both intimate partner violence (IPV) and nonpartner violence (NPV), was common in the sample, although NPV occurred at somewhat higher rates. When we included either IPV or NPV aggression or victimization, more than 40% reported involvement with physical violence, 30% with violence involving injury, and 86% with psychological aggression. Latent profile analysis including both aggression and victimization in partner and nonpartner relationships indicated a four-profile solution: no/low violence (NLV; n = 377), predominantly IPV (n = 219), predominantly NPV (n = 134), and high general violence (HGV; n = 109). Multinomial logistic regression analyses revealed that, compared with the NLV group, the remaining three groups differed in age, cocaine use, posttraumatic stress disorder (PTSD) symptoms, and legal involvement. Legal issues appeared to differentiate the profiles most, with the predominantly NPV and HGV profiles reporting more instances of driving under the influence and the HGV profile reporting legal problems related to aggression. IPV and NPV are fairly common among veterans seeking substance use treatment. The clinical characteristics of violence profiles indicate that cocaine use, PTSD symptoms, and legal involvement are treatment needs that vary with violence profile and may be useful for clinical decision making.

Non-muscle invasive bladder cancer: Are epicrises the ‘Bermuda Triangle’ of information transfer?

PubMed Central

May, Matthias; Wick, Anne-Kathrin; Roiner, Michael; Mathew, Marcella; Gilfrich, Christian; Schostak, Martin

2017-01-01

Introduction The aim of the study was to collect information regarding the quality of communication of risk-determining factors or risk profile, and the guideline conformity of recommendations for adjuvant treatment in patients with non-muscle invasive bladder cancer (NMIBC) between clinical and ambulatory urologists. Material and methods At three German urological clinics during the period between 2012-2014, epicrises of 1,033 NMIBC-patients were retrospectively summarised to 505 tumour episodes (tumour resection including any re-resections) and analysed regarding the endpoints 1) risk profile is explicitly named or recorded risk factors are sufficient for the determination of risk profile, and 2) guideline conformity of treatment recommendation. Independent factors influencing the endpoints were determined by means of multivariate logistic regression models. Results The risk profile was explicitly named for 3.6% of tumour episodes; for 68.9% a risk profile could be derived from the information in the epicrises. Treatment recommendations were given for 93.7% of tumour episodes, but only 17.8% were guideline compliant. 42.6% of the recommendations were not reliably effective; 33.1% and 0.2% resulted in under- and overtreatment respectively. Neither endpoint showed gender specific or regional differences, but both were considerably less likely to be achieved in case of recurrence. Conclusions The discrepancy between treatment recommendation (93.7%) and guideline compliance (17.8%) could indicate a lack of familiarity with guidelines. The quality of the epicrises of NMIBC-patients was poor and bore the potential risk of undertreatment. The results of this study are not necessarily applicable to other clinics, but could, however, prompt physicians to re-examine epicrises for the fulfillment of the quality criteria examined here. PMID:29104786

Non-muscle invasive bladder cancer: Are epicrises the 'Bermuda Triangle' of information transfer?

PubMed

Lebentrau, Steffen; May, Matthias; Wick, Anne-Kathrin; Roiner, Michael; Mathew, Marcella; Gilfrich, Christian; Schostak, Martin

2017-01-01

The aim of the study was to collect information regarding the quality of communication of risk-determining factors or risk profile, and the guideline conformity of recommendations for adjuvant treatment in patients with non-muscle invasive bladder cancer (NMIBC) between clinical and ambulatory urologists. At three German urological clinics during the period between 2012-2014, epicrises of 1,033 NMIBC-patients were retrospectively summarised to 505 tumour episodes (tumour resection including any re-resections) and analysed regarding the endpoints 1) risk profile is explicitly named or recorded risk factors are sufficient for the determination of risk profile, and 2) guideline conformity of treatment recommendation. Independent factors influencing the endpoints were determined by means of multivariate logistic regression models. The risk profile was explicitly named for 3.6% of tumour episodes; for 68.9% a risk profile could be derived from the information in the epicrises. Treatment recommendations were given for 93.7% of tumour episodes, but only 17.8% were guideline compliant. 42.6% of the recommendations were not reliably effective; 33.1% and 0.2% resulted in under- and overtreatment respectively. Neither endpoint showed gender specific or regional differences, but both were considerably less likely to be achieved in case of recurrence. The discrepancy between treatment recommendation (93.7%) and guideline compliance (17.8%) could indicate a lack of familiarity with guidelines. The quality of the epicrises of NMIBC-patients was poor and bore the potential risk of undertreatment. The results of this study are not necessarily applicable to other clinics, but could, however, prompt physicians to re-examine epicrises for the fulfillment of the quality criteria examined here.

Anxiety and oppositional behavior profiles among youth with selective mutism.

PubMed

Diliberto, Rachele A; Kearney, Christopher A

2016-01-01

Selective mutism (SM) is a debilitating condition in which a child does not speak in social situations where speech is expected. The clinical conceptualization of SM has been debated historically, with evidence pointing partly to anxious and oppositional behavior profiles. Behavioral characteristics were examined in a clinical sample of 57 youth formally diagnosed with selective mutism. Parents rated children across internalizing and externalizing behaviors on the Child Behavior Checklist. Eighteen highly rated items were subjected to exploratory and then confirmatory factor analysis. Anxiety and oppositional behavior factors were derived. The anxious behavior profile was associated with social anxiety disorder symptoms, social problems, and aggressive behaviors but not oppositional defiant disorder symptoms. The oppositional behavior profile was associated with aggressive behaviors, oppositional defiant disorder symptoms, social problems, and inversely to social anxiety disorder symptoms. Results are consistent with emerging research regarding subgroups of children with SM. Behavior profiles are discussed as well with respect to assessment and treatment implications. Readers will learn about the nature of children with selective mutism as well as behaviors that differentiate anxious and oppositional behavior profiles. Items that comprise anxious and oppositional behavior profiles are presented. These item profiles may have ramifications for assessment and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of genomic profiling on the treatment and outcomes of patients with advanced gastrointestinal malignancies.

PubMed

Dhir, Mashaal; Choudry, Haroon A; Holtzman, Matthew P; Pingpank, James F; Ahrendt, Steven A; Zureikat, Amer H; Hogg, Melissa E; Bartlett, David L; Zeh, Herbert J; Singhi, Aatur D; Bahary, Nathan

2017-01-01

The impact of genomic profiling on the outcomes of patients with advanced gastrointestinal (GI) malignancies remains unknown. The primary objectives of the study were to investigate the clinical benefit of genomic-guided therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) at 3 months, and its impact on progression-free survival (PFS) in patients with advanced GI malignancies. Clinical and genomic data of all consecutive GI tumor samples from April, 2013 to April, 2016 sequenced by FoundationOne were obtained and analyzed. A total of 101 samples from 97 patients were analyzed. Ninety-eight samples from 95 patients could be amplified making this approach feasible in 97% of the samples. After removing duplicates, 95 samples from 95 patients were included in the further analysis. Median time from specimen collection to reporting was 11 days. Genomic alteration-guided treatment recommendations were considered new and clinically relevant in 38% (36/95) of the patients. Rapid decline in functional status was noted in 25% (9/36) of these patients who could therefore not receive genomic-guided therapy. Genomic-guided therapy was utilized in 13 patients (13.7%) and 7 patients (7.4%) experienced clinical benefit (6 PR and 1 SD). Among these seven patients, median PFS was 10 months with some ongoing durable responses. Genomic profiling-guided therapy can lead to clinical benefit in a subset of patients with advanced GI malignancies. Attempting genomic profiling earlier in the course of treatment prior to functional decline may allow more patients to benefit from these therapies. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

The Convergence Insufficiency Treatment Trial: Design, Methods, and Baseline Data

PubMed Central

2009-01-01

Objective This report describes the design and methodology of the Convergence Insufficiency Treatment Trial (CITT), the first large-scale, placebo-controlled, randomized clinical trial evaluating treatments for convergence insufficiency (CI) in children. We also report the clinical and demographic characteristics of patients. Methods We prospectively randomized children 9 to 17 years of age to one of four treatment groups: 1) home-based pencil push-ups, 2) home-based computer vergence/accommodative therapy and pencil push-ups, 3) office-based vergence/accommodative therapy with home reinforcement, 4) office-based placebo therapy. Outcome data on the Convergence Insufficiency Symptom Survey (CISS) score (primary outcome), near point of convergence (NPC), and positive fusional vergence were collected after 12 weeks of active treatment and again at 6 and 12 months post-treatment. Results The CITT enrolled 221 children with symptomatic CI with a mean age of 12.0 years (SD = +2.3). The clinical profile of the cohort at baseline was 9Δ exophoria at near (+/− 4.4) and 2Δ exophoria (+/−2.8) at distance, CISS score = 30 (+/−9.0), NPC = 14 cm (+/− 7.5), and near positive fusional vergence break = 13 Δ (+/− 4.6). There were no statistically significant nor clinically relevant differences between treatment groups with respect to baseline characteristics (p > 0.05). Conclusion Hallmark features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a placebo treatment arm, masked outcome examinations, and the CISS score outcome measure. The baseline data reported herein define the clinical profile of those enrolled into the CITT. PMID:18300086

Clinical Practice Guideline for Physical Therapy Assessment and Treatment in Patients With Nonspecific Neck Pain.

PubMed

Bier, Jasper D; Scholten-Peeters, Wendy G M; Staal, J Bart; Pool, Jan; van Tulder, Maurits W; Beekman, Emmylou; Knoop, Jesper; Meerhoff, Guus; Verhagen, Arianne P

2018-03-01

The Royal Dutch Society for Physical Therapy (KNGF) issued a clinical practice guideline for physical therapists that addresses the assessment and treatment of patients with nonspecific neck pain, including cervical radiculopathy, in Dutch primary care. Recommendations were based on a review of published systematic reviews.During the intake, the patient is screened for serious pathologies and corresponding patterns. Patients with cervical radiculopathy can be included or excluded through corresponding signs and symptoms and possibly diagnostic tests (Spurling test, traction/distraction test, and Upper Limb Tension Test). History taking is done to gather information about patients' limitations, course of pain, and prognostic factors (eg, coping style) and answers to health-related questions.In case of a normal recovery (treatment profile A), management should be hands-off, and patients should receive advice from the physical therapist and possibly some simple exercises to supplement "acting as usual."In case of a delayed/deviant recovery (treatment profile B), the physical therapist is advised to use, in addition to the recommendations for treatment profile A, forms of mobilization and/or manipulation in combination with exercise therapy. Other interventions may also be considered. The physical therapist is advised not to use dry needling, low-level laser, electrotherapy, ultrasound, traction, and/or a cervical collar.In case of a delayed/deviant recovery with clear and/or dominant psychosocial prognostic factors (treatment profile C), these factors should first be addressed by the physical therapist, when possible, or the patient should be referred to a specialist, when necessary.In case of neck pain grade III (treatment profile D), the therapy resembles that for profile B, but the use of a cervical collar for pain reduction may be considered. The advice is to use it sparingly: only for a short period per day and only for a few weeks.

Uterine fibroid treatment patterns in a population of insured women.

PubMed

Lee, David W; Gibson, Teresa B; Carls, Ginger S; Ozminkowski, Ronald J; Wang, Shaohung; Stewart, Elizabeth A

2009-02-01

To profile women treated for uterine leiomyomas who are covered by commercial insurance from large, self-insured employers in the United States. Retrospective, observational study. Inpatient, outpatient, and prescription drug experience of women with employer-sponsored insurance in the United States. Data were obtained from the MarketScan insurance databases for 1999 through 2004 and weighted to represent the population of women with employer-sponsored health insurance in the United States. None. The proportion of women with clinically significant leiomyomas was determined in each year, based on inpatient and outpatient medical claims with diagnostic codes indicating leiomyoma. Patient characteristics, comorbidities, prescription drug treatments, and surgical interventions were profiled in 2004. Approximately 1% of women had clinically significant leiomyomas. Comorbid genital or menstrual conditions were common and much more prevalent for women with leiomyomas. Of women with leiomyomas, 18.4% received no surgical or prescription drug treatment, whereas 16.8% received only surgical treatment, 22.4% received only prescription drug treatment, and 42.4% received both. Hysterectomy was the most common surgical treatment. Generalizing from this sample, we estimate that 443,445 women with employer-sponsored insurance in the United States had clinically significant leiomyomas in 2004.

[Clinical evaluation of Divina in treatment of hormonal disturbances in women].

PubMed

Warenik-Szymankiewicz, A; Halerz-Nowakowska, B; Wiza, M; Grotowski, W

2001-03-01

The aim of this study was the assessment of clinical efficacy during hormonal treatment with Divina among women with hormonal cycle disturbances. Divina is a estrogen-progesatagen drug containing 2 mg valerate estradiol and 10 mg medroxyprogesteron acetate. The influence on lipid profile, liver and kidney activity and glucose tolerance was assessed. The measurement of bone density was performed twice before and after 6 months of treatment with Divina.

Evaluation of symptom, clinical chemistry and metabolomics profiles during Rehmannia six formula (R6) treatment: an integrated and personalized data analysis approach.

PubMed

van Wietmarschen, Herman A; van der Greef, Jan; Schroën, Yan; Wang, Mei

2013-12-12

Rehmannia Six Formula (R6, Chinese name is Liu Wei Di Huang Wan) is one of the most important classic Chinese medicine formula used to treat metabolic disorders related to aging. It was first reported in the Chinese medicine book titled 'Xiao Er Yao Zheng Zhi Jue by Qian Yi' (Chinese Song dynasty: 1035-1117). In modern times it is therefore often used to treat diabetes, pre-diabetes, fatigue and people with metabolic syndrome. The aim of this study is to measure changes in symptoms, clinical parameters and serum metabolite profiles during R6 treatment of human subjects with features of metabolic syndrome. Symptoms, clinical parameters and serum metabolites were measured before and after 4 and 8 weeks of R6 treatment. Nonlinear Principal Component Analysis was applied for the first time to conduct an integrated analysis of the three data sets. Correlation structures were compared before treatment and after 4 and 8 weeks of treatment. Additionally, a State Space Grid approach was used to study personalized changes in symptom profiles. The symptoms 'hectic fever' and 'spontaneous sweating' were found to be most relieved during R6 treatment. Most of the symptoms were less correlated with other variables after 8 weeks of R6 treatment. LDL-C, total cholesterol, systolic blood pressure and waist size were found to decrease during R6 treatment. Additionally, 10 of the 15 measured phosphatidylcholines were found to decrease. Personalized symptom profiles as described by Chinese medical terms show that most Yin deficiencies are addressed first by R6 treatment. However, in subjects with reduced or less Yin deficiency but which do have a substantial Qi deficiency a reduction of Qi deficiency is subsequently observed. R6 treatment was shown to improve the lipid profile indicating a reduction of cardiovascular risk. Additionally, the changes observed in correlation structure indicate a different angle of looking at treatment effects. Less strong correlations between symptoms and metabolites suggest a healthier situation after R6 treatment. A State Space Grid analysis showed that the effect of R6 was different for the Yin deficiency subjects and the Qi deficiency subjects. The observed decrease of Yin deficiency related symptoms is in agreement with the use of R6 in Chinese medicine to nourish Yin. Observing individual differences in treatment effects is therefore an essential step in the development of personalized medicine. © 2013 Elsevier Ireland Ltd. All rights reserved.

The convergence insufficiency treatment trial: design, methods, and baseline data.

PubMed

2008-01-01

This report describes the design and methodology of the Convergence Insufficiency Treatment Trial (CITT), the first large-scale, placebo-controlled, randomized clinical trial evaluating treatments for convergence insufficiency (CI) in children. We also report the clinical and demographic characteristics of patients. We prospectively randomized children 9 to 17 years of age to one of four treatment groups: 1) home-based pencil push-ups, 2) home-based computer vergence/accommodative therapy and pencil push-ups, 3) office-based vergence/accommodative therapy with home reinforcement, 4) office-based placebo therapy. Outcome data on the Convergence Insufficiency Symptom Survey (CISS) score (primary outcome), near point of convergence (NPC), and positive fusional vergence were collected after 12 weeks of active treatment and again at 6 and 12 months posttreatment. The CITT enrolled 221 children with symptomatic CI with a mean age of 12.0 years (SD = +2.3). The clinical profile of the cohort at baseline was 9Delta exophoria at near (+/- 4.4) and 2Delta exophoria (+/-2.8) at distance, CISS score = 30 (+/-9.0), NPC = 14 cm (+/- 7.5), and near positive fusional vergence break = 13 Delta (+/- 4.6). There were no statistically significant nor clinically relevant differences between treatment groups with respect to baseline characteristics (p > 0.05). Hallmark features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a placebo treatment arm, masked outcome examinations, and the CISS score outcome measure. The baseline data reported herein define the clinical profile of those enrolled into the CITT.

Emerging Applications of Stem Cell and Regenerative Medicine to Sports Injuries

PubMed Central

Ajibade, David A.; Vance, Danica D.; Hare, Joshua M.; Kaplan, Lee D.; Lesniak, Bryson P.

2014-01-01

Background: The treatment of sports-related musculoskeletal injuries with stem cells has become more publicized because of recent reports of high-profile athletes undergoing stem cell procedures. There has been increased interest in defining the parameters of safety and efficacy and the indications for potential use of stem cells in clinical practice. Purpose: To review the role of regenerative medicine in the treatment of sports-related injuries. Study Design: Review. Method: Relevant studies were identified through a PubMed search combining the terms stem cells and cartilage, ligament, tendon, muscle, and bone from January 2000 to August 2013. Studies and works cited in these studies were also reviewed. Results: Treatment of sports-related injuries with stem cells shows potential for clinical efficacy from the data available from basic science and animal studies. Conclusion: Cell-based therapies and regenerative medicine offer safe and potentially efficacious treatment for sports-related musculoskeletal injuries. Basic science and preclinical studies that support the possibility of enhanced recovery from sports injuries using cell-based therapies are accumulating; however, more clinical evidence is necessary to define the indications and parameters for their use. Accordingly, exposing patients to cell-based therapies could confer an unacceptable risk profile with minimal or no benefit. Continued clinical testing with animal models and clinical trials is necessary to determine the relative risks and benefits as well as the indications and methodology of treatment. PMID:26535296

Udenafil for the treatment of erectile dysfunction

PubMed Central

Cho, Min Chul; Paick, Jae-Seung

2014-01-01

Erectile dysfunction (ED) is often perceived by both patients and sexual partners as a serious problem that can jeopardize quality of life, psychosocial or emotional well-being, and the partnership in the long term. Since their introduction, oral phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be highly effective and well tolerated, and are available as the first-line therapy for the treatment of ED. Udenafil is one of the selective PDE5Is made available in recent years for the treatment of ED. Udenafil has clinical properties of both relatively rapid onset and long duration of action due to its pharmacokinetic profile, thereby providing an additional treatment option for ED men to better suit individual needs. There is positive evidence that udenafil is effective and well tolerated in the treatment of ED of a broad spectrum of etiologies or severity. Udenafil is as effective in the treatment of diabetes mellitus-associated ED as other PDE5Is. Due to the clinical property of relatively long duration of action, udenafil may be another option in daily dosing treatment for ED, as suggested by its favorable efficacy and safety profile. Most adverse effects reported from clinical trials are mild or moderate in severity, without any serious adverse event, with headache and flushing being the most common. Also, the concomitant use of anti-hypertensive drugs or alpha-1-blockers does not significantly affect the efficacy and safety profile of udenafil. However, additional studies with larger cohorts including prospective, multicenter, comparative studies with patients of different ethnicities are needed to further validate the favorable findings of udenafil in the treatment of ED. PMID:24868160

Concussion is Treatable: Statements of Agreement from the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting held in Pittsburgh, October 15–16, 2015

PubMed Central

Collins, Michael W.; Kontos, Anthony P.; Okonkwo, David O.; Almquist, Jon; Bailes, Julian; Barisa, Mark; Bazarian, Jeffrey; Bloom, O. Josh; Brody, David; Cantu, Robert; Cardenas, Javier; Clugston, Jay; Cohen, Randall; Echemendia, Ruben; Elbin, R.J.; Ellenbogen, Richard; Fonseca, Janna; Gioia, Gerard; Guskiewicz, Kevin; Heyer, Robert; Hotz, Gillian; Iverson, Grant L.; Jordan, Barry; Manley, Geoffrey; Maroon, Joseph; McAllister, Thomas; McCrea, Michael; Mucha, Anne; Pieroth, Elizabeth; Podell, Kenneth; Pombo, Matthew; Shetty, Teena; Sills, Allen; Solomon, Gary; Thomas, Danny G.; Valovich McLeod, Tamara C.; Yates, Tony; Zafonte, Ross

2016-01-01

Background Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment. Objective To describe the current landscape of treatment for concussion and provide summary agreements related to treatment in order to assist clinicians in the treatment of concussion. Methods On October 14–16, 2015, the Targeted Evaluation & Active Management (TEAM) Approaches To Treating Concussion meeting was convened in Pittsburgh, Pennsylvania, USA. 37 concussion experts from neuropsychology, neurology, neurosurgery, sports medicine, physical medicine and rehabilitation, physical therapy, athletic training, and research, and 12 individuals representing sport, military, and public health organizations attended the meeting. The 37 experts indicated their agreement on a series of statements using an audience response system clicker device. Results A total of 16 statements of agreement were supported covering: 1) Summary of the Current Approach to Treating Concussion, 2) Heterogeneity and Evolving Clinical Profiles of Concussion, 3) Targeted Evaluation and Active Management Approach to Concussion Treatment: Specific Strategies, and 4) Future Directions: A Call to Research. Support (ie, response of agree or somewhat agree) for the statements ranged from to 97–100%. Conclusion Concussions are characterized by diverse symptoms and impairments and evolving clinical profiles; recovery varies based on modifying factors, injury severity, and treatments. Active and targeted treatments may enhance recovery following concussion. Research is needed on concussion clinical profiles, biomarkers, and the effectiveness and timing of treatments. PMID:27741219

Clinical symptoms in fibromyalgia are associated to overweight and lipid profile.

PubMed

Cordero, Mario D; Alcocer-Gómez, Elísabet; Cano-García, Francisco J; Sánchez-Domínguez, Benito; Fernández-Riejo, Patricia; Moreno Fernández, Ana M; Fernández-Rodríguez, Ana; De Miguel, Manuel

2014-03-01

In order to analyze the association between body mass index (BMI), lipid profile and clinical symptoms in patients with fibromyalgia, we assessed BMI levels, lipid profile and its association with clinical symptoms in 183 patients with fibromyalgia. The patients were evaluated using tender points, FIQ and Visual Analogue Scales of pain (VAS). Serum lipid profile analysis (total cholesterol, triglyceride, HDL, LDL and VLDL), and biochemical parameters were measured in the biochemistry laboratory. The BMI distribution of the nonobese, overweight and obese patients' groups were relatively even with 37.7, 35.5 and 26.8%, respectively, with a mean BMI of 27.3 ± 4.9. The number of tender points showed significantly positive correlation with higher BMI (P < 0.05). A total of 57.9% of patients showed increased levels of total cholesterol, 63.4 % increased levels of LDL cholesterol and 19.9% high levels of triglycerides. BMI, total cholesterol and triglycerides showed high association with some clinical parameters. Overweight and lipid profile could be associated with fibromyalgia symptoms. A treatment program with weight loss strategies, and control in diet and increased physical activity is advised to patients.

A cluster-analytic profiling of heroin-dependent patients based on level, clinical adequacy, and patient-desired adjustment of buprenorphine dosage during buprenorphine-naloxone maintenance treatment in sixteen Spanish centers.

PubMed

Alcaraz, Saul; González-Saiz, Francisco; Trujols, Joan; Vergara-Moragues, Esperanza; Siñol, Núria; Pérez de Los Cobos, José

2018-06-01

Buprenorphine dosage is a crucial factor influencing outcomes of buprenorphine treatment for heroin use disorders. Therefore, the aim of the present study is to identify naturally occurring profiles of heroin-dependent patients regarding individualized management of buprenorphine dosage in clinical practice of buprenorphine-naloxone maintenance treatment. 316 patients receiving buprenorphine-naloxone maintenance treatment were surveyed at 16 Spanish centers during the stabilization phase of this treatment. Patients were grouped using cluster analysis based on three key indicators of buprenorphine dosage management: dose, adequacy according to physician, and adjustment according to patient. The clusters obtained were compared regarding different facets of patient clinical condition. Four clusters were identified and labeled as follows (buprenorphine average dose and percentage of participants in each cluster are given in brackets): "Clinically Adequate and Adjusted to Patient Desired Low Dosage" (2.60 mg/d, 37.05%); "Clinically Adequate and Adjusted to Patient Desired High Dosage" (10.71 mg/d, 29.18%); "Clinically Adequate and Patient Desired Reduction of Low Dosage" (3.38 mg/d, 20.0%); and "Clinically Inadequate and Adjusted to Patient Desired Moderate Dosage" (7.55 mg/d, 13.77%). Compared to patients from the other three clusters, participants in the latter cluster reported more frequent use of heroin and cocaine during last week, lower satisfaction with buprenorphine-naloxone as a medication, higher prevalence of buprenorphine-naloxone adverse effects and poorer psychological adjustment. Our results show notable differences between clusters of heroin-dependent patients regarding buprenorphine dosage management. We also identified a group of patients receiving clinically inadequate buprenorphine dosage, which was related to poorer clinical condition. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections.

PubMed

Khashab, Mohammed M; Xiang, Jim; Kahn, James B

2006-10-01

To compare safety data with levofloxacin 500 mg and 750 mg from clinical trials for the treatment of respiratory infections. We compared adverse event data for levofloxacin 500 mg and 750 mg from clinical trials in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and community-acquired pneumonia. Adverse events occurring after the initiation of therapy were classified as treatment-emergent adverse events (TEAE); drug-related adverse events (DRAE) were TEAE assessed by the clinical investigator as definitely/very likely or probably related to levofloxacin therapy. Overall, the safety profile of the two doses was similar but not identical. TEAE occurred in 49.0% (1601/3268) of those treated with 500 mg and in 45.5% (519/1141) of those treated with 750 mg (p = 0.042); the corresponding rates of DRAE were 7.6% (248/3268) and 8.0% (91/1141) (p = 0.699). There was no statistically significant difference in terms of overall TEAE and DRAE rates within each of the three infectious conditions, but there were in specific events, all of which are expected with levofloxacin therapy. The limitations of this analysis include that it utilized a subset of available safety data, that it includes data only from clinical trials, and that we report primarily on events occurring in > or = 2% of patients. Given similar adverse event profiles and the advantages of higher dose therapy, including shorter courses of therapy and potential impact on preventing resistance, clinicians should consider utilizing the 750 mg dose of levofloxacin when choosing between dosage strengths for treatment of indicated infections.

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

PubMed

Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J

2017-07-01

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

A patient-centred approach to teaching and learning in dental student clinical practice.

PubMed

Eriksen, H M; Bergdahl, J; Bergdahl, Maud

2008-08-01

A patient-centred clinical teaching profile in the undergraduate dental curriculum at The University of Tromsø is described. This teaching profile implies that treatment planning is primarily based on the patients' perceived needs and the students are trained to retrieve information from the patients in this context. The role of the clinical instructor is primarily as a facilitator rather than an expert. The 'best interest of the patient' is not always easy to disclose and consequences related to the patients' levels of understanding, students competence, educational challenges and professional ethics are topics for discussion through the clinical education programme.

The application of zero-profile anchored spacer in anterior cervical discectomy and fusion.

PubMed

Wang, Zhiwen; Jiang, Weimin; Li, Xuefeng; Wang, Heng; Shi, Jinhui; Chen, Jie; Meng, Bin; Yang, Huilin

2015-01-01

We aimed to analyze the clinical efficacy of the zero-profile anchored spacers in the treatment of one-level or two-level cervical degenerative disc disease. From April 2011 to April 2013, a total of 63 consecutive patients with cervical degenerative disc disease who underwent one- or two-level ACDF using either the zero-profile anchored spacer or the stand-alone cages and a titanium plate fixation were reviewed for the radiological and clinical outcomes and complications. The zero-profile anchored spacers were used in 30 patients (anchored group) and stand-alone cages with an anterior cervical plate were implanted in 33 cases (non-anchored group). Operative time, intraoperative blood loss, clinical and radiological results were compared between the anchored group and the non-anchored group. All patients were followed up for at least 12 months. There were not bolt loosening or rupture of anchoring clips, screws or titanium plates observed in two groups during follow-up period. There were no significant difference in neck disability index scores, Japanese Orthopedic Association scores, fusion rate, and cervical lordosis during follow-up between two groups (P > 0.05), but significant difference in the operation time, blood loss and the presence of dysphagia were found (P < 0.05). There were no adjacent disc degeneration and instability observed in two groups. The zero-profile anchored spacer achieved similar clinical outcomes compared to ACDF with anterior plating for the treatment of the cervical degenerative disc disease. However, zero-profile anchored spacer was associated with a lower risk of postoperative dysphagia, shorter operation time, less blood loss, and relatively greater simplicity than the stand-alone cage with a titanium plate.

Impact of Atraumatic Restorative Treatment (ART) on the treatment profile in pilot government dental clinics in Tanzania.

PubMed

Kikwilu, Emil Namakuka; Frencken, Jo; Mulder, Jan

2009-06-08

The predominant mode of treatment in government dental clinics in Tanzania has been tooth extraction because the economy could not support the conventional restorative care which depends on expensive equipment, electricity and piped water systems. Atraumatic Restorative Treatment (ART) was perceived as a suitable alternative. A 3.5-year study was designed to document the changes in the treatment profiles ascribed to the systematic introduction of ART in pilot government dental clinics. Dental practitioners who were working in 13 government dental clinics underwent a 7-day ART training. Treatment record data on teeth extracted and teeth restored by the conventional and ART approaches were collected from these clinics for the three study periods. The mean percentage of ART restorations to total treatment, ART restorations to total restorations, and total restorations to total treatments rendered were computed. Differences between variables were determined by ANOVA, t-test and Chi-square. The mean percentage of ART restorations to total treatment rendered was 0.4 (SE = 0.5) and 11.9 (SE = 1.1) during the baseline and second follow-up period respectively (ANOVA mixed model; P < 0.0001). The mean percentage of ART restorations to total restorations rendered at baseline and 2nd follow-up period was 8.4% and 88.9% respectively (ANOVA mixed model; P < 0.0001). The mean percentage of restorations to total treatment rendered at baseline and 2nd follow-up was 3.9% and 13.0%, respectively (ANOVA mixed model; P < 0.0001). Ninety-nine percent of patients were satisfied with ART restorations, 96.6% willing to receive ART restoration again in future, and 94.9% willing to recommend ART treatment to their close relatives. ART introduction in pilot government dental clinics raised the number of teeth saved by restorative care. Countrywide introduction of the ART approach in Tanzania is recommended.

An overview of the novel H1-antihistamine bilastine in allergic rhinitis and urticaria.

PubMed

Jáuregui, Ignacio; García-Lirio, Eduardo; Soriano, Ana María; Gamboa, Pedro M; Antépara, Ignacio

2012-01-01

Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

Comparison of two oral contraceptive forms containing cyproterone acetate and drospirenone in the treatment of patients with polycystic ovary syndrome: a randomized clinical trial.

PubMed

Kahraman, Korhan; Sükür, Yavuz Emre; Atabekoğlu, Cem Somer; Ateş, Can; Taşkın, Salih; Cetinkaya, Serife Esra; Tolunay, Harun Egemen; Ozmen, Batuhan; Sönmezer, Murat; Berker, Bülent

2014-08-01

To compare the effects of combined oral contraceptives (OCs) containing cyproterone acetate and drospirenone in the treatment of polycystic ovary syndrome (PCOS). Fifty-two patients with PCOS were randomized in two groups: group A (n = 26) received 0.035 mg ethinyl estradiol + 2 mg cyproterone acetate and group B (n = 26) received 0.03 mg ethinyl estradiol + 3 mg drospirenone-containing OCs for 12 months. Baseline clinical features including body mass index, waist to hip ratio (WHR), and modified Ferriman-Gallwey (mFG) score were noted. Baseline biochemical parameters included androgen profile, carbohydrate metabolism, lipid profile, and oxidative stress. The percentages of changes for all parameters were compared. The groups were comparable regarding the baseline characteristics. WHR decreased significantly from baseline (-4 % [-31 to 35]) in group B when compared to group A (0 % [-11 to 14]) (P = 0.033). The total mFG score decreased significantly from baseline (-35 % [-71 to 10]) in group A when compared to group B (-18 % [-72 to 30]) (P = 0.035). Changes in androgen hormone profile were comparable except DHEA-SO4 (-32 % [-53 to 15] in group B vs. -10 % [-49 to 63] in group A; P = 0.046). The effects of the drugs were similar regarding carbohydrate metabolism, lipid profile, and oxidative stress parameters. Cyproterone acetate containing OCs seem to be more effective to treat clinical hirsutism in patients with PCOS after 12 months of treatment.

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

NASA Astrophysics Data System (ADS)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

PubMed

Rodríguez, P C; Prada, D M; Moreno, E; Aira, L E; Molinero, C; López, A M; Gómez, J A; Hernández, I M; Martínez, J P; Reyes, Y; Milera, J M; Hernández, M V; Torres, R; Avila, Y; Barrese, Y; Viada, C; Montero, E; Hernández, P

2018-02-01

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients. © 2017 British Society for Immunology.

Nitrosoureas in the Management of Malignant Gliomas.

PubMed

Brandes, Alba A; Bartolotti, Marco; Tosoni, Alicia; Franceschi, Enrico

2016-02-01

Nitrosoureas represent one of the most active classes of agents in the treatment of high-grade gliomas and glioblastoma. In clinical practice, the most commonly used compounds are lomustine (either alone or in combination with procarbazine and vincristine), carmustine, and fotemustine. Given their toxicity profile and subsequent to the introduction of temozolomide in clinical practice, most of these agents were moved to the recurrent setting. This review focuses on the role of the nitrosoureas currently used in clinical practice for the treatment of malignant gliomas.

Two approaches to incorporate clinical data uncertainty into multiple criteria decision analysis for benefit-risk assessment of medicinal products.

PubMed

Wen, Shihua; Zhang, Lanju; Yang, Bo

2014-07-01

The Problem formulation, Objectives, Alternatives, Consequences, Trade-offs, Uncertainties, Risk attitude, and Linked decisions (PrOACT-URL) framework and multiple criteria decision analysis (MCDA) have been recommended by the European Medicines Agency for structured benefit-risk assessment of medicinal products undergoing regulatory review. The objective of this article was to provide solutions to incorporate the uncertainty from clinical data into the MCDA model when evaluating the overall benefit-risk profiles among different treatment options. Two statistical approaches, the δ-method approach and the Monte-Carlo approach, were proposed to construct the confidence interval of the overall benefit-risk score from the MCDA model as well as other probabilistic measures for comparing the benefit-risk profiles between treatment options. Both approaches can incorporate the correlation structure between clinical parameters (criteria) in the MCDA model and are straightforward to implement. The two proposed approaches were applied to a case study to evaluate the benefit-risk profile of an add-on therapy for rheumatoid arthritis (drug X) relative to placebo. It demonstrated a straightforward way to quantify the impact of the uncertainty from clinical data to the benefit-risk assessment and enabled statistical inference on evaluating the overall benefit-risk profiles among different treatment options. The δ-method approach provides a closed form to quantify the variability of the overall benefit-risk score in the MCDA model, whereas the Monte-Carlo approach is more computationally intensive but can yield its true sampling distribution for statistical inference. The obtained confidence intervals and other probabilistic measures from the two approaches enhance the benefit-risk decision making of medicinal products. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Clinical Heterogeneity in Patients with the Hypermobility Type of Ehlers-Danlos Syndrome

ERIC Educational Resources Information Center

De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska; De Backer, Tine; De Paepe, Anne; Calders, Patrick

2013-01-01

EDS-HT is a connective tissue disorder characterized by large inter-individual differences in the clinical presentation, complicating diagnosis and treatment. We aim to describe the clinical heterogeneity and to investigate whether differences in the symptom profile are also reflected as disparity in functional impairment and pain experience. In…

Adolescents with Internet Gaming Disorder (IGD): profiles and treatment response.

PubMed

Martín-Fernández, María; Matalí, Josep Lluís; García-Sánchez, Sara; Pardo, Marta; Lleras, María; Castellano-Tejedor, Carmina

2016-10-07

Demand for treatment for problems related to the use of video games have increased significantly in adolescents. Most cases have a comorbid mental disorder that jeopardises both pathologies. The aim of this study is to describe profiles of adolescents with Internet Gaming Disorder (IGD) according to comorbidity and analyze treatment response at 3 and 6 months. A sample of 86 patients which consulted in the Addictive Behavior Unit of a hospital was assessed with diagnostic criteria for IGD, the interview K-SADS-PL for mental disorders and the Clinical Global Impression (CGI) to treatment progress. Of the initial sample, 68,6% (n = 59) met diagnostic criteria for IGD. Of these, the 45,76% matched an internalizing profile, presenting comorbidity with Mood Disorders (44,4%), Anxiety Disorders (44,4%) and Personality Disorders (11,1%). The externalizing profile would comprise 52,54% of the sample presenting Disruptive Behavior Disorder (48,4%=, ADHD (29%) and Disruptive Behavior Disorders not otherwise specified (22,6%). Unlike externalizing, the internalizing patients had a family history of psychiatric problems (63%), difficulties in social relationships (77,8%) and seemed to use video games preferably to escape discomfort (66,7%). After 3 months the externalizing profile showed improvements. Comorbid disorders allow the discrimination of two IGD profiles in adolescents and these could influence treatment response. Therefore, it is important to assess comorbidities to design a more accurate intervention focused on the specificities of each profile.

Clinical and Demographic Profile of Patients Receiving Fingolimod in Clinical Practice in Germany and the Benefit-Risk Profile of Fingolimod After 1 Year of Treatment: Initial Results From the Observational, Noninterventional Study PANGAEA.

PubMed

Ziemssen, Tjalf; Lang, Michael; Tackenberg, Björn; Schmidt, Stephan; Albrecht, Holger; Klotz, Luisa; Haas, Judith; Lassek, Christoph; Medin, Jennie; Cornelissen, Christian

2018-01-01

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) to assess prospectively baseline characteristics and outcomes after 12 months (± 90 days) of fingolimod treatment. Patients were divided into 2 cohorts: fingolimod starter [first received fingolimod in PANGAEA (n = 3315)] and previous study [received fingolimod before enrollment in PANGAEA in RCTs (n = 875), some of whom also had baseline data at entry into RCTs (n = 505)]. At PANGAEA baseline, patients in the fingolimod starter versus the previous study cohort had a higher annualized relapse rate [ARR (95% confidence interval): 1.79 (1.75-1.83) vs 1.32 (1.25-1.40)] and Expanded Disability Status Scale score [3.11 (3.04-3.17) vs 2.55 (2.44-2.66)]. A greater proportion in the fingolimod starter versus previous study cohort had diabetes (2.0% vs 0.7%). After 12 months of fingolimod, ARRs were lower than in the 12 months before PANGAEA enrollment in the fingolimod starter [0.386 (0.360-0.414)] and previous study [0.276 (0.238-0.320)] cohorts. Expanded Disability Status Scale scores were stable versus baseline. Adverse events were experienced by similar proportions in both cohorts during fingolimod treatment. Relevant differences exist in disease activity and comorbidities between patients receiving fingolimod in clinical practice versus RCTs. Irrespective of baseline differences indicating a higher proportion at an advanced stage of multiple sclerosis in the real world versus RCTs, fingolimod remains effective, with a manageable safety profile.

Pegylated interferons Lambda-1a and alfa-2a display different gene induction and cytokine and chemokine release profiles in whole blood, human hepatocytes and peripheral blood mononuclear cells.

PubMed

Freeman, J; Baglino, S; Friborg, J; Kraft, Z; Gray, T; Hill, M; McPhee, F; Hillson, J; Lopez-Talavera, J C; Wind-Rotolo, M

2014-06-01

Pegylated interferon-lambda-1a (Lambda), a type III interferon (IFN) in clinical development for the treatment of chronic HCV infection, has shown comparable efficacy and an improved safety profile to a regimen based on pegylated IFN alfa-2a (alfa). To establish a mechanistic context for this improved profile, we investigated the ex vivo effects of Lambda and alfa on cytokine and chemokine release, and on expression of IFN-stimulated genes (ISGs) in primary human hepatocytes and peripheral blood mononuclear cells (PBMCs) from healthy subjects. Our findings were further compared with changes observed in blood analysed from HCV-infected patients treated with Lambda or alfa in clinical studies. mRNA transcript and protein expression of the IFN-λ-limiting receptor subunit was lower compared with IFN-α receptor subunits in all cell types. Upon stimulation, alfa and Lambda induced ISG expression in hepatocytes and PBMCs, although in PBMCs Lambda-induced ISG expression was modest. Furthermore, alfa and Lambda induced release of cytokines and chemokines from hepatocytes and PBMCs, although differences in their kinetics of induction were observed. In HCV-infected patients, alfa treatment induced ISG expression in whole blood after single and repeat dosing. Lambda treatment induced modest ISG expression after single dosing and showed no induction after repeat dosing. Alfa and Lambda treatment increased IP-10, iTAC, IL-6, MCP-1 and MIP-1β levels in serum, with alfa inducing higher levels of all mediators compared with Lambda. Overall, ex vivo and in vivo induction profiles reported in this analysis strongly correlate with clinical observations of fewer related adverse events for Lambda vs those typically associated with alfa. © 2014 John Wiley & Sons Ltd.

Why evidence-based medicine failed in patient care and medicine-based evidence will succeed.

PubMed

Horwitz, Ralph I; Singer, Burton H

2017-04-01

Evidence-based medicine (EBM) has succeeded in strengthening the evidence base for population medicine. Where EBM has failed is in answering the practicing doctor's question of what a likely outcome would be when a given treatment is administered to a particular patient with her own distinctive biological and biographical (life experience) profile. We propose Medicine-based evidence (MBE), based on the profiles of individual patients, as the evidence base for individualized or personalized medicine. MBE will build an archive of patient profiles using data from all study types and data sources, and will include both clinical and socio-behavioral information. The clinician seeking guidance for the management of an individual patient will start with the patient's longitudinal profile and find approximate matches in the archive that describes how similar patients responded to a contemplated treatment and alternative treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Profile of young people attending alcohol and other drug treatment services in Aotearoa, New Zealand: clinical file search.

PubMed

Schroder, Ria; Sellman, Doug; Frampton, Chris; Deering, Daryle

2008-11-01

The aim of the present study was to provide a profile of young people attending alcohol and other drug (AOD) treatment services in Aotearoa, New Zealand. Data were gathered from a clinical file search of 184 randomly selected young people aged 13-19 years who had attended one of eight youth AOD treatment services in New Zealand during 2003 or 2004. These services represented eight of the 11 youth-specific AOD services available to youth in New Zealand. Young people who attend youth-specific AOD services in New Zealand present with a range of complex needs including substance use and mental health issues, criminality, family conflict and disengagement from school. A total of 62.0% were male, 56.4% had criminal convictions, 40.6% had spent some time in Child, Youth and Family Services care and 53.8% were reported to have a coexisting substance use and mental health disorder. Low rates of reporting of substance use and mental health diagnoses in treatment files suggest that substance use and mental health disorders among this population are likely to be higher than those reported. This paper provides a unique profile of young people attending youth-specific AOD treatments in New Zealand. Such information is useful in informing treatment planning and funding and ensuring that service development occurs to specifically meet the complex needs of this patient group.

Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

PubMed Central

2013-01-01

Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure. Conclusions A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA. PMID:24267267

Anger Problem Profiles among Partner Violent Men: Differences in Clinical Presentation and Treatment Outcome

ERIC Educational Resources Information Center

Murphy, Christopher M.; Taft, Casey T.; Eckhardt, Christopher I.

2007-01-01

Cluster analysis of 139 partner violent men's self-reports on the State-Trait Anger Expression Inventory identified profiles reflecting pathological anger (PA), low anger control (LAC), and normal anger (NA). The PA group self-reported higher pretreatment partner abuse, interpersonal dysfunction, distress, and substance abuse and had lower…

Influence of facial convexity on facial attractiveness in Japanese.

PubMed

Ioi, H; Nakata, S; Nakasima, A; Counts, Al

2007-11-01

The purpose of this study was to assess and determine the range of the top three most-favored facial profiles for each sex from a series of varying facial convexity, and to evaluate the clinically acceptable facial profiles for Japanese adults. Questionnaire-based study. Silhouettes of average male and female profiles were constructed from the profiles of 30 Japanese males and females with normal occlusions. Chin positions were protruded or retruded by 2 degrees , 4 degrees , 6 degrees , 8 degrees and 10 degrees , respectively, from the average profile. Forty-one orthodontists and 50 dental students were asked to select the three most-favored profiles for each sex, and they were also asked to indicate whether they would seek surgical orthodontic treatment if that image represented their own profile. For males, both the orthodontists and dental students chose the average profile as the most-favored profile. For females, both the orthodontists and dental students chose a slightly more retruded chin position as the most-favored profile. Japanese raters tended to choose class II profiles as more acceptable profiles than class III profiles for both males and females. These findings suggest that Japanese patients with class III profiles tend to seek surgical orthodontic treatment more often.

The Relationship between Pre-Treatment Clinical Profile and Treatment Outcome in an Integrated Stuttering Program

ERIC Educational Resources Information Center

Huinck, Wendy J.; Langevin, Marilyn; Kully, Deborah; Graamans, Kees; Peters, Herman F. M.; Hulstijn, Wouter

2006-01-01

A procedure for subtyping individuals who stutter and its relationship to treatment outcome is explored. Twenty-five adult participants of the Comprehensive Stuttering Program (CSP) were classified according to: (1) stuttering severity and (2) severity of negative emotions and cognitions associated with their speech problem. Speech characteristics…

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

PubMed Central

Blanco, Victor M.; Cossio, Alexandra; Martinez, Javier D.; Saravia, Nancy Gore

2013-01-01

Treatment alternatives have seldom been evaluated in children with cutaneous leishmaniasis (CL). We examine the clinical/epidemiological profile of children with CL considering international guidelines for local treatment. Descriptive analyses were conducted using International Center for Medical Research and Training (CIDEIM) case reports of parasitologically diagnosed patients ≤ 14 years of age from 2004 to 2010. Eligibility for local treatment based on World Health Organization/Pan American Health Organization (WHO/PAHO) criteria was determined. Among 380 children, 90% presented lesions of < 3 months duration, 54% presented single lesions < 30 mm in diameter, and 45% were ≤ 5 years old. Lesions on the head and neck were more frequent among children 0–5 years, and lesions below the head/neck were more frequent among 11- to 14-year-old children (P = 0.004). Using PAHO and WHO criteria, 26% and 53% of children, respectively, were eligible for local treatment. Recommended local treatments for New World CL have potential but limited applicability in children. Individual risk–benefit assessment and effectiveness data in children may increase eligibility. PMID:23798581

Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia.

PubMed

Butler, Tom; Gribben, J G

2010-05-01

CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a "watch and wait" approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently "high-risk" that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question. Copyright 2010 Elsevier Ltd. All rights reserved.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

PubMed

Langhorst, J; Varnhagen, I; Schneider, S B; Albrecht, U; Rueffer, A; Stange, R; Michalsen, A; Dobos, G J

2013-09-01

The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18. © 2013 John Wiley & Sons Ltd.

Risk profiles for poor treatment response to internet-delivered CBT in people with social anxiety disorder.

PubMed

Tillfors, Maria; Furmark, Tomas; Carlbring, Per; Andersson, Gerhard

2015-06-01

In social anxiety disorder (SAD) co-morbid depressive symptoms as well as avoidance behaviors have been shown to predict insufficient treatment response. It is likely that subgroups of individuals with different profiles of risk factors for poor treatment response exist. This study aimed to identify subgroups of social avoidance and depressive symptoms in a clinical sample (N = 167) with SAD before and after guided internet-delivered CBT, and to compare these groups on diagnostic status and social anxiety. We further examined individual movement between subgroups over time. Using cluster analysis we identified four subgroups, including a high-problem cluster at both time-points. Individuals in this cluster showed less remission after treatment, exhibited higher levels of social anxiety at both assessments, and typically remained in the high-problem cluster after treatment. Thus, in individuals with SAD, high levels of social avoidance and depressive symptoms constitute a risk profile for poor treatment response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

PubMed

Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

2016-04-07

New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb mRNA profiles 0-2 weeks into chemotherapy predict the efficacy of treatment 6 weeks later. These observations advocate assaying dynamic bacterial phenotypes through drug therapy as biomarkers for treatment success.

Safety and efficacy of collagen crosslinking for the treatment of keratoconus.

PubMed

Kolli, Sai; Aslanides, Ioannis M

2010-11-01

Keratoconus is a condition that causes corneal ectasia and reduced vision in young adults. A proportion of these patients have progressive disease requiring corneal transplantation. A revolutionary new treatment that is purported to halt progression of keratoconus, known as collagen crosslinking (CXL), has recently been introduced into clinical practice. CXL involves the treatment of the cornea with riboflavin followed by photoactivation with UVA light leading to corneal strengthening. This article reviews the basic science, clinical protocols, safety aspects and clinical results of CXL. The reader will gain a comprehensive understanding of: i) the basic science of CXL; ii) the optimised protocols for clinical use of CXL; iii) the results of all the main clinical trials in the literature; iv) contraindications to treatment and v) full clinical safety profile of CXL. CXL represents a new treatment that uniquely allows the halt of progression of keratoconus, thus preventing visual loss and the need for surgical intervention. Available data suggest that this treatment has high efficacy and is very safe and may represent the future standard treatment for progressive keratoconus.

Avelumab: a new standard for treating metastatic Merkel cell carcinoma.

PubMed

Baker, Mairead; Cordes, Lisa; Brownell, Isaac

2018-04-01

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is chemosensitive, responses to traditional chemotherapeutic agents are not durable. Avelumab, a novel anti-PD-L1 immune checkpoint inhibitor, recently became the first FDA-approved agent for the treatment of metastatic MCC and represents a new option to improve patient survival. Areas covered: This article presents an overview of MCC and summarizes the development of avelumab in the treatment of metastatic MCC. Preclinical studies, phase 1 and phase 2 clinical trials, and the safety profile of avelumab are reviewed. Future perspectives and ongoing studies are also discussed. Expert commentary: Avelumab demonstrated rapid and durable responses and a manageable safety profile in the treatment of metastatic MCC. Patient outcomes are favorable when compared to historical responses to standard chemotherapy. Ongoing clinical trials will continue to characterize avelumab and its optimal use in MCC therapy.

SU-F-T-527: A Novel Dynamic Multileaf Collimator Leaf-Sequencing Algorithm in Radiation Therapy

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

Jing, J; Lin, H; Chow, J

Purpose: A novel leaf-sequencing algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimator (MLC). The efficiency of this dynamic MLC leaf-sequencing method was evaluated using external beam treatment plans delivered by intensity modulated radiation therapy technique. Methods: To qualify and validate this algorithm, integral test for the beam segment of MLC generated by the CORVUS treatment planning system was performed with clinical intensity map experiments. The treatment plans were optimized and the fluence maps for all photon beams were determined. This algorithm started with the algebraic expression for the area under the beammore » profile. The coefficients in the expression can be transformed into the specifications for the leaf-setting sequence. The leaf optimization procedure was then applied and analyzed for clinical relevant intensity profiles in cancer treatment. Results: The macrophysical effect of this method can be described by volumetric plan evaluation tools such as dose-volume histograms (DVHs). The DVH results are in good agreement compared to those from the CORVUS treatment planning system. Conclusion: We developed a dynamic MLC method to examine the stability of leaf speed including effects of acceleration and deceleration of leaf motion in order to make sure the stability of leaf speed did not affect the intensity profile generated. It was found that the mechanical requirements were better satisfied using this method. The Project is sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.« less

Blinatumomab: Enlisting serial killer T cells in the war against hematologic malignanciess

PubMed Central

Rogala, Britny; Freyer, Craig W.; Ontiveros, Evelena P.; Griffiths, Elizabeth A.; Wang, Eunice S.; Wetzler, Meir

2016-01-01

Introduction The approval of blinatumomab signals the long awaited arrival of immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for relapsed or refractory disease were restricted to combination cytotoxic chemotherapy with limited efficacy and significant toxicity. Through an innovative mechanism of action, blinatumomab stimulates a polyclonal antitumor T cell response, yielding unprecedented single agent efficacy in the relapsed/refractory setting. Success comes at the cost of immunological toxicities rarely encountered with previous therapies and challenging administration logistics requiring clinical expertise. Areas covered All published clinical and preclinical studies using blinatumomab were reviewed in addition to all registered ongoing clinical trials and data published in abstract form. The search was limited to the English language. The pharmacology, clinical efficacy, toxicity profile, and logistical considerations for drug administration are discussed. Expert Opinion Blinatumomab is an exciting addition to the treatment armamentarium for relapsed/refractory ALL, yet several questions remain regarding optimal implementation into the current treatment paradigm. A unique toxicity profile should be weighed against promising benefits in a poor prognosis population. Other emerging therapies, such as chimeric antigen receptor-modified T cells and inotuzumab ozogamicin, with different side effect profiles and administration schedules, may prove to be more beneficial for specific patient populations. PMID:25985814

Evaluating trifluridine + tipiracil hydrochloride in a fixed combination (TAS-102) for the treatment of colorectal cancer.

PubMed

Mulet, N; Matos, I; Noguerido, A; Martini, G; Élez, M E; Argilés, G; Tabernero, J

2018-04-01

Despite major progress in treating advanced colorectal cancer (CRC), prognosis in this population after progression on standard treatment remains dismal and the development of new drugs represents an unmet need. Historically, fluoropyrimidines have played a major role in the treatment of metastatic CRC. TAS-102, a novel combination of trifluridine and tipiracil hydrochloride, has demonstrated improvement in overall survival in the refractory CRC setting, with a safe toxicity profile. Areas covered: A literature review of published clinical studies was performed. Herein, the authors review the pharmacological and clinical data of TAS-102 when used in metastatic CRC, both as a single agent as well as in novel combinations under investigation. Expert opinion: The addition of TAS-102 to the therapeutic armamentarium of metastatic CRC is an encouraging breakthrough considering the demonstrated survival benefit and favorable tolerability profile. Combinations with other agents are under clinical investigation in different settings in an attempt to widen its use. To optimize treatment in today's era of molecular oncology, efforts should be focused on understanding primary and secondary resistance mechanisms, along with the identification of potential biomarkers of response.

Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management.

PubMed

Cheung, Steven W; Aranda, Derick; Driscoll, Colin L W; Parsa, Andrew T

2010-02-01

Complex medical decision making obligates tradeoff assessments among treatment outcomes expectations, but an accessible tool to perform the necessary analysis is conspicuously absent. We aimed to demonstrate methodology and feasibility of adapting conjoint analysis for mapping clinical outcomes expectations to treatment decisions in vestibular schwannoma (VS) management. Prospective. Tertiary medical center and US-based otologists/neurotologists. Treatment preference profiles among VS stakeholders-61 younger and 74 older prospective patients, 61 observation patients, and 60 surgeons-were assessed for the synthetic VS case scenario of a 10-mm tumor in association with useful hearing and normal facial function. Treatment attribute utility. Conjoint analysis attribute levels were set in accordance to the results of a meta-analysis. Forty-five case series were disaggregated to formulate microsurgery facial nerve and hearing preservation outcomes expectations models. Attribute utilities were computed and mapped to the realistic treatment choices of translabyrinthine craniotomy, middle fossa craniotomy, and gamma knife radiosurgery. Among the treatment attributes of likelihoods of causing deafness, temporary facial weakness for 2 months, and incurable cancer within 20 years, and recovery time, permanent deafness was less important to tumor surgeons, and temporary facial weakness was more important to tumor surgeons and observation patients (Wilcoxon rank-sum, p < 0.001). Inverse mapping of preference profiles to realistic treatment choices showed all study cohorts were inclined to choose gamma knife radiosurgery. Mapping clinical outcomes expectations to treatment decisions for a synthetic clinical scenario revealed inhomogeneous drivers of choice selection among study cohorts. Medical decision engines that analyze personal preferences of outcomes expectations for VS and many other diseases may be developed to promote shared decision making among health care stakeholders and transparency in the informed consent process.

The evolving clinical profile of abatacept (CTLA4–Ig): a novel co-stimulatory modulator for the treatment of rheumatoid arthritis

PubMed Central

2005-01-01

Abatacept (CTLA4–Ig) is a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28–CD80/86 pathway. Clinical trials have provided preliminary evidence of the efficacy of this compound in the treatment of rheumatoid arthritis. This review describes the molecular and biologic bases for the use of abatacept in rheumatoid arthritis and summarizes the current clinical data on its safety and effectiveness in this disease. PMID:15833145

Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans.

PubMed

Carter, Philip; Alifrangis, Costi; Cereser, Biancastella; Chandrasinghe, Pramodh; Del Bel Belluz, Lisa; Moderau, Nina; Poyia, Fotini; Schwartzberg, Lee S; Tabassum, Neha; Wen, Jinrui; Krell, Jonathan; Stebbing, Justin

2018-04-03

We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.

Integrating liquid biopsies into the management of cancer.

PubMed

Siravegna, Giulia; Marsoni, Silvia; Siena, Salvatore; Bardelli, Alberto

2017-09-01

During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA - arguably the most clinically advanced approach.

Statements of Agreement From the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting Held in Pittsburgh, October 15-16, 2015.

PubMed

Collins, Michael W; Kontos, Anthony P; Okonkwo, David O; Almquist, Jon; Bailes, Julian; Barisa, Mark; Bazarian, Jeffrey; Bloom, O Josh; Brody, David L; Cantu, Robert; Cardenas, Javier; Clugston, Jay; Cohen, Randall; Echemendia, Ruben; Elbin, R J; Ellenbogen, Richard; Fonseca, Janna; Gioia, Gerard; Guskiewicz, Kevin; Heyer, Robert; Hotz, Gillian; Iverson, Grant L; Jordan, Barry; Manley, Geoffrey; Maroon, Joseph; McAllister, Thomas; McCrea, Michael; Mucha, Anne; Pieroth, Elizabeth; Podell, Kenneth; Pombo, Matthew; Shetty, Teena; Sills, Allen; Solomon, Gary; Thomas, Danny G; Valovich McLeod, Tamara C; Yates, Tony; Zafonte, Ross

2016-12-01

Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment. To describe the current landscape of treatment for concussion and to provide summary agreements related to treatment to assist clinicians in the treatment of concussion. On October 14 to 16, 2015, the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion meeting was convened in Pittsburgh, Pennsylvania. Thirty-seven concussion experts from neuropsychology, neurology, neurosurgery, sports medicine, physical medicine and rehabilitation, physical therapy, athletic training, and research and 12 individuals representing sport, military, and public health organizations attended the meeting. The 37 experts indicated their agreement on a series of statements using an audience response system clicker device. A total of 16 statements of agreement were supported covering (1) Summary of the Current Approach to Treating Concussion, (2) Heterogeneity and Evolving Clinical Profiles of Concussion, (3) TEAM Approach to Concussion Treatment: Specific Strategies, and (4) Future Directions: A Call to Research. Support (ie, response of agree or somewhat agree) for the statements ranged from to 97% to 100%. Concussions are characterized by diverse symptoms and impairments and evolving clinical profiles; recovery varies on the basis of modifying factors, injury severity, and treatments. Active and targeted treatments may enhance recovery after concussion. Research is needed on concussion clinical profiles, biomarkers, and the effectiveness and timing of treatments. ARS, audience response systemCDC, Centers for Disease Control and PreventionDoD, Department of DefensemTBI, mild traumatic brain injuryNCAA, National Collegiate Athletic AssociationNFL, National Football LeagueNIH, National Institutes of HealthRCT, randomized controlled trialRTP, return to playSRC, sport- and recreation-related concussionTBI, traumatic brain injuryTEAM, Targeted Evaluation and Active Management.

Clinical challenges in the treatment of patients with posttraumatic stress disorder and substance abuse.

PubMed

Schäfer, Ingo; Najavits, Lisa M

2007-11-01

The aim of this article is to review the current literature on co-occuring posttraumatic stress disorder and substance-use disorder, with an emphasis on clinical aspects and emerging treatments. In clinical populations (focusing on either disorder), about 25-50% have a lifetime dual diagnosis of posttraumatic stress disorder and substance-use disorder. Patients with both disorders have a more severe clinical profile than those with either disorder alone, lower functioning, poorer well being, and worse outcomes across a variety of measures. In recent years, several promising treatment programs have been developed specifically for co-occuring posttraumatic stress disorder and substance-use disorder, with one model having been established as effective thus far. Comorbid posttraumatic stress disorder/substance-use disorder is a frequent diagnosis in clinical populations that severely affects course and outcome. Treatment approaches appropriate for this vulnerable population need to be evaluated further and implemented in routine practice.

Safety profile of levetiracetam.

PubMed

Arroyo, Santiago; Crawford, Pamela

2003-05-01

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

[Comparison of dissolution profile and plasma concentration-time profile of the thalidomide formulations made by Japanese, Mexican and British companies].

PubMed

Fujita, Yukiyoshi; Yamamoto, Koujirou; Aomori, Tohru; Murakami, Hirokazu; Horiuchi, Ryuya

2008-10-01

Thalidomide is an important advance in the treatment of multiple myeloma. In Japan thalidomide is now on the approval step for the treatment of multiple myeloma. The drug has some bothersome side effects such as defect of organogenesis, neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy and is changing multiple myeloma treatment. At this moment, Japanese patients must import the thalidomide preparations from Mexico, Britain and elsewhere, but after approval, they patients will be able to get the new Japanese thalidomide capsules. In order to determine appropriate amounts of Japanese thalidomide capsules in the treatment of multiple myeloma, we compared the dissolution profile and plasma thalidomide concentrations of Japanese and British capsules and Mexican tablets. The dissolution test was performed according to the Japanese and the United States Pharmacopoeia. The pharmacokinetic data for Japanese capsules were obtained from the clinical trial in Japanese subjects and compared with those data published for other formulations. The dissolution rate of the Japanese capsule was the fastest, followed by British and Mexican formulations. The pharmacokinetic profiles of Japanese and British capsules were similar, while the 100 mg Japanese thalidomide capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200 mg Mexican thalidomide tablet (1.7 vs. 1.1 microg/ml), greatly shortened t(max) (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic absorption profiles demonstrated a rank-order correlation. Physicians and pharmacists should be aware of the probable alteration in plasma thalidomide concentration when switching to the Japanese capsule, especially from the Mexican tablet, and should monitor clinical response carefully.

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease.

PubMed

Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark; Nielsen, Ole Haagen; Reed, Michelle Ac; Atkins, Karen; Günther, Ulrich Leonhard; Hao, Fuhua; Wang, Yulan

2017-10-16

One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors. Successive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1 H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB. Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting. 1 H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD.

An assessment of lifestyle modification versus medical treatment with clomiphene citrate, metformin, and clomiphene citrate-metformin in patients with polycystic ovary syndrome.

PubMed

Karimzadeh, Mohammad Ali; Javedani, Mojgan

2010-06-01

To compare the effect of clomiphene citrate, metformin, and lifestyle modification on treatment of patients with polycystic ovary syndrome (PCOS). Prospective randomized double-blind study. University-based infertility clinic and research center. Three hundred forty-three overweight infertile women with PCOS. The participating women were assigned to four groups: clomiphene (n = 90), metformin (n = 90), clomiphene + metformin (n = 88), and lifestyle modification (n = 75). The patients in each group received standardized dietary and exercise advice from a dietitian. The primary outcome variables were change in menstrual cycle, waist circumference measurements, endocrine parameters, and lipid profile. The main secondary outcome variable was clinical pregnancy rate. The clinical pregnancy rate was 12.2% in clomiphene group, 14.4% in metformin group, 14.8% in clomiphene + metformin group, and 20% in lifestyle modification group. Lifestyle modification group achieved a significant reduction in waist circumference, total androgen, and lipid profile. Lifestyle modification improves the lipid profile in PCOS patients. Therefore, lifestyle modification may be used as the first line of ovulation induction in PCOS patients. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Exploring evidence of a dissociative subtype in PTSD: Baseline symptom structure, etiology, and treatment efficacy for those who dissociate.

PubMed

Burton, Mark S; Feeny, Norah C; Connell, Arin M; Zoellner, Lori A

2018-05-01

With the inclusion of a dissociative subtype, recent changes to the DSM-5 diagnosis of posttraumatic stress disorder (PTSD) have emphasized the role of dissociation in the experience and treatment of the disorder. However, there is a lack of research exploring the clinical impact for highly dissociative groups receiving treatment for PTSD. The current study examined the presence and clinical impact of a dissociative subtype in a sample of individuals receiving treatment for chronic PTSD. This study used latent transition analyses (LTA), an expanded form of latent profile analyses (LPA), to examine latent profiles of PTSD and dissociation symptoms before and after treatment for individuals (N = 200) receiving prolonged exposure (PE) or sertraline treatment for chronic PTSD. The best fitting LTA model was one with a 4-class solution at both pretreatment and posttreatment. There was a latent class at pretreatment with higher levels of dissociative symptoms. However, this class was also marked by higher reexperiencing symptoms, and membership was not predicted by chronic child abuse. Further, although those in the class were less likely to transition to the responder class overall, this was not the case for exposure-based treatment specifically. These findings are not in line with the dissociative-subtype theoretical literature that proposes those who dissociate represent a clinically distinct group that may respond worse to exposure-based treatments for PTSD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Gender differences in treatment progress of drug-addicted patients.

PubMed

Fernández-Montalvo, Javier; López-Goñi, José J; Azanza, Paula; Arteaga, Alfonso; Cacho, Raúl

2017-03-01

The authors of this study explored the differences in treatment progress between men and women who were addicted to drugs. The differential rate of completion of/dropout from treatment in men and women with substance dependence was established. Moreover, comparisons between completers and dropouts, accounting for gender, were carried out for several variables related to treatment progress and clinical profile. A sample of 183 addicted patients (96 male and 87 female) who sought outpatient treatment between 2002 and 2006 was assessed. Information on socio-demographic, consumption, and associated characteristics was collected. A detailed tracking of each patient's progress was maintained for a minimum period of 8 years to assess treatment progression. The treatment dropout rate in the whole sample was 38.8%, with statistically significant differences between women (47.1%) and men (31.3%). Women who dropped out of treatment presented a more severe profile in most of the psychopathologic variables than women who completed it. Moreover, women who dropped out from treatment presented a more severe profile than men who dropped out. According to these results, drug-addicted women showed worse therapeutic progress than men with similar histories. Thus, women must be provided with additional targeted intervention to promote better treatment outcomes.

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.

PubMed

Cruz-Rodriguez, Nataly; Combita, Alba L; Enciso, Leonardo J; Quijano, Sandra M; Pinzon, Paula L; Lozano, Olga C; Castillo, Juan S; Li, Li; Bareño, Jose; Cardozo, Claudia; Solano, Julio; Herrera, Maria V; Cudris, Jennifer; Zabaleta, Jovanny

2016-04-05

B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer

PubMed Central

Blumenthal, Gideon M.; Luo, Lola; He, Kun; Fran, Ingrid; Lemery, Steven; Pazdur, Richard

2016-01-01

On March 11, 2016, after an expedited 5-month review, the U.S. Food and Drug Administration expanded the crizotinib metastatic non-small cell lung cancer (mNSCLC) indication to include the treatment of patients whose tumors harbor a ROS1 rearrangement. The approval was based on a clinically meaningful, durable objective response rate (ORR) in a multicenter, single-arm clinical trial (ROS1 cohort of Trial PROFILE 1001) in patients with ROS1-positive mNSCLC. The trial enrolled 50 patients (age range: 25–77 years) whose tumors were prospectively determined to have a ROS1 gene rearrangement by break-apart fluorescence in situ hybridization (96%) or reverse transcriptase polymerase chain reaction (4%) clinical trial assays. Crizotinib demonstrated an ORR of 66% (95% confidence interval [CI]: 51%–79%) with a median duration of response of 18.3 months by independent radiology review and 72% (95% CI: 58%–84%) by investigator review. Patients received crizotinib 250 mg twice daily and had a median duration of exposure of 34.4 months. The toxicity profile in ROS1-positive patients was generally consistent with the randomized safety data in the U.S. Product Insert from two ALK-positive mNSCLC trials. The most common (≥25%) adverse reactions and laboratory test abnormalities included vision disorders, elevation of alanine transaminase and aspartate transaminase levels, nausea, hypophosphatemia, diarrhea, edema, vomiting, constipation, neutropenia, and fatigue. There were no treatment-related deaths. A favorable benefit-to-risk evaluation led to the traditional approval of crizotinib for this new supplemental indication. Implications for Practice: Given the results from the ROS1 cohort of the clinical trial PROFILE 1001, crizotinib represents a new treatment option and the first approved therapy for patients with metastatic non-small cell lung cancer whose tumors are ROS1 positive. Crizotinib demonstrated efficacy irrespective of prior treatment status. PMID:27328934

Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer.

PubMed

Kazandjian, Dickran; Blumenthal, Gideon M; Luo, Lola; He, Kun; Fran, Ingrid; Lemery, Steven; Pazdur, Richard

2016-08-01

: On March 11, 2016, after an expedited 5-month review, the U.S. Food and Drug Administration expanded the crizotinib metastatic non-small cell lung cancer (mNSCLC) indication to include the treatment of patients whose tumors harbor a ROS1 rearrangement. The approval was based on a clinically meaningful, durable objective response rate (ORR) in a multicenter, single-arm clinical trial (ROS1 cohort of Trial PROFILE 1001) in patients with ROS1-positive mNSCLC. The trial enrolled 50 patients (age range: 25-77 years) whose tumors were prospectively determined to have a ROS1 gene rearrangement by break-apart fluorescence in situ hybridization (96%) or reverse transcriptase polymerase chain reaction (4%) clinical trial assays. Crizotinib demonstrated an ORR of 66% (95% confidence interval [CI]: 51%-79%) with a median duration of response of 18.3 months by independent radiology review and 72% (95% CI: 58%-84%) by investigator review. Patients received crizotinib 250 mg twice daily and had a median duration of exposure of 34.4 months. The toxicity profile in ROS1-positive patients was generally consistent with the randomized safety data in the U.S. Product Insert from two ALK-positive mNSCLC trials. The most common (≥25%) adverse reactions and laboratory test abnormalities included vision disorders, elevation of alanine transaminase and aspartate transaminase levels, nausea, hypophosphatemia, diarrhea, edema, vomiting, constipation, neutropenia, and fatigue. There were no treatment-related deaths. A favorable benefit-to-risk evaluation led to the traditional approval of crizotinib for this new supplemental indication. Given the results from the ROS1 cohort of the clinical trial PROFILE 1001, crizotinib represents a new treatment option and the first approved therapy for patients with metastatic non-small cell lung cancer whose tumors are ROS1 positive. Crizotinib demonstrated efficacy irrespective of prior treatment status. ©AlphaMed Press.

Clinical characteristics of patients with type 2 diabetes mellitus at the time of insulin initiation: INSTIGATE observational study in Spain

PubMed Central

Dilla, Tatiana; Reviriego, Jesús; Castell, Conxa; Goday, Albert

2009-01-01

Little information is available on the management of patients with type 2 diabetes mellitus (DM2) in regular clinical practice, prior to and at the point of initiating treatment with insulin. The INSTIGATE study provides a description of the clinical profile of the patient with DM2 who begins treatment with insulin in both primary and secondary care. A total of 224 patients who had been diagnosed with DM2, were not responding to oral treatment, and began receiving insulin were included in the INSTIGATE study in Spain. Demographic data were collected, as well as data on macro- and microvascular complications of diabetes and comorbidities, past medical history of diabetes and oral treatment administered, the clinical severity of diabetes (HbA1c concentration) and insulin treatment initiated. Mean age of the sample was 65.4 years and 56.7% were men. There were 87% of patients who had a diagnosis of at least one significant comorbidity, notably hypertension and hyperlipidemia. The patient profile for metabolic syndrome was met by 75.1% of the patients. There was a higher incidence of macrovascular complications (38.4%) than microvascular complications (16.1%). Prior to insulin initiation, the most recent mean HbA1c was 9.2%. The majority of patients had been treated in the last 12 months with sulfonylureas and/or metformin (69.6 and 57.6%). The most common treatment prior to insulinization was the co-administration of two oral antidiabetics (OADs) (37.5%). Patients with DM2 observed in the study presented with elevated mean HbA1c and body mass index levels, comorbidities and complications related to diabetes at the time of insulin initiation. Changes and adjustments in treatment from diagnosis of diabetes occur when HbA1c levels are far above those recommended by the IDF (International Diabetes Federation), a factor which could be contributing to the development of both macrovascular and microvascular complications in the patient profile described in the study. PMID:19855919

Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors

PubMed Central

Ananda, Guruprasad; Mockus, Susan; Lundquist, Micaela; Spotlow, Vanessa; Simons, Al; Mitchell, Talia; Stafford, Grace; Philip, Vivek; Stearns, Timothy; Srivastava, Anuj; Barter, Mary; Rowe, Lucy; Malcolm, Joan; Bult, Carol; Karuturi, Radha Krishna Murthy; Rasmussen, Karen; Hinerfeld, Douglas

2015-01-01

Background The continued development of targeted therapeutics for cancer treatment has required the concomitant development of more expansive methods for the molecular profiling of the patient’s tumor. We describe the validation of the JAX Cancer Treatment Profile™ (JAX-CTP™), a next generation sequencing (NGS)-based molecular diagnostic assay that detects actionable mutations in solid tumors to inform the selection of targeted therapeutics for cancer treatment. Methods NGS libraries are generated from DNA extracted from formalin fixed paraffin embedded tumors. Using hybrid capture, the genes of interest are enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by variant detection and functional and clinical annotation for the generation of a clinical report. Results The JAX-CTP™ detects actionable variants, in the form of single nucleotide variations and small insertions and deletions (≤50bp) in 190 genes in specimens with a neoplastic cell content of ≥10%. The JAX-CTP™ is also validated for the detection of clinically actionable gene amplifications. Conclusions There is a lack of consensus in the molecular diagnostics field on the best method for the validation of NGS-based assays in oncology, thus the importance of communicating methods, as contained in this report. The growing number of targeted therapeutics and the complexity of the tumor genome necessitates continued development and refinement of advanced assays for tumor profiling to enable precision cancer treatment. PMID:25562415

Clinically relevant characteristics associated with early treatment drug use versus abstinence.

PubMed

Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

2014-04-04

This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein.

PubMed

Subbiah, Vivek; Westin, Shannon N; Wang, Kai; Araujo, Dejka; Wang, Wei-Lien; Miller, Vincent A; Ross, Jeffrey S; Stephens, Phillip J; Palmer, Gary A; Ali, Siraj M

2014-01-14

Oncologic patients who are extreme responders to molecularly targeted therapy provide an important opportunity to better understand the biologic basis of response and, in turn, inform clinical decision making. Malignant neoplasms with an uncertain histologic and immunohistochemical characterization present challenges both on initial diagnostic workups and then later in management, as current treatment algorithms are based on a morphologic diagnosis. Herein, we report a case of a difficult to characterize sarcoma-like lesion for which genomic profiling with clinical next generation sequencing (NGS) identified the molecular underpinnings of arrested progression(stable disease) under combination targeted therapy within a phase I clinical trial. Genomic profiling with clinical next generation sequencing was performed on the FoundationOne™ platform (Foundation Medicine, Cambridge MA). Histopathology and immunohistochemical studies were performed in the Department of Pathology, MD Anderson Cancer Center (Houston, TX). Treatment was administered in the context of a phase I clinical trial ClinicalTrials.gov Identifier: (NCT01187199). The histology of the tumor was that of a spindle cell neoplasm, grade 2 by FNCLCC standards. Immunohistochemical staining was positive for S100 and CD34. Genomic profiling identified the following alterations: a KIAA1549-BRAF gene fusion resulting from a tandem duplication event, a homozygous deletion of PTEN, and frameshift insertion/deletions in CDKN2A A68fs*51, SUFU E283fs*3, and MAP3K1 N325fs*3. The patient had a 25% reduction in tumor (RECIST v1.1) following combination therapy consisting of sorafenib, temsirolimus, and bevazicumab within a phase I clinical trial. The patient responded to combination targeted therapy that fortuitously targeted KIAA1549-BRAF and PTEN loss within a spindle cell neoplasm, as revealed by genomic profiling based on NGS. This is the first report of a tumor driven by a KIAA1549-BRAF fusion responding to sorafenib-based combination therapy.

Temperament profiles of Sasang typology in a child clinical sample.

PubMed

Lee, Soo Jin; Park, Soo Hyun; Chae, Han

2012-12-01

Sasang typology is a personalized traditional medicine widely used in clinical diagnosis and treatment in Korea. The aim of this study was to examine the biopsychological personality profiles of traditional Korean Sasang typology in a clinical sample of Korean children. A total of 150 children were classified as one of three traditional Korean Sasang types (19 So-Yang, 118 Tae-Eum, and 13 So-Eum) by two clinical experts in Sasang typology. The childrens' mothers completed the Korean version of the Junior Temperament and Character Inventory (JTCI). The four temperament dimensions of JTCI were compared between the different Sasang types using analysis of variance (ANOVA) and profile analysis. There were no significant differences in age, gender, and parents' education levels across the Sasang types. The JTCI temperament profile for each of the child Sasang types was significantly different (profile analysis, df = 5.315, F  = 2.508, p  = 0.027). There were significant differences in novelty-seeking ( F  = 3.850, p  = 0.023) and novelty-seeking subscales, but not with other temperament dimensions. These results demonstrated distinct temperament traits associated with traditional Korean Sasang types in children using an objective biopsychological personality inventory. With further investigation into the biopsychological profiles of the children, the longitudinal stability of the Sasang typology can be examined.

Internalizing and externalizing personality and subjective effects in a sample of adolescent cannabis users.

PubMed

García-Sánchez, Sara; Matalí, Josep Lluís; Martín-Fernández, María; Pardo, Marta; Lleras, Maria; Castellano-Tejedor, Carmina; Haro, Josep Maria

2016-10-06

Cannabis is the illicit substance most widely used by adolescents. Certain personality traits such as impulsivity and sensation seeking, and the subjective effects experienced after substance use (e.g. euphoria or relaxation) have been identified as some of the main etiological factors of consumption. This study aims to categorize a sample of adolescent cannabis users based on their most dominant personality traits (internalizing and externalizing profile). Then, to make a comparison of both profiles considering a set of variables related to consumption, clinical severity and subjective effects experienced. From a cross-sectional design, 173 adolescents (104 men and 69 women) aged 13 to 18 asking for treatment for cannabis use disorder in an Addictive Behavior Unit (UCAD) from the hospital were recruited. For the assessment, an ad hoc protocol was employed to register consumption, the Millon Adolescent Clinical Inventory (MACI) and the Addiction Research Center Inventory (ARCI) 49-item short form were also administered. Factor analysis suggested a two-profile solution: Introverted, Inhibited, Doleful, Dramatizing (-), Egotistic (-), Self-demeaning and Borderline tendency scales composed the internalizing profile, and Submissive (-), Unruly, Forceful, Conforming (-) and Oppositional scales composed the externalizing profile. The comparative analysis showed that the internalizing profile has higher levels of clinical severity and more subjective effects reported than the externalizing profile. These results suggest the need to design specific intervention strategies for each profile.

Antimicrobial Resistance Profiles and Diversity in Salmonella from Humans and Cattle, 2004-2011.

PubMed

Afema, J A; Mather, A E; Sischo, W M

2015-11-01

Analysis of long-term anti-microbial resistance (AMR) data is useful to understand source and transmission dynamics of AMR. We analysed 5124 human clinical isolates from Washington State Department of Health, 391 cattle clinical isolates from the Washington Animal Disease Diagnostic Laboratory and 1864 non-clinical isolates from foodborne disease research on dairies in the Pacific Northwest. Isolates were assigned profiles based on phenotypic resistance to 11 anti-microbials belonging to eight classes. Salmonella Typhimurium (ST), Salmonella Newport (SN) and Salmonella Montevideo (SM) were the most common serovars in both humans and cattle. Multinomial logistic regression showed ST and SN from cattle had greater probability of resistance to multiple classes of anti-microbials than ST and SN from humans (P < 0.0001). While these findings could be consistent with the belief that cattle are a source of resistant ST and SN for people, occurrence of profiles unique to cattle and not observed in temporally related human isolates indicates these profiles are circulating in cattle only. We used various measures to assess AMR diversity, conditional on the weighting of rare versus abundant profiles. AMR profile richness was greater in the common serovars from humans, although both source data sets were dominated by relatively few profiles. The greater profile richness in human Salmonella may be due to greater diversity of sources entering the human population compared to cattle or due to continuous evolution in the human environment. Also, AMR diversity was greater in clinical compared to non-clinical cattle Salmonella, and this could be due to anti-microbial selection pressure in diseased cattle that received treatment. The use of bootstrapping techniques showed that although there were shared profiles between humans and cattle, the expected and observed number of profiles was different, suggesting Salmonella and associated resistance from humans and cattle may not be wholly derived from a common population. © 2014 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial.

PubMed

De la Hoz Restrepo, Fernando; Porras Ramírez, Alexandra; Rico Mendoza, Alejandro; Córdoba, Freddy; Rojas, Diana Patricia

2012-12-01

In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28-day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. assessed through adverse events. A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

Improving Access to Mental Health Care by Delivering Psychotherapeutic Care in the Workplace: A Cross-Sectional Exploratory Trial.

PubMed

Rothermund, Eva; Kilian, Reinhold; Rottler, Edit; Mayer, Dorothea; Hölzer, Michael; Rieger, Monika A; Gündel, Harald

2017-01-01

Common mental disorders like mood and anxiety disorders and somatoform disorders have high costs, yet under-treatment is still frequent. Many people with common mental disorders are employed, so the workplace is potentially a suitable context in which to provide early treatment. Our study investigates whether a change of setting (workplace versus standard care) improves access to treatment for common mental disorders. Conditional latent profile analysis was applied to identify user profiles for work ability (WAI), clinical symptoms like depression (patient health questionnaire depression, PHQ-9), health-related quality of life (QoL, SF-12), and work-related stress (Maslach Burnout Inventory, irritation scale). Patients were recruited consecutively, via psychotherapeutic consultation in the workplace (n = 174) or psychotherapeutic consultation in outpatient care (n = 193). We identified four user profiles in our model: 'severe' (n = 99), 'moderate I-low QoL' (n = 88), 'moderate II-low work ability' (n = 83), and 'at risk' (n = 97). The 'at risk' profile encompassed individuals with reduced work ability (36.0, 34.73 to 37.37), only mild clinical symptoms (PHQ-9 5.7, 4.92 to 6.53), no signs of work-related stress and good quality of life. A higher proportion of the 'at risk' group than of the 'severe' group sought help via the psychotherapeutic consultation in the workplace (OR 0.287, P < 0.01); this effect remained after controlling for gender. Offering secondary mental health care in the workplace is feasible and accepted by users. Offering treatment in the workplace as an alternative to standard outpatient settings is a viable strategy for improving access to treatment for common mental disorders.

Improving Access to Mental Health Care by Delivering Psychotherapeutic Care in the Workplace: A Cross-Sectional Exploratory Trial

PubMed Central

Kilian, Reinhold; Rottler, Edit; Mayer, Dorothea; Hölzer, Michael; Rieger, Monika A.; Gündel, Harald

2017-01-01

Objective Common mental disorders like mood and anxiety disorders and somatoform disorders have high costs, yet under-treatment is still frequent. Many people with common mental disorders are employed, so the workplace is potentially a suitable context in which to provide early treatment. Our study investigates whether a change of setting (workplace versus standard care) improves access to treatment for common mental disorders. Methods Conditional latent profile analysis was applied to identify user profiles for work ability (WAI), clinical symptoms like depression (patient health questionnaire depression, PHQ-9), health-related quality of life (QoL, SF-12), and work-related stress (Maslach Burnout Inventory, irritation scale). Patients were recruited consecutively, via psychotherapeutic consultation in the workplace (n = 174) or psychotherapeutic consultation in outpatient care (n = 193). Results We identified four user profiles in our model: ‘severe’ (n = 99), ‘moderate I—low QoL’ (n = 88), ‘moderate II—low work ability’ (n = 83), and ‘at risk’ (n = 97). The ‘at risk’ profile encompassed individuals with reduced work ability (36.0, 34.73 to 37.37), only mild clinical symptoms (PHQ-9 5.7, 4.92 to 6.53), no signs of work-related stress and good quality of life. A higher proportion of the ‘at risk’ group than of the ‘severe’ group sought help via the psychotherapeutic consultation in the workplace (OR 0.287, P < 0.01); this effect remained after controlling for gender. Conclusions Offering secondary mental health care in the workplace is feasible and accepted by users. Offering treatment in the workplace as an alternative to standard outpatient settings is a viable strategy for improving access to treatment for common mental disorders. PMID:28056101

Lung-MAP Clinical Trial

Cancer.gov

A collection of material about the Lung-MAP study, which will examine treatment outcomes for patients with squamous cell lung cancer assigned to different targeted drugs based on the results of genomic tumor profiling.

A novel convolution-based approach to address ionization chamber volume averaging effect in model-based treatment planning systems

NASA Astrophysics Data System (ADS)

Barraclough, Brendan; Li, Jonathan G.; Lebron, Sharon; Fan, Qiyong; Liu, Chihray; Yan, Guanghua

2015-08-01

The ionization chamber volume averaging effect is a well-known issue without an elegant solution. The purpose of this study is to propose a novel convolution-based approach to address the volume averaging effect in model-based treatment planning systems (TPSs). Ionization chamber-measured beam profiles can be regarded as the convolution between the detector response function and the implicit real profiles. Existing approaches address the issue by trying to remove the volume averaging effect from the measurement. In contrast, our proposed method imports the measured profiles directly into the TPS and addresses the problem by reoptimizing pertinent parameters of the TPS beam model. In the iterative beam modeling process, the TPS-calculated beam profiles are convolved with the same detector response function. Beam model parameters responsible for the penumbra are optimized to drive the convolved profiles to match the measured profiles. Since the convolved and the measured profiles are subject to identical volume averaging effect, the calculated profiles match the real profiles when the optimization converges. The method was applied to reoptimize a CC13 beam model commissioned with profiles measured with a standard ionization chamber (Scanditronix Wellhofer, Bartlett, TN). The reoptimized beam model was validated by comparing the TPS-calculated profiles with diode-measured profiles. Its performance in intensity-modulated radiation therapy (IMRT) quality assurance (QA) for ten head-and-neck patients was compared with the CC13 beam model and a clinical beam model (manually optimized, clinically proven) using standard Gamma comparisons. The beam profiles calculated with the reoptimized beam model showed excellent agreement with diode measurement at all measured geometries. Performance of the reoptimized beam model was comparable with that of the clinical beam model in IMRT QA. The average passing rates using the reoptimized beam model increased substantially from 92.1% to 99.3% with 3%/3 mm and from 79.2% to 95.2% with 2%/2 mm when compared with the CC13 beam model. These results show the effectiveness of the proposed method. Less inter-user variability can be expected of the final beam model. It is also found that the method can be easily integrated into model-based TPS.

Roles and practices of general practitioners and psychiatrists in management of depression in the community

PubMed Central

Tardieu, Sophie; Bottero, Alain; Blin, Patrick; Bohbot, Michael; Goni, Sylvia; Gerard, Alain; Gasquet, Isabelle

2006-01-01

Background Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1°) sociodemographic and clinical profile of their patients considered as depressed 2°) patterns of care provision. Methods The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder. Results Compared to patients identified as depressed by GPs, those identified by psychiatrists were younger, more often urban (10.5% v 5.4% – OR = 2.4), educated (42.4% v 25.4% – OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% – OR = 2.9), had been hospitalized for depression (26.1% v 15.6% – OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). Conclusion Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear to reflect more the organization of the French care system than the competence of providers. PMID:16445855

Rapid Improvement of Glycemic Control in Type 2 Diabetes Using Weekly Intensive Multifactorial Interventions: Structured Glucose Monitoring, Patient Education, and Adjustment of Therapy—A Randomized Controlled Trial

PubMed Central

Rodbard, David; Zanella, Maria Teresa

2011-01-01

Abstract Background We evaluated intensive intervention in poorly controlled patients with type 2 diabetes mellitus involving weekly clinic visits and adjustment of therapy with analysis of three seven-point glucose profiles and intervention from an interdisciplinary staff. Methods Sixty-three patients were randomized to an intensive treatment group that obtained self-monitoring of blood glucose (SMBG) profiles (six or seven values per day, 3 days/week) and were seen in the clinic at Weeks 1–6 and 12. SMBG results were downloaded, analyzed using Accu-Chek® 360° software (Roche Diagnostics, Indianapolis, IN), and used to adjust therapy. Control group subjects obtained glucose profiles and had clinic visits only at Weeks 0, 6, and 12. Results There were highly statistically significant improvements in the intensive treatment group compared with the control group between Weeks 0 and 6 with greater reductions in weekly mean glycemia (WMG) (−76.7±8.9 mg/dL vs. −20.5±8.1 mg/dL), glycemic variability (SD) (−16.3±3.1 mg/dL vs. −5.0±3.1 mg/dL), and glycated hemoglobin (−1.82±0.16% vs. −0.66±0.22%) without significant changes in frequency of hypoglycemia or weight. Improvements were sustained in the intensive treatment group through Week 12. A minimal but statistically significant degree of improvement was seen in the control group at Week 12. Conclusions This short-term pilot study of an intensive monitoring, educational, and pharmacological interventions program resulted in dramatic improvement of glycemic control within 6 weeks, and these effects are sustained through Week 12. SMBG glucose profiles, calculation of WMG and SD, and graphical displays of glucose data can improve the effectiveness of adjustment of therapy at weekly clinic visits when combined with intensive support from a multidisciplinary team. PMID:21751888

Periodontal Examination Profiles and Treatment Approaches of a Group of Turkish General Dentists.

PubMed

Ercan, Esra; Uysal, Cihan; Uzun, Cansu; Yılmaz, Mümün

2015-01-01

To investigate the periodontal examination profiles and treatment approaches of a group of Turkish general dentists. 457 general dentists were called and 173 dentists agreed to participate in the study. The questionnaire comprised 10 questions including gender, years of experience, periodontal probing during examination, oral hygiene motivation methods (do you perform, yes/no; the oral hygiene motivation method; verbal expression or using visual materials), periodontal treatments (supragingival scaling, subgingival scaling and planing or surgery) and knowledge about diagnosis and treatment for aggressive and chronic periodontitis. The participants were grouped according to their years of clinical experience: group 1: 0 to 10 years of clinical practice (n = 58); group 2: 10 to 20 years (n = 68); group 3: >20 years (n = 47). The 'periodontal probing' performance percentages were 70.69%, 26.47% and 40.43% in groups 1, 2 and 3, respectively. The oral hygiene motivation rate was high in the first 10 years of clinical practice (60.3%). In addition, 72.4% of the dentists in group 1 used visual materials in addition to verbal expression during oral hygiene motivation. 72.25% of the general dentists performed supragingival scaling. The knowledge of diagnosis and treatment of chronic periodontitis was present in >90% of the dentists surveyed. In contrast, >50% of the general dentists were not knowledgeable in the diagnosis and treatment of aggressive periodontitis. Periodontal probing is a gold standard for periodontal diagnosis, but as the dentists' clinical experience increases, the frequency of its performance decreases. The percentage of the knowledge and treatment of chronic periodontitis is higher than that of aggressive periodontitis. Postgraduate education in periodontology is important to keep general dentists up to date on current periodontal practice and improve awareness of periodontal diseases.

Therapist turnover and new program sustainability in mental health clinics as a function of organizational culture, climate, and service structure.

PubMed

Glisson, Charles; Schoenwald, Sonja K; Kelleher, Kelly; Landsverk, John; Hoagwood, Kimberly Eaton; Mayberg, Stephen; Green, Philip

2008-03-01

The present study incorporates organizational theory and organizational characteristics in examining issues related to the successful implementation of mental health services. Following the theoretical foundations of socio-technical and cultural models of organizational effectiveness, organizational climate, culture, legal and service structures, and workforce characteristics are examined as correlates of therapist turnover and new program sustainability in a nationwide sample of mental health clinics. Results of General Linear Modeling (GLM) with the organization as the unit of analysis revealed that organizations with the best climates as measured by the Organizational Social Context (OSC) profiling system, had annual turnover rates (10%) that were less than half the rates found in organizations with the worst climates (22%). In addition, organizations with the best culture profiles sustained new treatment or service programs over twice as long (50 vs. 24 months) as organizations with the worst cultures. Finally, clinics with separate children's services units had higher turnover rates than clinics that served adults and children within the same unit. The findings suggest that strategies to support the implementation of new mental health treatments and services should attend to organizational culture and climate, and to the compatibility of organizational service structures with the demand characteristics of treatments.

Temporomandibular joint dysfunction syndrome. A clinical report.

PubMed

Passero, P L; Wyman, B S; Bell, J W; Hirschey, S A; Schlosser, W S

1985-08-01

We have presented two clinical case reports of patients with TMJ dysfunction syndrome as an example of coordinated treatments between dentists and physical therapists. The clinical profiles of these patients with craniocervical pain were compiled from comprehensive physical therapy and dental-orthopedic evaluations. The significance of the relationship between the rest position of the mandible and forward head posture has been shown by the changes observed after correction of the postural deviations and vertical resting dimensions by dental treatments and physical therapy. Additional research is necessary to determine long-term effects of this combined approach in TMJ dysfunction syndrome.

Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

PubMed Central

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-01-01

Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the ultimate goal of fruitfully driving both preclinical and clinical research on anticancer targeted therapy. In the light of its theoretical nature, the prediction performance of this model must be validated before it can be implemented in the clinical setting. PMID:20706624

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

PubMed

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-08-10

The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the ultimate goal of fruitfully driving both preclinical and clinical research on anticancer targeted therapy. In the light of its theoretical nature, the prediction performance of this model must be validated before it can be implemented in the clinical setting.

Future clinical challenges in multiple sclerosis: Relevance to sphingosine 1-phosphate receptor modulator therapy.

PubMed

Hohlfeld, Reinhard; Barkhof, Frederik; Polman, Chris

2011-02-22

The limitations of established therapies for multiple sclerosis (MS) are well-known and include the need for injections, treatment adherence and convenience issues, partial efficacy, and, in some cases, a risk of potentially life-threatening adverse events, such as progressive multifocal leukoencephalopathy. Recently, attention has focused on developing more effective therapies that are administered orally and target neurodegeneration as well as inflammation. In this review, we provide an outlook on the future clinical challenges for MS treatment and management, and focus specifically on the emerging sphingosine 1-phosphate receptor (S1PR) modulators. We highlight the importance of improving our understanding of the neurobiological basis of MS to develop well-tolerated targeted therapies and the need to include advanced MRI assessments that quantify neurodegeneration in interventional studies in MS. As more treatments become available, often with complex pharmacodynamic actions, objective assessment of benefit-to-risk profiles becomes increasingly important to ensure that patients receive appropriate care. Pharmacovigilance and immune monitoring will become important aspects of patient treatment and management in the future. With respect to S1PR modulation, we review the experimental agents that are in clinical development for MS and summarize the steps taken in postmarketing surveillance to ensure that fingolimod (FTY720) has a well-characterized safety profile.

A treatment-oriented typology of self-identified hypersexuality referrals.

PubMed

Cantor, James M; Klein, Carolin; Lykins, Amy; Rullo, Jordan E; Thaler, Lea; Walling, Bobbi R

2013-07-01

Men and women have been seeking professional assistance to help control hypersexual urges and behaviors since the nineteenth century. Despite that the literature emphasizes that cases of hypersexuality are highly diverse with regard to clinical presentation and comorbid features, the major models for understanding and treating hypersexuality employ a "one size fits all" approach. That is, rather than identify which problematic behaviors might respond best to which interventions, existing approaches presume or assert without evidence that all cases of hypersexuality (however termed or defined) represent the same underlying problem and merit the same approach to intervention. The present article instead provides a typology of hypersexuality referrals that links individual clinical profiles or symptom clusters to individual treatment suggestions. Case vignettes are provided to illustrate the most common profiles of hypersexuality referral that presented to a large, hospital-based sexual behaviors clinic, including: (1) Paraphilic Hypersexuality, (2) Avoidant Masturbation, (3) Chronic Adultery, (4) Sexual Guilt, (5) the Designated Patient, and (6) better accounted for as a symptom of another condition.

Clinical and microbiological profile of infectious keratitis in children

PubMed Central

2013-01-01

Background Infectious keratitis is a sight-threatening condition for children. The purpose of this study was to describe the clinical profile, risk factors and microbiological profile of infectious keratitis in children. Methods Retrospective review of clinical records of patients under 16 years of age with history of microbial keratitis seen at a tertiary referral center. Clinical characteristics, risk factors, visual and surgical outcomes as well as the microbiological profile are analyzed. Results Forty-one eyes of 41 patients. Mean age was 8.7 years. Time between the onset of symptoms and ophthalmological examination was 12.7 days. Predisposing factors were found in 78%; ocular trauma was the most common (25%). Visual acuity equal or worse than 20/200 at admission correlated positively with a poorer visual outcome, p=0.002. Positivity of cultures was 34%. Gram-positive bacteria were isolated in 78.5%; Staphylococcus epidermidis (28.6%) was the most common microorganism. Conclusions Our study emphasizes the importance of a prompt diagnosis and treatment of infectious corneal ulcers in children. Trauma and contact lenses were the main predisposing factors. Gram-positive organisms were isolated in the vast majority of cases and visual outcomes are usually poor. PMID:24131681

Clinical profiles of stigma experiences, self-esteem and social relationships among people with schizophrenia, depressive, and bipolar disorders.

PubMed

Oliveira, Sandra E H; Esteves, Francisco; Carvalho, Helena

2015-09-30

Some mental illnesses and certain mental health care environments can be severely stigmatizing, which seems to be related to decreased self-esteem and a deterioration of the quality of social relationships for people with mental illness. This study aims to identify clinical profiles characterized by clinical diagnoses more strongly associated with the treatment settings and related to internalized stigma, self-esteem and satisfaction with social relationships. It also aimed to analyze associations between clinical profiles and socio-demographic indicators. Multiple correspondence analysis and cluster analysis were performed on a sample of 261 individuals with schizophrenia and mood disorders, from hospital-based and community-based facilities. MCA showed four distinct clinical profiles allowing a differentiation among levels of: internalized stigma, social relationship satisfaction and self-esteem. Overall, results revealed that internalized stigma remains a pervasive problem for some people with schizophrenia and mood disorders. Particularly, internalized stigma and social relationships dissatisfaction and associated socio-demographic indicators appear to be a risk factor for social isolation for individuals with schizophrenia, which may worsen the course of the disorder. Our findings highlight the importance to develop structured interventions aimed to reduce internalized stigma, and exclusion of those who suffer the loss of their social roles and networks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

PubMed

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA , NF1 , CDKN2A , or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics. © AlphaMed Press 2017.

Evidence base and future research directions in the management of low back pain.

PubMed

Abbott, Allan

2016-03-18

Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care.

Use of Intra-Articular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice

PubMed Central

Cooper, Cyrus; Rannou, François; Richette, Pascal; Bruyère, Olivier; Al-Daghri, Nasser; Altman, Roy D.; Brandi, Maria Luisa; Basset, Sabine Collaud; Herrero-Beaumont, Gabriel; Migliore, Alberto; Pavelka, Karel; Uebelhart, Daniel; Reginster, Jean-Yves

2017-01-01

This review emphasizes the safety profile of intra-articular hyaluronic acid treatment of knee osteoarthritis, as well as its moderate but real efficacy on symptoms, which is in the same range than other pharmacological modalities used in this indication. Effectiveness of intra-articular hyaluronic acid has also been highlighted based on ‘real-life’ data, together with the clinical benefit of systematic repeated treatment cycles, and the influence of the molecular weight of hyaluronic acid on treatment outcome. These aspects should be particularly helpful to clinicians when making personalized care decisions. PMID:28118523

Electroconvulsive therapy in treatment-resistant schizophrenia: prediction of response and the nature of symptomatic improvement.

PubMed

Chanpattana, Worrawat; Sackeim, Harold A

2010-12-01

The clinical features of patients with schizophrenia who respond to electroconvulsive therapy (ECT) are uncertain. There is a longstanding belief that the duration of illness and/or the presence of affective symptoms associate with good prognosis. There is also little information on the nature of symptomatic improvement with this treatment. We examined the demographic and clinical history features associated with response, the symptom profile predictive of response, and the profile of symptomatic improvement. Using a standardized protocol, 253 patients with treatment-resistant schizophrenia were prospectively treated with a combination of ECT and flupenthixol. Of this group, 138 patients (54.5%) met the response criteria. Independence of sex, longer duration of current episode, and greater severity of baseline negative symptoms were predictive of poorer outcome. Duration of illness had weak relations with outcome only among females. There were marked sex differences in other clinical features and symptoms associated with response. In contrast, no sex differences were observed in the nature of symptomatic improvement. Treatment resulted in marked improvement in specific positive symptoms, with an intermediate effect on affective symptoms and no effect or worsening of specific negative symptoms. The findings challenge recommendations that long duration of illness or absence of affective symptoms portends poor response to ECT in patients with treatment-resistant schizophrenia. Sex may play a critical role in determining the features of the illness that predict outcome.

Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis.

PubMed

Konstantonis, Dimitrios; Vasileiou, Dimitrios; Papageorgiou, Spyridon N; Eliades, Theodore

2018-06-01

The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convexity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made. © 2018 Eur J Oral Sci.

Evaluating Integrative Cancer Clinics With the Claim Assessment Profile: An Example With the InspireHealth Clinic.

PubMed

Hilton, Lara; Elfenbaum, Pamela; Jain, Shamini; Sprengel, Meredith; Jonas, Wayne B

2018-03-01

The evaluation of freestanding integrative cancer clinical programs is challenging and is rarely done. We have developed an approach called the Claim Assessment Profile (CAP) to identify whether evaluation of a practice is justified, feasible, and likely to provide useful information. A CAP was performed in order to (1) clarify the healing claims at InspireHealth, an integrative oncology treatment program, by defining the most important impacts on its clients; (2) gather information about current research capacity at the clinic; and (3) create a program theory and path model for use in prospective research. This case study design incorporates methods from a variety of rapid assessment approaches. Procedures included site visits to observe the program, structured qualitative interviews with 26 providers and staff, surveys to capture descriptive data about the program, and observational data on program implementation. The InspireHealth program is a well-established, multi-site, thriving integrative oncology clinical practice that focuses on patient support, motivation, and health behavior engagement. It delivers patient-centered care via a standardized treatment protocol. There arehigh levels of research interest from staff and resources by which to conduct research. This analysis provides the primary descriptive and claims clarification of an integrative oncology treatment program, an evaluation readiness report, a detailed logic model explicating program theory, and a clinical outcomes path model for conducting prospective research. Prospective evaluation of this program would be feasible and valuable, adding to our knowledge base of integrative cancer therapies.

Summarizing the incidence of adverse events using volcano plots and time intervals.

PubMed

Zink, Richard C; Wolfinger, Russell D; Mann, Geoffrey

2013-01-01

Adverse event incidence analyses are a critical component for describing the safety profile of any new intervention. The results typically are presented in lengthy summary tables. For therapeutic areas where patients have frequent adverse events, analysis and interpretation are made more difficult by the sheer number and variety of events that occur. Understanding the risk in these instances becomes even more crucial. We describe a space-saving graphical summary that overcomes the limitations of traditional presentations of adverse events and improves interpretability of the safety profile. We present incidence analyses of adverse events graphically using volcano plots to highlight treatment differences. Data from a clinical trial of patients experiencing an aneurysmal subarachnoid hemorrhage are used for illustration. Adjustments for multiplicity are illustrated. Color is used to indicate the treatment with higher incidence; bubble size represents the total number of events that occur in the treatment arms combined. Adjustments for multiple comparisons are displayed in a manner to indicate clearly those events for which the difference between treatment arms is statistically significant. Furthermore, adverse events can be displayed by time intervals, with multiple volcano plots or animation to appreciate changes in adverse event risk over time. Such presentations can emphasize early differences across treatments that may resolve later or highlight events for which treatment differences may become more substantial with longer follow-up. Treatment arms are compared in a pairwise fashion. Volcano plots are space-saving tools that emphasize important differences between the adverse event profiles of two treatment arms. They can incorporate multiplicity adjustments in a manner that is straightforward to interpret and, by using time intervals, can illustrate how adverse event risk changes over the course of a clinical trial.

Managing migraine by patient profile: role of frovatriptan.

PubMed

Cady, Roger K; Farmer, Kathleen

2016-01-01

For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the "5-Ps": pattern, phenotype, patient, pharmacology, and precipitants. Attending to these five components of information can assist in developing an individualized behavioral, pharmacological, and nonpharmacological comprehensive treatment plan for most migraine patients. This clinical approach is then focused on frovatriptan because of its unique molecular signature and potential novel clinical applications. Frovatriptan like all triptans is indicated for acute treatment of migraine but its role has been explored in management of several unique migraine phenotypes. Frovatriptan has the longest half-life of any triptan and consequently is often promoted for acute treatment of migraine of longer duration. It has also been studied as a short-term preventive treatment in women with menstrual-related migraine. Given that 60% of female migraineurs suffer from menstrual-related migraine, this population is the obvious group for continued study. Small studies have also explored frovatriptan's use in treating migraine predicted by premonitory symptoms as a preventive for the headache phase of migraine. By identifying patient and attack profiles, clinicians may effectively determine the viability of frovatriptan as an effective pharmacological intervention for migraine.

Managing migraine by patient profile: role of frovatriptan

PubMed Central

Cady, Roger K; Farmer, Kathleen

2016-01-01

For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the “5-Ps”: pattern, phenotype, patient, pharmacology, and precipitants. Attending to these five components of information can assist in developing an individualized behavioral, pharmacological, and nonpharmacological comprehensive treatment plan for most migraine patients. This clinical approach is then focused on frovatriptan because of its unique molecular signature and potential novel clinical applications. Frovatriptan like all triptans is indicated for acute treatment of migraine but its role has been explored in management of several unique migraine phenotypes. Frovatriptan has the longest half-life of any triptan and consequently is often promoted for acute treatment of migraine of longer duration. It has also been studied as a short-term preventive treatment in women with menstrual-related migraine. Given that 60% of female migraineurs suffer from menstrual-related migraine, this population is the obvious group for continued study. Small studies have also explored frovatriptan’s use in treating migraine predicted by premonitory symptoms as a preventive for the headache phase of migraine. By identifying patient and attack profiles, clinicians may effectively determine the viability of frovatriptan as an effective pharmacological intervention for migraine. PMID:27103792

Frequently Asked Questions about Music Therapy

MedlinePlus

... of clients, develop and implement treatment plans, and evaluate and document clinical changes. Once the music therapy ... of the profession is published. This includes a descriptive statistical profile of the profession. Music therapists' salaries ...

[Biological agents].

PubMed

Amano, Koichi

2009-03-01

There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

Safety and efficacy of elbasvir and grazoprevir for treatment of hepatitis C.

PubMed

Carrion, Andres F; Martin, Paul

2016-06-01

The combination of elbasvir and grazoprevir in a single co-formulated tablet is highly effective for treatment of hepatitis C virus (HCV) infection. This regimen affords profound inhibition of NS3/4A protease and NS5A activity, resulting in potent activity against HCV genotypes 1, 4, and 6 with high rates of sustained virological response. This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy and safety profile of elbasvir/grazoprevir including special populations such as individuals with compensated and decompensated cirrhosis, HCV/HIV co-infection, advanced chronic kidney disease, and those that previously failed antiviral therapy. Elbasvir/grazoprevir is an effective antiviral regimen for treatment of genotypes 1 and 4 and has a very favorable safety profile based on extensive data from several pre-licensure clinical trials that included patient subgroups at increased risk of toxicity. This regimen is currently the only one licensed for use in individuals with advanced chronic kidney disease requiring hemodialysis.

Comparing wavefront-optimized, wavefront-guided and topography-guided laser vision correction: clinical outcomes using an objective decision tree.

PubMed

Stonecipher, Karl; Parrish, Joseph; Stonecipher, Megan

2018-05-18

This review is intended to update and educate the reader on the currently available options for laser vision correction, more specifically, laser-assisted in-situ keratomileusis (LASIK). In addition, some related clinical outcomes data from over 1000 cases performed over a 1-year are presented to highlight some differences between the various treatment profiles currently available including the rapidity of visual recovery. The cases in question were performed on the basis of a decision tree to segregate patients on the basis of anatomical, topographic and aberrometry findings; the decision tree was formulated based on the data available in some of the reviewed articles. Numerous recent studies reported in the literature provide data related to the risks and benefits of LASIK; alternatives to a laser refractive procedure are also discussed. The results from these studies have been used to prepare a decision tree to assist the surgeon in choosing the best option for the patient based on the data from several standard preoperative diagnostic tests. The data presented here should aid surgeons in understanding the effects of currently available LASIK treatment profiles. Surgeons should also be able to appreciate how the findings were used to create a decision tree to help choose the most appropriate treatment profile for patients. Finally, the retrospective evaluation of clinical outcomes based on the decision tree should provide surgeons with a realistic expectation for their own outcomes should they adopt such a decision tree in their own practice.

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

PubMed

Elfar, Ahmed; Sambandam, Kamalanathan K

2017-08-01

The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

Quantitative evaluation of the voice range profile in patients with voice disorder.

PubMed

Ikeda, Y; Masuda, T; Manako, H; Yamashita, H; Yamamoto, T; Komiyama, S

1999-01-01

In 1953, Calvet first displayed the fundamental frequency (pitch) and sound pressure level (intensity) of a voice on a two-dimensional plane and created a voice range profile. This profile has been used to evaluate clinically various vocal disorders, although such evaluations to date have been subjective without quantitative assessment. In the present study, a quantitative system was developed to evaluate the voice range profile utilizing a personal computer. The area of the voice range profile was defined as the voice volume. This volume was analyzed in 137 males and 175 females who were treated for various dysphonias at Kyushu University between 1984 and 1990. Ten normal subjects served as controls. The voice volume in cases with voice disorders significantly decreased irrespective of the disease and sex. Furthermore, cases having better improvement after treatment showed a tendency for the voice volume to increase. These findings illustrated the voice volume as a useful clinical test for evaluating voice control in cases with vocal disorders.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles

PubMed Central

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S.C.; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2016-01-01

Abstract Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders. PMID:27893485

Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone

PubMed Central

Moody, Laura R; Herbst, Allen J; Yoo, Han Sang; Vanderloo, Joshua P

2009-01-01

Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis. The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology. In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays. In total, 164 genes were differentially regulated during prion infection. Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease. A 0.4% cuprizone diet was utilized as a control for comparative expression profiling. Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry. Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes. After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified. Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection. PMID:19535908

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

PubMed

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S C; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2017-02-01

Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

Proteomics of gliomas: Initial biomarker discovery and evolution of technology

PubMed Central

Kalinina, Juliya; Peng, Junmin; Ritchie, James C.; Van Meir, Erwin G.

2011-01-01

Gliomas are a group of aggressive brain tumors that diffusely infiltrate adjacent brain tissues, rendering them largely incurable, even with multiple treatment modalities and agents. Mostly asymptomatic at early stages, they present in several subtypes with astrocytic or oligodendrocytic features and invariably progress to malignant forms. Gliomas are difficult to classify precisely because of interobserver variability during histopathologic grading. Identifying biological signatures of each glioma subtype through protein biomarker profiling of tumor or tumor-proximal fluids is therefore of high priority. Such profiling not only may provide clues regarding tumor classification but may identify clinical biomarkers and pathologic targets for the development of personalized treatments. In the past decade, differential proteomic profiling techniques have utilized tumor, cerebrospinal fluid, and plasma from glioma patients to identify the first candidate diagnostic, prognostic, predictive, and therapeutic response markers, highlighting the potential for glioma biomarker discovery. The number of markers identified, however, has been limited, their reproducibility between studies is unclear, and none have been validated for clinical use. Recent technological advancements in methodologies for high-throughput profiling, which provide easy access, rapid screening, low sample consumption, and accurate protein identification, are anticipated to accelerate brain tumor biomarker discovery. Reliable tools for biomarker verification forecast translation of the biomarkers into clinical diagnostics in the foreseeable future. Herein we update the reader on the recent trends and directions in glioma proteomics, including key findings and established and emerging technologies for analysis, together with challenges we are still facing in identifying and verifying potential glioma biomarkers. PMID:21852429

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

PubMed

Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

2017-01-01

Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia

PubMed Central

Sarkar, Sukanto; Nizamie, S. Haque

2018-01-01

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response. PMID:29675276

Recurrent seminomas: Clinical features and biologic implications

PubMed Central

Som, Avik; Zhu, Rui; Guo, Charles C.; Efstathiou, Eleni; Xiao, Li; Pisters, Louis L.; Matin, Angabin; Tu, Shi-Ming

2013-01-01

Objectives Certain patients with seminoma and clinically atypical phenotypes—visceral metastases, elevated levels of βhuman chorionic gonadotropin (βHCG), and/or recurrent disease— have a poor prognosis. The primary goal of this pilot study was to characterize the clinical characteristics and treatment profile of these rare patients. We also wished to test whether these tumors expressed any specific biomarkers that might distinguish them as a unique subtype of seminoma. Materials and methods We retrospectively identified 25 patients with a history of seminoma plus visceral metastases, βHCG levels >200 mU/ml, and/or recurrent disease. We reviewed these patients’ histories for treatment efficacy and clinical outcome. Tissue samples were available from 6 of those patients, and we studied them for expression of the markers OCT 3/4, PLAP, CD30, TRA-1-60, c-kit, and gp200. We compared our results with the expression of those markers in tissue samples from mixed seminoma/embryonal carcinomas and classic seminomas. Results Our analysis suggested that certain chemotherapeutic regimens (such as ifosfamide, paclitaxel, and cisplatin) are efficacious for the treatment of patients with these atypical seminomas. Further, specimens from the atypical seminomas generally had staining profiles that resembled those of classic seminomas and the seminoma components in mixed germ-cell tumors, but the profiles differed from those of the embryonal carcinoma components in the same mixed germ-cell tumors. Conclusions Although these atypical seminomas tend to be resistant to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our pilot immunohistochemical study also suggested that the unique phenotypes associated with these atypical seminomas do not result from any relationship with embryonal carcinomas. More study is needed to confirm these initial findings. PMID:20822932

Anti-IL-23 Phase II Data for Psoriasis: A Review.

PubMed

Beroukhim, Kourosh; Danesh, Melissa J; Nguyen, Catherine; Austin, Annemieke; Koo, John; Levin, Ethan

2015-10-01

Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

PubMed

El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

2018-01-01

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.

PubMed

Ortiz, Michael V; Kobos, Rachel; Walsh, Michael; Slotkin, Emily K; Roberts, Stephen; Berger, Michael F; Hameed, Meera; Solit, David; Ladanyi, Marc; Shukla, Neerav; Kentsis, Alex

2016-08-01

Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials. © 2016 Wiley Periodicals, Inc.

Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts Differential Drug Sensitivity Profiles toward Kinase Inhibitors.

PubMed

Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

2018-05-01

A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Safety Profile during Initiation of Propranolol for Treatment of Infantile Hemangiomas in an Ambulatory Day-Care Hospitalization Setting.

PubMed

Fogel, Itay; Ollech, Ayelet; Zvulunov, Alex; Valdman-Greenshpon, Yulia; Atar-Sagie, Vered; Friedland, Rivka; Lapidoth, Moshe; Ben-Amitai, Dan

2018-03-24

Propranolol is the mainstay of treatment for infantile hemangioma. Despite its good safety profile, it is not risk-free. Guidelines for propranolol initiation and monitoring have been suggested, but protocols vary among practitioners. This study sought to assess the prevalence of adverse events and clinically significant fluctuations in hemodynamic parameters in children with infantile hemangioma during initiation of treatment with propranolol in a day-hospitalization setting. Children with infantile hemangioma treated with propranolol in a day-hospitalization department of a tertiary pediatric medical center in 2008-2014 were identified retrospectively. The pretreatment evaluation included clinical examination by a pediatric dermatologist and electrocardiography, echocardiography, and clinical examination by a pediatric cardiologist. The propranolol dosage was escalated from 0.5mg/kg/day to 2mg/kg/day, divided into 3 doses/day, over 3 days. Heart rate, blood pressure, and blood glucose level were measured before treatment onset and 60 min after the first two doses each day. The third dose was given at home. The cohort included 220 children aged 1 month to 5 years. No severe treatment-related adverse events were documented; 27 patients had minor side effects. There was a significant decrease in heart rate each day after the first two doses (p<0.001), and in systolic blood pressure, on day 2 (1mg/kg/day) after the first dose (p=0.01). Blood glucose level remained stable. The hemodynamic changes were clinically asymptomatic and did not require intervention. Propranolol treatment (2mg/kg/day in three doses) for infantile hemangioma is well tolerated and safe and may be administered and monitored in an ambulatory setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Management of chronic spontaneous urticaria in the elderly.

PubMed

Ventura, Maria Teresa; Cassano, Nicoletta; Romita, Paolo; Vestita, Michelangelo; Foti, Caterina; Vena, Gino Antonio

2015-04-01

The guidelines for the management of urticaria in adults and children have been revised and updated recently. However, there are few data in the literature concerning several aspects of this disease in the elderly (e.g., epidemiology, etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and safety profiles of treatments, and management strategies). This is an obvious deficiency in the data, as this disease causes a deterioration in quality of life, affecting the quality of sleep, everyday life habits and activities, and inducing severe disability. Chronic spontaneous urticaria (CSU) can also be associated with internal, infectious, autoimmune, or neoplastic diseases. It is therefore necessary to pay particular attention to these clinical issues through appropriate clinical examinations. At the same time, the specific features of medications used to treat CSU in the elderly should be carefully evaluated, as its pharmacological treatment raises a number of problems related both to the clinical condition of the patient and to concomitant diseases, as well as to the polypharmacotherapy, which is common in older subjects and may cause safety problems because of the drug interactions. Non-sedating new-generation antihistamines are the mainstay treatment of CSU for the elderly. The efficacy and safety of alternative treatment options have not been assessed in the geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin) should be used by this population with extreme caution. Similarly, there are no data regarding the actual safety profile of the new-generation antihistamines at higher doses than those recommended in elderly patients.

Rapid Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates Directly from Clinical Samples by Use of Amplicon Sequencing: a Proof-of-Concept Study

PubMed Central

Anderson, Julia; Lemmer, Darrin; Lehmkuhl, Erik; Georghiou, Sophia B.; Heaton, Hannah; Wiggins, Kristin; Gillece, John D.; Schupp, James M.; Catanzaro, Donald G.; Crudu, Valeriu; Cohen, Ted; Rodwell, Timothy C.; Engelthaler, David M.

2016-01-01

Increasingly complex drug-resistant tuberculosis (DR-TB) is a major global health concern and one of the primary reasons why TB is now the leading infectious cause of death worldwide. Rapid characterization of a DR-TB patient's complete drug resistance profile would facilitate individualized treatment in place of empirical treatment, improve treatment outcomes, prevent amplification of resistance, and reduce the transmission of DR-TB. The use of targeted next-generation sequencing (NGS) to obtain drug resistance profiles directly from patient sputum samples has the potential to enable comprehensive evidence-based treatment plans to be implemented quickly, rather than in weeks to months, which is currently needed for phenotypic drug susceptibility testing (DST) results. In this pilot study, we evaluated the performance of amplicon sequencing of Mycobacterium tuberculosis DNA from patient sputum samples using a tabletop NGS technology and automated data analysis to provide a rapid DST solution (the Next Gen-RDST assay). One hundred sixty-six out of 176 (94.3%) sputum samples from the Republic of Moldova yielded complete Next Gen-RDST assay profiles for 7 drugs of interest. We found a high level of concordance of our Next Gen-RDST assay results with phenotypic DST (97.0%) and pyrosequencing (97.8%) results from the same clinical samples. Our Next Gen-RDST assay was also able to estimate the proportion of resistant-to-wild-type alleles down to mixtures of ≤1%, which demonstrates the ability to detect very low levels of resistant variants not detected by pyrosequencing and possibly below the threshold for phenotypic growth methods. The assay as described here could be used as a clinical or surveillance tool. PMID:27225403

A patient-centred approach to treatment with incretin-based agents in patients with type 2 diabetes.

PubMed

Cornell, Susan A

2013-06-01

The 2012 position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommends a haemoglobin A1c level of <7% for most patients with type 2 diabetes (T2D). Initial therapy consists of lifestyle changes plus metformin, with an emphasis on a patient-centred approach to management. Addition of incretin-based therapy is recommended as an add-on after metformin failure, and later on in combination with basal insulin. Basal insulin is recommended from the onset in patients with A1c ≥10%. The possibility of incorporating incretin-based therapy in the patient-centred approach will be investigated both in the literature and clinical experience. Incretin-based therapy targets multiple dysfunctional organ systems in T2D and provides sustained glycaemic control, with extraglycaemic benefits and low risk of hypoglycaemia. To initiate an incretin-based therapy that best fits an individual patient's needs, the patient's A1c level, preference and comorbid conditions should be considered along with any drug safety and adherence-related issues. There is good evidence to support the patient-centred approach to T2D management. This approach allows patient treatment goals and personal preferences to be matched with the clinical profile(s) of one or more agents to formulate a treatment plan that can best achieve the goals. Incretin-based therapies are an important class of agents to consider after metformin monotherapy failure and later in combination with basal insulin. By matching patient needs with the clinical profiles of the various treatment options, pharmacists can actively engage in the practice of patient-centred care and management. © 2013 Blackwell Publishing Ltd.

Autoantibodies, C-reactive protein, erythrocyte sedimentation rate and serum cytokine profiling in monitoring of early treatment.

PubMed

Brzustewicz, Edyta; Henc, Izabella; Daca, Agnieszka; Szarecka, Maria; Sochocka-Bykowska, Malgorzata; Witkowski, Jacek; Bryl, Ewa

2017-01-01

Currently used clinical scale and laboratory markers to monitor patients with early rheumatoid arthritis (RA) seem to be not sufficient. It has been demonstrated that disease- related cytokines may be elevated very early in RA development and cytokines are considered as the biomarkers potentially useful for RA monitoring. The group of patients with undifferentiated arthritis (UA) developing RA (UA→RA) was identified from a total of 121 people with arthralgia. UA→RA (n = 16) and healthy control (n = 16) subjects underwent clinical and laboratory evaluation, including acute phase reactants (APRs) and autoantibodies. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1b, IL-2 in sera were assayed using flow cytometric bead array test. 34.5% of patients with UA developed RA. DAS28 reduced as early as 3 months after initiation of treatment. No DAS28 difference between groups of autoantibody (RF, anti-CCP, ANA-HEp-2) -positive and -negative patients was observed, however, comparing groups of anti-CCP and RF-double negative and -double positive patients, the trend of sooner clinical improvement was visible in the second abovementioned group. After the treatment introduction, the ESR level reduced significantly, while CRP level reduction was not significant. Serum cytokine levels of IL-10, IL-6 and IL-17A reduced after 6 months since introduction of treatment. The positive correlations between ESR, CRP and specific cytokine levels were observed. The autoantibody and APR profile is poorly connected with the RA course. The serum cytokine profile change in the course of RA and may be potentially used for optimization of RA monitoring.

Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Nicholas, Michael K; Hodges, Paul W

2018-01-01

To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP). Cross-sectional observational study. Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic. People (N=102) seeking treatment for LBP. Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment-Based Classification (TBC), and O'Sullivan Classification (OSC). Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme. Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes. Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Practical use of a plastic scintillator for quality assurance of electron beam therapy.

PubMed

Yogo, Katsunori; Tatsuno, Yuya; Tsuneda, Masato; Aono, Yuki; Mochizuki, Daiki; Fujisawa, Yoshiki; Matsushita, Akihiro; Ishigami, Minoru; Ishiyama, Hiromichi; Hayakawa, Kazushige

2017-06-07

Quality assurance (QA) of clinical electron beams is essential for performing accurate and safe radiation therapy. However, with advances in radiation therapy, QA has become increasingly labor-intensive and time-consuming. In this paper, we propose a tissue-equivalent plastic scintillator for quick and easy QA of clinical electron beams. The proposed tool comprises a plastic scintillator plate and a charge-coupled device camera that enable the scintillation light by electron beams to be recorded with high sensitivity and high spatial resolution. Further, the Cerenkov image is directly subtracted from the scintillation image to discriminate Cerenkov emissions and accurately measure the dose profiles of electron beams with high spatial resolution. Compared with conventional methods, discrepancies in the depth profile improved from 7% to 2% in the buildup region via subtractive corrections. Further, the output brightness showed good linearity with dose, good reproducibility (deviations below 1%), and dose rate independence (within 0.5%). The depth of 50% dose measured with the tool, an index of electron beam quality, was within  ±0.5 mm of that obtained with an ionization chamber. Lateral brightness profiles agreed with the lateral dose profiles to within 4% and no significant improvement was obtained using Cerenkov corrections. Field size agreed to within 0.5 mm with those obtained with ionization chamber. For clinical QA of electron boost treatment, a disk scintillator that mimics the shape of a patient's breast is applied. The brightness distribution and dose, calculated using a treatment planning system, was generally acceptable for clinical use, except in limited zones. Overall, the proposed plastic scintillator plate tool efficiently performs QA for electron beam therapy and enables simultaneous verification of output constancy, beam quality, depth, and lateral dose profiles during monthly QAs at lower doses of irradiation (small monitor units, MUs).

Classification of Clinically Relevant Microorganisms in Non-Medical Environments

DTIC Science & Technology

2004-05-06

settings largely due to the rapidity of its evolutionary response to treatment. The first antibiotic-resistant strains of S . aureus were isolated only...studies have assigned isolates of the bacteria to known strains. The objectives of this study were to collect, isolate and characterize samples of S ...internal fragments of seven genes were obtained for 36 S . aureus isolates and assigned a unique allelic profile. These profiles, like fingerprints

Tear cytokine profile as a noninvasive biomarker of inflammation for ocular surface diseases: standard operating procedures.

PubMed

Wei, Yi; Gadaria-Rathod, Neha; Epstein, Seth; Asbell, Penny

2013-12-23

To provide standard operating procedures (SOPs) for measuring tear inflammatory cytokine concentrations and to validate the resulting profile as a minimally invasive objective metric and biomarker of ocular surface inflammation for use in multicenter clinical trials on dry eye disease (DED). Standard operating procedures were established and then validated with cytokine standards, quality controls, and masked tear samples collected from local and distant clinical sites. The concentrations of the inflammatory cytokines in tears were quantified using a high-sensitivity human cytokine multiplex kit. A panel of inflammatory cytokines was initially investigated, from which four key inflammatory cytokines (IL-1β, IL-6, INF-γ, and TNF-α) were chosen. Results with cytokine standards statistically satisfied the manufacturer's quality control criteria. Results with pooled tear samples were highly reproducible and reliable with tear volumes ranging from 4 to 10 μL. Incorporation of the SOPs into clinical trials was subsequently validated. Tear samples were collected at a distant clinical site, stored, and shipped to our Biomarker Laboratory, where a masked analysis of the four tear cytokines was successfully performed. Tear samples were also collected from a feasibility study on DED. Inflammatory cytokine concentrations were decreased in tears of subjects who received anti-inflammatory treatment. Standard operating procedures for human tear cytokine assessment suitable for multicenter clinical trials were established. Tear cytokine profiling using these SOPs may provide objective metrics useful for diagnosing, classifying, and analyzing treatment efficacy in inflammatory conditions of the ocular surface, which may further elucidate the mechanisms involved in the pathogenesis of ocular surface disease.

Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

PubMed

Halbreich, Uriel; O'Brien, P M Shaughn; Eriksson, Elias; Bäckström, Torbjörn; Yonkers, Kimberly A; Freeman, Ellen W

2006-01-01

Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.

Applications of stable isotopes in clinical pharmacology

PubMed Central

Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

2011-01-01

This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance. Secondly, stable isotopes may be used for the assessment of drug products or drug delivery systems by determination of parameters such as the bioavailability or the release profile. Thirdly, patients may be assessed in relation to patient-specific drug treatment; this concept is often called personalized medicine. In this article, the application of stable isotope technology in the aforementioned three areas is reviewed, with emphasis on developments over the past 25 years. The applications are illustrated with examples from clinical studies in humans. PMID:21801197

Profile of addicted patients who reenter treatment programs.

PubMed

López-Goñi, José J; Fernández-Montalvo, Javier; Cacho, Raúl; Arteaga, Alfonso

2014-01-01

Clinical experience shows that some patients who suffer from drug addiction are readmitted to treatment programs multiple times because of relapses that occur after they leave these programs. Patients who reenter treatment programs repeatedly may do so because they have problems or difficulties that were not addressed or that were not satisfactorily solved during previous treatment periods. This study explored the differential profile of addicted patients who reenter treatment programs. A sample of 252 addicted patients (203 male and 49 female) who sought outpatient treatment was assessed. Data regarding sociodemographic factors, drug consumption factors (assessed using the EuropASI), psychopathological factors (assessed using the Symptom Checklist-90-Revised [SCL-90-R]), and personality variables (assessed using the Millon Clinical Multiaxial Inventory II [MCMI-II]) were collected. A 65.9% (n = 166) of drug-addicted patients were readmitted into treatment programs. All of the variables for which data were collected were compared between these treatment repeaters and patients who were admitted for the first time. Significant differences between the 2 groups of patients were found for some of the variables that we examined. Treatment repeaters were generally older and had a poorer employment situation than first-time admits. Treatment repeaters were also more likely to report polyconsumption and to have sought treatment for alcohol abuse. Moreover, some of the scores for several EuropASI, SCL-90-R, and MCMI-II variables were statistically significantly different from those of the first-time admits. According to these results, patients who reenter treatment programs often present with more severe addiction problems. All of these data suggest that treatment programs should incorporate a detailed analysis regarding the existence and nature of prior treatments into the baseline protocols and they should offer follow-up services to patients who have completed their treatments. The implications of these results for further research and clinical practice are discussed.

Clinical and investigative profile of biopsy-proven sarcoid uveitis in India.

PubMed

Ganesh, Sudha K; Agarwal, Manisha

2008-01-01

Retrospective analysis of the clinical features, investigative profile, response to treatment, and final visual outcome in histopathologically confirmed cases of sarcoid uveitis. Retrospective case series analysis was done of 15 eyes of 9 patients seen between July 1999 and August 2003 with biopsy-proven sarcoid uveitis. There were 3 were males and 6 females. The mean age at presentation was 44.1 years (range 11-62 years), The mean follow-up was 28.4 months. Six patients had bilateral ocular involvement and 3 had unilateral involvement. Five out of 9 patients had primarily ocular involvement. The most common presentation was intermediate uveitis and granulomatous anterior uveitis in 7 patients. Eight of 9 patients responded well to the medical treatment with systemic and periocular steroids. Ocular lesions can be the primary manifestation of systemic sarcoidosis. Sarcoid uveitis in the Asian Indian population often presents an intermediate uveitis with granulomatous anterior uveitis.

Evidence base and future research directions in the management of low back pain

PubMed Central

Abbott, Allan

2016-01-01

Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care. PMID:27004162

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

PubMed Central

Thanos, Panayotis K.; Robison, Lisa S.; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M.; Komatsu, David E.; Hadjiargyrou, Michael; Volkow, Nora D.

2015-01-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. PMID:25641666

Safety of vedolizumab in the treatment of Crohn's disease and ulcerative colitis.

PubMed

Hagan, Matilda; Cross, Raymond K

2015-01-01

Vedolizumab is the latest FDA-approved anti-integrin therapy for treatment of moderate-to-severe inflammatory bowel disease (IBD). The safety and efficacy of vedolizumab have been studied in short-term clinical trials. This paper reviews the safety profile of vedolizumab compared with other biologics. It also highlights the mechanism of action of the medication. We discuss the current position of vedolizumab in our current algorithm for IBD management and comment on future prospects of the drug. Vedolizumab appears to be a safe and effective option in the treatment of moderate-to-severe IBD in the short term. Long-term observational studies and post-marketing safety data are needed to ascertain the long-term efficacy and side effect profile.

Antiretroviral Simplification with Darunavir/Ritonavir Monotherapy in Routine Clinical Practice: Safety, Effectiveness, and Impact on Lipid Profile

PubMed Central

Santos, José R.; Moltó, José; Llibre, Josep M.; Negredo, Eugenia; Bravo, Isabel; Ornelas, Arelly; Clotet, Bonaventura; Paredes, Roger

2012-01-01

Background Simplification of antiretroviral treatment (ART) with darunavir/ritonavir (DRV/r) monotherapy has achieved sustained suppression of plasma viral load (pVL) in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. Methodology/Principal Findings We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL <50 copies/mL under ART and at least 1 subsequent follow-up visit in our clinic. The primary study endpoints were the percentage of patients with virological failure (VF, defined as 2 consecutive pVL>50 copies/mL) at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR) of 73 (57–92) weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433–837) and 238 (150–376) cells/mm3, respectively. Patients had previously received a median of 5 (3–9) ART lines and maintained a pVL<50 copies/mL for a median of 76 (32–176) weeks before initiating DRV/r monotherapy. Nine (9.8%) patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1–47.8) weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3), rash (n = 1), and impaired CD4 recovery (n = 2). Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001). Conclusions/Significance Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels. PMID:22666357

The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives.

PubMed

Bosch, Annet M; Stroek, Kevin; Abeling, Nico G; Waterham, Hans R; Ijlst, Lodewijk; Wanders, Ronald J A

2012-10-29

The Brown-Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months.

The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives

PubMed Central

2012-01-01

The Brown-Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months. PMID:23107375

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

PubMed Central

Iffland, Kerstin; Grotenhermen, Franjo

2017-01-01

Abstract Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking. PMID:28861514

Emerging Minimally Invasive Treatment Options for Male Lower Urinary Tract Symptoms.

PubMed

Magistro, Giuseppe; Chapple, Christopher R; Elhilali, Mostafa; Gilling, Peter; McVary, Kevin T; Roehrborn, Claus G; Stief, Christian G; Woo, Henry H; Gratzke, Christian

2017-12-01

Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques. A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented. Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement. With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated. Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients. Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Evaluating Integrative Cancer Clinics With the Claim Assessment Profile: An Example With the InspireHealth Clinic

PubMed Central

Hilton, Lara; Elfenbaum, Pamela; Jain, Shamini; Sprengel, Meredith; Jonas, Wayne B.

2016-01-01

Background: The evaluation of freestanding integrative cancer clinical programs is challenging and is rarely done. We have developed an approach called the Claim Assessment Profile (CAP) to identify whether evaluation of a practice is justified, feasible, and likely to provide useful information. Objectives: A CAP was performed in order to (1) clarify the healing claims at InspireHealth, an integrative oncology treatment program, by defining the most important impacts on its clients; (2) gather information about current research capacity at the clinic; and (3) create a program theory and path model for use in prospective research. Study Design/Methods: This case study design incorporates methods from a variety of rapid assessment approaches. Procedures included site visits to observe the program, structured qualitative interviews with 26 providers and staff, surveys to capture descriptive data about the program, and observational data on program implementation. Results: The InspireHealth program is a well-established, multi-site, thriving integrative oncology clinical practice that focuses on patient support, motivation, and health behavior engagement. It delivers patient-centered care via a standardized treatment protocol. There arehigh levels of research interest from staff and resources by which to conduct research. Conclusions: This analysis provides the primary descriptive and claims clarification of an integrative oncology treatment program, an evaluation readiness report, a detailed logic model explicating program theory, and a clinical outcomes path model for conducting prospective research. Prospective evaluation of this program would be feasible and valuable, adding to our knowledge base of integrative cancer therapies. PMID:29444602

Medicine Based Evidence for Individualized Decision Making: Case Study of Systemic Lupus Erythematosus.

PubMed

Wivel, Ashley E; Lapane, Kate; Kleoudis, Christi; Singer, Burton H; Horwitz, Ralph I

2017-11-01

To guide management decisions for an index patient, evidence is required from comparisons between approximate matches to the profile of the index case, where some matches contain responses to treatment and others act as controls. We describe a method for constructing clinically relevant histories/profiles using data collected but unreported from 2 recent phase 3 randomized controlled trials assessing belimumab in subjects with clinically active and serologically positive systemic lupus erythematosus. Outcome was the Systemic lupus erythematosus Responder Index (SRI) measured at 52 weeks. Among 1175 subjects, we constructed an algorithm utilizing 11 trajectory variables including 4 biological, 2 clinical, and 5 social/behavioral. Across all biological and social/behavioral variables, the proportion of responders based on the SRI whose value indicated clinical worsening or no improvement ranged from 27.5% to 42.3%. Kappa values suggested poor agreement, indicating that each biological and patient-reported outcome provides different information than gleaned from the SRI. The richly detailed patient profiles needed to guide decision-making in clinical practice are sharply at odds with the limited information utilized in conventional randomized controlled trial analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

New clinical trial will test COXEN’s ability to choose best therapy for patients with advanced bladder cancer | Center for Cancer Research

Cancer.gov

The Genitourinary Malignancies Branch is now enrolling participants for a clinical trial that will evaluate whether analyzing a tumor’s genetic profile can identify which approved anticancer drugs are most likely to benefit individual patients whose bladder cancer has stopped responding to standard treatments. Learn more...

Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy

PubMed Central

Darwish, Mona; Hamed, Ehab; Messina, John

2010-01-01

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP. PMID:20634985

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

Zhang, J; Li, X; Ding, X

Purpose: We investigate the spot characteristic and dose profiles properties from a compact gantry proton therapy system. This compact design features a dedicated pencil beam scanning nozzle with the scanning magnet located upstream of the final 60 degree bending magnet. Due to the unique beam line design, uncertainty has been raised in the virtual source-to-axis distance (SAD). We investigate its potential clinical impact through measurements and simulation. Methods: A scintillator camera based detector was used to measure spot characteristics and position accuracy. An ion chamber array device was used to measure planar dose profile. Dose profile in-air simulation was performedmore » using in-house built MATLAB program based on additional spot parameters directly from measurements. Spot characteristics such as position and in-air sigma values were used to general simulated 2D elliptical Gaussian spots. The virtual SAD distance changes in the longitudinal direction were also simulated. Planar dose profiles were generated by summation of simulated spots at the isocenter, 15 cm above the isocenter, and 15 cm below the isocenter for evaluation of potential clinical dosimetric impact. Results: We found that the virtual SAD varies depending on the spot location on the longitudinal axis. Measurements have shown that the variable SAD changes from 7 to 12 meters from one end to the other end of the treatment field in the longitudinal direction. The simulation shows that the planer dose profiles differences between the fixed SAD and variable SAD are within 3% from the isocenter profile and the lateral penumbras are within 1 mm difference. Conclusion: Our measurements and simulations show that there are minimum effects on the spot characteristics and dose profiles for this up-stream scanning compact system proton system. Further treatment planning study is needed with the variable virtual SAD accounted for in the planning system to show minimum dosimetric impact.« less

Time perception and psychopathology: Influence of time perspective on quality of life of severe mental illness.

PubMed

Oyanadel, Cristián; Buela-Casal, Gualberto

2014-01-01

The study of time perception and mental illness has given priority to time estimation over time perspective. Considering Zimbardo’s theory on five dimensions of time perspective, and balanced time perspective profile, this study has aimed to compare people with severe mental illness (SMI) and healthy people, with measurements of time perspective and time estimation and to assess whether the time perspective profile influences the quality of life in people with SMI. Using a quasi-experimental design, a clinical group (n=167) corresponding to four samples of severe mental disorders (major depression, bipolar disorder, schizophrenia and personality disorders) and healthy people (n=167) were compared in their performance regarding time perspective and time estimation. After, the clinical sample was grouped according to their deviation from the balanced time perspective profile (DBTP) and negative profile (DNTP). These groups were evaluated with health measures and time estimation tasks. Through the ANOVA, it can be seen that the time perspective profile affects health measurements. There are significant differences between the clinical sample and controls regarding time perspective and time estimation. Within the group of patients, it was observed that those who were closer to the BTP profile had better physical health, and less hopelessness (p<.05). This measurement may favor interventions related to a balanced profile. Results are discussed in relation to contribution of time perspective in the assessment, treatment and quality of life of people with SMI.

Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx].

PubMed

Bonassi, Stefano; Prinzi, Giulia; Lamonaca, Palma; Russo, Patrizia; Paximadas, Irene; Rasoni, Giuseppe; Rossi, Raffaella; Ruggi, Marzia; Malandrino, Salvatore; Sánchez-Flores, Maria; Valdiglesias, Vanessa; Benassi, Barbara; Pacchierotti, Francesca; Villani, Paola; Panatta, Martina; Cordelli, Eugenia

2018-01-22

Numerous health benefits have been attributed to the Ginkgo biloba leaf extract (GBLE), one of the most extensively used phytopharmaceutical drugs worldwide. Recently, concerns of the safety of the extract have been raised after a report from US National Toxicology Program (NTP) claimed high doses of GBLE increased liver and thyroid cancer incidence in mice and rats. A safety study has been designed to assess, in a population of elderly residents in nursing homes, clinical and genomic risks associated to GBLE treatment. GiBiEx is a multicentre randomized clinical trial, placebo controlled, double blinded, which compared subjects randomized to twice-daily doses of either 120-mg of IDN 5933 (also known as Ginkgoselect®Plus) or to placebo for a 6-months period. IDN 5933 is extracted from dried leaves and contains 24.3% flavone glycosides and 6.1% of terpene lactones (2.9% bilobalide, 1.38% ginkgolide A, 0.66% ginkgolide B, 1.12% ginkgolide C) as determined by HPLC. The study was completed by 47 subjects, 20 in the placebo group and 27 in the treatment group. Clinical (adverse clinical effect and liver injury) and genomic (micronucleus frequency, comet assay, c-myc, p53, and ctnnb1 expression profile in lymphocytes) endpoints were assessed at the start and at the end of the study. No adverse clinical effects or increase of liver injury markers were reported in the treatment group. The frequency of micronuclei [Mean Ratio (MR) = 1.01, 95% Confidence Intervals (95% CI) 0.86-1.18), and DNA breaks (comet assay) (MR = 0.91; 95% CI 0.58-1.43), did not differ in the two study groups. No significant difference was found in the expression profile of the three genes investigated. None of the markers investigated revealed a higher risk in the treatment group, supporting the safety of IDN 5933 at doses prescribed and for duration of six months. ClinicalTrials.gov Identifier: NCT03004508 , December 20, 2016. Trial retrospectively registered.

Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

PubMed Central

Saulnier Sholler, Giselle L; Bond, Jeffrey P; Bergendahl, Genevieve; Dutta, Akshita; Dragon, Julie; Neville, Kathleen; Ferguson, William; Roberts, William; Eslin, Don; Kraveka, Jacqueline; Kaplan, Joel; Mitchell, Deanna; Parikh, Nehal; Merchant, Melinda; Ashikaga, Takamaru; Hanna, Gina; Lescault, Pamela Jean; Siniard, Ashley; Corneveaux, Jason; Huentelman, Matthew; Trent, Jeffrey

2015-01-01

The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients. PMID:25720842

Prediction of clinical behaviour and treatment for cancers.

PubMed

Futschik, Matthias E; Sullivan, Mike; Reeve, Anthony; Kasabov, Nikola

2003-01-01

Prediction of clinical behaviour and treatment for cancers is based on the integration of clinical and pathological parameters. Recent reports have demonstrated that gene expression profiling provides a powerful new approach for determining disease outcome. If clinical and microarray data each contain independent information then it should be possible to combine these datasets to gain more accurate prognostic information. Here, we have used existing clinical information and microarray data to generate a combined prognostic model for outcome prediction for diffuse large B-cell lymphoma (DLBCL). A prediction accuracy of 87.5% was achieved. This constitutes a significant improvement compared to the previously most accurate prognostic model with an accuracy of 77.6%. The model introduced here may be generally applicable to the combination of various types of molecular and clinical data for improving medical decision support systems and individualising patient care.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy

PubMed Central

Byron, Sara A.; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A.; Carpten, John D.; Craig, David W.; Whitsett, Timothy G.

2017-01-01

Background Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Methods Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Conclusions Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes. PMID:28586388

American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

PubMed Central

Burstein, Harold J.; Prestrud, Ann Alexis; Seidenfeld, Jerome; Anderson, Holly; Buchholz, Thomas A.; Davidson, Nancy E.; Gelmon, Karen E.; Giordano, Sharon H.; Hudis, Clifford A.; Malin, Jennifer; Mamounas, Eleftherios P.; Rowden, Diana; Solky, Alexander J.; Sowers, MaryFran R.; Stearns, Vered; Winer, Eric P.; Somerfield, Mark R.; Griggs, Jennifer J.

2010-01-01

Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy. PMID:20625130

Hay fever & homeopathy: a case series evaluation.

PubMed

Pandey, Vinita

2016-05-01

Seasonal allergic rhinitis (hay fever) is common and can considerably reduce the quality of life of sufferers. Despite the wide everyday application and promising results with homeopathy, scientific evidence of its effectiveness for most ailments is scarce. The assessment of the clinical effectiveness of homeopathic remedies in the alleviation of hay fever symptoms in a typical clinical setting. We performed a clinical observational study of eight patients in the treatment of hay fever symptoms over a two-year period (2012 and 2013) using Measure Yourself Medical Outcome Profile (MYMOP) self-evaluation questionnaires at baseline and again after two weeks and four weeks of homeopathic treatment. The individualized prescription - either a single remedy or multiple remedies - was based on the totality of each patient's symptoms. The average MYMOP scores for the eyes, nose, activity and wellbeing had improved significantly after two and four weeks of homeopathic treatment. The overall average MYMOP profile score at baseline was 3.83 (standard deviation, SD, 0.78). After 14 and 28 days of treatment the average score had fallen to 1.14 (SD, 0.36; P<0.001) and 1.06 (SD, 0.25; P<0.001) respectively. Individualized homeopathic treatment was associated with significant alleviation of hay fever symptoms, enabling the reduction in use of conventional treatment. The results presented in this study can be considered as a step towards a pilot pragmatic study that would use more robust outcome measures and include a larger number of patients prescribed a single or a multiple homeopathic prescription on an individualized basis. Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Genomics of NSCLC patients both affirm PD-L1 expression and predict their clinical responses to anti-PD-1 immunotherapy.

PubMed

Brogden, Kim A; Parashar, Deepak; Hallier, Andrea R; Braun, Terry; Qian, Fang; Rizvi, Naiyer A; Bossler, Aaron D; Milhem, Mohammed M; Chan, Timothy A; Abbasi, Taher; Vali, Shireen

2018-02-27

Programmed Death Ligand 1 (PD-L1) is a co-stimulatory and immune checkpoint protein. PD-L1 expression in non-small cell lung cancers (NSCLC) is a hallmark of adaptive resistance and its expression is often used to predict the outcome of Programmed Death 1 (PD-1) and PD-L1 immunotherapy treatments. However, clinical benefits do not occur in all patients and new approaches are needed to assist in selecting patients for PD-1 or PD-L1 immunotherapies. Here, we hypothesized that patient tumor cell genomics influenced cell signaling and expression of PD-L1, chemokines, and immunosuppressive molecules and these profiles could be used to predict patient clinical responses. We used a recent dataset from NSCLC patients treated with pembrolizumab. Deleterious gene mutational profiles in patient exomes were identified and annotated into a cancer network to create NSCLC patient-specific predictive computational simulation models. Validation checks were performed on the cancer network, simulation model predictions, and PD-1 match rates between patient-specific predicted and clinical responses. Expression profiles of these 24 chemokines and immunosuppressive molecules were used to identify patients who would or would not respond to PD-1 immunotherapy. PD-L1 expression alone was not sufficient to predict which patients would or would not respond to PD-1 immunotherapy. Adding chemokine and immunosuppressive molecule expression profiles allowed patient models to achieve a greater than 85.0% predictive correlation among predicted and reported patient clinical responses. Our results suggested that chemokine and immunosuppressive molecule expression profiles can be used to accurately predict clinical responses thus differentiating among patients who would and would not benefit from PD-1 or PD-L1 immunotherapies.

Clinical utility of gene expression profiling data for clinical decision-making regarding adjuvant therapy in early stage, node-negative breast cancer: a case report.

PubMed

Schuster, Steven R; Pockaj, Barbara A; Bothe, Mary R; David, Paru S; Northfelt, Donald W

2012-09-10

Breast cancer is the most common malignancy among women in the United States with the second highest incidence of cancer-related death following lung cancer. The decision-making process regarding adjuvant therapy is a time intensive dialogue between the patient and her oncologist. There are multiple tools that help individualize the treatment options for a patient. Population-based analysis with Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used tools in patients with early stage, node-negative breast cancer. This case report illustrates a situation in which the population-based prognostic and predictive information differed dramatically from that obtained from genomic profiling and affected the patient's decision. In light of this case, we discuss the benefits and limitations of these tools.

Enteric fever in Mumbai--clinical profile, sensitivity patterns and response to antimicrobials.

PubMed

Jog, S; Soman, R; Singhal, T; Rodrigues, C; Mehta, A; Dastur, F D

2008-04-01

Enteric fever is endemic in Mumbai and its diagnosis poses several problems. Our main aim was to study the clinical profile, haematological features of culture proven typhoid cases, the antimicrobial susceptibility pattern of the isolates and the time to defervescence with the treatment received. This was a retospective chart review of all cases of culture proven enteric fever carried out at a tertiary care private hospital in Mumbai over the period January 2003 to September 2005. Culture positivity in our study was 52.6%. Sixty one percent of the isolates were Salmonella typhi while 39% were Salmonella paratyphi A. An absolute eosinopenia was seen in 76.9% of the patients. Before being admitted to the hospital, 46.2% received antibiotics. The mean time to defervescence in patients who received prior antibiotics was 4.5 days while that in those who did not receive prior antibiotics was 5.1 days. A high culture positivity despite prior or ongoing antibiotic treatment was seen. Absolute eosinophil count of 0% could be an important marker of typhoid. High prevalence of nalidixic acid resistance, a marker of resistance to fluoroquinolones was observed. Combination treatment was not found to be superior to treatment with a single antibiotic.

Transient hyperthyroidism of hyperemesis gravidarum.

PubMed

Tan, Jackie Y L; Loh, Keh Chuan; Yeo, George S H; Chee, Yam Cheng

2002-06-01

To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. Prospective observational study. Hospital inpatient gynaecological ward. Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

Finding Success in Failure: Using Latent Profile Analysis to Examine Heterogeneity in Psychosocial Functioning among Heavy Drinkers Following Treatment

PubMed Central

Wilson, Adam D.; Bravo, Adrian J.; Witkiewitz, Katie

2016-01-01

Aims To estimate differences in post-treatment psychosocial functioning among treatment “failures” (i.e., heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials, and to compare these levels of functioning to those of the purported treatment “successes” (i.e., non-heavy drinkers). Design Separate latent profile analyses of data from COMBINE and Project MATCH, comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. Setting Eleven U.S. academic sites in COMBINE, 27 U.S. treatment sites local to nine research sites in Project MATCH. Participants 962 individuals in COMBINE (69% male, 77% white, mean age: 44 years) treated January 2001 to January 2004 and 1,528 individuals in Project MATCH (75% male, 80% white, mean age: 40 years) treated April 1991 to September 1994. Measurements In COMBINE, we analyzed health, quality of life, mental health symptoms, and alcohol consequences 12-months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms, and alcohol consequences 15-months post-baseline. Findings Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment “failures,” characterized by high-functioning, average-functioning, and low-functioning individuals. The high-functioning treatment “failures” were generally performing better across measures of psychosocial functioning at follow-up than participants designated treatment “successes” by virtue of being abstainers or light drinkers. Conclusions Current Food and Drug Administration guidance to use heavy drinking as indicative of treatment “failure” fails to take into account substantial psychosocial improvements made by individuals who continue to occasionally drink heavily post-treatment. PMID:27367263

A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis.

PubMed

Poole, Michael; Anon, Jack; Paglia, Margaret; Xiang, Jim; Khashab, Mohammed; Kahn, James

2006-01-01

Compare two dosage strengths of levofloxacin in the treatment of acute bacterial sinusitis. Multicenter clinical trial comparing levofloxacin 750 mg for 5 days vs levofloxacin 500 mg for 10 days. Sinus fluid samples were obtained by antral puncture (59.2%) or by sinus endoscopy (40.8%). Among microbiologically evaluable patients, 91.4% (139/152) of patients receiving levofloxacin 750 mg achieved clinical success vs 88.6% (132/149) of patients receiving levofloxacin 500 mg (95% CI -10.0, 4.2). Clinical success rates by pathogen were above 90% in both treatment groups for the 3 typical pathogens of acute sinusitis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The safety profile of the 2 dosage strengths was similar. Levofloxacin 750 mg for 5 days is noninferior to levofloxacin 500 mg for 10 days. Levofloxacin 750 mg for 5 days represents a safe and effective treatment regimen for acute bacterial sinusitis. A-1b.

Liquid chromatography/mass spectrometry-based plasma metabolic profiling study of escitalopram in subjects with major depressive disorder.

PubMed

Bandu, Raju; Lee, Hyun Jeong; Lee, Hyeong Min; Ha, Tae Hyon; Lee, Heon-Jeong; Kim, Se Joo; Ha, Kyooseob; Kim, Kwang Pyo

2018-05-01

Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma metabolite profiles in major depressive disorder patients treated with escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17-item Hamilton Depression Rating Scale. Metabolic profiles were derived from major depressive disorder subject blood samples collected after ECTP treatment. Blood plasma was separated and processed in order to effectively extract metabolites, which were then analyzed using LC-MS. We identified 19 metabolites and elucidated their structures using LC-tandem MS (LC-MS/MS) combined with elemental compositions derived from accurate mass measurements. We further used online H/D exchange experiments to verify the structural elucidations of each metabolite. Identifying molecular metabolites may provide critical insights into the pharmacological and clinical effects of ECTP treatment and may also provide useful information informing the development of new antidepressant treatments. These detailed plasma metabolite analyses may also be used to identify optimal dose concentrations in psychopharmacotherapeutic treatment through drug monitoring, as well as forming the basis for response predictions in depressed subjects. Copyright © 2018 John Wiley & Sons, Ltd.

Bariatric Arterial Embolization for Obesity: A Review of Early Clinical Evidence.

PubMed

Zhong, Bin-Yan; Abiola, Godwin; Weiss, Clifford R

2018-06-05

Obesity is a worldwide public health epidemic that leads to increased morbidity, mortality, and cost burden to health care. Although bariatric surgery has been recognized as a standard invasive treatment for obesity, it is accompanied by relatively high morbidity and cost burden, as well as limited treatment outcome. Therefore, alternative treatments with lower morbidity and cost for surgery that target patients who are obese, but not morbidly obese, are needed. A minimally invasive trans-catheter procedure, named bariatric arterial embolization or bariatric embolization (BAE), has been identified as a potential solution, based on its safety and preliminary efficacy profiles. The purpose of this review is to introduce up-to-date clinical data and discuss future directions for BAE for the treatment of obesity.

Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City

PubMed Central

Martinez-Orozco, Jose Arturo; Nuñez-Luna, Blanca A; Narváez-Diaz, Luis A; Pilar, Mariela Segura-Del; Mujica-Sanchez, Mario; Salazar-Lezama, Miguel Angel; Mireles-Davalos, Christian D

2017-01-01

Abstract Background Drug resistance tuberculosis, specially MDR and XDR are a big challenge for diagnosis and treatment. In Mexico the prevalence of MDR is between 3–5%, a number probably underestimated due to lack of diagnostic tests for susceptibility. The National Institute of Respiratory Diseases in Mexico City is the national referral center for MDR/XDR tuberculosis. In our country there is no data about the gene mutations involved in drug resistance to first line antituberculosis treatment nor the clinical characteristics that accompany these findings. Objective: Evaluate the prevalence of genotyping profiles according to a line probe assay (LPA) in patients with drug resistance tuberculosis and their associated clinical characteristics Methods Retrospective cohort from 2010 to 2014 of M. tuberculosis isolates with any type of resistance to first line antituberculosis drugs identified by MGIT SIRE and in which GenoType MTBDRplus/sl were performed, we evaluate prevalence of genotyping profiles according to the LPA within the isolates and gather data from those with complete medical records to asses clinical characteristics. Results In 52 and 33 isolates phenotyping and genotyping MTBDRplus/sl respectively were performed, 41 resistant to Isoniazid INH with 75% genotypic concordance, 33 resistant to rifampicin RIF with 75.6% concordance, 14 to streptomycin SM with 23% concordance and 10 to ethambutol EMB with 100% concordance, 54% MDR tuberculosis. The genotyping profile for RIF was absence of probes rpoB Wild Type 8 (WT) 57.7%, WT 7 30.8% and presence of rpoB mutation 3 (MUT) 19.2%. For INH absence of InhA WT2 48.1% and InhA WT1 19.2%. For EMB absence of embB WT1 30.8% and for SM absence of rrs WT1 (19%). Absence of InhA WT1 was associated with female (P = 0.01) and DM2 (P = 0.032) patients, other clinical/biochemical characteristics and mortality was not different in patients with o without the genotypic profile for each drug. Cavitary disease by CT was more frequent in patients with WT probe absence in RIF and INH than those who did not have a LPA suggestive of resistance for this drugs. Conclusion Wild Type probe absense is the frequent finding in our isolates according to LPA in RIF, INH, EMB and SM, intrisic host factors and clinical characteristics seem not to be related to a particular resistant gene profile. Disclosures All authors: No reported disclosures.

Childhood leprosy: a retrospective descriptive study from Government Medical College, Kozhikode, Kerala, India.

PubMed

Sasidharanpillai, Sarita; Binitha, Manikoth Payyanadan; Riyaz, Najeeba; Ambooken, Betsy; Mariyath, Olasseri Kalathingal Reena; George, Biju; Janardhanan, Anisha Kanhirangattil; Sherjeena, Pentam Veli Beegum

2014-06-01

To assess the profile and describe the clinical presentations and complications of childhood leprosy in a tertiary care hospital in North Kerala, South India during 2003-2012 and to analyse any change in the age-sex profile and the clinical pattern of leprosy in children below the age of 15 years over the 10-year study period. A retrospective descriptive study of children less than 15 years of age diagnosed with leprosy and registered for treatment in a tertiary care institution from 2003 to 2012. Demographic, clinical, investigative and treatment data were collected using a pre-set proforma. 138 (12.1%) of the total 1143 leprosy cases registered for treatment during the 10-year period were below 15 years of age. The 10-year study period witnessed a statistically insignificant decrease in the new childhood leprosy cases registered for treatment in our tertiary care institution. The majority of cases belonged to the 6-12 year age group (61.6%) with a male predominance. Borderline tuberculoid (BT) was the commonest clinical type (65.9%) followed by indeterminate leprosy (18.8%); 101 patients required paucibacillary (PB) and 37 needed multibacillary (MB) treatment. The number of patients requiring MB treatment showed a statistically significant increase and there was a significant decline in number of cases requiring PB treatment. During the entire study period no Type 2 lepra reaction was documented in patients below Hema 15 years and only two patients manifested Type 1 reaction. Ten (7.2%) out of the 138 patients were cases of relapse. There was a clear female predilection among relapse cases with the majority belonging to the adolescent age. Childhood leprosy still contributes to a significant proportion of the total case load denoting the continuing active horizontal transmission of leprosy. The rise in number of patients with more extensive disease in the background of declining disease prevalence is suggestive of the delay in diagnosis and treatment. A high relapse rate noted in the present study may be due to incorrect classification and treatment of MB as PB leprosy which in turn might have resulted in treatment failure due to inadequate treatment.

Precision medicine in colorectal cancer: the molecular profile alters treatment strategies.

PubMed

Tran, Nguyen H; Cavalcante, Ludmila L; Lubner, Sam J; Mulkerin, Daniel L; LoConte, Noelle K; Clipson, Linda; Matkowskyj, Kristina A; Deming, Dustin A

2015-09-01

When considering treatment options for patients with metastatic colorectal cancer (mCRC), molecular profiling has become a pivotal component in guiding clinical decisions. FOLFOX and FOLFIRI (fluorouracuil, leucovorin plus oxaliplatin or ininotecan, respectively) are the standard base regimens used for the treatment of mCRC. Biologic agents, such as the epidermal growth factor receptor (EGFR) targeted therapies, cetuximab and panitumumab and the vascular endothelial growth factor monoclonal antibody, bevacizumab, are safe and effective in the first-line setting. The most efficacious use of these agents in terms of timing and selection of the right patient population continues to be debated. Here we review multiple investigations into the effectiveness of treatment options as a function of the mutations present in colon cancers. Early studies have reported that KRAS mutations at exon 2 predict resistance to EGFR targeted therapies. More recently the data have expanded to include KRAS mutations at exons 3 and 4 and NRAS mutations at exons 2, 3 and 4 as well as other biomarkers including BRAF and PIK3CA, leading to the evolution of the treatment of mCRC to a more precision-based approach. As our understanding of relevant biomarkers increases, and data from both molecular profiling and treatment response become more readily available, treatment options will become more precise and their outcomes more effective.

Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.

PubMed

De Rycker, Manu; Thomas, John; Riley, Jennifer; Brough, Stephen J; Miles, Tim J; Gray, David W

2016-04-01

Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.

Imaging technique for the complete edentulous patient treated conventionally or with mini implant overdenture

PubMed Central

Meleşcanu Imre, M; Preoteasa, E; Țâncu, AM; Preoteasa, CT

2013-01-01

Rationale. The imaging methods are more and more used in the clinical process of modern dentistry. Once the implant based treatment alternatives are nowadays seen as being the standard of care in edentulous patients, these techniques must be integrated in the complete denture treatment. Aim. The study presents some evaluation techniques for the edentulous patient treated by conventional dentures or mini dental implants (mini SKY Bredent) overdentures, using the profile teleradiography. These offer data useful for an optimal positioning of the artificial teeth and the mini dental implants, favoring to obtain an esthetic and functional treatment outcome. We proposed also a method to conceive a simple surgical guide that allows the prosthetically driven implants placement. Material and method. Clinical case reports were made, highlighting the importance of cephalometric evaluation on lateral teleradiographs in complete edentulous patients. A clinical case that gradually reports the surgical guide preparation (Bredent silicon radio opaque), in order to place the mini dental implants in the best prosthetic and anatomic conditions, was presented. Conclusions. The profile teleradiograph is a useful tool for the practitioner. It allows establishing the optimal site for implant placement, in a good relation with the overdenture. The conventional denture can be easily and relatively costless transformed in a surgical guide used during implant placement. PMID:23599828

Global absenteeism and presenteeism in mental health patients referred through primary care.

PubMed

Bailey, S Kathleen; Haggarty, John; Kelly, Sara

2015-01-01

Disability from mental health (MH) symptoms impairs workers' functioning. Most of what is known about the MH of workers relates to their experiences after intervention or work absence. To profile the clinical symptoms, self-reported absenteeism and presenteeism and treatment response of workers with MH symptoms at the point of accessing MH care and compare the characteristics of patients referred with or without problems related to work. Analysis of 11 years of patient data collected in a Shared Mental Health Care (SMHC) clinic referred within a primary care setting in Ontario, Canada. Multiple regression with MH disorders was used to predict absenteeism and presenteeism. Absenteeism and presenteeism were assessed using the 12-item self-administered version of the WHO-DAS 2. Symptom profiles were assessed with the Patient Health Questionnaire (PHQ). Some psychiatric disorders (depression, somatization, anxiety) contributed more to predicting absenteeism and presenteeism than others. Patients referred with work-related problems differed from the general SMHC population in terms of sex and type and number of symptoms. Treatment response was good in both groups after a mean of three treatment visits. Patients with work-related mental health complaints formed a distinct clinical group that benefitted equally from the intervention(s) provided by SMHC.

Clinical profile, treatment and survival outcomes of peadiatric germ cell tumours: A Pakistani perspective.

PubMed

Islam Nasir, Irfan Ul; Ashraf, Muhammad Ijaz; Ahmed, Nouman; Shah, Muhammad Fahd; Pirzada, Muhammad Taqi; Syed, Amir Ali; Qazi, Abid Quddus

2016-10-01

Germ Cell Tumours (GCTs) are rare tumours. Generally 80% are benign and 20% malignant with a bimodal age distribution. The retrospective study was conducted at Shaukat Khanum Cancer Hospital, Lahore, Pakistan, and comprised all paediatric patients below 18 years of age who received treatment for histology-proven GCT from 2006 to 2014. Of the 207 patients, 98(42.3%) were males and 109(52.7%) were females. The most common GCT was yolk sac tumour in 90(43.5%) children followed by mixed GCT in 40(19.3%) and dysgerminoma in 34(16.4%). Gonads were most commonly involved in 165(79.7%) patients with metastasis in 24(11.6%) at presentation and recurrence in 26(12.5%) patients. Overall, 133(64.3%) patients are well and followed up at regular intervals and 55(26.5%) have been lost to follow-up with an expected overall 5-year median survival of 45%. Despite the distinct clinical profile of paediatric GCT, survival can be improved by early diagnosis, regimented treatment according to set guidelines, protocols and by improving follow-up.

The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity

PubMed Central

Tubman, Venée N.; Mejia, Pedro; Shmukler, Boris E.; Bei, Amy K.; Alper, Seth L.; Mitchell, James R.

2015-01-01

Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development. PMID:26459896

Clinical needs of in-treatment pregnant women with co-occurring disorders: implications for primary care.

PubMed

Lee King, Patricia A; Duan, Lei; Amaro, Hortensia

2015-01-01

We investigated social vulnerability and behavioral health clinical profiles (symptom severity) of pregnant women with co-occurring disorders, defined as substance abuse, mental illness, and trauma at treatment entry compared to their nonpregnant counterparts and the role of interpersonal abuse in clinical presentation among pregnant women. Our objective was to provide primary health care providers with insight into the needs of pregnant patients with high behavioral health risks to serve them better during the critical window of opportunity for long-term impact. We conducted cross-sectional secondary analysis of baseline data from women enrolled in treatment programs in the Women, Co-occurring Disorders and Violence Study from nine sites across the United States. We used analysis of variance and Cochran-Mantel-Haenszel statistical analyses to compare means and frequencies of social vulnerability indicators and baseline Addiction Severity Index, Brief Symptom Inventory of mental health, and Posttraumatic Stress Diagnostic Scale scores between 152 pregnant and 2,577 nonpregnant women, and between pregnant women with and without current interpersonal abuse. Compared to nonpregnant women, pregnant women evidenced more social vulnerability but better behavioral health clinical profiles at treatment entry. Current interpersonal abuse was associated with increased mental health and trauma symptomatology but not with alcohol or drug abuse severity among pregnant women. The prenatal period is an important time for screening and intervention for factors such as social vulnerability and co-occurring disorders, known to affect pregnancy and infant outcomes; social and behavioral health services are particularly essential among pregnant women with co-occurring disorders.

Addition of pimecrolimus cream 1% to a topical corticosteroid treatment regimen in paediatric patients with severe atopic dermatitis: a randomized, double-blind trial.

PubMed

Meurer, Michael; Eichenfield, Lawrence F; Ho, Vincent; Potter, Paul C; Werfel, Thomas; Hultsch, Thomas

2010-05-01

Pimecrolimus and topical corticosteroids (TCS) combination therapy may provide an alternative treatment for patients with severe atopic dermatitis (AD), with faster clearance of disease flares, consequently reducing the duration of TCS treatment. To assess the safety profile of pimecrolimus cream 1% combined with fluticasone versus fluticasone alone in paediatric patients with severe AD. Patients (n = 376) were randomized to a combination of pimecrolimus cream 1% with fluticasone or vehicle plus fluticasone for 4 weeks. The primary outcome measure was the frequency of clinically relevant pre-defined adverse events (AEs) associated with the topical use of corticosteroids in patients with severe AD. Erythematous rash was the only AE, occurring more frequently in the combination group, while there were no noticeable differences in the frequency of other AEs of clinical interest between treatment groups. Efficacy variables were comparable between the two groups. A trend for greater time to relapse was observed for the combination of pimecrolimus cream 1% with fluticasone in patients who were clear at the end of treatment, with a marked improvement in facial AD. In paediatric patients with severe AD the overall safety profile of pimecrolimus cream 1% combined with fluticasone was similar to that of fluticasone alone.

Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection.

PubMed

Koizumi, Yoshiki; Ohashi, Hirofumi; Nakajima, Syo; Tanaka, Yasuhito; Wakita, Takaji; Perelson, Alan S; Iwami, Shingo; Watashi, Koichi

2017-02-21

With the introduction of direct-acting antivirals (DAAs), treatment against hepatitis C virus (HCV) has significantly improved. To manage and control this worldwide infectious disease better, the "best" multidrug treatment is demanded based on scientific evidence. However, there is no method available that systematically quantifies and compares the antiviral efficacy and drug-resistance profiles of drug combinations. Based on experimental anti-HCV profiles in a cell culture system, we quantified the instantaneous inhibitory potential (IIP), which is the logarithm of the reduction in viral replication events, for both single drugs and multiple-drug combinations. From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. We also compared intrinsic antiviral activities of a panel of drug combinations. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials.

Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

NASA Astrophysics Data System (ADS)

Lok, Edwin

Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Denosumab for the Treatment of Osteoporosis

PubMed Central

Zaheer, Sarah; LeBoff, Meryl; Lewiecki, E. Michael

2015-01-01

Introduction Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile. Areas covered This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date. Expert Opinion Denosumab is an efficacious and safe osteoporosis treatment option, with current data up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab. PMID:25614274

Prospects of poisoning - a multi facet study.

PubMed

Mishra, Pradeep K; Kulkarni, Rashmi; Sane, Mandar R; Deshpande, Ajit; Kushwah, Manish

2016-01-01

Aim of the study is to find out demographic profile, clinical characteristics and analysis of poison in clinical set up. The study carried out in Sri Aurobindo Medical College and PG Institute Indore, Madhya Pradesh. Total 75 cases of poisoning were studied for demographic profile, vitals (BP, pulse, heart rate, pupils, etc.), clinical features (such as vomiting, salivation, consciousness, etc.), type of poison and its analysis. Results: Poisoning was more common in cases between 15 and 25 years of age, in males than in females and in Hindu religion. Poisoning cases were predominantly from rural areas and in married people. Majority of cases were discharged after proper treatment and counseling. Altered vitals and clinical features were found in most of the cases. Organophosphate and aluminum phosphide compound were evaluated in most of the cases. Conclusions: Preventive measures should be applied through educating people, proper counseling, promoting poison information centers, and introducing separate toxicological units in hospitals.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

PubMed Central

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. PMID:28740389

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity.

PubMed

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD.

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

PubMed

Grob, Charles S; Danforth, Alicia L; Chopra, Gurpreet S; Hagerty, Marycie; McKay, Charles R; Halberstadt, Adam L; Greer, George R

2011-01-01

Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. A clinical research unit within a large public sector academic medical center. Twelve adults with advanced-stage cancer and anxiety. In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. clinicaltrials.gov Identifier: NCT00302744.

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray

PubMed Central

Etges, Tilden; Karolia, Kari; Grint, Thomas; Taylor, Adam; Lauder, Heather; Daka, Brian; Wright, Stephen

2016-01-01

The global exposure of Sativex® (Δ9-tetrahydrocannabinol [THC]:cannabidiol [CBD], nabiximols) is estimated to be above 45,000 patient-years since it was given marketing approval for treating treatment-resistant spasticity in multiple sclerosis (MS). An observational registry to collect safety data from patients receiving THC:CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice. Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients’ use of THC:CBD, clinically significant adverse events (AEs), and special interest events. The Registry contains data from 941 patients with 2,213.98 patient-years of exposure. Within this cohort, 60% were reported as continuing treatment, while 83% were reported as benefiting from the treatment. Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs. Psychiatric AEs of clinical significance were reported in 6% of the patients, 6% reported falls requiring medical attention, and suicidality was reported in 2%. Driving ability was reported to have worsened in 2% of patients, but improved in 7%. AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness (2.3%) and fatigue (1.7%). There were no signals to indicate abuse, diversion, or dependence. The long-term risk profile from the Registry is consistent with the known (labeled) safety profile of THC:CBD, and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity. No evidence of new long-term safety concerns has emerged. PMID:27956834

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray.

PubMed

Etges, Tilden; Karolia, Kari; Grint, Thomas; Taylor, Adam; Lauder, Heather; Daka, Brian; Wright, Stephen

2016-01-01

The global exposure of Sativex ® (Δ 9 -tetrahydrocannabinol [THC]:cannabidiol [CBD], nabiximols) is estimated to be above 45,000 patient-years since it was given marketing approval for treating treatment-resistant spasticity in multiple sclerosis (MS). An observational registry to collect safety data from patients receiving THC:CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice. Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients' use of THC:CBD, clinically significant adverse events (AEs), and special interest events. The Registry contains data from 941 patients with 2,213.98 patient-years of exposure. Within this cohort, 60% were reported as continuing treatment, while 83% were reported as benefiting from the treatment. Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs. Psychiatric AEs of clinical significance were reported in 6% of the patients, 6% reported falls requiring medical attention, and suicidality was reported in 2%. Driving ability was reported to have worsened in 2% of patients, but improved in 7%. AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness (2.3%) and fatigue (1.7%). There were no signals to indicate abuse, diversion, or dependence. The long-term risk profile from the Registry is consistent with the known (labeled) safety profile of THC:CBD, and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity. No evidence of new long-term safety concerns has emerged.

Use of treatment algorithms for depression.

PubMed

Trivedi, Madhukar H; Fava, Maurizio; Marangell, Lauren B; Osser, David N; Shelton, Richard C

2006-01-01

Depression continues to be a treatment challenge for many physicians-psychiatrists and primary care physicians alike-in part because of the nature of the disorder, but also because of the wide variety of medications and other treatments available, each with a distinct efficacy and safety profile. One way of negotiating treatment decisions is to use treatment guidelines and algorithms. This Commentary, which appears in the September 2006 issue of The Journal of Clinical Psychiatry (2006;67:1458-1465), provides the primary care clinician with insight into the pros and cons of using treatment algorithms to guide the treatment of depression. -Larry Culpepper, M.D.

Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma.

PubMed

Daud, Adil; Soon, Christopher; Dummer, Reinhard; Eggermont, Alexander M M; Hwu, Wen-Jen; Grob, Jean Jacques; Garbe, Claus; Hauschild, Axel

2012-08-01

Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.

Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer

PubMed Central

Scholz, Arne; Lienau, Philip; Siemeister, Gerhard; Kosemund, Dirk; Bohlmann, Rolf; Briem, Hans; Terebesi, Ildiko; Meyer, Kirstin; Prelle, Katja; Denner, Karsten; Bömer, Ulf; Schäfer, Martina; Eis, Knut; Valencia, Ray; Ince, Stuart; von Nussbaum, Franz; Mumberg, Dominik; Ziegelbauer, Karl; Klebl, Bert; Choidas, Axel; Nussbaumer, Peter; Baumann, Matthias; Schultz‐Fademrecht, Carsten; Rühter, Gerd; Eickhoff, Jan; Brands, Michael

2017-01-01

Abstract Selective inhibition of exclusively transcription‐regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY‐958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited the best overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAY 1143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer. PMID:28961375

Incidence, Clinical Correlates and Treatment Effect of Rage in Anxious Children

PubMed Central

Salloum, Alison; De Nadai, Alessandro S.; McBride, Nicole; Crawford, Erika A.; Lewin, Adam B.; Storch, Eric A.

2015-01-01

Episodic rage represents an important and underappreciated clinical feature in pediatric anxiety. This study examined the incidence and clinical correlates of rage in children with anxiety disorders. Change in rage during treatment for anxiety was also examined. Participants consisted of 107 children diagnosed with an anxiety disorder and their parents. Participants completed structured clinical interviews and questionnaire measures to assess rage, anxiety, functional impairment, family accommodation and caregiver strain, as well as the quality of the child's relationship with family and peers. Rage was a common feature amongst children with anxiety disorders. Rage was associated with a more severe clinical profile, including increased anxiety severity, functional impairment, family accommodation and caregiver strain, as well as poorer relationships with parents, siblings, extended family and peers. Rage was more common in children with separation anxiety, comorbid anxiety, attention deficit/hyperactivity disorder and behavioral disorders, but not depressive symptoms. Rage predicted higher levels of functional impairment, beyond the effect of anxiety severity. Rage severity reduced over treatment in line with changes in anxiety symptoms. Findings suggest that rage is a marker of greater psychopathology in anxious youth. Standard cognitive behavioral treatment for anxiety appears to reduce rage without adjunctive treatment. PMID:26235476

End points and assessments in esthetic dental treatment.

PubMed

Ishida, Yuichi; Fujimoto, Keiko; Higaki, Nobuaki; Goto, Takaharu; Ichikawa, Tetsuo

2015-10-01

There are two key considerations for successful esthetic dental treatments. This article systematically describes the two key considerations: the end points of esthetic dental treatments and assessments of esthetic outcomes, which are also important for acquiring clinical skill in esthetic dental treatments. The end point and assessment of esthetic dental treatment were discussed through literature reviews and clinical practices. Before designing a treatment plan, the end point of dental treatment should be established. The section entitled "End point of esthetic dental treatment" discusses treatments for maxillary anterior teeth and the restoration of facial profile with prostheses. The process of assessing treatment outcomes entitled "Assessments of esthetic dental treatment" discusses objective and subjective evaluation methods. Practitioners should reach an agreement regarding desired end points with patients through medical interviews, and continuing improvements and developments of esthetic assessments are required to raise the therapeutic level of esthetic dental treatments. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt−/− Mouse Model of Preeclampsia/Fetal Growth Restriction

PubMed Central

Stanley, Joanna L.; Sulek, Karolina; Andersson, Irene J.; Davidge, Sandra T.; Kenny, Louise C.; Sibley, Colin P.; Mandal, Rupasri; Wishart, David S.; Broadhurst, David I.; Baker, Philip N.

2015-01-01

Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT−/−) and endothelial nitric oxide synthase (Nos3−/−) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT−/− mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3−/−, COMT−/− and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3−/− and C57BL/6J mice (p < 0.05) and in 18 metabolites between C57BL/6J and COMT−/− mice (p < 0.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p < 0.05) remained in COMT−/− mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT−/− mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action. PMID:26667607

Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system.

PubMed

Salmen, A; Gold, R; Chan, A

2014-05-01

The therapeutic armamentarium for autoimmune diseases of the central nervous system, specifically multiple sclerosis and neuromyelitis optica, is steadily increasing, with a large spectrum of immunomodulatory and immunosuppressive agents targeting different mechanisms of the immune system. However, increasingly efficacious treatment options also entail higher potential for severe adverse drug reactions. Especially in cases failing first-line treatment, thorough evaluation of the risk-benefit profile of treatment alternatives is necessary. This argues for the need of algorithms to identify patients more likely to benefit from a specific treatment. Moreover, paradigms to stratify the risk for severe adverse drug reactions need to be established. In addition to clinical/paraclinical measures, biomarkers may aid in individualized risk-benefit assessment. A recent example is the routine testing for anti-John Cunningham virus antibodies in natalizumab-treated multiple sclerosis patients to assess the risk for the development of progressive multi-focal leucoencephalopathy. Refined algorithms for individualized risk assessment may also facilitate early initiation of induction treatment schemes in patient groups with high disease activity rather than classical escalation concepts. In this review, we will discuss approaches for individiualized risk-benefit assessment both for newly introduced agents as well as medications with established side-effect profiles. In addition to clinical parameters, we will also focus on biomarkers that may assist in patient selection. © 2013 British Society for Immunology.

Safety of treatment options for spondyloarthritis: a narrative review.

PubMed

D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo

2018-05-01

Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.

Comparison of 2 Zero-Profile Implants in the Treatment of Single-Level Cervical Spondylotic Myelopathy: A Preliminary Clinical Study of Cervical Disc Arthroplasty versus Fusion.

PubMed

Shi, Sheng; Zheng, Shuang; Li, Xin-Feng; Yang, Li-Li; Liu, Zu-De; Yuan, Wen

2016-01-01

Cervical disc arthroplasty (CDA) with Discover prosthesis or anterior cervical discectomy and fusion (ACDF) with Zero-P cage has been widely used in the treatment of cervical spondylotic myelopathy (CSM). However, little is known about the comparison of the 2 zero-profile implants in the treatment of single-level CSM. The aim was to compare the clinical outcomes and radiographic parameters of CDA with Discover prosthesis and ACDF with Zero-P cage for the treatment of single-level CSM. A total of 128 consecutive patients who underwent 1-level CDA with Discover prosthesis or ACDF with Zero-P cage for single-level CSM between September 2009 and December 2012 were included in this study. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI). For radiographic assessment, the overall sagittal alignment (OSA), functional spinal unit (FSU) angle, and range of motion (ROM) at the index and adjacent levels were measured before and after surgery. Additionally, the complications were also recorded. Both treatments significantly improved all clinical parameters (P < 0.05), without statistically relevant differences between the 2 groups. The OSA and FSU angle increased significantly in both groups (P <0.05). Compared with Zero-P group, ROMs at the index levels were well maintained in the Discover group (P < 0.05). However, there were no statistical differences in the ROMs of adjacent levels between the 2 groups (P > 0.05). Besides, no significant differences existed in dysphagia, subsidence, or adjacent disc degeneration between the 2 groups (P > 0.05). However, significant differences occurred in prosthesis migration in CDA group. The results of this study showed that clinical outcomes and radiographic parameters were satisfactory and comparable with the 2 techniques. However, more attention to prosthesis migration of artificial cervical disc should be paid in the postoperative early-term follow-up.

Caspofungin in the treatment of invasive fungal infections.

PubMed

Keady, Simon; Thacker, Meera

2006-02-01

Caspofungin is a member of a new class of antifungals called Echinocandins and is the first to have marketing authorisation in the United Kingdom. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of caspofungin. The article also discusses the warnings and precautions associated with the use of this drug. Caspofungin is an effective treatment option in the management of fungal infections.

Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome.

PubMed

Kriplani, Alka; Periyasamy, Anurekha Janaki; Agarwal, Nutan; Kulshrestha, Vidushi; Kumar, Anand; Ammini, Ariachery Chinnama

2010-08-01

A prospective randomized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives (COC) with desogestrel-containing COC in women with polycystic ovary-syndrome (PCOS) not desirous of child-bearing. Sixty women were randomized into study group [ethinylestradiol (EE) 30 mcg+drospirenone 3 mg] and control group (EE 30 mcg+desogestrel 150 mcg), treated for 6 months and followed up at 1 month, 3 months, 6 months, during treatment and 3 and 6 months post-treatment. Acne and hirsutism scoring, bodyweight, body mass index (BMI), blood pressure (BP), ultrasound parameters, lipid profile, glycemic profile and hormonal profile were compared. Cycles were regular in both groups during treatment. Effect of regular cycles persisted in 44.83% (13/30) vs. 17.24% (5/30) in study vs. control group at 6 months post-treatment with 33.3% decreased hirsutism score in the study group (versus no change in control group) even at 6 months after stopping treatment. With treatment, BMI fell by 0.52 kg/m(2) in the study group; systolic and diastolic BP fell in the study group while it rose in the control group. Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group (p<.05). The study group showed a significant fall in fasting/postprandial blood sugar and insulin and total testosterone against a rise in the control group. In women with PCOS, a drospirenone containing COC has better outcome in terms of persistent regular cycles, antiandrogenic effect, fall in BMI and BP, better lipid profile, favorable glycemic and hormonal profile than desogestrel-containing COC. Copyright 2010 Elsevier Inc. All rights reserved.

Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors.

PubMed

Beswick, Paul; Bingham, Sharon; Bountra, Chas; Brown, Terry; Browning, Kerry; Campbell, Ian; Chessell, Iain; Clayton, Nick; Collins, Sue; Corfield, John; Guntrip, Stephen; Haslam, Claudine; Lambeth, Paul; Lucas, Fiona; Mathews, Neil; Murkit, Graham; Naylor, Alan; Pegg, Neil; Pickup, Elizabeth; Player, Hazel; Price, Helen; Stevens, Alexander; Stratton, Sharon; Wiseman, Joanne

2004-11-01

GW406381 (8), currently undergoing clinical evaluation for the treatment of inflammatory pain is a member of a novel series of 2,3-diaryl-pyrazolo[1,5-b]pyridazine based cyclooxygenase-2 (COX-2) inhibitors, which have been shown to be highly potent and selective. Several examples of the series, in addition to possessing favourable pharmacokinetic profiles and analgesic activity in vivo, have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.

Acquired Methemoglobinemia - A Sporadic Holi Disaster.

PubMed

Masavkar, Sanjeevani Satish; Mauskar, Anupama; Patwardhan, Gaurav; Bhat, Vasudeva; Manglani, Mamta V

2017-06-15

To study clinical profile and outcome in patients with methemoglobinemia following exposure to toxic colors during Holi festival. This retrospective study included 112 children (5 to 12 years) admitted with methemoglobinemia after playing Holi. Clinical and treatment details were reviewed. The common symptoms were giddiness, vomiting and headache. Treatment included thorough skin wash, intravenous fluid and methylene blue in 111 children. Age 7-9 and > 11 years, vomiting, giddiness, cyanosis, PaO2 < 80 mm Hg and oxygen saturation < 95% were associated with higher need for methylene blue. All children had a good outcome. Timely diagnosis and management of acquired methemoglobinemia can save lives.

Active multimodal psychotherapy in children and adolescents with suicidality: description, evaluation and clinical profile.

PubMed

Högberg, Goran; Hällström, Tore

2008-07-01

The aim of this study was to describe and evaluate the clinical pattern of 14 youths with presenting suicidality, to describe an integrative treatment approach, and to estimate therapy effectiveness. Fourteen patients aged 10 to 18 years from a child and adolescent outpatient clinic in Stockholm were followed in a case series. The patients were treated with active multimodal psychotherapy. This consisted of mood charting by mood-maps, psycho-education, wellbeing practice and trauma resolution. Active techniques were psychodrama and body-mind focused techniques including eye movement desensitization and reprocessing. The patients were assessed before treatment, immediately after treatment and at 22 months post treatment with the Global Assessment of Functioning Scale. The clinical pattern of the group was observed. After treatment there was a significant change towards normality in the Global Assessment of Functioning scale both immediately post-treatment and at 22 months. A clinical pattern, post trauma suicidal reaction, was observed with a combination of suicidality, insomnia, bodily symptoms and disturbed mood regulation. We conclude that in the post trauma reaction suicidality might be a presenting symptom in young people. Despite the shortcomings of a case series the results of this study suggest that a mood-map-based multimodal treatment approach with active techniques might be of value in the treatment of children and youth with suicidality.

The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity.

PubMed

Tubman, Venée N; Mejia, Pedro; Shmukler, Boris E; Bei, Amy K; Alper, Seth L; Mitchell, James R; Brugnara, Carlo; Duraisingh, Manoj T

2016-01-01

Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Alteration of metabolite profiling by cold atmospheric plasma treatment in human myeloma cells.

PubMed

Xu, Dehui; Xu, Yujing; Ning, Ning; Cui, Qingjie; Liu, Zhijie; Wang, Xiaohua; Liu, Dingxin; Chen, Hailan; Kong, Michael G

2018-01-01

Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

SU-E-T-149: Electron Beam Profile Differences Between Elekta MLCi2 and Elekta Agility Treatment Heads

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

Wu, C; Hatcher, C

2014-06-01

Purpose: To report and investigate observed differences in electron beam profiles at various energies/applicators between Elekta MLCi2 and Agility treatment head on Elekta Infinity LINAC Methods: When we upgraded from MLCi2 to Agility on one of our Elekta Infinity LINAC's, electron beam PDDs and profiles were acquired for comparison purpose. All clinical electron energies (6/9/12/15/12/18 MeV) and electron applicators (6/10/14/20/25 square) were included in measurement. PDDs were acquired at 100 SSD in water (PTW MP3 water tank) with a plane-parallel ion chamber (PTW Roos). X and Y Profiles were acquired using IC Profiler (Sun Nuclear Corp.) at 1cm and maximummore » PDD depths (water equivalent). Results: All PDD curves match very well between MLCi2 and Agility treatment head. However, some significant differences on electron profiles were found. On Agility, even after increasing the default auto-tracking offset values for backup diaphragms in Y and MLC in X by 2.8 cm (the maximum allowed change is 3.0 cm), electron profiles still have rounder shoulders comparing to corresponding MLCi2 profiles. This difference is significantly more pronounced at larger applicators (20 and 25 square), for all electron energies. Conclusion: The significant design change between MLCi2 and Agility beam limiting device seems to affect exit electron beam profiles. In IEC1217 X direction, the main change on Agility is the removal of the original MLCi2 X backup diaphragms and replacing it with MLC leaves; In Y direction, the main change is the radius and materials on Y backup diaphragms.« less

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples

PubMed Central

Hintzsche, Jennifer; Kim, Jihye; Yadav, Vinod; Amato, Carol; Robinson, Steven E; Seelenfreund, Eric; Shellman, Yiqun; Wisell, Joshua; Applegate, Allison; McCarter, Martin; Box, Neil; Tentler, John; De, Subhajyoti

2016-01-01

Objective Currently, there is a disconnect between finding a patient’s relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. Methods and materials The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. Results IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. Conclusion IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine. IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT. PMID:27026619

IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples.

PubMed

Hintzsche, Jennifer; Kim, Jihye; Yadav, Vinod; Amato, Carol; Robinson, Steven E; Seelenfreund, Eric; Shellman, Yiqun; Wisell, Joshua; Applegate, Allison; McCarter, Martin; Box, Neil; Tentler, John; De, Subhajyoti; Robinson, William A; Tan, Aik Choon

2016-07-01

Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine.IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.

PubMed

Dodick, David W; Turkel, Catherine C; DeGryse, Ronald E; Diener, Hans-Christoph; Lipton, Richard B; Aurora, Sheena K; Nolan, Marissa E; Silberstein, Stephen D

2015-02-01

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial.

PubMed

Inoue, Nagamu; Kobayashi, Kiyonori; Naganuma, Makoto; Hirai, Fumihito; Ozawa, Morio; Arikan, Dilek; Huang, Bidan; Robinson, Anne M; Thakkar, Roopal B; Hibi, Toshifumi

2017-07-01

Intestinal Behçet's disease (BD) is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671). Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs) were examined. The efficacy was assessed on the basis of marked improvement (MI) and complete remission (CR) using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments. Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years). No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively. This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

PubMed Central

Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

2015-01-01

Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response. PMID:26664413

The medicinal use of realgar (As₄S₄) and its recent development as an anticancer agent.

PubMed

Wu, Jinzhu; Shao, Yanbin; Liu, Jialiang; Chen, Gang; Ho, Paul C

2011-06-01

Arsenicals have been known as poisons and paradoxically as therapeutic agents. In the early 1970s, Chinese physicians from Harbin revived the medicinal use of arsenicals as anticancer agents. Notable success was observed in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). The FDA approved ATO injection in the year 2000 for the treatment of APL. In contrast, the clinical use of the other arsenical, realgar (As₄S₄), is currently much less established, though it has also long been used in medical history. According to ancient medical records and recent findings in clinical trials, realgar was found as effective as ATO, but with relatively good oral safety profiles even on chronic administration. These give realgar an advantage over ATO in maintenance treatment. Though there is increasing understanding on the mechanisms of action and metabolic profiles of ATO, similar aspects of realgar are unclear to date. We outline the use of realgar in traditional medicines, especially in traditional Chinese medicines (TCM) from ancient times to present. The clinical and experimental observations on realgar as a therapeutic agent are described with an emphasis on those findings that may imply the rationale and future directions of realgar as a potential anticancer drug candidate. There is an increasing understanding in the mechanisms of action of realgar as an antileukemic agent. However, there is still sparse information on its metabolism and toxicity profiles. Realgar is poorly soluble in water. Recently, several types of realgar nanoparticles (NPs) have been developed. Some of these realgar NPs also possess the unique optical properties of quantum dots. The activities and bioavailability of realgar NPs are much influenced by their sizes, making realgar an interesting biomedical and pharmaceutical research candidate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study.

PubMed

Tagliaferri, Valeria; Romualdi, Daniela; Immediata, Valentina; De Cicco, Simona; Di Florio, Christian; Lanzone, Antonio; Guido, Maurizio

2017-05-01

Due to the central role of metabolic abnormalities in the pathophysiology of polycystic ovary syndrome (PCOS), insulin sensitizing agents have been proposed as a feasible treatment option. To investigate which is the more effective between metformin and myoinositol (MYO) on hormonal, clinical and metabolic parameters in obese patients with PCOS. Crossover randomized controlled study. Thirty-four PCOS obese women (age: 25·62 ± 4·7 years; BMI: 32·55 ± 5·67 kg/m 2 ) were randomized to receive metformin (850 mg twice a day) or MYO (1000 mg twice a day) for 6 months. After a 3 month washout, the same subjects received the other compound for the following 6 months. Ultrasonographic pelvic examinations, hirsutism score, anthropometric and menstrual pattern evaluation, hormonal profile assays, oral glucose tolerance test (OGTT) and lipid profile at baseline and after 6 months of treatment were performed. Both metformin and MYO significantly reduced the insulin response to OGTT and improved insulin sensitivity. Metformin significantly decreased body weight and improved menstrual pattern and Ferriman-Gallwey score. Metformin treatment was also associated with a significant decrease in LH and oestradiol levels, androgens and anti-müllerian hormone levels. None of these clinical and hormonal changes were observed during MYO administration. Both treatments improved the glyco-insulinaemic features of obese PCOS patients, but only metformin seems to exert a beneficial effect on the endocrine and clinical features of the syndrome. © 2017 John Wiley & Sons Ltd.

Biobehavioral pain profile in individuals with chronic spine pain.

PubMed

Matteliano, Deborah; Scherer, Yvonne Krall; Chang, Yu-Ping

2014-03-01

Pain in the spine is the most frequently described pain problem in primary care, afflicting at least 54 million Americans. When spinal pain becomes chronic, the prognosis for recovery is poor, often leading to disability and reduced quality of life. Clinical treatment is inadequate, often focusing on physical pathology alone. To improve treatment outcomes for chronic pain as recommended by current guidelines, the Biobehavioral Pain Profile (BPP), which includes six pain response subscales, was developed to guide cognitive behavioral therapy (CBT). The purpose of this study was to describe the BPP in 100 individuals with chronic spine pain and examine the associations between the BPP and important clinical outcomes, including chronic pain, disability, and quality of life. Participants reported a high level of pain, a low quality of life, and a high level of disability despite receiving treatment with opioids. Scores on BPP subscales including evaluating loss of control, past and current experience, physiologic responsivity, and thoughts of disease progression were elevated, indicating a need for CBT. Five of the six BPP subscales had a significant association with quality of life, chronic pain, and disability with the thought of disease progression being a strong factor for most of the clinical outcome variables. By identifying BPP, clinicians can provide appropriate treatments to improve individuals' quality of life and prevent further disability. Further study using the BPP to guide CBT is needed. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Cyclin-Dependent Kinase Inhibitors for the Treatment of Breast Cancer: Past, Present, and Future.

PubMed

DiPippo, Adam J; Patel, Neelam K; Barnett, Chad M

2016-06-01

Treatment of metastatic breast cancer (MBC) that is resistant to endocrine therapy presents a significant clinical challenge. The well-known role of cell cycle dysregulation in these patients is partly mediated by cyclin-dependent kinase (CDK) activity. Specific cyclin and CDK complexes regulate cell cycle progression by managing the transition through the cell cycle, and inhibition of CDKs represents an important target for novel agents. First-generation CDK inhibitors (e.g., flavopiridol) were relatively nonselective and had an unacceptable toxicity profile in early trials. Second-generation CDK inhibitors were designed to target the CDK4 and CDK6 (CDK4/6) pathway and have shown promising clinical activity with an acceptable toxicity profile in patients with MBC. Palbociclib is a first-in-class CDK4/6 inhibitor that was granted accelerated U.S. Food and Drug Administration approval in combination with letrozole for the treatment of MBC in the first-line setting (February 2015) as well as in combination with fulvestrant for MBC that had progressed on previous endocrine therapy (February 2016). Other CDK4/6 inhibitors, including ribociclib and abemaciclib, are under investigation as monotherapy and in combination with endocrine or anti-human epidermal growth receptor 2 therapy for the treatment of MBC. Ongoing clinical trials should provide additional information to guide the appropriate use of these agents and identify patient populations that could derive the most benefit. © 2016 Pharmacotherapy Publications, Inc.

Patients’ perceptions of gene expression profiling in breast cancer treatment decisions

PubMed Central

Bombard, Y.; Rozmovits, L.; Trudeau, M.E.; Leighl, N.B.; Deal, K.; Marshall, D.A.

2014-01-01

Introduction Determining the likely benefit of adjuvant chemotherapy for early-stage breast cancer patients depends on estimating baseline recurrence risk. Gene expression profile (gep) testing of tumours informs risk prediction, but evidence of its clinical utility is limited. We explored patient perceptions of gep testing and the impact of those perceptions on chemotherapy decisions. Methods We conducted one focus group (n = 4) and individual interviews (n = 24) with patients who used gep testing, recruited through clinics at two hospitals in Ontario. Data were analyzed using content analysis and constant comparison techniques. Results Patients’ understanding of gep testing was variable, and misapprehensions were common. Patients valued the test because it provided them with certainty amidst confusion, with options and a sense of empowerment, and with personalized, authoritative information. They commonly believed that the test was better and fundamentally different from other clinical tests, attributing to it unique power and truth-value. This kind of “magical thinking” was derived from an amplified perception of the test’s validity and patients’ need for reassurance about their treatment choices. Despite misperceptions or magical thinking, gep was widely considered to be the deciding factor in treatment decisions. Conclusions Patients tend to overestimate the truth-value of gep testing based on misperceptions of its validity. Our results identify a need to better support patient understanding of the test and its limitations. Findings illustrate the deep emotional investment patients make in gep test results and the impact of that investment on their treatment decisions. PMID:24764705

[Hypothesis of the correlation of personality characteristics and the clinical history of bronchogenic cancer].

PubMed

Beltrami, V; Buonsanto, A; Di Nuzzo, D; Lattanzio, R

1995-01-01

A correlation between the personality profile and the clinical history in lung cancer patients was studied. Selection of cases included in the sample only surgical patients with a medium educational level and a tested capability to understand a specific questionnaire. One hundred and seventy patients were selected and the so-called C.R.I.C.S. (Clinical-Rated Inventory of Character Style) was applied. Score variations were recorded after curative resection as well as during relapse. Changes in the character profile pattern were found in all subjects who experienced the disease and its surgical treatment. These changes occurred either in "regression"-with an increase of schizoid, narcissistic or hysterical aspects-or in a "positive evolution", with a decrease of paranoid traits and into a depressive position. The two groups of responses demonstrated a similar percentage.

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

Characterizing severe and enduring anorexia nervosa: An empirical approach.

PubMed

Wildes, Jennifer E; Forbush, Kelsie T; Hagan, Kelsey E; Marcus, Marsha D; Attia, Evelyn; Gianini, Loren M; Wu, Wei

2017-04-01

Targeted approaches for the treatment of severe and enduring anorexia nervosa (SE-AN) have been recommended, but there is no consensus definition of SE-AN to inform research and clinical practice. This study aimed to take initial steps toward developing an empirically based definition of SE-AN by characterizing associations among putative indicators of severity and chronicity in eating disorders. Patients with AN (N = 355) completed interviews and questionnaires at treatment admission and discharge; height and weight were assessed to calculate body mass index (BMI). Structural equation mixture modeling was used to test whether associations among potential indicators of SE-AN (illness duration, treatment history, BMI, binge eating, purging, quality-of-life) formed distinct subgroups, a single group with one or more dimensions, or a combination of subgroups and dimensions. A three-factor (dimensional), two-profile (categorical) mixture model provided the best fit to the data. Factor 1 included eating disorder behaviors; Factor 2 comprised quality-of-life domains; Factor 3 was characterized by illness duration, number of hospitalizations, and admission BMI. Profiles differed on eating disorder behaviors and quality-of-life, but not on indicators of chronicity or BMI. Factor scores, but not profile membership, predicted outcome at discharge from treatment. Data suggest that patients with AN can be classified on the basis of eating disorder behaviors and quality-of-life, but there was no evidence for a chronic subgroup of AN. Rather, indices of chronicity varied dimensionally within each class. Given that current definitions of SE-AN rely on illness duration, these findings have implications for research and clinical practice. © 2016 Wiley Periodicals, Inc.

Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis.

PubMed

Vázquez-Bourgon, Javier; Pérez-Iglesias, Rocío; Ortiz-García de la Foz, Víctor; Suárez Pinilla, Paula; Díaz Martínez, Álvaro; Crespo-Facorro, Benedicto

2018-01-01

The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment. One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment. After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment. We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

U.S. National Football League athletes seeking unproven stem cell treatments.

PubMed

Matthews, Kirstin R W; Cuchiara, Maude L

2014-12-01

From professionals to weekend warriors, many athletes seek unproven stem cell (SC) treatments in an effort to heal injuries nonsurgically and/or to accelerate recovery times after surgery. Among the elite athletes opting for these treatments are high-profile U.S. National Football League (NFL) players. Over the past 5 years, several NFL players have publicly advocated for SC types of treatments and credit them as a major reason they could continue their careers after injuries. In this article, we describe the current problems associated with unproven SC treatments, focusing on treatments without U.S. Food and Drug Administration approval undertaken by NFL players in the past 5 years. Specifically, we highlight the types of treatments obtained and how the clinics advertise specifically to athletes. We also review the intended and unintended consequences of high-profile players receiving and advocating for these types of therapies. Our findings suggest that NFL players increasingly seek out unproven SC therapies to help accelerate recoveries from injuries. While most seem to receive treatment within the United States, several have traveled abroad for therapies unavailable domestically.

Profiles and clinical management of hepatitis C patients in Spain: disHCovery study.

PubMed

Buti, Maria; Franco, Alejandro; Carmona, Isabel; Sánchez-Ruano, Juan Jose; Sansó, Andreu; Berenguer, Marina; García-Buey, Luisa; Hernández-Guerra, Manuel; Morillas, Rosa Maria; Ledesma, Francisco; Esteban, Rafael

2015-06-01

To assess the clinical profile and management of patients with hepatitis C (HCV) infection in an observational study in Spanish hospitals. The study included an initial cross-sectional phase (study phase I), in which investigators at 48 hospitals from 14 Spanish regions collected data from approximately 20 consecutive patients each (a total of 1,000 patients) to assess the general features of HCV-infected patients of any genotype. During the second phase (study phase II), data from 878 patients that were infected exclusively with genotype 1 HCV were assessed retrospectively. Eight pre-defined clinical profiles were established, in order to assess clinical and previous treatments characteristics. Among the HCV-infected individuals that were analysed during the first part, HCV genotype 1 was found to be predominant (with a prevalence of 76.6%), prevailing the subtype 1b (69.8%), with other significant groups infected by genotype 3 (12.3%) and 4 (7.4%). In the second part of the study, 44% of the HCV genotype 1-infected patients were at a F3/F4 fibrosis stage. 15.9% had never been treated, and previously unsuccessfully treated patients that were no longer receiving anti-HCV treatment accounted for 50.8% of cases. Individuals with a sustained virologic response (SVR) to previous dual therapies (based on Interferon and Ribavirin) were only 14.5% and patients under treatment during the study accounted for the remaining 18.8%. A total of 713 patients (81.2%) in the second phase were not receiving any type of therapy over the period analysed, mainly due to the anticipation of new anti-HCV drugs (41.8%), SVR achievement (17.8%) and unresponsiveness to therapies available at the time of the study (9.5%). HCV genotype 1, predominately 1b, is the most prevalent type in Spain. Advanced fibrosis or cirrhosis is frequent in this group, mainly patients not yet cured.

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).

PubMed

Saiag, P; Gutzmer, R; Ascierto, P A; Maio, M; Grob, J-J; Murawa, P; Dreno, B; Ross, M; Weber, J; Hauschild, A; Rutkowski, P; Testori, A; Levchenko, E; Enk, A; Misery, L; Vanden Abeele, C; Vojtek, I; Peeters, O; Brichard, V G; Therasse, P

2016-10-01

Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study.This study is registered at www.clinicatrials.gov NCT00942162. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Valbenazine for Tardive Dyskinesia.

PubMed

Freudenreich, Oliver; Remington, Gary

Tardive dyskinesia (TD) remains a clinical concern for any patient who receives an antipsychotic. While the overall risk of developing TD is lower with newer antipsychotics compared to older agents, a significant number of patients who require long-term treatment will develop TD. Recently, valbenazine (brand name Ingrezza) became the first drug to be approved by the FDA specifically for the treatment of TD. In this New Drug Review, we summarize the basic pharmacology and clinical trial results for valbenazine. Valbenazine is a modified metabolite of the vesicular monoamine transporter 2 (VMAT-2) inhibitor tetrabenazine, which is approved for the treatment of the hyperkinetic movement disorder, Huntington's disease. In short-term clinical trials, valbenazine at a dose of 80 mg/day improved TD, with an effect size that is clinically significant (d=0.90). The effect size for the 40-mg/day dose was lower (d=0.52). Compared to tetrabenazine, valbenazine has better clinical characteristics (i.e., once-a-day dosing, better short-term side effect profile). However, only long-term experience in routine clinical populations can delineate valbenazine's full benefits, optimal dosing, and risks not identified during short-term registration trials.

Two Sides of the Same Coin: Cannabis Dependence and Mental Health Problems in Help-Seeking Adolescent and Young Adult Outpatients

ERIC Educational Resources Information Center

Norberg, Melissa M.; Battisti, Robert A.; Copeland, Jan; Hermens, Daniel F.; Hickie, Ian B.

2012-01-01

The aim of the current study was to delineate the psychiatric profile of cannabis dependent young people (14-29 years old) with mental health problems (N = 36) seeking treatment via a research study. To do so, the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Structured Clinical Interview for DSM-IV Childhood Diagnoses were…

Safety evaluation of trelagliptin in the treatment of Japanese type 2 diabetes mellitus patients.

PubMed

Kaku, Kohei

2017-11-01

Trelagliptin is a novel, long-acting dipeptidyl peptidase-4 (DPP-4) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM) in japan. The safety and efficacy of trelagliptin has been evaluated in three published clinical trials to date: one phase II and two phase III studies. As trelagliptin only requires dosing once per week, this new agent has the potential to improve compliance and subsequently, glycaemic control, in patients with T2DM. Areas covered: This article reviews the available safety data for trelagliptin from published clinical trials, and evaluates the published safety profile relative to competitor once-daily and once-weekly DPP-4 inhibitors. Expert opinion: Clinical trial data to date suggest that trelagliptin is a safe and efficacious medication with a similar safety profile to once-daily DPP-4 inhibitors, and to the once-weekly DPP-4 inhibitor, omarigliptin. Trelagliptin is well tolerated when given alone, and in combination with other anti-diabetic medications. An advantage of trelagliptin over existing once-daily DPP-4 inhibitors is the decrease of dosing frequency, rather than once-daily. No specific, serious adverse events have been reported for trelagliptin in published clinical trials, making it an attractive alternative to other DPP-4 inhibitors.

Comparing the profile of child patients attending dental general anaesthesia and conscious sedation services.

PubMed

Hariharan, S; Hosey, M T; Bernabe, E

2017-05-12

Aims To compare the profile of paediatric patients receiving dental treatment under general anaesthesia (GA) or conscious sedation (CS). A second aim was to explore whether there is an overlap between the two patient groups.Design This service evaluation study was based on sociodemographic and clinical data extracted from clinical records of patients attending dental appointments for GA or CS services at King's College Hospital. Sociodemographic and clinical differences between GA and CS groups were explored using logistic regression models.Results Data from 113 children (58 GA and 55 CS) were analysed. There were differences between groups in terms of age and numbers of quadrants and teeth treated, but not in terms of sex, ethnicity or deprivation scores. In the adjusted model, older children and those having more teeth treated were more likely to be in the GA than in the CS group. An overlap between the GA and CS groups was found, with 50% of children aged four to nine years having two to four teeth treated in both groups.Conclusion Age and number of teeth treated were the main characteristics associated with receiving care under GA or CS. Some overlap between children receiving dental treatment under GA or CS existed despite demographic and clinical differences between both groups.

Efficacy and safety of darunavir (Prezista®) with low-dose ritonavir and other antiretroviral medications in subtype F HIV-1 infected, treatment-experienced subjects in Romania: a post-authorization, open-label, one-cohort, non-interventional, prospective study

PubMed Central

Benea, Otilia Elisabeta; Streinu-Cercel, Adrian; Dorobăţ, Carmen; Rugină, Sorin; Negruţiu, Lucian; Cupşa, Augustin; Duiculescu, Dan; Chiriac, Carmen; Itu, Corina; Prisăcariu, Liviu Jany; Iosif, Ionel

2014-01-01

Introduction The aim of the study was to assess the safety and efficacy of darunavir (Prezista®) used in subtype F human immunodeficiency virus – type 1 (HIV-1) infected, antiretroviral therapy (ART)-experienced patients in Romania in routine clinical practice. Methods This was a post-authorization, open-label, one-cohort, non-interventional, prospective study conducted at multiple sites in Romania to assess efficacy (CD4 cell count, viral load, and treatment compliance) and safety ([serious] adverse events, clinical laboratory evaluation, and vital signs) of darunavir in combination with low-dose ritonavir (DRV/r) and other antiretroviral (ARV) medications in subtype F HIV-1 infected subjects in naturalistic settings. Seventy-eight subjects were recruited by 9 investigational sites and received 600/100 mg DRV/r twice daily. Results Treatment with DRV/r administered with other ARV medications resulted in the expected, statistically relevant improvement of CD4 cell count and viral load in subjects eligible for such treatment. In addition, adherence to treatment was high and the treatment-emergent safety profile observed during this study was consistent with the established safety profile of darunavir. Conclusion DRV/r administered in combination with other ARV medications in subtype F HIV-1 infected subjects in naturalistic settings proved to be an effective and safe treatment in Romania. Trial registration NCT01253967 PMID:25276665

Expression of NK Cell Surface Receptors in Breast Cancer Tissue as Predictors of Resistance to Antineoplastic Treatment

PubMed Central

Mariel, Garcia-Chagollan; Edith, Carranza-Torres Irma; Pilar, Carranza-Rosales; Elena, Guzmán-Delgado Nancy; Humberto, Ramírez-Montoya; Guadalupe, Martínez-Silva María; Ignacio, Mariscal-Ramirez; Alfredo, Barrón-Gallardo Carlos; Laura, Pereira-Suárez Ana; Adriana, Aguilar-Lemarroy; Felipe, Jave-Suárez Luis

2018-01-01

Background: Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells. However, the role of NK cells in resistance to systemic therapy in breast cancer remains unclear. The present project aims to evaluate the gene expression profile of human NK cells in breast cancer tissue resistant to treatment with taxanes–anthracyclines. Methods: Biopsies from tumor tissues were obtained from patients with breast cancer without prior treatment. Histopathological analysis and ex vivo exposure to antineoplastic chemotherapeutics were carried out. Alamar blue and lactate dehydrogenase release assays were performed for quantitative analysis of tumor viability. Gene expression profiles from tumor tissues without prior exposure to therapeutic drugs were analyzed by gene expression microarrays and verified by polymerase chain reaction. Results: A significant decrease in gene expression of cell-surface receptors related to NK cells was observed in tumor samples resistant to antineoplastic treatment compared with those that were sensitive to treatment. Conclusion: A decrease in NK cell infiltration into tumor tissue might be a predictive marker for failure of chemotherapeutic treatment in breast cancer. PMID:29558872

Expression of NK Cell Surface Receptors in Breast Cancer Tissue as Predictors of Resistance to Antineoplastic Treatment.

PubMed

Mariel, Garcia-Chagollan; Edith, Carranza-Torres Irma; Pilar, Carranza-Rosales; Elena, Guzmán-Delgado Nancy; Humberto, Ramírez-Montoya; Guadalupe, Martínez-Silva María; Ignacio, Mariscal-Ramirez; Alfredo, Barrón-Gallardo Carlos; Laura, Pereira-Suárez Ana; Adriana, Aguilar-Lemarroy; Felipe, Jave-Suárez Luis

2018-01-01

Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells. However, the role of NK cells in resistance to systemic therapy in breast cancer remains unclear. The present project aims to evaluate the gene expression profile of human NK cells in breast cancer tissue resistant to treatment with taxanes-anthracyclines. Biopsies from tumor tissues were obtained from patients with breast cancer without prior treatment. Histopathological analysis and ex vivo exposure to antineoplastic chemotherapeutics were carried out. Alamar blue and lactate dehydrogenase release assays were performed for quantitative analysis of tumor viability. Gene expression profiles from tumor tissues without prior exposure to therapeutic drugs were analyzed by gene expression microarrays and verified by polymerase chain reaction. A significant decrease in gene expression of cell-surface receptors related to NK cells was observed in tumor samples resistant to antineoplastic treatment compared with those that were sensitive to treatment. A decrease in NK cell infiltration into tumor tissue might be a predictive marker for failure of chemotherapeutic treatment in breast cancer.

Comparison of effects of 3 mg drospirenone plus 20 μg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome.

PubMed

Fruzzetti, Franca; Perini, Daria; Lazzarini, Veronica; Parrini, Donatella; Gambacciani, Marco; Genazzani, Andrea Riccardo

2010-10-01

To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 μg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). Randomized, open-label clinical trial. Academic medical clinic. Forty-eight hirsute women with PCOS. Patients were randomized to treatment with DRP/20EE or with DRP/20EE plus metformin (1,500 mg/d) or with DRP/20EE plus CPA (12.5 mg/d, 10 days per cycle) for 6 months. Blood pressure, lipid profile, and indexes of glucose tolerance and insulin sensitivity were assessed before and after 6 months of treatment. Body mass index and blood pressure were not modified by any treatment. Treatment with DRP/EE20 did not change the lipid profile; DRP/EE20 plus metformin significantly increased high-density lipoprotein cholesterol concentrations; DRP/EE20 plus CPA significantly increased triglycerides and total cholesterol. The area under the curve for insulin was significantly decreased by DRP/EE20 and DRP/EE20 plus metformin, but it was significantly increased by DRP/EE20 plus CPA. Treatment with DRP/EE20 plus CPA significantly increased the homeostasis model assessment of insulin resistance index and significantly reduced the glucose to insulin ratio index. Treatment with DRP/EE20 significantly increased the glucose to insulin ratio index. Treatment with DRP/EE20 improved insulin sensitivity in hirsute women with PCOS, with no deterioration of lipid profile. This effect was not ameliorated by the addition of metformin. The positive metabolic effects of DRP are abolished by the concomitant use of CPA. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Atypical antipsychotics: recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria.

PubMed

Murray, Robin; Correll, Christoph U; Reynolds, Gavin P; Taylor, David

2017-03-01

Available evidence suggests that second-generation atypical antipsychotics are broadly similar to first-generation agents in terms of their efficacy, but may have a more favourable tolerability profile, primarily by being less likely to cause extrapyramidal symptoms. However, atypical antipsychotics are variably associated with disturbances in the cardiometabolic arena, including increased body weight and the development of metabolic syndrome, which may reflect differences in their receptor binding profiles. Effective management of schizophrenia must ensure that the physical health of patients is addressed together with their mental health. This should therefore involve consideration of the specific tolerability profiles of available agents and individualization of treatment to minimize the likelihood of adverse metabolic sequelae, thereby improving long-term adherence and optimizing overall treatment outcomes. Alongside this, modifiable risk factors (such as exercise, diet, obesity/body weight and smoking status) must be addressed, in order to optimize patients' overall health and quality of life (QoL). In addition to antipsychotic-induced side effects, the clinical management of early nonresponders and psychopharmacological approaches for patients with treatment-resistant schizophrenia remain important unmet needs. Evidence suggests that antipsychotic response starts early in the course of treatment and that early nonresponse accurately predicts nonresponse over the longer term. Early nonresponse therefore represents an important modifiable risk factor for poor efficacy and effectiveness outcomes, since switching or augmenting antipsychotic treatment in patients showing early nonresponse has been shown to improve the likelihood of subsequent treatment outcomes. Recent evidence has also demonstrated that patients showing early nonresponse to treatment with lurasidone at 2 weeks may benefit from an increase in dose at this timepoint without compromising tolerability/safety. However, further research is required to determine whether these findings are generalizable to other antipsychotic agents.

Out-patient chronic pain service in Hong Kong: prospective study.

PubMed

Chen, P P; Chen, J; Gin, T; Ma, M; Fung, K C; Woo, K H; Wong, P Y

2004-06-01

To examine the profile and referral pattern of patients attending an out-patient pain management service in Hong Kong. Prospective cross-sectional survey. Regional public hospitals, Hong Kong. All patients attending out-patient pain management clinics in the New Territories East public hospitals between 1 September and 31 December 2002. Demographic profiles, referring specialty, pain diagnosis, pain sites, duration and severity of pain, treatment modality, litigation, compensation, and social welfare status. Data were collected using a standardised questionnaire. Two hundred and forty-eight patients were interviewed. Most patients (70%) were middle-aged, with 21% over 60 years. Seventy-nine percent of patients were referred to the clinics either from orthopaedic surgeons (64.1%), general and other surgeons (14.9%), or general practitioners (3.6%). The median (range) duration of pain was 2.3 (0.08-26.7) years. The most common pain diagnoses were musculoskeletal back pain (46.4%) and neuropathic pain (27.8%). A total of 11.3% of the patients had two pain diagnoses, while 40.7% complained of pain in more than one location. Pain in the limbs was the most frequent complaint followed by the head, neck, and back. Approximately 38% of patients had tried four or more treatment modalities. Oral medication was the most common method (86.7%) of pain-relief treatment. More than half of the patients had also tried physiotherapy and traditional Chinese medicine. Approximately 37% of the patients were unemployed, while 31% were receiving social security subsidy. Eighty-six patients had pain associated with a work-related injury, and of these patients, 80% were involved in compensation claims. The profile of patients referred to the pain management clinics was complex. Patients were mainly referred from specialists. The economic implication in this group of patients is likely to be significant as many patients utilised multiple treatment modalities, were unemployed and on social welfare benefits, and were involved in compensation and litigation proceedings.

Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study.

PubMed

Wheler, Jennifer J; Janku, Filip; Naing, Aung; Li, Yali; Stephen, Bettzy; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Karp, Daniel; Falchook, Gerald S; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Anderson, Roosevelt; Ke, Danxia; Miller, Vincent; Yelensky, Roman; Lee, J Jack; Hong, David S; Kurzrock, Razelle

2016-07-01

Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly targeted drugs. We report the findings of a prospective, single-center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N = 122/188, 65%) or unmatched therapy (N = 66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1-14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease ≥6 months/partial/complete remission [22% (high scores) vs. 9% (low scores), P = 0.024], longer time-to-treatment failure [hazard ratio (HR) = 0.52; 95% confidence interval (CI) = 0.36-0.74; P = 0.0003], and survival (HR = 0.65; 95% CI = 0.43-1.0; P = 0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented. Cancer Res; 76(13); 3690-701. ©2016 AACR. ©2016 American Association for Cancer Research.

Using a graphical risk tool to examine willingness to take migraine prophylactic medications.

PubMed

Turner, Dana P; Golding, Adrienne N; Houle, Timothy T

2016-10-01

Many migraine sufferers use daily prophylactic therapy to reduce the frequency of their headache attacks. The Food and Drug Administration has approved several different medications for migraine prophylaxis, but it is not clear whether sufferers perceive these treatments to provide clinically significant benefits given their side effect profiles. Three hundred headache sufferers were recruited from the community and local headache clinics using print and television advertising. Participants reported experiencing problematic headache attacks with a median (IQR) frequency of 7.0 (4-13) headache days per month. These sufferers participated in a cross-sectional, single-site, study that used a specially designed computer assessment task. Participants were instructed on the probability of experiencing the 3 most commonly experienced side effects for several blinded medication profiles: divalproex sodium, venlafaxine, gabapentin, propranolol, and topiramate. After learning the likelihood of experiencing side effect profiles of each medication, participants were asked whether they would be willing to take the medication for a given headache reduction level, which ranged from 0 to 7 days per month. The side effect profile for divalproex sodium was associated with the smallest willingness to take, with gabapentin, propranolol, and topiramate perceived to be much more agreeable. However, <60% of participants reported willingness to take any of these medications even if they provided a 50% reduction in headache frequency. Several general predictors of willingness to take were observed including high headache-related disability, depressive symptoms, and pain medication concerns including fear of tolerance. These findings suggest that if properly informed of the side effect profiles of these medications, many patients might opt for other treatments.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern. After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Chronic non-cancer pain: Focus on once-daily tramadol formulations

PubMed Central

Coluzzi, Flaminia; Mattia, Consalvo

2007-01-01

Despite progress in pain management, chronic non-cancer pain (CNCP) represents still a clinical challenge. The efficacy and safety profile of tramadol make it suitable as a long-term treatment in a variety of CNCP conditions. New once-daily (OD) formulations of tramadol have been marketed in various countries, in order to offer the advantage of a reduced dosing regimen and to improve patients’ compliance. This review focuses on the technology, pharmacology, clinical efficacy, and safety of different once-daily tramadol formulations. Hydrophilic vs hydrophobic matrix systems and newer technologies used in once-daily formulations to control drug delivery are discussed. Three randomized controlled trials (RCTs) established OD tramadol analgesic efficacy to be superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Three RCTs demonstrated similar rates of efficacy between OD tramadol and immediate-release (IR) or sustained-release (SR) formulations, with a better adverse events profile. An open trial on long term tolerability showed that OD tramadol is generally safe in rheumatological pain treatment. PMID:18473006

The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients

PubMed Central

Jung, Donald; AbdelHameed, Magdy H; Hunter, John; Teitelbaum, Philip; Dorr, Albert; Griffy, Kay

1999-01-01

Aims We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients. Methods In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment. Results The presence of trimethoprim significantly decreased CLr (12.9%, P = 0.0068) and increased t1/2 (18.1%, P = 0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprim. Conclusions There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered. PMID:10215748

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

PubMed Central

2015-01-01

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile. PMID:26288683

Cervical Radiculopathy due to Cervical Degenerative Diseases : Anatomy, Diagnosis and Treatment

PubMed Central

Kim, Kyoung-Tae

2010-01-01

A cervical radiculopathy is the most common symptom of cervical degenerative disease and its natural course is generally favorable. With a precise diagnosis using appropriate tools, the majority of patients will respond well to conservative treatment. Cervical radiculopathy with persistent radicular pain after conservative treatment and progressive or profound motor weakness may require surgery. Options for surgical management are extensive. Each technique has strengths and weaknesses, so the choice will depend on the patient's clinical profile and the surgeon's judgment. PMID:21430971

Safety profile: fifteen years of clinical experience with ibuprofen.

PubMed

Royer, G L; Seckman, C E; Welshman, I R

1984-07-13

Since its introduction in the United States in 1974, ibuprofen (Motrin, Upjohn) has been shown to be safe and effective for the treatment of pain, dysmenorrhea, inflammation, and fever. A careful review of pre-registration and postmarketing data from both patients and normal subjects clearly indicates ibuprofen's remarkable safety profile compared with that of aspirin and other commonly prescribed nonsteroidal anti-inflammatory agents. Continued safety can be anticipated on the basis of the past 15 years of review experience.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film.

PubMed

Sonier, Marcus; Wronski, Matt; Yeboah, Collins

2015-03-08

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose pro-files under large-area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central-axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤ 10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ~ 25% occur-ring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level.

SU-F-T-399: Migration of Treatment Planning Systems Without Beam Data Measurement

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

Tolakanahalli, R; Tewatia, D

2016-06-15

Purpose: Data acquisition for commissioning is steered by Treatment Planning System (TPS) requirements which can be cumbersome and time consuming involving significant clinic downtime. The purpose of this abstract is to answer if we could circumvent this by extracting data from existing TPS and speed up the process. Methods: Commissioning beam data was obtained from a clinically commissioned TPS (Pinnacle™) using Matlab™ generated Pinnacle™ executable scripts to commission a secondary 3D dose verification TPS (Eclipse™). Profiles and output factors for commissioning as required by Eclipse™ were computed on a 50 cm{sup 3} water phantom at a dose grid resolution ofmore » 2mm3. Verification doses were computed and compared to clinical TPS dose profiles as per TG-106 guidelines. Standard patient plans from Pinnacle™ including IMRT and VMAT plans were re-computed keeping the same monitor units (in order to perform true comparison) using Eclipse™. Computed dose was exported back to Pinnacle for comparison to original plans. This methodology enables us to alleviate all ambiguities that arise in such studies. Results: Profile analysis using in-house software for 6x, showed that for all field sizes including small MLC generated fields, 100% of infield and penumbra data points of Eclipse™ match Pinnacle™ generated and measured profiles with 2%/2 mm gamma criteria. Excellent agreement was observed in the penumbra regions, with all data points passing DTA criteria for complex C-shaped and S-shaped profiles. Patient plan dose volume histograms (DVHs) and isodose lines agreed well to within a 1.5% for target coverage. Conclusion: Secondary 3D dose checking is of utmost importance with advanced techniques such as IMRT and VMAT. Migration of TPS is possible without compromising accuracy or enduring the cumbersome measurement of commissioning data. Economizing time for commissioning such a verification system or for migration of TPS can add great QA value and minimize downtime.« less

Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

PubMed Central

Amsberg, Gunhild Keller-von; Koschmieder, Steffen

2013-01-01

Bosutinib (SKI-606) is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML). Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML. PMID:23493838

Safety and tolerability of atomoxetine in treatment of attention deficit hyperactivity disorder in adult patients: an integrated analysis of 15 clinical trials.

PubMed

Camporeale, Angelo; Porsdal, Vibeke; De Bruyckere, Katrien; Tanaka, Yoko; Upadhyaya, Himanshu; Deix, Claudia; Deberdt, Walter

2015-01-01

The safety profile of atomoxetine in the treatment of attention deficit hyperactivity disorder has been studied in many clinical trials. We performed an integrated safety analysis of 15 clinical trials in adults with attention deficit hyperactivity disorder. The analysis pooled patient data into three groups: acute placebo-controlled trials; long-term placebo-controlled trials; all trials. In total, 4829 adults (18-77 years, median: 36 years) were exposed to atomoxetine. Statistically significantly more atomoxetine-treated than placebo-treated patients experienced treatment-emergent adverse events (81.3% vs. 68.3% acute; 90.6% vs. 76.8% long term) and discontinued due to adverse events (8.9% vs. 4.0% acute; 17.9% vs. 6.3% long term). No statistically significant differences were observed in the proportion of patients experiencing serious adverse events. No previously unknown adverse events were identified. The most common adverse events included nausea, dry mouth, decreased appetite, insomnia and erectile dysfunction. Mean increases in heart rate (+5.2 beats per min) and blood pressure (systolic +2 mmHg, diastolic +1.9 mmHg) were modest. The proportion of patients experiencing clinically significant increases in blood pressure and heart rate at any time was statistically significantly higher with atomoxetine (systolic blood pressure 13-17%, diastolic blood pressure 37-40%, heart rate 42-43%) compared to placebo (systolic blood pressure 8-13%, diastolic blood pressure 29-34%, heart rate 21-26%). There was no increased risk of suicidal ideation or behaviour. Our findings confirm atomoxetine's known safety profile. From a safety perspective, atomoxetine is a useful treatment option for adults with attention deficit hyperactivity disorder. © The Author(s) 2014.

Evaluation of the biochemical, inflammatory and oxidative profile of obese patients given clinical treatment and bariatric surgery.

PubMed

Schmatz, Roberta; Bitencourt, Mariana R; Patias, Luciana D; Beck, Maristela; da C Alvarez, Glauco; Zanini, Daniela; Gutierres, Jessié M; Diehl, Lia Natália; Pereira, Luciane B; Leal, Claudio Alberto; Duarte, Marta Frescura; Schetinger, Maria Rosa; Morsch, Vera Maria

2017-02-01

We investigated the biochemical and inflammatory parameters as well as biomarkers of oxidative stress in morbidly obese patients before and after bariatric surgery and clinical treatment. This study was conducted using 60 individuals (10 men and 50 women) distributed into 3 groups: the control group, 20 non-diabetic obese patients given clinical treatment, the bariatric group, 20 non-diabetic obese patients given a Roux-en-Y bypass gastroplasty, and the bariatric diabetic group, 20 diabetic obese patients given a Roux-en-Y bypass gastroplasty. Measurements were made before and 1, 3, 6, and 12months after surgery and clinical treatment. We showed a significant decrease in body weight, body mass index (BMI) and waist circumference, accompanied by a decrease in the lipid profile and glucose and glycated hemoglobin concentrations in the groups that received bariatric surgery. The concentrations of lipid peroxidation, carbonyl protein and NPSH, as well as superoxide dismutase (SOD) and catalase (CAT) activity, significantly decreased in both groups after surgery. The concentrations of inteleukin-6, inteleukin-1, TNF-α and resistin were also significantly lower, while adiponectin concentrations significantly increased 12months after bariatric surgery. No significant alterations were observed in the biochemical, inflammatory or oxidative parameters of the control group. Our findings demonstrate a decrease in body mass and a subsequent improvement in biochemical, metabolic and anthropometric parameters in patients given bariatric surgery. This may contribute to the reduction of oxidative damage in these patients and consequently a reduction in the risk of the development and progression of multiple co-morbidities associated with obesity. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.

PubMed

Samwald, Matthias; Miñarro Giménez, Jose Antonio; Boyce, Richard D; Freimuth, Robert R; Adlassnig, Klaus-Peter; Dumontier, Michel

2015-02-22

Every year, hundreds of thousands of patients experience treatment failure or adverse drug reactions (ADRs), many of which could be prevented by pharmacogenomic testing. However, the primary knowledge needed for clinical pharmacogenomics is currently dispersed over disparate data structures and captured in unstructured or semi-structured formalizations. This is a source of potential ambiguity and complexity, making it difficult to create reliable information technology systems for enabling clinical pharmacogenomics. We developed Web Ontology Language (OWL) ontologies and automated reasoning methodologies to meet the following goals: 1) provide a simple and concise formalism for representing pharmacogenomic knowledge, 2) finde errors and insufficient definitions in pharmacogenomic knowledge bases, 3) automatically assign alleles and phenotypes to patients, 4) match patients to clinically appropriate pharmacogenomic guidelines and clinical decision support messages and 5) facilitate the detection of inconsistencies and overlaps between pharmacogenomic treatment guidelines from different sources. We evaluated different reasoning systems and test our approach with a large collection of publicly available genetic profiles. Our methodology proved to be a novel and useful choice for representing, analyzing and using pharmacogenomic data. The Genomic Clinical Decision Support (Genomic CDS) ontology represents 336 SNPs with 707 variants; 665 haplotypes related to 43 genes; 22 rules related to drug-response phenotypes; and 308 clinical decision support rules. OWL reasoning identified CDS rules with overlapping target populations but differing treatment recommendations. Only a modest number of clinical decision support rules were triggered for a collection of 943 public genetic profiles. We found significant performance differences across available OWL reasoners. The ontology-based framework we developed can be used to represent, organize and reason over the growing wealth of pharmacogenomic knowledge, as well as to identify errors, inconsistencies and insufficient definitions in source data sets or individual patient data. Our study highlights both advantages and potential practical issues with such an ontology-based approach.

Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling.

PubMed

Hicks, Chindo; Kumar, Ranjit; Pannuti, Antonio; Miele, Lucio

2012-01-01

Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER(+) breast cancer patients treated with tamoxifen and 125 ER(+) controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets.

Mind styles and the hypnotic induction profile: measure and match to enhance medical treatment.

PubMed

Greenleaf, Marcia

2006-07-01

Modern medical technology and economic impositions tend to dehumanize the medical patient. This paper describes a targeted use of the hypnotic modality for relationship building, symptom management, and restoring a sense of self to the patient. To humanize medical care one patient at a time, examples are given for the use of the Hypnotic Induction Profile, the Eye Roll sign and AOD (Apollonian-Odyssean-Dionysian) Mind-Style Questionnaire as a basis for choosing bio-psycho-social treatment strategies. This trio of assessments can be used together, in approximately 10 to 15 minutes, or separately, if treatment decisions need to be made in a few minutes or less. The hypothesis presented is that matching treatment strategies, with or without formal hypnosis, to hypnotic capacity and mind style can increase respectful care and efficacy of treatment outcome. Clinical examples will illustrate this approach to enhance recovery, morale, and maximize patients' ability to become active partners on their own behalf.

Avelumab for the treatment of urothelial cancer.

PubMed

Rodriguez-Vida, Alejo; Bellmunt, Joaquim

2018-05-01

Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years. Similarly, before the advent of the immune checkpoint inhibitors, there were no FDA-approved drugs for second-line therapy. In the last few years, impressive signs of anti-tumor activity have been reported with several immunotherapy agents targeting the programmed cell death-1 (PD-1) pathway. Avelumab, a PD-1 ligand (PD-L1) inhibitor, is currently being investigated for the treatment of UC. Areas covered: This article will review the pharmacological characteristics of avelumab, the efficacy studies which led to its approval, its safety profile, as well as its place within the management of urothelial carcinoma with immunotherapy. For that matter, we undertook a literature review of all the studies assessing the pharmacology of avelumab and its efficacy within clinical trials. Expert commentary: Avelumab has shown promising antitumor activity and a manageable safety profile in patients with UC. Its dual mechanism of action, blocking the interaction between PD-L1 and PD-1 and promoting antibody-dependent cell-mediated cytotoxicity could potentially be of great interest since it could produce synergistic clinical efficacy.

New life to an old treatment: pegylated Interferon beta 1a in the management of multiple sclerosis.

PubMed

Ortiz, Miguel Angel; Espino-Paisan, Laura; Nunez, Concepcion; Alvarez-Lafuente, Roberto; Urcelay, Elena

2018-02-25

In the 1990s, the betainterferons and glatiramer acetate were introduced for treating relapsing-remitting multiple sclerosis. These medications have a demonstrated record of efficacy and safety, although they require frequent administration via injection and are only partially effective. The optimization of treatment in patients who do not respond adequately to this first-line therapy is essential for attaining the best long-term outcomes. Switching to the recently approved emergent therapies is a strategy to consider for treatment of patients with a suboptimal response. This review summarizes the mechanisms of action, clinical benefits, and safety profiles of current multiple sclerosis disease-modifying therapies, including highly efficacious monoclonal antibodies or convenient oral therapies. Although the first-line interferon beta exhibits a favorable benefit-to-risk profile, treatment compliance is compromised potentially due to its known adverse events and frequent injectable administration. Less frequent dosing and improved pharmacological properties have been achieved by reaction of interferon beta with chemically activated polyethylene glycol. Provided that none of the available therapies shows better effectiveness for all outcomes and their safety in clinical practice is a fundamental concern, the pegylated form of interferon beta seems to keep its place as a competitive therapeutic option. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A model to characterize psychopathological features in adults with Prader-Willi syndrome.

PubMed

Thuilleaux, Denise; Laurier, Virginie; Copet, Pierre; Tricot, Julie; Demeer, Geneviève; Mourre, Fabien; Tauber, Maithé; Jauregi, Joseba

2018-01-01

High prevalence of behavioral and psychiatric disorders in adults with Prader-Willi Syndrome (PWS) has been reported in last few years. However, data are confusing and often contradictory. In this article, we propose a model to achieve a better understanding of the psychopathological features in adults with PWS. The study is based on clinical observations of 150 adult inpatients, males and females. Non-parametric statistics were performed to analyse the association of psychopathological profiles with genotype, gender and age. We propose a model of psychiatric disorders in adults with PWS based on cognitive, emotional and behavioural issues. This model defines four psychopathological profiles: Basic, Impulsive, Compulsive, and Psychotic. The Basic profile is defined by traits and symptoms that are present in varying degrees in all persons with PWS. In our cohort, this Basic profile corresponds to 55% of the patients. The rest show, in addition to these characteristics, salient features of impulsivity (Impulsive profile, 19%), compulsivity (Compulsive profile, 7%), or psychosis (Psychotic profile, 19%). The analysis of factors associated with different profiles reveals an effect of genotype on Basic and Psychotic profiles (Deletion: 70% Basic, 9% Psychotic; Non-deletion: 23% Basic, 43% Psychotic) and a positive correlation between male sex and impulsivity, unmediated by sex hormone treatment. This is a clinical study, based on observation proposing an original model to understand the psychiatric and behavioural disorders in adults with PWS. Further studies are needed in order to test the validity of this model. © 2017 Wiley Periodicals, Inc.

Note on concurrent validation of the personality assessment inventory in law enforcement.

PubMed

Hays, J R

1997-08-01

This study compared the Personality Assessment Inventory and MMPI-168 profiles of 9 law enforcement applicants with published MMPI profiles to provide concurrent validation for the use of the Personality Assessment Inventory to assess personality pathology of peace officer applicants. The sample showed subclinical elevations of the Positive Impression and Treatment Rejection scales on the Personality Assessment Inventory and subclinical elevations on the MMPI validity scales of Lie and Correction and the clinical scales of Psychopathic Deviate and Hypomania. The applicants' mean MMPI profile provided concurrent validation for the use of the Personality Assessment Inventory in this decision on fitness to serve.

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis.

PubMed

Ward, Jeanine; Kanchagar, Chitra; Veksler-Lublinsky, Isana; Lee, Rosalind C; McGill, Mitchell R; Jaeschke, Hartmut; Curry, Steven C; Ambros, Victor R

2014-08-19

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

PubMed

Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

2010-08-01

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

PubMed

Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

2015-09-01

The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

PubMed Central

van Kempen, Pauline M W; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, Robert J J; Willems, Stefan M

2015-01-01

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC. PMID:26194878

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) Cohort

PubMed Central

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio SG; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-01-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). PMID:24639444

Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: expert consensus by a panel of Italian and Spanish psychiatrists.

PubMed

Fagiolini, Andrea; Alfonsi, Emilia; Amodeo, Giovanni; Cenci, Mario; Di Lella, Michele; Farinella, Francesco; Ferraiuolo, Fabrizio; Fraguas, David; Loparco, Natale; Gutierrez-Rojas, Luis; Mignone, Maria Laura; Pataracchia, Giuseppe; Pillai, Gianluca; Russo, Felicia; Sanchez-Gistau, Vanessa; Spinogatti, Franco; Toscano, Marco; Villari, Vincenzo; De Filippis, Sergio

2016-01-01

Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process.

Physical activity and sedentary behavior levels in children and adolescents with type 1 diabetes using insulin pump or injection therapy - The importance of parental activity profile.

PubMed

Michaud, Isabelle; Henderson, Mélanie; Legault, Laurent; Mathieu, Marie-Eve

2017-02-01

In children and adolescents, treatments for type 1 diabetes (T1D) have recently evolved with the introduction of the insulin pump. However, little is known about how a pump is associated with physical activity (PA) patterns. The goal of the study was to examine the activity profile of Canadian children and adolescents with T1D according to their insulin treatment (pump vs. injections), as well as barriers to exercise and parental lifestyle habits. A self-administered questionnaire was completed by 188 subjects with T1D aged 6 to 17 and their parents at the endocrinology clinic of Sainte-Justine's University Hospital Center (Montreal, Canada). Sixty percent of patients used an insulin pump. There were no significant differences in any components of the PA profile, sedentary habits, and exercise barriers between subjects using injections and those using a pump. Fear of hypoglycemia was the main PA barrier in both treatment groups. A more diverse PA practice by parents was associated with more moderate-to-vigorous PA and less screen time in adolescents. In conclusion, type of treatment was not associated with more activity in pediatric patients with T1D and a varied parental PA profile was the main factor of interest for healthier habits in adolescents with T1D. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

PubMed Central

Lerner, Jason T; Salamon, Noriko; Sankar, Raman

2010-01-01

Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk. PMID:21127692

Valbenazine as the first and only approved treatment for adults with tardive dyskinesia.

PubMed

Sarva, Harini; Henchcliffe, Claire

2018-03-01

Valbenazine is a selective VMAT2 inhibitor that the FDA approved in April 2017 for the specific treatment of tardive dyskinesia (TD), a movement disorder commonly caused by dopamine blocking agents. Valbenazine acts to decrease dopamine release, reducing excessive movement found in TD. Areas covered: This drug profile reviews the development of valbenazine and the clinical trials that led to its approval as the first treatment specific to TD. The literature search was performed with the PubMed online database. Expert commentary: Two clinical trials assessing the efficacy of valbenazine have shown the reduction of antipsychotic-induced involuntary movement. No life threatening adverse effects were found. Data from a 42-week extension study demonstrated sustained response.

Behavioral, Social, and Emotional Symptom Comorbidities and Profiles in Adolescent Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

PubMed

Brinkman, Tara M; Li, Chenghong; Vannatta, Kathryn; Marchak, Jordan G; Lai, Jin-Shei; Prasad, Pinki K; Kimberg, Cara; Vuotto, Stefanie; Di, Chongzhi; Srivastava, Deokumar; Robison, Leslie L; Armstrong, Gregory T; Krull, Kevin R

2016-10-01

In the general population, psychological symptoms frequently co-occur; however, profiles of symptom comorbidities have not been examined among adolescent survivors of childhood cancer. Parents of 3,893 5-year survivors of childhood cancer who were treated between 1970 and 1999 and who were assessed in adolescence (age 12 to 17 years) completed the Behavior Problems Index. Age- and sex-standardized z scores were calculated for symptom domains by using the Childhood Cancer Survivor Study sibling cohort. Latent profile analysis identified profiles of comorbid symptoms, and multivariable multinomial logistic regression modeling examined associations between cancer treatment exposures and physical late effects and identified symptom profiles. Odds ratios (ORs) and 95% CIs for latent class membership were estimated and analyses were stratified by cranial radiation therapy (CRT; CRT or no CRT). Four symptoms profiles were identified: no significant symptoms (CRT, 63%; no CRT, 70%); elevated anxiety and/or depression, social withdrawal, and attention problems (internalizing; CRT, 31%; no CRT, 16%); elevated headstrong behavior and attention problems (externalizing; CRT, no observed; no CRT, 9%); and elevated internalizing and externalizing symptoms (global symptoms; CRT, 6%; no CRT, 5%). Treatment with ≥ 30 Gy CRT conferred greater risk of internalizing (OR, 1.7; 95% CI, 1.0 to 2.8) and global symptoms (OR, 3.2; 95% CI, 1.2 to 8.4). Among the no CRT group, corticosteroid treatment was associated with externalizing symptoms (OR, 1.9; 95% CI, 1.2 to 2.8) and ≥ 4.3 g/m(2) intravenous methotrexate exposure was associated with global symptoms (OR, 1.5; 95% CI, 0.9 to 2.4). Treatment late effects, including obesity, cancer-related pain, and sensory impairments, were significantly associated with increased risk of comorbid symptoms. Behavioral, emotional, and social symptoms frequently co-occur in adolescent survivors of childhood cancer and are associated with treatment exposures and physical late effects. Assessment and consideration of symptom profiles are essential for directing appropriate mental health treatment for adolescent survivors. © 2016 by American Society of Clinical Oncology.

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

PubMed Central

Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-01-01

Objective. Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. Methods. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. Results. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. Conclusion. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. Trial registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329 PMID:27143789

Personality modulates the efficacy of treatment in patients with major depressive disorder.

PubMed

Wardenaar, Klaas J; Conradi, Henk Jan; Bos, Elisabeth H; de Jonge, Peter

2014-09-01

Effects of depression treatment are obscured by heterogeneity among patients. Personality types could be one source of heterogeneity that explains variability in treatment response. Clinically meaningful variations in personality patterns could be captured with data-driven subgroups. The aim of this study was to identify such personality types and to explore their predictive value for treatment efficacy. Participants (N = 146) in the current exploratory study came from a randomized controlled trial in primary care depressed patients, conducted between January 1998 and June 2003, comparing different treatments. All participants were diagnosed with a major depressive disorder (MDD) according to the DSM-IV. Primary (care as usual [CAU] or CAU plus a psychoeducational prevention program [PEP]) and specialized (CAU + PEP + psychiatric consultation or cognitive-behavioral therapy) treatment were compared. Personality was assessed with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI). Personality classes were identified with latent profile analysis (LPA). During 1 year, weekly depression ratings were obtained by trimonthly assessment with the Composite International Diagnostic Interview. Mixed models were used to analyze the effects of personality on treatment efficacy. A 2-class LPA solution fit best to the NEO-FFI data: Class 1 (vulnerable, n = 94) was characterized by high neuroticism, low extraversion, and low conscientiousness, and Class 2 (resilient, n = 52) by medium neuroticism and extraversion and higher agreeableness and conscientiousness. Recovery was quicker in the resilient class (class × time: P < .001). Importantly, specialized treatment had added value only in the vulnerable class, in which it was associated with quicker recovery than primary treatment (class × time × treatment: P < .001). Personality profile may predict whether specialized clinical efforts have added value, showing potential implications for planning of treatments. © Copyright 2014 Physicians Postgraduate Press, Inc.

Combat Wound Initiative program.

PubMed

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Public Health Literature Review of Fragile X Syndrome

PubMed Central

Raspa, Melissa; Wheeler, Anne C.; Riley, Catharine

2017-01-01

OBJECTIVES The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. METHODS An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. RESULTS The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. CONCLUSIONS The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families. PMID:28814537

Public Health Literature Review of Fragile X Syndrome.

PubMed

Raspa, Melissa; Wheeler, Anne C; Riley, Catharine

2017-06-01

The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families. Copyright © 2017 by the American Academy of Pediatrics.

[Intractable diarrhoea and severe weight loss by roflumilast].

PubMed

Horna, Oihana; Toyas, Carla

2013-08-04

Roflumilast is a recently marketed drug, indicated for maintenance treatment of severe chronic obstructive pulmonary disease associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment. The safety data of this drug have always been subjected to controversy and concerns. The Food and Drug Administration rejected the drug after the first evaluation, asking the company to clarify the adverse reactions during the investigation process, the European Medicines Agency approved the drug including a Risk Management Plan, designed to promote a safe use of the drug. During the first months after the marketing process, the Spanish Pharmacovigilance System has already been acquainted of several adverse events notifications; therefore, these patients may be closely monitored, mainly because of digestive and psychiatric disorders. Here we report the case of a female patient who showed a serious digestive clinical profile and a severe weight loss, more than 25% of her initial weight, when a treatment with roflumilast was started. The suspicion of a side effect as the cause of the reported clinical profile and its resolution required 3 hospital admissions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Quantitative radiomic profiling of glioblastoma represents transcriptomic expression.

PubMed

Kong, Doo-Sik; Kim, Junhyung; Ryu, Gyuha; You, Hye-Jin; Sung, Joon Kyung; Han, Yong Hee; Shin, Hye-Mi; Lee, In-Hee; Kim, Sung-Tae; Park, Chul-Kee; Choi, Seung Hong; Choi, Jeong Won; Seol, Ho Jun; Lee, Jung-Il; Nam, Do-Hyun

2018-01-19

Quantitative imaging biomarkers have increasingly emerged in the field of research utilizing available imaging modalities. We aimed to identify good surrogate radiomic features that can represent genetic changes of tumors, thereby establishing noninvasive means for predicting treatment outcome. From May 2012 to June 2014, we retrospectively identified 65 patients with treatment-naïve glioblastoma with available clinical information from the Samsung Medical Center data registry. Preoperative MR imaging data were obtained for all 65 patients with primary glioblastoma. A total of 82 imaging features including first-order statistics, volume, and size features, were semi-automatically extracted from structural and physiologic images such as apparent diffusion coefficient and perfusion images. Using commercially available software, NordicICE, we performed quantitative imaging analysis and collected the dataset composed of radiophenotypic parameters. Unsupervised clustering methods revealed that the radiophenotypic dataset was composed of three clusters. Each cluster represented a distinct molecular classification of glioblastoma; classical type, proneural and neural types, and mesenchymal type. These clusters also reflected differential clinical outcomes. We found that extracted imaging signatures does not represent copy number variation and somatic mutation. Quantitative radiomic features provide a potential evidence to predict molecular phenotype and treatment outcome. Radiomic profiles represents transcriptomic phenotypes more well.

Uveitis profile and treatment response in Iranian patients with sarcoidosis.

PubMed

Mahmoudzadeh, Pouya; Tousi, Adib; Ramezani, Alireza; Soheilian, Roham; Soheilian, Masoud

2015-06-01

The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

Sertindole: a clinical efficacy profile.

PubMed

Hale, A

2002-01-01

Sertindole is an effective atypical antipsychotic drug that is associated with significant improvements in the symptoms of schizophrenia. It is at least as efficacious as haloperidol and risperidone in treating the overall and positive symptoms of schizophrenia and has been shown to have advantages over these two drugs with respect to the treatment of the negative symptoms of schizophrenia. In clinical trials, notable improvements in patients' quality of life were observed, which suggest that patients prescribed sertindole would be more likely to adhere to treatment and continue taking the drug as part of their long-term treatment regimen. Continued treatment gives patients the best chance of avoiding relapse. Indeed, other benefits of sertindole demonstrated in clinical trials include relatively low relapse and re-admission rates. Sertindole could theoretically reduce the financial burden of schizophrenia on health- and social-care systems by reducing the need for re-hospitalization and by enabling patients to manage their illness and to live as normal a life as possible.

Incidence, clinical correlates and treatment effect of rage in anxious children.

PubMed

Johnco, Carly; Salloum, Alison; De Nadai, Alessandro S; McBride, Nicole; Crawford, Erika A; Lewin, Adam B; Storch, Eric A

2015-09-30

Episodic rage represents an important and underappreciated clinical feature in pediatric anxiety. This study examined the incidence and clinical correlates of rage in children with anxiety disorders. Change in rage during treatment for anxiety was also examined. Participants consisted of 107 children diagnosed with an anxiety disorder and their parents. Participants completed structured clinical interviews and questionnaire measures to assess rage, anxiety, functional impairment, family accommodation and caregiver strain, as well as the quality of the child's relationship with family and peers. Rage was a common feature amongst children with anxiety disorders. Rage was associated with a more severe clinical profile, including increased anxiety severity, functional impairment, family accommodation and caregiver strain, as well as poorer relationships with parents, siblings, extended family and peers. Rage was more common in children with separation anxiety, comorbid anxiety, attention deficit/hyperactivity disorder and behavioral disorders, but not depressive symptoms. Rage predicted higher levels of functional impairment, beyond the effect of anxiety severity. Rage severity reduced over treatment in line with changes in anxiety symptoms. Findings suggest that rage is a marker of greater psychopathology in anxious youth. Standard cognitive behavioral treatment for anxiety appears to reduce rage without adjunctive treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome].

PubMed

Seijas-Gomez, R; Esteso-Orduna, B; Melero-Llorente, J; Fournier-Del Castillo, M C

2018-05-01

Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.

Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

PubMed

Tsimberidou, Apostolia-Maria

In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Donald R. Korb, OD, FAAO: Clinician Scientist, Colleague, and Teacher.

PubMed

Polse, Kenneth A

2009-10-01

Discovery often begins with a clinical observation that leads to major biomedical discovery. Therefore, well-trained clinical scientists are an important part of the discovery process. Unfortunately, both medicine and optometry have too few well-trained clinician scientists. However, among the few, Dr. Donald Korb stands out as the quintessential optometric clinical scientist. This profile provides insights into the life, thoughts, and unusually productive professional career of Dr. Korb. Of particular interest for many contact lens clinicians is a discussion with Dr. Korb on how some of his clinical observations led to improved diagnostic and treatment procedures.

Adjuvant tamoxifen influences the lipid profile in breast cancer patients.

PubMed

Lin, Che; Chen, Li-Sheng; Kuo, Shou-Jen; Chen, Dar-Ren

2014-02-01

Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs.

PubMed

van Dijl, I C; Le Traon, G; van de Meulengraaf, B D A M; Burgaud, S; Horspool, L J I; Kooistra, H S

2014-01-01

Oral levothyroxine (l-T4 ) supplementation is commonly used to treat hypothyroid dogs. Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4 ) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Ten dogs with naturally occurring hypothyroidism. After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax , 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Silodosin and its potential for treating premature ejaculation: a preliminary report.

PubMed

Sato, Yoshikazu; Tanda, Hitoshi; Nakajima, Hisao; Nitta, Toshikazu; Akagashi, Keigo; Hanzawa, Tatsuo; Tobe, Musashi; Haga, Kazunori; Uchida, Kosuke; Honma, Ichiya

2012-03-01

Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective α1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. α1-Adrenoceptor antagonists are widely used for lower urinary tract symptoms, and clinical studies on silodosin have shown excellent clinical efficacy for lower urinary tract symptoms. However, compared with other α1-adrenoceptor antagonists, silodosin appeared to suppress ejaculation in a relatively higher percent of trial participants. This suppression of ejaculation by silodosin suggested its potential for treating premature ejaculation. Consequently, we evaluated the feasibility of off-label silodosin as a new treatment option for premature ejaculation. Eight patients suffering premature ejaculation were treated with silodosin. Silodosin (4 mg) was given 2 h before sexual intercourse. Intravaginal ejaculatory latency time, premature ejaculation profile item, clinical global impression change in premature ejaculation and systemic adverse events were recorded. Intravaginal ejaculatory latency time was significantly prolonged (from 3.4 min to 10.1 min, P = 0.003). All patients answered better (much better) or slightly better for their own premature ejaculation problem compared with pretreatment condition in the clinical global impression change. Premature ejaculation profile also significantly improved. Two (25%), three (37.5%) and seven patients (87.5%) experienced anejaculation, reduced semen volume and discomfort during orgasm, respectively. However, these problems were not of major concern for the participants. No systemic adverse effects were reported. The current results support the possible use of silodosin as a new treatment option for premature ejaculation, and suggest that a placebo controlled study assessing its clinical usefulness would be worthwhile. © 2011 The Japanese Urological Association.

Psychological profile and work status of a predominantly Hispanic worker's compensation population with chronic limb pain.

PubMed

Monsivais, Jose J; Robinson, Kris

2008-12-01

The purposes of this study were to describe the psychosocial profile and to measure function (posttreatment work status) after surgical and non-surgical treatment in a predominantly Hispanic worker's compensation population with chronic limb pain. We conducted an archival review of records from 91 patients treated for neuropathic pain in a specialty clinic over a 10-year period who had extreme difficulty accepting or managing pain. Medical records from individuals with proven nerve dysfunction experiencing pain >3 months and whose record contained a full psychological evaluation were included. All patients received patient-centered care, a prescription to return to work, periodic pain assessment, and clinical evaluation of sensory and motor function plus pharmacologic pain management. Surgery was determined by the degree of sensory-motor abnormalities in the absence of untreated psychological distress regardless of pain level or worker's compensation status. The majority of patients returned to work after treatment of nerve injury. No differences were noted between surgical/non-surgical treatment groups on initial pain level (p = 0.2), litigation status (p > 0.5), and posttreatment work status (p > 0.05). However, individuals expecting surgery also expected total relief of pain with surgical intervention. Psychosocial assessment, support, and adequate pain treatment seem to mediate the ability of an individual with chronic limb pain to return to work regardless of surgical/non-surgical treatment. Patients' expectations of surgery may be unrealistic and are best addressed prior to treatment.

Psychological Profile and Work Status of a Predominantly Hispanic Worker’s Compensation Population With Chronic Limb Pain

PubMed Central

Monsivais, Jose J.

2008-01-01

The purposes of this study were to describe the psychosocial profile and to measure function (posttreatment work status) after surgical and non-surgical treatment in a predominantly Hispanic worker’s compensation population with chronic limb pain. We conducted an archival review of records from 91 patients treated for neuropathic pain in a specialty clinic over a 10-year period who had extreme difficulty accepting or managing pain. Medical records from individuals with proven nerve dysfunction experiencing pain >3 months and whose record contained a full psychological evaluation were included. All patients received patient-centered care, a prescription to return to work, periodic pain assessment, and clinical evaluation of sensory and motor function plus pharmacologic pain management. Surgery was determined by the degree of sensory-motor abnormalities in the absence of untreated psychological distress regardless of pain level or worker’s compensation status. The majority of patients returned to work after treatment of nerve injury. No differences were noted between surgical/non-surgical treatment groups on initial pain level (p = 0.2), litigation status (p > 0.5), and posttreatment work status (p > 0.05). However, individuals expecting surgery also expected total relief of pain with surgical intervention. Psychosocial assessment, support, and adequate pain treatment seem to mediate the ability of an individual with chronic limb pain to return to work regardless of surgical/non-surgical treatment. Patients’ expectations of surgery may be unrealistic and are best addressed prior to treatment. PMID:18780006

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma

NASA Astrophysics Data System (ADS)

Jalbert, Llewellyn E.; Elkhaled, Adam; Phillips, Joanna J.; Neill, Evan; Williams, Aurelia; Crane, Jason C.; Olson, Marram P.; Molinaro, Annette M.; Berger, Mitchel S.; Kurhanewicz, John; Ronen, Sabrina M.; Chang, Susan M.; Nelson, Sarah J.

2017-03-01

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

[Personalised treatment of disorders in the use of alcohol and nicotine].

PubMed

Dom, G; van den Brink, W; Schellekens, A

There is an increasing interest in personalised treatment based on the individual characteristics of the patient in the field of addiction care. To summarise the present state of staging and profiling possibilities within addiction care. A literature review highlighting the current scientific findings and proposing a theoretical model. There are currently an insufficient number of studies to allow for a fully data driven model. However, research identifying biomarkers is growing and some clinically implementable findings can be put forward. a personalised approach in addiction care holds promise. There is an urgent need for better and larger datasets to empirically support models aimed for clinical use.

Arterial Embolization for the Treatment of Renal Masses and Traumatic Renal Injuries.

PubMed

Ramaswamy, Raja S; Darcy, Michael D

2016-09-01

Renal artery embolization (RAE) for a variety of indications has been performed for several decades. RAE techniques have been refined over time for clinical efficacy and a more favorable safety profile. Owing to improved catheters, embolic agents for precise delivery, and clinical experience, RAE is increasingly used as an adjunct to, or as the preferred alternative to surgical interventions. The indications for RAE are expanding for many urologic and medical conditions. In this article, we focus on the role and technical aspects of RAE in the treatment of renal masses and traumatic renal injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

Vemurafenib in BRAF-mutant metastatic melanoma patients in real-world clinical practice: prognostic factors associated with clinical outcomes.

PubMed

Schouwenburg, Maartje G; Jochems, Anouk; Leeneman, Brenda; Franken, Margreet G; van den Eertwegh, Alfons J M; Haanen, John B A G; van Zeijl, Michiel C T; Aarts, Maureen J; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; Blokx, Willeke A M; de Groot, Jan Willem B; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger H; Kruit, Wim H; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; van der Hoeven, Jacobus J M

2018-08-01

The aim of this population-based study was to identify the factors associated with clinical outcomes in vemurafenib-treated patients and to evaluate outcomes across subgroups of patients with different risk profiles. Data were retrieved from the Dutch Melanoma Treatment Registry. Time to next treatment (TTNT) and overall survival (OS) of all metastatic melanoma patients who received vemurafenib between 2012 and 2015 were assessed using Kaplan-Meier estimates. A risk score was developed on the basis of all prognostic factors associated with TTNT and OS derived from multivariable Cox regression analyses. Patients were stratified according to the presence of prognostic risk factors by counting the number of factors, ranging from 0 to 6. A total of 626 patients received vemurafenib with a median follow-up of 35.8 months. The median TTNT and OS were 4.7 months [95% confidence intervals (CI): 4.4-5.1] and 7.3 months (95% CI: 6.6-8.0). The strongest prognostic factors were serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance score, number of organ sites involved and brain metastases. Patients with a favourable risk profile (no risk factors) had a median TTNT and OS of 7.1 (95% CI: 5.8-8.5) and 15.4 months (95% CI: 10.0-20.9). The median OS more than halved for patients with greater than or equal to 2 risk factors compared with patients with no risk factors. The clinical outcomes of vemurafenib in metastatic melanoma patients with a favourable risk profile are comparable with the results of the trials. Combining prognostic factors into a risk score could be valuable to stratify patients into favourable and poor-prognosis groups.

Gene expression profiling in psoriatic scalp hair follicles: clobetasol propionate shampoo 0.05% normalizes psoriasis disease markers.

PubMed

Aubert, J; Reiniche, P; Fogel, P; Poulin, Y; Lui, H; Lynde, C; Shapiro, J; Villemagne, H; Soto, P; Voegel, J J

2010-11-01

Clobetasol propionate shampoo is effective and safe in treatment of scalp psoriasis (SP). Gene expression profiling of psoriatic skin biopsies led to the identification of numerous disease-related genes. However, it remained unknown whether the gene expression profile of hair follicles of SP patients was also affected. To determine whether psoriasis-related genes are differentially regulated in the hair follicles of SP patients and whether the modulation of these genes can be correlated with clinical severity scores. A single arm, open study was conducted in three centres. SP patients received daily treatment with clobetasol propionate shampoo. At Baseline, Weeks 2 and 4, investigators assessed clinical severity parameters and collected scalp hair follicles in anagen phase. Total RNA extracted from hair follicles was used to determine the expression level of 44 genes, which were reported previously to be upregulated in the skin of psoriasis patients. RNA of good quality and sufficient quantity was obtained from hair follicles of psoriasis patients and healthy volunteers (HV). The expression level of 10 inflammation-related genes was significantly increased in psoriatic hair follicles. The patient's exploratory transcriptomic score, defined as the mean fold modulation of these 10 genes compared with HV, correlated with clinical severity scores. Clobetasol propionate shampoo was effective in decreasing both the exploratory transcriptomics and the clinical severity scores. Hair follicles of SP patients are affected by the inflammatory process. The change in the expression level of inflammation-related genes correlates with the severity of the disease. © 2010 Galderma R&D. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Clinical profile of patients with type 2 diabetes mellitus treated with sodium- glucose cotransporter-2 inhibitors and experience in real-world clinical practice in Spain.

PubMed

Cuatrecasas, Gabriel; Goñi-Goicoechea, Fernando

2016-11-01

The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy. The present study reviews the most appropriate patient profile for SGLT2i therapy, based on their safety and efficacy demonstrated in controlled clinical trials. The article discusses which patients are at risk of experiencing the possible secondary effects due to the mechanism of action of this new therapeutic class, in whom SGLT2i should be used with caution. These considerations on the profile of patients suitable for SGLT2i therapy are contrasted with the results obtained in daily clinical practice, both in retrospective studies from other countries and from real-world experiences in Spain. This article presents a selection of studies performed in distinct centres with a minimum follow-up of 6 months and compares their results with those from clinical trials. SGLT2i are used in clinical practice in any therapeutic step and the efficacy results are very similar to those reported by controlled clinical trials, with a slightly higher proportion of genitourinary infections and a low dropout rate. Half the reported patients are diabetics receiving insulin therapy plus a gliflozin, showing the wide uptake of this therapeutic strategy by clinicians. SGLT2i are especially attractive due to their additional effectiveness in weight and blood pressure control and the possibility of using them in association with other antidiabetic agents or in monotherapy in patients at any stage of type 2 diabetes. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis.

PubMed

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-05-21

To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.

Mindfulness and Psychological Health Outcomes: A Latent Profile Analysis among Military Personnel and College Students.

PubMed

Bravo, Adrian J; Pearson, Matthew R; Kelley, Michelle L

2018-02-01

Previous research on trait mindfulness facets using person-centered analyses (e.g., latent profile analysis [LPA]) has identified four distinct mindfulness profiles among college students: a high mindfulness group (high on all facets of the Five-Factor Mindfulness Questionnaire [FFMQ]), a judgmentally observing group (highest on observing, but low on non-judging of inner experience and acting with awareness), a non-judgmentally aware group (high on non-judging of inner experience and acting with awareness, but very low on observing), and a low mindfulness group (low on all facets of the FFMQ). In the present study, we used LPA to identify distinct mindfulness profiles in a community based sample of U.S. military personnel (majority veterans; n = 407) and non-military college students ( n = 310) and compare these profiles on symptoms of psychological health outcomes (e.g., suicidality, PTSD, anxiety, rumination) and percentage of participants exceeding clinically significant cut-offs for depressive symptoms, substance use, and alcohol use. In the subsample of college students, we replicated previous research and found four distinct mindfulness profiles; however, in the military subsample we found three distinct mindfulness profiles (a combined low mindfulness/judgmentally observing class). In both subsamples, we found that the most adaptive profile was the "high mindfulness" profile (i.e., demonstrated the lowest scores on all psychological symptoms and the lowest probability of exceeding clinical cut-offs). Based on these findings, we purport that the comprehensive examination of an individual's mindfulness profile could help clinicians tailor interventions/treatments that capitalize on individual's specific strengths and work to address their specific deficits.

Wedding Rigorous Scientific Methodology and Ancient Herbal Wisdom to Benefit Cancer Patients: The Development of PHY906.

PubMed

Chu, Edward

2018-02-15

Our research group has extensively characterized the preclinical and clinical activities of PHY906, a traditional Chinese herbal medicine, as a modulator of irinotecan-based chemotherapy for the treatment of colorectal cancer. This article reviews the critical issues of quality control and standardization of PHY906 and highlights the importance of high-quality material for the conduct of preclinical and clinical studies. Studies to investigate the potential biological mechanisms of action using a systems biology approach play a pivotal role in providing the preclinical rationale to move forward with clinical studies. For early-phase clinical studies, translational biomarkers should be incorporated to characterize the biological effects of the herbal medicine. These biomarkers include tumor mutational load, cytokine/chemokine expression, metabolomic profiling, and the presence of key herbal metabolites. Sophisticated bioinformatic approaches are critical for mining the data and identifying those biomarkers that can define the subset of patients who will benefit from PHY906 or any other herbal medicine, in terms of reduced treatment toxicity, improved quality of life, and/or enhanced clinical activity of treatment.

Fundamentals in the management of multiple myeloma.

PubMed

Fadilah, S A W

2010-09-01

Progress in our understanding of multiple myeloma and its treatment has resulted in a more tailored approach to patient management, with different therapeutics regimens for different patient populations. The decision to initiate therapy depends primarily on the presence of symptoms which has to balance the chance of tumor clearance and against the risks of treatment related mortality. Selection of appropriate initial treatment should be based primarily on patient's characteristics (biologic age, co-morbidities), the disease characteristics (tumor burden and genetic risk profile) and the expected toxicity profile of the different regimens. When treatment begins, in younger transplant eligible patients the goal is to achieve high quality responses with intensive therapies as the quality of response appears to be important surrogates for long-term outcome. In the majority of myeloma patients in whom intensive treatment is not an option due to advanced age and co-morbidities, treatment should emphasize on optimal disease control to obtain symptomatic relief and to maintain a satisfactory quality of life. The introduction of novel agents has substantially changed the treatment paradigm of this otherwise incurable disease. The utilization of these drugs has moved from relapse setting to the front line setting and has benefited all patient groups. Because of these rapid developments and many treatment options we need good quality clinical studies to guide clinical practice in the management of patients with multiple myeloma. This review presents an update on current concepts of diagnosis and treatment of patients with multiple myeloma and provides recommendations on tailored therapies with particular reference to the local practice. The information presented herein may be used by the health care providers caring for myeloma patients as a guideline to counsel patients to understand their disease and the treatment better.

Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

PubMed

Kohn, Elise C

2014-01-01

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

PubMed

Porta, Gilda; Carvalho, Elisa de; Santos, Jorge L; Gama, Jorge; Borges, Cristian V; Seixas, Renata B P M; Ferreira, Alexandre R; Miura, Irene K; Silveira, Themis R; Silva, Luciana R; Fagundes, Eleonora D T; Bellomo-Brandao, Maria A; Sawamura, Regina; Vieira, Sandra M; Melere, Melina U; Marques, Cibele D F; Pugliese, Renata P; Danesi, Vera L; Porta, Adriana; Marsillac, Marise E; Valladares, Marcia A; Menezes, Daniela G; Kieling, Carlos; Paula, Mariana N de; Vasconcelos, Juliana R; Ferreira, Cristina T; Perin, Nilza; Resende, Leonardo R; Maia, Jussara; Tommaso, Adriana M A De; Hessel, Gabriel

2018-05-30

This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death. Copyright © 2018. Published by Elsevier Editora Ltda.

Effects of dysthymia on personality assessment.

PubMed

Lecic-Tosevski, D; Divac-Jovanovic, M

1996-01-01

Twenty-eight dysthymic patients (82.1% with personality disorders) were investigated with questionnaires for personality and depression before and after treatment. When in asymptomatic state, defined by clinical criteria and HAM-D score 6 or lower, the personality profile of 15 patients (group I) was significantly changed from the one before treatment (avoidant, passive-aggressive, borderline and schizotypal dimensions were lower, and narcissistic dimension higher [P < 0.01]). Thirteen patients (group II) had an unchanged profile. The first group showed significant state-trait dependence, especially of the borderline personality dimension. The second group manifested a permanent characterological affective syndrome, or a core borderline personality disorder. The limitations of personality assessment during affective episodes are discussed as well as the borderline level of functioning related to it.

Caregiver Treatment Preferences for Children with a New Versus Existing Attention-Deficit/Hyperactivity Disorder Diagnosis

PubMed Central

Park, Alex; Ng, Xinyi; Frosch, Emily; Reeves, Gloria; Cunningham, Charles; Janssen, Ellen M.; Bridges, John F.P.

2017-01-01

Abstract Objectives: Parental experiences with managing their child's attention-deficit/hyperactivity disorder (ADHD) can influence priorities for treatment. This study aimed to identify the ADHD management options caregivers most prefer and to determine if preferences differ by time since initial ADHD diagnosis. Methods: Primary caregivers (n = 184) of a child aged 4–14 years old in care for ADHD were recruited from January 2013 through March 2015 from community-based pediatric and mental health clinics and family support organizations across the state of Maryland. Participants completed a survey that included child/family demographics, child clinical treatment, and a Best–Worst Scaling (BWS) experiment to elicit ADHD management preferences. The BWS comprised 18 ADHD management profiles showing seven treatment attributes, where the best and worst attribute levels were selected from each profile. A conditional logit model using effect-coded variables was used to estimate preference weights stratified by time since ADHD diagnosis. Results: Participants were primarily the mother (84%) and had a college or postgraduate education (76%) with 75% of the children on stimulant medications. One-on-one caregiver behavior training, medication use seven days a week, therapy in a clinic, and an individualized education program were most preferred for managing ADHD. Aside from caregiver training and monthly out-of-pocket costs, caregivers of children diagnosed with ADHD for less than two years prioritized medication use lower than other care management attributes and caregivers of children diagnosed with ADHD for two or more years preferred school accommodations, medication, and provider specialty. Conclusions: Preferences for ADHD treatment differ based on the duration of the child's ADHD. Acknowledging that preferences change over the course of care could facilitate patient/family-centered care planning across a range of resources and a multidisciplinary team of professionals. PMID:27991834

Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

PubMed

Ray, Rajat; Dhawan, Anju; Chopra, Anita

2013-10-01

The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies.

PubMed

Giovannoni, Gavin; Kappos, Ludwig; Gold, Ralf; Khatri, Bhupendra O; Selmaj, Krzysztof; Umans, Kimberly; Greenberg, Steven J; Sweetser, Marianne; Elkins, Jacob; McCroskery, Peter

2016-09-01

Daclizumab has been evaluated in multicentre, randomised, double-blind studies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Safety and tolerability are key considerations in MS treatment selection, as they influence adherence to medication. Evaluate the safety of daclizumab in patients with RRMS from an integrated analysis of six clinical studies. Patients treated with at least one dose of subcutaneous daclizumab 150mg or 300mg monthly in three completed and three ongoing clinical studies were included in this integrated analysis. Cumulative incidence of treatment-emergent adverse events (AEs) was the primary endpoint. This analysis included 2236 patients with 5214 patient-years of exposure to daclizumab. The cumulative incidence of any AE was 84% and of any serious AE excluding MS relapse was 16%. The incidences of AEs when evaluated by 6-month intervals remained stable over the 6.5 years of maximum follow-up. Most AEs were mild or moderate in severity. An important safety concern associated with daclizumab therapy involved hepatic AEs (16%) and serum transaminase elevations at least three times the upper limit of normal (10%), most of which were asymptomatic, self-limiting, and non-recurring. Cumulative incidences of cutaneous, infectious, and gastrointestinal AEs were 33%, 59%, and 25%, respectively; most events either resolved spontaneously or were treated successfully with standard medical interventions and did not result in discontinuation of treatment. This integrated analysis demonstrates that treatment of RRMS with daclizumab for periods of up to 6.5 years is associated with an acceptable safety profile with no evidence of cumulative toxicity over time. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Caregiver Treatment Preferences for Children with a New Versus Existing Attention-Deficit/Hyperactivity Disorder Diagnosis.

PubMed

dosReis, Susan; Park, Alex; Ng, Xinyi; Frosch, Emily; Reeves, Gloria; Cunningham, Charles; Janssen, Ellen M; Bridges, John F P

2017-04-01

Parental experiences with managing their child's attention-deficit/hyperactivity disorder (ADHD) can influence priorities for treatment. This study aimed to identify the ADHD management options caregivers most prefer and to determine if preferences differ by time since initial ADHD diagnosis. Primary caregivers (n = 184) of a child aged 4-14 years old in care for ADHD were recruited from January 2013 through March 2015 from community-based pediatric and mental health clinics and family support organizations across the state of Maryland. Participants completed a survey that included child/family demographics, child clinical treatment, and a Best-Worst Scaling (BWS) experiment to elicit ADHD management preferences. The BWS comprised 18 ADHD management profiles showing seven treatment attributes, where the best and worst attribute levels were selected from each profile. A conditional logit model using effect-coded variables was used to estimate preference weights stratified by time since ADHD diagnosis. Participants were primarily the mother (84%) and had a college or postgraduate education (76%) with 75% of the children on stimulant medications. One-on-one caregiver behavior training, medication use seven days a week, therapy in a clinic, and an individualized education program were most preferred for managing ADHD. Aside from caregiver training and monthly out-of-pocket costs, caregivers of children diagnosed with ADHD for less than two years prioritized medication use lower than other care management attributes and caregivers of children diagnosed with ADHD for two or more years preferred school accommodations, medication, and provider specialty. Preferences for ADHD treatment differ based on the duration of the child's ADHD. Acknowledging that preferences change over the course of care could facilitate patient/family-centered care planning across a range of resources and a multidisciplinary team of professionals.

Molecular Profiling of Glatiramer Acetate Early Treatment Effects in Multiple Sclerosis

PubMed Central

Achiron, Anat; Feldman, Anna; Gurevich, Michael

2009-01-01

Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood. Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC). Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS. Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation. Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity. PMID:19893201

Orthodontic camouflage versus orthodontic-orthognathic surgical treatment in class II malocclusion: a systematic review and meta-analysis.

PubMed

Raposo, R; Peleteiro, B; Paço, M; Pinho, T

2018-04-01

This systematic review was performed to compare dental, skeletal, and aesthetic outcomes between orthodontic camouflage and surgical-orthodontic treatment, in patients with a skeletal class II malocclusion and a retrognathic mandible who have already finished their growth period. A literature search was conducted, and a modified Downs and Black checklist was used to assess methodological quality. The meta-analysis was conducted using the DerSimonian-Laird random-effects method to obtain summary estimates of the standardized mean differences and corresponding 95% confidence intervals. Nine articles were included in the qualitative synthesis and seven in the meta-analysis. The difference between treatments was not statistically significant regarding SNA angle, linear measurement of the lower lip to Ricketts' aesthetic line, convexity of the skeletal profile, or the soft tissue profile excluding the nose. In contrast, surgical-orthodontic treatment was more effective with regard to ANB, SNB, and ML/NSL angles and the soft tissue profile including the nose. Different treatment effects on overjet and overbite were found according to the severity of the initial values. These results should be interpreted with caution, due to the limited number of studies included and because they were non-randomized clinical trials. Further studies with larger sample sizes and similar pre-treatment conditions are needed. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Radioimmunotherapy for treatment of B-cell lymphomas and other hematologic malignancies.

PubMed

Park, Steven I; Press, Oliver W

2007-11-01

Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. Recent data suggest that radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. The safety and efficacy of radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define radioimmunotherapy's role in the treatment of lymphomas.

Molecular analysis of transplant rejection: marching onward

PubMed Central

Lakkis, Fadi G.

2013-01-01

Transcriptional profiling of organ transplants is increasingly defining the biological pathways responsible for graft rejection at the molecular level and identifying gene transcripts that diagnose or predict rejection. These advances hold significant promise for the treatment of organ rejection and for improving clinical outcomes after transplantation, but hurdles remain. PMID:24145950

Personality Profiles of Intimate Partner Violence Offenders with and without PTSD

ERIC Educational Resources Information Center

Hoyt, Tim; Wray, Alisha M.; Wiggins, Kathryn T.; Gerstle, Melissa; Maclean, Peggy C.

2012-01-01

Intimate partner violence (IPV) is a serious forensic and clinical problem throughout the United States. Research aimed at defining and differentiating subgroups of IPV offenders using standardized personality instruments may eventually help with matching treatments to specific individuals to reduce recidivism. The current study used a convenience…

Cognitive status and profile validity on the Personality Assessment Inventory (PAI) in offenders with serious mental illness.

PubMed

Matlasz, Tatiana M; Brylski, Jamie L; Leidenfrost, Corey M; Scalco, Matt; Sinclair, Samuel J; Schoelerman, Ronald M; Tsang, Valerie; Antonius, Daniel

Cognitive impairment among seriously mentally ill offenders has implications for legal matters (e.g., competency to stand trial), as well as clinical treatment and care. Thus, being able to identify potential cognitive concerns early in the adjudication process can be important when deciding on further interventions. In this study, we examined the validity scales of the Personality Assessment Inventory (PAI), scores on the Wechsler Adult Intelligence Scale-IV (WAIS-IV), and competency findings in male inmates (n=61) diagnosed with a serious mental illness. Lower scores on the WAIS-IV significantly (p=0.001) predicted invalid, versus valid, PAI profiles, with working memory impairment being the most significant (p=0.004) predictor of an invalid profile. Ancillary analyses on a smaller sample (n=18) indicate that those with invalid PAI profiles were more likely to be deemed legally incompetent (p=0.03). These findings suggest that the PAI validity scales may be informative in detecting cognitive concerns and help clinicians make determinations about competency restoration and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen's disease: a tear proteomic study.

PubMed

Mukhopadhyay, Somnath; Sen, Swarnali; Datta, Himadri

2015-01-01

To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. CTRI/2013/07/003802. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer

PubMed Central

Blackhall, Fiona; Ross Camidge, D; Shaw, Alice T; Soria, Jean-Charles; Solomon, Benjamin J; Mok, Tony; Hirsh, Vera; Jänne, Pasi A; Shi, Yuankai; Yang, Pan-Chyr; Pas, Tommaso De; Hida, Toyoaki; Carpeño, Javier De Castro; Lanzalone, Silvana; Polli, Anna; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D; Kim, Dong-Wan

2017-01-01

Purpose Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005, the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC. Patients and methods PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg twice daily; 3 week continuous treatment cycles) in patients with ALK-positive NSCLC after failure of ≥1 lines of systemic treatment for locally advanced/metastatic disease. Patients’ tumour ALK status was initially determined by a central laboratory until a protocol amendment permitted enrolment of patients based on locally determined ALK status. Co-primary endpoints were objective response rate (ORR), evaluated using Response Evaluation Criteria in Solid Tumours V.1.1 and adverse events (AEs). Cancer-specific patient-reported outcomes (PROs) were also assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 and its lung cancer module QLQ-LC13. Results 1069 patients were enrolled; 1066 received crizotinib. The as-treated population comprised 908 and 158 patients, in whom tumour positive ALK-status was determined centrally (± locally) or locally only, respectively. At baseline, a majority of patients were <65 years (84%), 66% were never smokers and 46% were Asian. Derived investigator-assessed ORR was 54% (95% CI 51 to 57) and 41% (95% CI 33 to 49) in the central-testing and local-testing subgroups, respectively. The most common treatment-related AEs in the overall population (any grade) were vision disorder (58%), nausea (51%), diarrhoea (47%) and vomiting (47%). PRO scores demonstrated clinically meaningful improvement in lung cancer symptoms and global quality of life. Conclusion The efficacy, safety and PRO profiles of crizotinib in this cohort of 1066 patients with ALK-positive NSCLC are consistent with previous reports. Trial registration number Phase 2 trial (NCT00932451); Results. PMID:29209525

Could single nucleotide polymorphisms influence on the efficacy of platelet-rich plasma in the treatment of sport injuries?

PubMed Central

Pruna, Ricard; Til, Lluis; Artells, Rosa

2014-01-01

Summary Platelet-rich plasma (PRP) is a new powerful biological tool in sports medicine, when used to treat tendon, ligament and muscle injuries. PRP is a fraction of autologous whole blood containing an increased number of platelets and a wide variety of cytokines that can improve and accelerate the healing of various tissues. An analysis of the literature shows promising pre-clinical results for PRP treatment, but there is a lack of solid clinical proof to support its use in sports medicine, and in fact, clinical findings on individual responses to PRP treatment are contradictory. These contradictions may be due to interindividual differences in the presence of single nucleotide polymorphisms (SNPs) in genes related to PRPs and/or their receptors. These SNPs can determine a greater or lesser response to this treatment and consequently a shorter or longer recovery time. We have focused our attention in the study of genes related to PRP with the aim to develope a genetic profile that will identify the individuals and injuries most likely to benefit from PRP treatment. PMID:24932449

Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2011-2012.

PubMed

Galindo, Jaime; Amariles, Pedro; Mueses-Marín, Héctor F; Hincapié, Jaime A; González-Avendaño, Sebastián; Galindo-Orrego, Ximena

2016-10-03

Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients. A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load <40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal, skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians. Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42 patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant increase (172 cells/mm 3 ) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of the percentage of cardiovascular risk. The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary ARV drugs. Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202 . Registered 19 November 2015.

The Phenomenology and Treatment Response in Catatonia: A Hospital Based Descriptive Study

PubMed Central

Swain, Sarada Prasanna; Behura, Sushree Sangita; Dash, Manoj Kumar

2017-01-01

Background: Literatures regarding clinical symptomatology and treatment response of catatonia are very few. Objective: To assess onset, clinical profile, diagnostic break up, treatment response and outcome in patients diagnosed as Catatonia, reported to a tertiary care hospital. Methods: The present study was a cross-sectional descriptive study conducted in indoor of Mental Health Institute (Centre of Excellence), S.C.B. Medical College, between March 2015 to March 2016. A total of 34 patients were included in the study who reported at outdoor department of Mental Health Institute with catatonic symptoms. All patients admitted in inpatient department were routinely assessed through a detailed semi-structured interview. The diagnosis of catatonia was made if the patients present with three or more symptoms out of twelve symptoms fulfilling the criteria of DSM-5. All the patients were assessed through Bush-Francis Catatonia Rating Scale. They were initially given parental lorazepam at the doses ranging from 4-12 mg per day as per requirement. Patients who did not respond to lorazepam trial were given ECT. Results: The patients were predominantly presented with retarded symptoms of catatonia such as staring, mutism, withdrawal, posturing and negativism. Schizophrenia and other psychotic spectrum disorders were more commonly presented as catatonia as compared to mood disorders. Younger age group patients were mainly responded to lorazepam only, whereas older age group patients responded to both ECT and lorazepam. Conclusion: This study has came out with very important insights in the age of incidence, phenomenology, clinical profile, source of referral, diagnostic break up and treatment response with lorazepam and ECT in catatonic patients following mental disorder. PMID:28615768

Immune response of patients with recurrent aphthous stomatitis challenged with a symbiotic.

PubMed

Mimura, Maria Angela Martins; Borra, Ricardo Carneiro; Hirata, Cleonice Hitomi Watashi; de Oliveira Penido, Norma

2017-10-01

There are indications that Th1 polarization of immune response plays an important role in the pathogenesis of recurrent aphthous stomatitis (RAS), and that the use of probiotics can stimulate immune regulatory activity, influencing the course of the disease. The aim of this study was to characterize the initial immune profile of RAS patients and evaluate clinical and serological response following a challenge with symbiotic treatment containing fructooligosaccharide, Lactobacillus, and Bifidobacterium. The immune responses of the 45 patients with RAS, submitted to symbiotic or placebo for 120 days, in relation to 30 RAS-free controls, were evaluated over a period of 6 months. Peripheral blood was collected from all patients at 0 (T0), 120 (T4), and 180 days (T6) after the start of treatment and Th1 (IL12-p70, IFN-γ), Th2 (IL-4), Treg (IL-10), Th17 (IL-17A), inflammatory (TNF-α, IL-6)-associated cytokines, and clinical parameters were quantified. At T0, significant differences were found in the serological levels of the IFN-γ, IL-4, and IL-6 cytokines of the RAS patients in comparison with the controls. It was observed that the cytokine profile of the RAS group was comprised of 2 distinct clusters: a pure Th2 and a Mixed (Th1/Th2) subtype and that symbiotic treatment induced an improvement in pain and an increase in IFN-γ levels, producing a reduction in Th2 response. In RAS, symbiotic treatment based on a fructooligosaccharide, Lactobacillus, and Bifidobacterium composition produced an alteration in the Th2 serological immune profile in the direction of Th1 and improved pain symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical, epidemiological, and therapeutic profile of dermatophytosis*

PubMed Central

Pires, Carla Andréa Avelar; da Cruz, Natasha Ferreira Santos; Lobato, Amanda Monteiro; de Sousa, Priscila Oliveira; Carneiro, Francisca Regina Oliveira; Mendes, Alena Margareth Darwich

2014-01-01

BACKGROUND The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. OBJECTIVE To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. METHOD A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. RESULTS The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). CONCLUSION This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement. PMID:24770502

Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

PubMed Central

Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

2014-01-01

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature.

PubMed

Cossu, Giulia; Levivier, Marc; Daniel, Roy Thomas; Messerer, Mahmoud

2015-01-01

We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients. A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition. A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered. No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.

Demographic and Clinical Profile of Patients With Dementia Receiving Electroconvulsive Therapy: A Case-Control Study.

PubMed

Zhang, Qing-E; Sha, Sha; Ungvari, Gabor S; Chiu, Helen F K; Ng, Chee H; He, Hong-Bo; Forester, Brent P; Xiang, Yu-Tao

2016-09-01

Little is known about the clinical characteristics of patients with dementia receiving electroconvulsive therapy (ECT) for the treatment of behavioral symptoms. This study examined the demographic and clinical profile of patients with dementia receiving ECT in China. This was a retrospective, case-control study. The sample was composed of 23 patients with dementia treated with ECT and 71 sex- and age-matched controls treated for a period of 8 years (2007-2014) at the National Clinical Research Centre of Mental Disorders, China. Sociodemographic and clinical data were collected from the electronic chart management system. Multiple logistic regression analysis revealed that ECT was independently associated with high risk for suicide at admission. The recorded indications for ECT included both high risk for suicide and aggressive behavior. Most patients responded to ECT satisfactorily (56.5%) or partially (34.8%) with only mild-moderate transient memory impairment (30.4%). Although this is a preliminary study limited by the retrospective design and small sample size, findings suggest that ECT is an effective and safe therapeutic intervention to reduce the risk for suicide and aggressive behavior in dementia.

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

PubMed

Benson, Al B; Venook, Alan P; Cederquist, Lynette; Chan, Emily; Chen, Yi-Jen; Cooper, Harry S; Deming, Dustin; Engstrom, Paul F; Enzinger, Peter C; Fichera, Alessandro; Grem, Jean L; Grothey, Axel; Hochster, Howard S; Hoffe, Sarah; Hunt, Steven; Kamel, Ahmed; Kirilcuk, Natalie; Krishnamurthi, Smitha; Messersmith, Wells A; Mulcahy, Mary F; Murphy, James D; Nurkin, Steven; Saltz, Leonard; Sharma, Sunil; Shibata, David; Skibber, John M; Sofocleous, Constantinos T; Stoffel, Elena M; Stotsky-Himelfarb, Eden; Willett, Christopher G; Wu, Christina S; Gregory, Kristina M; Freedman-Cass, Deborah

2017-03-01

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions. Copyright © 2017 by the National Comprehensive Cancer Network.

A precision medicine approach to a patient with unresolved pain following orthopedic surgery: a case report.

PubMed

Gazzaniga, David; Brenton, Ashley; Meshkin, Brian

2017-02-24

Precision medicine is a promising technology in patient care that combines genetic analysis with clinical data, such as health, behavioral, functional, environment, and lifestyle information. Here we present the case of a 54-year old woman who, following an accident, had uncontrolled chronic pain and was subsequently labeled a drug seeker. A 54-year-old white woman who was experiencing severe calf pain was referred for treatment. Her pain was insufficiently controlled immediately following knee arthroplasty with multiple opioid medications, as well as non-opioids. Precision medicine testing was ordered for her so that we could assess her pain sensitivity objectively to determine if the pill seeker designation was correct and to determine the best medications for her. Based on the Proove profiles, we determined that she had moderately low pain sensitivity, which means that clinically she may underreport pain and may have decreased medication needs. This result suggested that her continued reporting of unresolved pain was probably due to a condition unresolved by her right knee arthroplasty. In addition, she was found to be at low risk of opioid addiction, based on the Proove Opioid Risk Profile. Taken together, along with the high levels of pain she described, we determined that her pain was not properly controlled and that the designation of pill seeker was incorrect. The next step was to determine which medications and which doses would result in the most favorable outcomes for our patient. To determine this, we used the results of the Proove Opioid Response, Proove Drug Metabolism, and Proove Non-Opioid Profiles to guide her treatment. We reduced her pain medications to a single opioid, Vicodin (acetaminophen and hydrocodone), which also eliminated the adverse side effects she experienced. Precision medicine offers an important health care decision tool which can reduce emotional and physical costs to patients and may reduce the economic health care burden of unnecessary surgeries and ineffective medication. The information provided by these profiles can be used clinically to guide treatment decisions and evaluate patient pain.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

PubMed

Ilag, L L; Deeg, M A; Costigan, T; Hollander, P; Blevins, T C; Edelman, S V; Konrad, R J; Ortmann, R A; Pollom, R K; Huster, W J; Zielonka, J S; Prince, M J

2016-02-01

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Concurrent and prognostic utility of subtyping anorexia nervosa along dietary and negative affect dimensions.

PubMed

Forbush, Kelsie T; Hagan, Kelsey E; Salk, Rachel H; Wildes, Jennifer E

2017-03-01

Bulimia nervosa can be reliably classified into subtypes based on dimensions of dietary restraint and negative affect. Community and clinical studies have shown that dietary-negative affect subtypes have greater test-retest reliability and concurrent and predictive validity compared to subtypes based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Although dietary-negative affect subtypes have shown utility for characterizing eating disorders that involve binge eating, this framework may have broader implications for understanding restrictive eating disorders. The purpose of this study was to test the concurrent and predictive validity of dietary-negative affect subtypes among patients with anorexia nervosa (AN; N = 194). Latent profile analysis was used to identify subtypes of AN based on dimensions of dietary restraint and negative affect. Chi-square and multivariate analysis of variance were used to characterize baseline differences between identified subtypes. Structural equation modeling was used to test whether dietary-negative affect subtypes would outperform DSM categories in predicting clinically relevant outcomes. Results supported a 2-profile model that replicated dietary-negative affect subtypes: Latent Profile 1 (n = 68) had clinically elevated scores on restraint only; Latent Profile 2 (n = 126) had elevated scores on both restraint and negative affect. Validation analyses showed that membership in the dietary-negative affect profile was associated with greater lifetime psychiatric comorbidity and psychosocial impairment compared to the dietary class. Dietary-negative affect subtypes only outperformed DSM categories in predicting quality-of-life impairment at 1-year follow-up. Findings highlight the clinical utility of subtyping AN based on dietary restraint and negative affect for informing future treatment-matching or personalized medicine strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Stanulla, Martin; Fine, Bernard M; Teuffel, Oliver; Neuhoff, Nils V; Schrauder, André; Flohr, Thomas; Schäfer, Beat W; Bartram, Claus R; Welte, Karl; Schlegelberger, Brigitte; Schrappe, Martin

2005-01-15

Treatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL.

The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease.

PubMed

Malerba, Mario; Radaeli, Alessandro; Santini, Giuseppe; Morjaria, Jaymin; Mores, Nadia; Mondino, Chiara; Macis, Giuseppe; Montuschi, Paolo

2018-06-01

Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M 3 muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs. Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area. The following aspects are covered: a) the discovery and medicinal chemistry of aclidinium bromide; b) an overview of the market; c) its mechanism of action; d) its pharmacokinetic/pharmacodynamic profile derived from pre-clinical studies; e) the clinical studies which led to its licensing; f) the evidence from meta-analyses; g) the aclidinium/formoterol fixed dose combination for COPD and h) priorities in this area of research. Expert opinion: Aclidinium bromide has the pharmacological properties, safety and efficacy profile and inhaler characteristics which makes it a valuable therapeutic option for pharmacological management of patients with COPD. Due to its rapid biotransformation into inactive metabolites, aclidinium is potentially one of the safest LAMAs. Further head-to-head randomized clinical trials are required to define efficacy and safety of aclidinium when compared to once-daily LAMAs. The clinical relevance of airway anti-remodeling effects of aclidinium has to be defined.

An overview of early drug development for endometriosis.

PubMed

Leone Roberti Maggiore, Umberto; Ferrero, Simone

2016-01-01

Endometriosis is an estrogen-dependent chronic disease of women of fertile age requiring chronic therapy. Although available drugs have good efficacy and safety profiles, some patients experience partial or no improvement of pain with conventional treatment and recurrence of symptoms after discontinuation of the therapies. For these reasons, many new compounds are currently under investigation for the treatment of endometriosis. This review offers the reader a complete and updated overview on emerging therapies for the treatment of endometriosis. The authors describe, in detail, the laboratory and clinical studies on these therapies and highlight the potential advantages and limitations associated with the administration of these new agents. Gonadotropin-releasing hormone antagonists are the most intriguing emerging agents for the treatment of patients with endometriosis. It should be noted that while there are a number of drugs under investigation, a large majority of these new compounds have only been investigated in laboratory studies with more extensive research required to better elucidate their efficacy and safety profiles.

VMAT2 Inhibitors: New Drugs for the Treatment of Tardive Dyskinesia.

PubMed

Kim, Anne P; Baker, Danial E; Levien, Terri L

2018-04-01

To provide a review of tardive dyskinesia (TD) symptoms, etiology, pathophysiology, and treatments. PubMed, Web of Science, ClinicalTrials. gov, and Google Scholar were searched for relevant literature using a combination of the following terms: tardive dyskinesia, treatment, management, guidelines, tetrabenazine, deutetrabenazine, and valbenazine. Sources were limited to human data. Articles were reviewed for relevance to TD therapy. Reference lists were manually searched for other relevant articles. Selected literature was published between 1968 and 2017. This article reviews treatment options available for patients with TD. Many agents have been tried off-label to manage symptoms, with limited evidence of benefit. The Food and Drug Administration approved the first drug to treat TD valbenazine on April 11, 2017. TD is largely iatrogenic. Valbenazine's approval by the Food and Drug Administration was followed by the approval of deutetrabenazine, a drug with similar mechanism of action. Further data from postmarketing studies will be needed to verify that valbenazine's adverse effect profile is different from the profiles of tetrabenazine and deutetrabenazine.

Integrating hinge axis approximation and the virtual facial simulation of prosthetic outcomes for treatment with CAD-CAM immediate dentures: A clinical report of a patient with microstomia.

PubMed

Kuric, Katelyn M; Harris, Bryan T; Morton, Dean; Azevedo, Bruno; Lin, Wei-Shao

2017-09-29

This clinical report describes a digital workflow using extraoral digital photographs and volumetric datasets from cone beam computed tomography (CBCT) imaging to create a 3-dimensional (3D), virtual patient with photorealistic appearance. In a patient with microstomia, hinge axis approximation, diagnostic casts simulating postextraction alveolar ridge profile, and facial simulation of prosthetic treatment outcome were completed in a 3D, virtual environment. The approach facilitated the diagnosis, communication, and patient acceptance of the treatment of maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) of immediate dentures at increased occlusal vertical dimension. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.

PubMed

Lancaster, Lisa H; de Andrade, Joao A; Zibrak, Joseph D; Padilla, Maria L; Albera, Carlo; Nathan, Steven D; Wijsenbeek, Marlies S; Stauffer, John L; Kirchgaessler, Klaus-Uwe; Costabel, Ulrich

2017-12-31

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Copyright ©ERS 2017.

Assessment Practices of Child Clinicians.

PubMed

Cook, Jonathan R; Hausman, Estee M; Jensen-Doss, Amanda; Hawley, Kristin M

2017-03-01

Assessment is an integral component of treatment. However, prior surveys indicate clinicians may not use standardized assessment strategies. We surveyed 1,510 clinicians and used multivariate analysis of variance to explore group differences in specific measure use. Clinicians used unstandardized measures more frequently than standardized measures, although psychologists used standardized measures more frequently than nonpsychologists. We also used latent profile analysis to classify clinicians based on their overall approach to assessment and examined associations between clinician-level variables and assessment class or profile membership. A four-profile model best fit the data. The largest profile consisted of clinicians who primarily used unstandardized assessments (76.7%), followed by broad-spectrum assessors who regularly use both standardized and unstandardized assessment (11.9%), and two smaller profiles of minimal (6.0%) and selective assessors (5.5%). Compared with broad-spectrum assessors, unstandardized and minimal assessors were less likely to report having adequate standardized measures training. Implications for clinical practice and training are discussed.

Current and future immunotherapeutic approaches in Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Borchmann, Peter; Engert, Andreas

2016-09-01

Hodgkin lymphoma (HL) has become a highly curable malignancy even in advanced stages when treated adequately. However, relapsed or refractory disease and treatment-related toxicity constitute a significant clinical challenge. Innovative approaches are thus needed to improve treatment of these mainly young patients. In HL lesions, very few malignant Hodgkin and Reed-Sternberg (HRS) cells are embedded in an immunosuppressive microenvironment of reactive cells. Novel approaches such as bispecific antibodies, antibody-drug conjugates, immune-checkpoint inhibitors or adoptive cellular therapies are currently being investigated with promising results in relapsed or refractory patients. Encouraging response rates and a favorable toxicity profile have recently been reported in early phase clinical trials with antibodies blocking the programed-death receptor 1 (PD1). This review will summarize the current clinical knowledge on mechanism, safety and efficacy of the different agents and discuss potential future strategies, which are partly already investigated within clinical trials.

MAO-inhibitors in Parkinson's Disease

PubMed Central

Laux, Gerd

2011-01-01

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD. PMID:22110357

Comparison between zero-profile spacer and plate with cage in the treatment of single level cervical spondylosis.

PubMed

Lan, Tao; Lin, Jian-Ze; Hu, Shi-Yu; Yang, Xin-Jian; Chen, Yang

2018-01-01

Retrospective study of 68 patients of symptomatic cervical spondylosis who were treated by anterior cervical discectomy and fusion (ACDF). The purpose of this study was to compare the clinical and radiological outcomes of patients with single level cervical spondylosis using either zero-profile spacer (group A) or anterior cervical plate and cage (group B). Clinical and radiological data of 68 patients undergoing ACDF from C3-C7 were collected retrospectively. There were 35 patients with a mean age of 54.05 years who received treatment by zero-profile implant. A total of 33 patients with a mean age of 52.09 years underwent fusion by traditional plate with cage. Group A and group B were followed up for an average of 23.68 months and 24.39 months, respectively. Age, blood loss, and operation time were assessed. The clinical outcomes were evaluated by JOA and VAS score before and after surgery. In addition, incidence of dysphagia was recorded. The Cobb angle (from C2 to C7) change was measured on the lateral cervical spine radiographs. There was no significant difference in terms of operation time and blood loss between two groups. The postoperative JOA significantly increased and the VAS decreased correspondently in both groups. The postoperative Cobb angle increased and showed statistical difference compared with preoperative Cobb angle in both groups. There was no significant difference between group A and group B in achieving clinical symptoms and radiograph improvement according to postoperative JOA, VAS and Cobb angle comparison. The incidence of postoperative dysphagia was lower in the group A than group B. Our study suggests that the application of zero-p spacer can achieve similar clinical and radiological improvement compared with traditional plate and cage. Meanwhile, zero-p is superior to plate and cage with a lower incidence of postoperative dysphagia.

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes.

PubMed

Kullenberg, Torbjörn; Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-08-01

Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. ClincialTrials.gov, clinicaltrials.gov, NCT00069329. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Drospirenone/Ethinyl Estradiol Versus Rosiglitazone Treatment in Overweight Adolescents with Polycystic Ovary Syndrome: Comparison of Metabolic, Hormonal, and Cardiovascular Risk Factors

PubMed Central

Tfayli, Hala; Ulnach, Julia Warren; Lee, SoJung; Sutton-Tyrrell, Kim

2011-01-01

Context: Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. Objective: Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. Design: We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. Outcome Measures: The primary outcome measure was insulin sensitivity, hepatic with [6,6-2H2]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. Results: Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. Conclusions: In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to test insulin sensitizers in the treatment of the reproductive and cardiometabolic aspects of PCOS. PMID:21325466

Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.

PubMed

Tfayli, Hala; Ulnach, Julia Warren; Lee, SoJung; Sutton-Tyrrell, Kim; Arslanian, Silva

2011-05-01

Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to test insulin sensitizers in the treatment of the reproductive and cardiometabolic aspects of PCOS.

The 14th Hoyt Lecture: Ischemic Optic Neuropathy: The Evolving Profile, 1966-2015.

PubMed

Arnold, Anthony C

2016-06-01

Since the first English language description by Miller and Smith in 1966 of ischemic optic neuropathy as a distinct ophthalmic syndrome, a long series of studies has refined the clinical profile to what we consider to be accurate today. From the specifics of pathogenesis to the clinical appearance to the effect of therapy, the basic tenets of diagnosis and management have evolved over 5 decades. What we thought we knew about the following topics has changed: location of vasculopathy; incidence; age at onset; optic disc appearance; risk factors for development; natural history; rate of fellow eye involvement; ischemia as an all-or-none phenomenon; and treatment. A look back at these discoveries shows both how far we have come and how far we have to go in managing this disorder.

Ethnic variations regarding clinical profiles and symptom representation in prisoners with psychotic disorders.

PubMed

Denzel, A Dorina; Harte, Joke M; van den Bergh, Mattis; Scherder, Erik J A

2018-01-01

Black and minority ethnic (BME) groups are known to have higher prevalences of psychotic disorders and are over-represented in western penitentiaries and forensic psychiatric institutions. Research from regular mental healthcare settings suggests that they could show different and more severe psychotic symptoms. Aims To explore ethnic variations in severity of symptomatology of BME and non-BME detainees with psychotic disorders. In this study, 824 patients with psychotic disorders from seven different ethnic groups, imprisoned in a penitentiary psychiatric centre in the Netherlands, were compared on symptom severity and symptom representation using the BPRS-E clinical interview. Data were analysed by means of a multilevel analysis. BME patients with psychotic disorders are over-represented in forensic psychiatry, and symptom profiles of prisoners with psychotic disorders vary by ethnicity. Additionally, severity levels of overall psychopathology differ between ethnic groups: patients with an ethnic majority status show more severe levels of psychopathology compared with BME patients. There are differences in symptom severity and symptom profiles between BME patients and non-BME patients. Disregarding these differences could have an adverse effect on the outcome of the treatment. Possible explanations and clinical impact are discussed. Declaration of interest None.

Advances in the molecular genetics of gliomas - implications for classification and therapy.

PubMed

Reifenberger, Guido; Wirsching, Hans-Georg; Knobbe-Thomsen, Christiane B; Weller, Michael

2017-07-01

Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

GUIDELINES OF CARE FOR THE MANAGEMENT OF ATOPIC DERMATITIS

PubMed Central

Sidbury, Robert; Davis, Dawn M.; Cohen, David E.; Cordoro, Kelly M.; Berger, Timothy G.; Bergman, James N.; Chamlin, Sarah L.; Cooper, Kevin D.; Feldman, Steven R.; Hanifin, Jon M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Silverman, Robert A.; Simpson, Eric L.; Tom, Wynnis L.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Eichenfield, Lawrence F.

2014-01-01

Atopic dermatitis (AD) is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2-3% of adults. This guideline addresses important clinical questions that arise in AD management and care, providing recommendations based on the available evidence. In this third of four sections, treatment of AD with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option. PMID:24813298

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

XM17 Follitropin Alfa (Ovaleap(®)): A Review in Reproductive Endocrine Disorders.

PubMed

Hoy, Sheridan M

2016-08-01

The subcutaneous recombinant human follicle-stimulating hormone XM17 follitropin alfa (Ovaleap(®)) is approved in the EU as a biosimilar of follitropin alfa (Gonal-f(®)) for use in all indications for which the reference product is approved, including as a multifollicular stimulant in women undergoing superovulation for assisted reproductive technology (ART) treatment. In a nonblind, phase I study in healthy female volunteers, the pharmacokinetic profile of XM17 follitropin alfa was bioequivalent to that of reference follitropin alfa following single dosing. Moreover, in a multinational, phase III study, the efficacy of XM17 follitropin alfa as a multifollicular stimulant was equivalent to that of reference follitropin alfa in terms of the number of retrieved oocytes (primary endpoint) in women undergoing controlled ovarian stimulation for ART treatment. There were no clinically relevant differences in oocyte quality between XM17 follitropin alfa and reference follitropin alfa, with biochemical, clinical and ongoing pregnancy rates and take-home baby rates not significantly differing between the treatment groups. XM17 follitropin alfa was generally well tolerated in this patient population, with its tolerability profile generally similar to that of reference follitropin alfa and with no new unexpected tolerability concerns identified. Thus, XM17 follitropin alfa is an effective treatment option in patients requiring follitropin alfa therapy for various reproductive endocrine disorders, providing a useful alternative to reference follitropin alfa.

Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study.

PubMed

Tagliaferri, Valeria; Romualdi, Daniela; Scarinci, Elisa; Cicco, Simona De; Florio, Christian Di; Immediata, Valentina; Tropea, Anna; Santarsiero, Carla Mariaflavia; Lanzone, Antonio; Apa, Rosanna

2018-02-01

The objective of the study was to investigate the effects of 6 months of melatonin administration on clinical, endocrine, and metabolic features of women affected by polycystic ovary syndrome (PCOS). This is a prospective cohort study including 40 normal-weight women with PCOS between January and September 2016, enrolled in an academic research environment. Ultrasonographic pelvic examinations, hirsutism score evaluation, hormonal profile assays, oral glucose tolerance test, and lipid profile at baseline and after 6 months of melatonin administration were performed. Melatonin treatment significantly decreased androgens levels (free androgen index: P < .05; testosterone: P < .01; 17 hydroxyprogesterone: P < .01). Follicle-stimulating hormone levels significantly raised ( P < .01), and anti-Mullerian hormone serum levels significantly dropped after 6 months of melatonin treatment ( P < .01). No significant changes occurred in glucoinsulinemic and lipid parameters after treatment except a significant decrease of low-density lipoprotein cholesterol. Almost 95% of participants experienced an amelioration of menstrual cycles. Until now, only few data have been published about the role of melatonin in women with PCOS. This is the first study focused on the effects of exogenous oral melatonin administration on the clinical, endocrine, and metabolic characteristics of patients with PCOS. After 6 months of treatment, melatonin seems to improve menstrual irregularities and biochemical hyperandrogenism in women with PCOS through a direct, insulin-independent effect on the ovary. Based on our results, melatonin could be considered a potential future therapeutic agent for women affected by PCOS.

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) cohort.

PubMed

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio S G; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-02-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

PubMed

Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-10-01

Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles After Dermal Application of Rivastigmine Patch.

PubMed

Nozaki, Sachiko; Yamaguchi, Masayuki; Lefèvre, Gilbert

2016-07-01

Rivastigmine is an inhibitor of acetylcholinesterases and butyrylcholinesterases for symptomatic treatment of Alzheimer disease and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the plasma concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks after misuse of the patch (e.g., longer application than 24 h, multiple patches applied at the same time, and so forth). The model comprised 2 compartments which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine and PK parameters after intravenous administration. The model was fitted to the clinical PK profiles after single application of rivastigmine patch to obtain model parameters. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and area under the drug plasma concentration-time curve) conformed to the observed values and then was used to simulate the PK profiles of rivastigmine. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after patch misuse. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Lung tumor diagnosis and subtype discovery by gene expression profiling.

PubMed

Wang, Lu-yong; Tu, Zhuowen

2006-01-01

The optimal treatment of patients with complex diseases, such as cancers, depends on the accurate diagnosis by using a combination of clinical and histopathological data. In many scenarios, it becomes tremendously difficult because of the limitations in clinical presentation and histopathology. To accurate diagnose complex diseases, the molecular classification based on gene or protein expression profiles are indispensable for modern medicine. Moreover, many heterogeneous diseases consist of various potential subtypes in molecular basis and differ remarkably in their response to therapies. It is critical to accurate predict subgroup on disease gene expression profiles. More fundamental knowledge of the molecular basis and classification of disease could aid in the prediction of patient outcome, the informed selection of therapies, and identification of novel molecular targets for therapy. In this paper, we propose a new disease diagnostic method, probabilistic boosting tree (PB tree) method, on gene expression profiles of lung tumors. It enables accurate disease classification and subtype discovery in disease. It automatically constructs a tree in which each node combines a number of weak classifiers into a strong classifier. Also, subtype discovery is naturally embedded in the learning process. Our algorithm achieves excellent diagnostic performance, and meanwhile it is capable of detecting the disease subtype based on gene expression profile.

Noninvasive selective cryolipolysis and reperfusion recovery for localized natural fat reduction and contouring.

PubMed

Sasaki, Gordon H; Abelev, Natalie; Tevez-Ortiz, Ana

2014-03-01

Cryolipolysis is a contemporary method of reducing fat by controlled extraction of heat from adipocytes. The authors recorded temperature profiles during a single cryolipolysis treatment/recovery cycle (with and without massage) and report on the clinical safety and efficacy of this procedure. In the pilot study group (PSG), the abdomens of 6 patients were treated with cryolipolysis and subdermal temperatures were recorded. In the clinical treatment group (CTG), 112 patients were treated without temperature recordings and results were evaluated through matched comparison of standardized photographs, caliper measurements, ultrasound imaging, and global assessments. Thirty minutes into the cooling phase, subdermal temperatures of patients in the PSG declined precipitously from pretreatment levels and remained low until the end of treatment. During recovery, subdermal temperatures of the only subject who received massage returned faster and to higher levels than the temperatures of subjects who did not receive massage. Patients in the CTG who were available for follow-up measurements at 6 months (n = 85) demonstrated an average fat reduction of 21.5% by caliper measurements; 6 random patients from this group also showed an average of 19.6% fat reduction by ultrasound imaging at 6 months. Global assessments were highest for the abdomen, hip, and brassiere rolls. Minimal side effects were observed, and patients experienced no significant downtime. Noninvasive cryolipolysis results in a predictable and noticeable fat reduction within 6 months and does not cause skin damage. Profiling of subdermal temperatures may provide additional insights for improving clinical effectiveness and safety. 3.

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

PubMed

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical comparison of Zero-profile interbody fusion device and anterior cervical plate interbody fusion in treating cervical spondylosis.

PubMed

Yan, Bin; Nie, Lin

2015-01-01

the aim of the study was to compare the clinical effect of Zero-profile interbody fusion device (Zero-P) with anterior cervical plate interbody fusion system (PCB) in treating cervical spondylosis. a total of 98 patients with cervical spondylosis (110 segments) in February 2011 to January 2013 were included in our hospital. All participants were randomly divided into observation group and control group with 49 cases in each group. The observation group was treated with Zero-P, while the control group received PCB treatment. Comparison of the two groups in neurological function score (JOA), pain visual analogue scale (VAS), the neck disability index (NDI), quality of life score (SF-36) and cervical curvature (Cobb angle) change were recorded and analyzed before and after treatment. The observation group was found with 90% excellent and good rate, which was higher than that of the control group (80%). Dysphagia rate in observational group was 16.33% (8/49), which was significantly less than that in control group (46.94%). Operation time and bleeding volume in the observation group was less than those in control group. Postoperative improvements of JOA score, VAS score, and NDI in observational group were also significantly better than that in control group (P<0.05). The clinical effect of Zero-P and PCB for the treatment of cervical spondylosis was quite fair, but Zero-P showed a better therapeutic effect with improvement of life quality.

Case Report: The Effects of Massage Therapy on a Woman with Thoracic Outlet Syndrome

PubMed Central

Wakefield, Mary Lillias

2014-01-01

Introduction Thoracic outlet syndrome (TOS) refers to a group of conditions resulting from compression of the neurovascular structures of the thoracic outlet. The parameters for physical therapy include myofascial release (MFR), neuromuscular therapy (NMT), muscle strengthening, and stretching. This case study examined the effects of neuromuscular therapy, massage, and other manual therapies on a 56-year-old female presenting with bilateral numbness over the forearms and hands on waking. Numbness occurred most days, progressing to “dead rubbery” forearms and hands once or twice a month. Methods The treatment plan was implemented over eight weeks and consisted of six, 50-minute bodywork sessions. Several nonbodywork strategies were also employed to address potential contributing factors to the TOS symptomology experienced by the client. Objective measurements included posture analysis (PA), range of movement (ROM), and Roos and Adson’s tests. The Measure Your Own Medical Outcome Profile (MYMOP2), a client-generated measure of clinical outcome, was used to measure clinical change. Results MYMOP2 overall profile score results demonstrated an improvement of 2.25 from pretreatment to post-treatment measurement. Clinically meaningful change was measured by the individual and was indicative of substantial symptom improvement where a score change of over one was considered as meaningful. Conclusions A course of massage was effective for numbness symptoms in an individual with TOS, and results lasted over a year without additional treatments. Further research is needed to fully understand the effects of massage for TOS symptoms. PMID:25452819

Clinical pharmacology review of safinamide for the treatment of Parkinson's disease.

PubMed

Fabbri, Margherita; Rosa, Mario M; Abreu, Daisy; Ferreira, Joaquim J

2015-12-01

Safinamide (Xadago™) is an oral α-aminoamide derivative marketed for the treatment of Parkinson's disease (PD). The drug has both dopaminergic properties, namely highly selective and reversible inhibition of monoamine oxidase B, and nondopamimetic properties, namely selective sodium channel blockade and calcium channel modulation, with consequent inhibition of excessive glutamate release. In 2014, safinamide was approved in the European Economic Area, as "an add-on therapy to stable dose levodopa, alone or in combination with other PD therapies in mid- to late-stage-fluctuating PD patients." In addition, evidence has been provided for safinamide in the treatment of motor symptoms in early PD patients. This article summarizes the pharmacological properties, development program, clinical indications for PD treatment, stratified according to several disease's stages and the safety profile of safinamide. A meta-analysis of the most frequent adverse events among Phase III trials has been also performed.

The current status of immunotherapy in peritoneal carcinomatosis.

PubMed

Ströhlein, Michael Alfred; Heiss, Markus Maria; Jauch, Karl-Walter

2016-10-01

Peritoneal carcinomatosis (PC) is a cancer disease with an urgent need for effective treatment. Conventional chemotherapy failed to show acceptable results. Cytoreductive surgery and hyperthermic chemoperfusion (HIPEC) are only beneficial in few patients with resectable peritoneal metastasis. Immunotherapy could be attractive against PC, as all requirements for immunotherapy are available in the peritoneal cavity. This review analyzes the present literature for immunotherapy of PC. Advances from immune stimulators, radionucleotide-conjugated- and bispecific antibodies to future developments like adoptive engineered T-cells with chimeric receptors are discussed. The clinical development of catumaxomab, which was the first intraperitoneal immunotherapy to be approved for clinical treatment, is discussed. The requirements for future developments are illustrated. Expert commentary: Immunotherapy of peritoneal carcinomatosis is manageable, showing striking cancer cell killing. Improved profiles of adverse events by therapy-induced cytokine release, enhanced specific killing and optimal treatment schedules within multimodal treatment will be key factors.

Personalized medicine in rheumatology

PubMed Central

Kłak, Anna; Kwiatkowska, Brygida; Raciborski, Filip

2016-01-01

In the era of the 21st century, rheumatoid arthritis (RA) is still poorly characterized. Rheumatoid arthritis is a common but heterogeneous disease, not only in the course and clinical symptoms, but also in the clinical response to treatment. Now it is known that early, correct diagnosis and starting treatment with disease-modifying drugs (DMARDs), of which methotrexate (MTX) remains the gold standard in the treatment of RA, is crucial in order to prevent joint destruction, functional disability and an unfavourable disease outcome. Early diagnosis of rheumatoid arthritis is significant in so much as the primary treatment can be started better. Pharmacogenetic and pharmacogenomic studies, which help determine the genetic profile of individual patients, may bring us closer to personalized medicine. Further studies on RA should allow for the identification of disease-specific genes at the stage when their tolerance by the organism is still preserved (before auto-aggression develops). PMID:27826172

Matching Electron Beams Without Secondary Collimation for Treatment of Extensive Recurrent Chest-Wall Carcinoma

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

Feygelman, Vladimir; Department of Physics, University of Manitoba, Winnipeg, MB; Mandelzweig, Yuri

2015-01-15

Matching electron beams without secondary collimators (applicators) were used for treatment of extensive, recurrent chest-wall carcinoma. Due to the wide penumbra of such beams, the homogeneity of the dose distribution at and around the junction point is clinically acceptable and relatively insensitive to positional errors. Specifically, dose around the junction point is homogeneous to within ±4% as calculated from beam profiles, while the positional error of 1 cm leaves this number essentially unchanged. The experimental isodose distribution in an anthropomorphic phantom supports this conclusion. Two electron beams with wide penumbra were used to cover the desired treatment area with satisfactorymore » dose homogeneity. The technique is relatively simple yet clinically useful and can be considered a viable alternative for treatment of extensive chest-wall disease. The steps are suggested to make this technique more universal.« less

Orthodontic Camouflage: A Treatment Option – A Clinical Case Report

PubMed Central

Mazzini, William Ubilla; Torres, Fátima Mazzini

2017-01-01

Orthodontic camouflage provides an alternative treatment for angle III malocclusion since patients with limited economic resources cannot opt for orthognathic surgery, it being clear that correction will be achieved at the dental level and not at the bone complex. Objective: To determine an alternative treatment for patients who do not have the possibility of having orthognathic surgery. Clinical case: A 13-year-old female patient, dolico facial biotype with slightly concave profile, with Class III Skeletal by mandibular prognathism, anterior crossbite, anterior diastema, and large mandibular body, molar class, and canine III. Alexander technique brackets were placed; premolar extraction was not planned. Once the case was completed, the correction of the anterior crossbite was achieved, thanks to the use of the spaces that existed at the beginning of the treatment and also that a correct distalization of canines and retraction of the lower anterior segment were performed. PMID:29326524

Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

PubMed Central

Nakamura, Yutaro; Suda, Takafumi

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

PubMed

Magistro, Giuseppe; Wagenlehner, Florian M E; Grabe, Magnus; Weidner, Wolfgang; Stief, Christian G; Nickel, J Curtis

2016-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy. A comprehensive review of published randomized controlled trials (RCTs) on the treatment of CP/CPPS and practical best evidence recommendations for management. Medline and the Cochrane database were screened for RCTs on the treatment of CP/CPPS from 1998 to December 2014, using the National Institutes of Health Chronic Prostatitis Symptom Index as an objective outcome measure. Published data in concert with expert opinion were used to formulate a practical best evidence statement for the management of CP/CPPS. Twenty-eight RCTs identified were eligible for this review and presented. Trials evaluating antibiotics, α-blockers, anti-inflammatory and immune-modulating substances, hormonal agents, phytotherapeutics, neuromodulatory drugs, agents that modify bladder function, and physical treatment options failed to reveal a clear therapeutic benefit. With its multifactorial pathophysiology and its various clinical presentations, the management of CP/CPPS demands a phenotypic-directed approach addressing the individual clinical profile of each patient. Different categorization algorithms have been proposed. First studies applying the UPOINTs classification system provided promising results. Introducing three index patients with CP/CPPS, we present practical best evidence recommendations for management. Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favor of a monotherapy for management. No efficient monotherapeutic option is available. The best evidence-based management of CP/CPPS strongly suggests a multimodal therapeutic approach addressing the individual clinical phenotypic profile. Chronic prostatitis/chronic pelvic pain syndrome presents a variable syndrome. Successful management of this condition is challenging. It appears that a tailored treatment strategy addressing individual patient characteristics is more effective than one single therapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada.

PubMed

Quon, Peter; Le, Hoa H; Raymond, Vincent; Mtibaa, Mondher; Moshyk, Andriy

2016-06-01

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada. Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($). Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies. Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.

Monte Carlo based electron treatment planning and cutout output factor calculations

NASA Astrophysics Data System (ADS)

Mitrou, Ellis

Electron radiotherapy (RT) offers a number of advantages over photons. The high surface dose, combined with a rapid dose fall-off beyond the target volume presents a net increase in tumor control probability and decreases the normal tissue complication for superficial tumors. Electron treatments are normally delivered clinically without previously calculated dose distributions due to the complexity of the electron transport involved and greater error in planning accuracy. This research uses Monte Carlo (MC) methods to model clinical electron beams in order to accurately calculate electron beam dose distributions in patients as well as calculate cutout output factors, reducing the need for a clinical measurement. The present work is incorporated into a research MC calculation system: McGill Monte Carlo Treatment Planning (MMCTP) system. Measurements of PDDs, profiles and output factors in addition to 2D GAFCHROMICRTM EBT2 film measurements in heterogeneous phantoms were obtained to commission the electron beam model. The use of MC for electron TP will provide more accurate treatments and yield greater knowledge of the electron dose distribution within the patient. The calculation of output factors could invoke a clinical time saving of up to 1 hour per patient.

Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

PubMed Central

2013-01-01

Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

USDA-ARS?s Scientific Manuscript database

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and ge...

d-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS.

PubMed

Cianci, Antonio; Panella, Marco; Fichera, Michele; Falduzzi, Cristina; Bartolo, Manuela; Caruso, Salvatore

2015-06-01

To evaluate the effects of the combination of d-chiro-inositol (DCI) and alpha lipoic acid on menses and metabolic disorders in women with polycystic ovary syndrome (PCOS). Forty-six women (26 study group subjects and 20 controls) of reproductive age with PCOS according to Rotterdam criteria were enrolled in this prospective study. Fasting serum samples were collected from each woman. Homeostasis model of insulin resistance, insulin levels, lipid profile, frequency of menstrual cycles, number of ovarian peripheral cysts and BMI of both groups were investigated at baseline and after 180 days. Clinical and metabolic aspects of women on DCI and lipoic acid treatment underwent improvement (p < 0.5) with respect to the control group. Regarding lipid profile, no statistically difference was observed in total cholesterol and triglycerides levels in both groups at follow-up with respect the baseline values (p = NS). DCI and alpha lipoic acid treatment has been thought because it plays an essential role in mitochondrial specific pathways that generate energy from glucose and its potent effect as antioxidant. The association might have a strong impact on metabolic profile even with a short-term treatment. Further investigations are needed to evaluate other effects on reproductive physiology of women with PCOS.

A comparison of neuropsychological dysfunction in first-episode psychosis patients with unipolar depression, bipolar disorder, and schizophrenia.

PubMed

Hill, S Kristian; Reilly, James L; Harris, Margret S H; Rosen, Cherise; Marvin, Robert W; Deleon, Ovidio; Sweeney, John A

2009-09-01

The severity and profile of cognitive dysfunction in first episode schizophrenia and psychotic affective disorders were compared before and after antipsychotic treatment. Parallel recruitment of consecutively admitted study-eligible first-episode psychotic patients (30 schizophrenia, 22 bipolar with psychosis, and 21 psychotic depression) reduced confounds of acute and chronic disease/medication effects as well as differential treatment and course. Patient groups completed a neuropsychological battery and were demographically similar to healthy controls (n=41) studied in parallel. Prior to treatment, schizophrenia patients displayed significant deficits in all cognitive domains. The two psychotic affective groups were also impaired overall, generally performing intermediate between the schizophrenia and healthy comparison groups. No profile differences in neuropsychological deficits were observed across patient groups. Following 6 weeks of treatment, no patient group improved more than practice effects seen in healthy individuals, and level of performance improvement was similar for affective psychosis and schizophrenia groups. Although less severe in psychotic affective disorders, similar profiles of generalized neuropsychological deficits were observed across patient groups. Recovery of cognitive function after clinical stabilization was similar in mood disorders and schizophrenia. To the extent that these findings are generalizable, neuropsychological deficits in psychotic affective disorders, like schizophrenia, may be trait-like deficits with persistent functional implications.

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib

PubMed Central

Muller, Ittai B; de Langen, Adrianus J; Giovannetti, Elisa; Peters, Godefridus J

2017-01-01

A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors. PMID:28979145

Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib.

PubMed

Muller, Ittai B; de Langen, Adrianus J; Giovannetti, Elisa; Peters, Godefridus J

2017-01-01

A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors.

Do hormone treatments for prostate cancer cause anxiety and depression?

PubMed

Sharpley, Christopher F; Christie, David R H; Bitsika, Vicki

2014-01-01

To investigate the relationship between hormone therapy (HT) and incidence of anxiety and depression among prostate cancer patients (PCa). 526 PCa patients completed a survey about their cancer status, treatment received, anxiety, and depression status. Total scores on anxiety and depression inventories, plus symptom profiles that discriminated between patients with current HT, past HT, and never having received HT, were compiled for analysis. Patients who were currently receiving HT had significantly higher total anxiety and depression scores than patients who had previously received HT or who had never received HT. Analysis of the symptoms of anxiety and depression which distinguished between these groups of patients suggested that patients who had never received HT had significantly lower scores than current or past HT patients. Although several symptoms could be directly allocated to PCa and/or HT, symptom profiles were indicative of clinically significant anxiety and/or depression in patients who were currently receiving, or who had previously received, HT. Current HT may lead to symptoms of anxiety and/or depression which require clinical attention. These effects seem to decrease after completion of HT.

The development of the rotigotine transdermal patch: a historical perspective.

PubMed

Waters, Cheryl

2013-08-01

The rotigotine transdermal system is a dopamine receptor agonist delivered over a 24-hour period. It is approved for the treatment of idiopathic Parkinson's disease (PD). This article reviews the development of the rotigotine transdermal system, including rotigotine's receptor profile, steady-state pharmacokinetics, and metabolism. Preclinical studies of rotigotine in animal models of PD and proof-of-concept studies in patients with PD are reviewed. These preclinical and clinical studies established this system as an effective method for providing continuous rotigotine delivery across the skin providing the basis for continued clinical development of rotigotine for the treatment of early and advanced PD. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutations in histone modulators are associated with prolonged survival during azacitidine therapy

PubMed Central

Tobiasson, Magnus; McLornan, Donal P.; Karimi, Mohsen; Dimitriou, Marios; Jansson, Monika; Azenkoud, Asmaa Ben; Jädersten, Martin; Lindberg, Greger; Abdulkadir, Hani; Kulasekararaj, Austin; Ungerstedt, Johanna; Lennartsson, Andreas; Ekwall, Karl; Mufti, Ghulam J.; Hellström-Lindberg, Eva

2016-01-01

Early therapeutic decision-making is crucial in patients with higher-risk MDS. We evaluated the impact of clinical parameters and mutational profiles in 134 consecutive patients treated with azacitidine using a combined cohort from Karolinska University Hospital (n=89) and from King's College Hospital, London (n=45). While neither clinical parameters nor mutations had a significant impact on response rate, both karyotype and mutational profile were strongly associated with survival from the start of treatment. IPSS high-risk cytogenetics negatively impacted overall survival (median 20 vs 10 months; p<0.001), whereas mutations in histone modulators (ASXL1, EZH2) were associated with prolonged survival (22 vs 12 months, p=0.01). This positive association was present in both cohorts and remained highly significant in the multivariate cox model. Importantly, patients with mutations in histone modulators lacking high-risk cytogenetics showed a survival of 29 months compared to only 10 months in patients with the opposite pattern. While TP53 was negatively associated with survival, neither RUNX1-mutations nor the number of mutations appeared to influence survival in this cohort. We propose a model combining histone modulator mutational screening with cytogenetics in the clinical decision-making process for higher-risk MDS patients eligible for treatment with azacitidine. PMID:26959885

Bupropion Augmentation in a Case of Compulsive Buying Disorder.

PubMed

Sepede, Gianna; Di Iorio, Giuseppe; Sarchione, Fabiola; Fiori, Federica; Di Giannantonio, Massimo

Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition. A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion. Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

PubMed

Humbert, M; Segal, E S; Kiely, D G; Carlsen, J; Schwierin, B; Hoeper, M M

2007-08-01

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis

PubMed Central

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-01-01

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents. PMID:26019471

NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys.

PubMed

Kurzrock, Razelle; Colevas, A Dimitrios; Olszanski, Anthony; Akerley, Wallace; Arteaga, Carlos L; Carson, William E; Clark, Jeffrey W; DiPersio, John F; Ettinger, David S; Morgan, Robert J; Schwartzberg, Lee S; Venook, Alan P; Gocke, Christopher D; Tait, Jonathan; Stewart, F Marc

2015-11-01

With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care. Copyright © 2015 by the National Comprehensive Cancer Network.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

The Hypolipidemic and Pleiotropic Effects of Rosuvastatin Are Not Enhanced by Its Association with Zinc and Selenium Supplementation in Coronary Artery Disease Patients: A Double Blind Randomized Controlled Study

PubMed Central

Sena-Evangelista, Karine Cavalcanti Maurício; Pedrosa, Lucia Fatima Campos; Paiva, Maria Sanali Moura Oliveira; Dias, Paula Cristina Silveira; Ferreira, Diana Quitéria Cabral; Cozzolino, Sílvia Maria Franciscato; Faulin, Tanize Espírito Santo; Abdalla, Dulcinéia Saes Parra

2015-01-01

Objective Statins treatment may modify the levels of zinc and selenium, minerals that can improve vascular function and reduce oxidative damage and inflammation in atherosclerotic patients. This study aimed to evaluate the effects of rosuvastatin, alone or associated with zinc and selenium supplementation, on lipid profile, antioxidant enzymes and mineral status in coronary artery disease patients. Material and Methods A double-blind randomized clinical trial was performed in which patients (n = 76) were treated with 10 mg rosuvastatin over 4 months associated or not with zinc (30 mg/d) and selenium (150 μg/d) supplementation. The following parameters were analyzed before and after the intervention: anthropometric measurements, lipid profile, high sensitivity C-reactive protein (hs-CRP), electronegative low density lipoprotein (LDL(-)) concentrations, activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), zinc and selenium concentrations in blood plasma and erythocytes. Significance was determined using an α of 5% (two-tailed). Results We found that rosuvastatin therapy was efficient in reducing total cholesterol, LDL-cholesterol, non-HDL cholesterol, triglycerides, and hs-CRP independently of mineral supplementation. Neither treatment was associated with significant changes in LDL(-). Similarly, the antioxidant enzymes GPx and SOD activity were unchanged by treatments. Neither treatment was associated with significant differences in concentrations of zinc or selenium in blood plasma and erythocytes of studied groups. Conclusion Rosuvastatin treatment did not affect zinc and selenium levels in coronary artery disease patients. The zinc and selenium supplementation at doses used in this study did not change lipid profile or SOD and GPx activity in patients receiving rosuvastatin. Further studies should be focused on testing alternative doses and supplements in different populations to contribute for a consensus on the ideal choice of antioxidants to be used as possible complementary therapies in atherosclerotic patients. Trial Registration ClinicalTrials.gov NCT01547377 PMID:25785441

Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

PubMed

Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

2013-07-01

Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

Sporotrichosis: an update on epidemiology, etiopathogenesis, laboratory and clinical therapeutics.

PubMed

Orofino-Costa, Rosane; Macedo, Priscila Marques de; Rodrigues, Anderson Messias; Bernardes-Engemann, Andréa Reis

2017-01-01

In the late 90's there was a change in both the route of transmission and the people at risk for sporotrichosis. This zoonotic cat-man alternative transmission route elicited changes in strategies to control the epidemic. There was a progressive increase in the number of cases involving especially children and the elderly. In addition to becoming hyperendemic, uncommon clinical pictures like immunoreactive clinical presentations or severe systemic cases have emerged. New species were identified and classified through molecular tools using more virulent clinical isolates, like S. brasiliensis, compared to the environmental isolates. Likewise, different species of Sporothrix have been associated with different geographic regions. The serological and molecular techniques are used as an auxiliary tool for the diagnosis and/or for species identification, although the isolation and the identification of Sporothrix spp. in clinical specimen is still the gold standard. Currently sporotrichosis epidemics requires the knowledge of the epidemiological-molecular profile to control the disease and the specific treatment. Itraconazole, potassium iodide, terfinafine, and amphotericin B are the available drugs in Brazil to treat sporotrichosis. The drug of choice, its posology, and treatment duration vary according to the clinical presentation, the Sporothrix species, and host immune status. New treatment choices, including a vaccine, are being developed; nevertheless, more clinical trials are required to confirm its efficacy.

Sporotrichosis: an update on epidemiology, etiopathogenesis, laboratory and clinical therapeutics*

PubMed Central

Orofino-Costa, Rosane; de Macedo, Priscila Marques; Rodrigues, Anderson Messias; Bernardes-Engemann, Andréa Reis

2017-01-01

In the late 90's there was a change in both the route of transmission and the people at risk for sporotrichosis. This zoonotic cat-man alternative transmission route elicited changes in strategies to control the epidemic. There was a progressive increase in the number of cases involving especially children and the elderly. In addition to becoming hyperendemic, uncommon clinical pictures like immunoreactive clinical presentations or severe systemic cases have emerged. New species were identified and classified through molecular tools using more virulent clinical isolates, like S. brasiliensis, compared to the environmental isolates. Likewise, different species of Sporothrix have been associated with different geographic regions. The serological and molecular techniques are used as an auxiliary tool for the diagnosis and/or for species identification, although the isolation and the identification of Sporothrix spp. in clinical specimen is still the gold standard. Currently sporotrichosis epidemics requires the knowledge of the epidemiological-molecular profile to control the disease and the specific treatment. Itraconazole, potassium iodide, terfinafine, and amphotericin B are the available drugs in Brazil to treat sporotrichosis. The drug of choice, its posology, and treatment duration vary according to the clinical presentation, the Sporothrix species, and host immune status. New treatment choices, including a vaccine, are being developed; nevertheless, more clinical trials are required to confirm its efficacy. PMID:29166494

Cerebrospinal Fluid Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe Traumatic Brain Injury

PubMed Central

Santarsieri, Martina; Niyonkuru, Christian; McCullough, Emily H.; Dobos, Julie A.; Dixon, C. Edward; Berga, Sarah L.

2014-01-01

Abstract Despite significant advances in the management of head trauma, there remains a lack of pharmacological treatment options for traumatic brain injury (TBI). While progesterone clinical trials have shown promise, corticosteroid trials have failed. The purpose of this study was to (1) characterize endogenous cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2) determine relationships between CSF and serum profiles, and (3) assess the utility of these hormones as predictors of long-term outcomes. We evaluated 130 adults with severe TBI. Serum samples (n=538) and CSF samples (n=746) were collected for 6 days post-injury, analyzed for cortisol and progesterone, and compared with healthy controls (n=13). Hormone data were linked with clinical data, including Glasgow Outcome Scale (GOS) scores at 6 and 12 months. Group based trajectory (TRAJ) analysis was used to develop temporal hormone profiles delineating distinct subpopulations. Compared with controls, CSF cortisol levels were significantly and persistently elevated during the first week after TBI, and high CSF cortisol levels were associated with poor outcome. As a precursor to cortisol, progesterone mediated these effects. Serum and CSF levels for both cortisol and progesterone were strongly correlated after TBI relative to controls, possibly because of blood–brain barrier disruption. Also, differentially impaired hormone transport and metabolism mechanisms after TBI, potential de novo synthesis of steroids within the brain, and the complex interplay of cortisol and pro-inflammatory cytokines may explain these acute hormone profiles and, when taken together, may help shed light on why corticosteroid trials have previously failed and why progesterone treatment after TBI may be beneficial. PMID:24354775

'Muscle-sparing' statins: preclinical profiles and future clinical use.

PubMed

Pfefferkorn, Jeffrey A

2009-03-01

Coronary heart disease (CHD) is a leading cause of death in the US, and hypercholesterolemia is a key risk factor for this disease. The current standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of CHD and secondary prevention of coronary events. Results from several recent clinical trials have demonstrated that increasingly aggressive cholesterol-lowering therapy might offer additional protection against CHD compared with less aggressive treatment standards. While higher doses of current statin therapies are capable of achieving these more aggressive treatment goals, in certain cases statin-induced myalgia, the muscle pain or weakness that sometimes accompanies high-dose statin therapy, limits patient compliance with a treatment regimen. To address this limitation, efforts have been undertaken to develop highly hepatoselective statins that are capable of delivering best-in-class efficacy with minimized risk of dose-limiting myalgia. In this review, the preclinical and early clinical data for these next generation statins are discussed.

[Personality profile among cocaine users].

PubMed

Sánchez Huesca, R; Guisa Cruz, V M; Cedillo González, A; Pascual Blanco, Y

2002-01-01

Due to the psychiatric comorbidity seen among cocaine addicts, it is of clinical interest to know the personality traits associated to the use of this substance. Personality-profile comparative study of cocaine users and multiple-substance users obtained through the Multistage Personality Inventory. The study analyzed a sample of 30 cocaine users and 26 users of various substances who asked for treatment at a specialized institution. Results show the same profile for both groups, with high 8-4-2 scales. According to the Multistage Personality Inventory, this profile corresponds to an antisocial personality disorder with depressive and schizoid traits. The fact that there is a single profile for different drug users leads us to the hypothesis that there are addictive personality characteristics rather than specific traits related to the use of each substance. These subjects' personality characteristics suggest that the fear to relate to others could make it very difficult to establish a therapeutic link. This, in addition to the acting up tendency seen among users, constitutes a call of alert in terms of their likely abandonment of treatment. Further more, as they take impulses into actions, they build a barrier before words. This could be called acting up, doing instead of saying, which can become an obstacle for the appropriate development of the therapeutic process. The result must consider the size of the sample.

Understanding the positive benefit:risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical Development Program.

PubMed

Havrdova, Eva; Cohen, Jeffrey A; Horakova, Dana; Kovarova, Ivana; Meluzinova, Eva

2017-01-01

The introduction of high-efficacy therapies for relapsing-remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss. In two of the studies, alemtuzumab-treated patients had a significantly reduced risk of 6-month confirmed disease worsening, compared with subcutaneous interferon beta-1a. Benefits were maintained throughout 5 years, with a majority of patients receiving no alemtuzumab retreatment or other disease-modifying therapy. Trial results support alemtuzumab's manageable, consistent safety profile in relapsing-remitting multiple sclerosis. Infusion-associated reactions, the most frequent adverse events (AEs), can be minimized by corticosteroid pretreatment, monitoring, and symptomatic management. Other AEs include infections and autoimmune events. Oral anti-herpes prophylaxis should be initiated on the first day of each alemtuzumab treatment course and continued according to local guidelines. Overall cancer risk was lower in the alemtuzumab clinical trials than in a reference population; however, continuing surveillance will determine if alemtuzumab may be associated with certain malignancies such as thyroid papillary carcinoma and melanoma, which are currently identified as potential risks. The post-approval risk management strategy includes a safety monitoring program. Autoimmune AEs (thyroid events, immune thrombocytopenia, nephropathies) can be detected in a timely manner with the monitoring program, which includes physician and patient education about the signs and symptoms, monthly renal and hematologic monitoring, and quarterly thyroid function monitoring for 48 months after the last alemtuzumab course. Education, vigilance by physicians and patients, and monthly laboratory monitoring are recommended to maintain alemtuzumab's positive benefit:risk profile.

Enhanced anti-tumor activity and safety profile of targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate in the treatment of bone malignances

PubMed Central

Segal, Ehud; Pan, Huaizhong; Benayoun, Liat; Kopečková, Pavla; Shaked, Yuval; Kopeček, Jindčrich; Satchi-Fainaro, Ronit

2015-01-01

Bone neoplasms, such as osteosarcoma, exhibit a propensity for systemic metastases resulting in adverse clinical outcome. Traditional treatment consisting of aggressive chemotherapy combined with surgical resection, has been the mainstay of these malignances. Therefore, bone-targeted non-toxic therapies are required. We previously conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. HPMA copolymer-ALN-TNP-470 conjugate exhibited improved anti-angiogenic and anti-tumor activity compared with the combination of free ALN and TNP-470 when evaluated in a xenogeneic model of human osteosarcoma. The immune system has major effect on toxicology studies and on tumor progression. Therefore, in this manuscript we examined the safety and efficacy profiles of the conjugate using murine osteosarcoma syngeneic model. Toxicity and efficacy evaluation revealed superior anti-tumor activity and decreased organ-related toxicities of the conjugate compared with the combination of free ALN plus TNP-470. Finally, comparative anti-angiogenic activity and specificity studies, using surrogate biomarkers of circulating endothelial cells (CEC), highlighted the advantage of the conjugate over the free agents. The therapeutic platform described here may have clinical translational relevance for the treatment of bone-related angiogenesis-dependent malignances. PMID:21429572

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.

PubMed

Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

2017-05-01

We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML

PubMed Central

Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

2017-01-01

We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3. PMID:27833094

Psychometric properties of the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) in youth with OCD.

PubMed

Bussing, Regina; Murphy, Tanya K; Storch, Eric A; McNamara, Joseph P H; Reid, Adam M; Garvan, Cynthia W; Goodman, Wayne K

2013-02-28

This study evaluated the psychometric properties of the treatment-emergent activation and suicidality assessment profile (TEASAP) in a clinical sample of 56 youth aged 7-17 with obsessive-compulsive disorder (OCD) who participated in a double-blind randomized controlled trial. The 38-item TEASAP demonstrated good internal consistency for its total score (α=0.93) and adequate to good performance for its five subscale scores (α=0.65-0.92). One-week test-retest stability (N=18) was adequate (Intraclass correlation coefficient [ICC]=0.68-0.80) except for Self-Injury (ICC=0.46). Construct validity was supported by total and subscale TEASAP score relationships with related constructs, including irritability, hyperactivity, externalizing behaviors, manic symptoms, and suicidal ideation, and the absence of relationships with unrelated constructs. Predictive validity was established for the Disinhibition subscale through significant associations with subsequent activation events. Furthermore, TEASAP sensitivity to change in activation scores over time was supported by longitudinal associations of TEASAP scores with clinician ratings of activation over the course of treatment. Findings indicate that the TEASAP has acceptable psychometric properties in a clinical sample of youth with OCD and merits further study in larger samples for additional refinement of its measurement approaches. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.

PubMed

Keefe, John R; Mao, Jun J; Soeller, Irene; Li, Qing S; Amsterdam, Jay D

2016-12-15

Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile. We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined. Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred. Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD. Copyright © 2016 Elsevier GmbH. All rights reserved.

New antibiotics for healthcare-associated pneumonia.

PubMed

Neuner, Elizabeth A; Ritchie, David J; Micek, Scott T

2009-02-01

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

Vertebral body fracture after anterior cervical discectomy and fusion with zero-profile anchored cages in adjacent levels: a cautionary tale.

PubMed

Mattei, Tobias A; Teles, Alisson R; Dinh, Dzung H

2016-01-05

Zero-profile (also called self-locking, anchored or stand-alone cages) have been recently proposed as an interesting alternative for anterior cervical discectomy and fusion (ACDF), as they are supposed to reduce the rates of post-operative cage extrusion without necessarily incurring in the additional surgical time and increased rates of dysphagia associated with plating. Nevertheless, the exact indications of zero-profile anchored cages have not yet been established in the literature. To report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels and to review the available literature on hardware-related complications after multi-level ACDFs with zero-profile anchored cages. Case report and systematic literature review. The authors report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels. The patient presented with refractory mechanical neck pain at the 1-month post-operative follow-up, ultimately requiring a posterior instrumented fusion. A comprehensive systematic literature review on the available data regarding the safety, complications as well as radiological and clinical outcomes of zero-profile anchored cages is also performed. In the reported case, the use of zero-profile anchored cages in adjacent levels on the cervical spine led to a fracture of the vertebral body between the cages at the 1-month follow-up, with anterior avulsion of the part of the vertebral body where the blades from the two cages converged. According to the systematic literature review which included 409 patients from 10 different clinical series (with a total cumulative follow-up of approximately 535 patients-year), there were only two reported hardware-related complications after ACDF with zero-profile anchored cages, none of them involving fracture at the level of convergence of blades or screws. Although hardware-related complications after the use of zero-profile anchored cages seem to be rare events, future biomechanical and clinical studies are warranted in order to evaluate the safety of employing such devices for the treatment of multilevel degenerative disc disease in the cervical spine.

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

PubMed

Piwko, Charles; Prady, Catherine; Yunger, Simon; Pollex, Erika; Moser, Aurelie

2015-08-01

Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

Biomarkers for personalized oncology: recent advances and future challenges.

PubMed

Kalia, Madhu

2015-03-01

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and gastrointestinal tumors; anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALk fusion; HER2/neu blockage in HER2/neu-positive breast cancer; and epidermal growth factor receptors (EGFR) inhibition in EGFR-mutated lung cancer. This review presents the current state of our knowledge of biomarkers in five selected cancers: chronic myeloid leukemia, colorectal cancer, breast cancer, non-small cell lung cancer and melanoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term Safety and Efficacy of Low-dose Azathioprine and Allopurinol Cotherapy in Inflammatory Bowel Disease: A Large Observational Study.

PubMed

Pavlidis, Polychronis; Stamoulos, Panagiotis; Abdulrehman, Answar; Kerr, Patrick; Bull, Claire; Duley, John; Ansari, Azhar

2016-07-01

Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) with the benefit of overcoming side effects regularly associated with thiopurine monotherapy and poor responses. Concerns regarding safety remain, while a layer of complexity has been added by the trend toward treatment directed by red cell thioguanine nucleotide (TGN) profiling. We report on the clinical efficacy and safety of LDAA use in IBD undirected by metabolite profiling. Observational study of clinical practice from a single IBD center. Patient outcomes were defined clinically based on established activity scores and corticosteroid withdrawal. Red cell TGN was monitored only for suspected nonadherence. Overall, 113/164 (69%) patients with Crohn's disease and 83/136 (61%) patients with ulcerative/unclassified colitis had a clinical response by the end of follow-up (median 19 months), while 85 (52%) patients with Crohn's disease and 74 (54%) patients with ulcerative/unclassified colitis were in clinical remission. Clinical response was seen in 45/57 (79%) patients with Crohn's disease and 34/53 (64%) patients with ulcerative/unclassified colitis who were thiopurine naive, had active IBD, and received LDAA as the first line immunomodulator, while in 35 (61%) and 28 (53%), respectively, remission was achieved. LDAA was stopped in 20/300 (7%) patients because of side effects, all of which resolved on drug cessation. This is the largest cohort supporting the favorable safety profile and high efficacy of LDAA in IBD. It presents 2 advances in therapy: prescribing LDAA for thiopurine-naive patients, and bypassing TGN monitoring in favor of clinical monitoring (blood counts, etc.), which will make it more accessible for clinics without access to TGN assays.

Treating Pain in Pregnancy with Acupuncture: Observational Study Results from a Free Clinic in New Zealand.

PubMed

Soliday, Elizabeth; Betts, Debra

2018-02-01

Clinic-based acupuncturists, midwives, and physiotherapists have reported using acupuncture to treat lumbopelvic pain in pregnancy, a common condition that may affect functioning and quality of life. To contribute to the emerging evidence on treatment outcomes, we collected patient-reported pain reduction data from women treated during pregnancy in a no-pay, hospital-based acupuncture service in New Zealand. Observational study of patient-reported symptom reduction.The main outcome measure was the MYMOP (Measure Your Medical Outcome Profile), a brief, validated self-report instrument. Open-ended questions on treatment experiences and adverse events were included. Of the 81 women on whom we had complete treatment data, the majority (N = 72, 89%) reported clinically meaningful symptom reduction. Patient-reported adverse events were infrequent and mild. Patient-reported and treatment-related lumbopelvic pain symptom reduction findings provide further evidence that acupuncture in pregnancy is safe and beneficial in a field setting. We discuss this study's unique contributions in providing guidance for clinicians who practice acupuncture in pregnancy, including midwives, physiotherapists, and physicians. Copyright © 2018. Published by Elsevier B.V.

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

PubMed Central

2013-01-01

Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients. PMID:23697612

Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

PubMed

Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

2013-06-01

Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study.

PubMed

Denoeud-Ndam, Lise; Dicko, Alassane; Baudin, Elisabeth; Guindo, Ousmane; Grandesso, Francesco; Sagara, Issaka; Lasry, Estrella; Palma, Pedro Pablo; Parra, Angeles M Lima; Stepniewska, Kasia; Djimde, Abdoulaye A; Barnes, Karen I; Doumbo, Ogobara K; Etard, Jean-François

2015-06-12

Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking. The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile. In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded. Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program. Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons. This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children. ClinicalTrials.gov: NCT01958905.

Preclinical toxicity profile of oral bilastine.

PubMed

Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

2012-06-01

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells.

PubMed

Kim, Kyu-Tae; Lee, Hye Won; Lee, Hae-Ock; Kim, Sang Cheol; Seo, Yun Jee; Chung, Woosung; Eum, Hye Hyeon; Nam, Do-Hyun; Kim, Junhyong; Joo, Kyeung Min; Park, Woong-Yang

2015-06-19

Intra-tumoral genetic and functional heterogeneity correlates with cancer clinical prognoses. However, the mechanisms by which intra-tumoral heterogeneity impacts therapeutic outcome remain poorly understood. RNA sequencing (RNA-seq) of single tumor cells can provide comprehensive information about gene expression and single-nucleotide variations in individual tumor cells, which may allow for the translation of heterogeneous tumor cell functional responses into customized anti-cancer treatments. We isolated 34 patient-derived xenograft (PDX) tumor cells from a lung adenocarcinoma patient tumor xenograft. Individual tumor cells were subjected to single cell RNA-seq for gene expression profiling and expressed mutation profiling. Fifty tumor-specific single-nucleotide variations, including KRAS(G12D), were observed to be heterogeneous in individual PDX cells. Semi-supervised clustering, based on KRAS(G12D) mutant expression and a risk score representing expression of 69 lung adenocarcinoma-prognostic genes, classified PDX cells into four groups. PDX cells that survived in vitro anti-cancer drug treatment displayed transcriptome signatures consistent with the group characterized by KRAS(G12D) and low risk score. Single-cell RNA-seq on viable PDX cells identified a candidate tumor cell subgroup associated with anti-cancer drug resistance. Thus, single-cell RNA-seq is a powerful approach for identifying unique tumor cell-specific gene expression profiles which could facilitate the development of optimized clinical anti-cancer strategies.

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

PubMed Central

Wronski, Matt; Yeboah, Collins

2015-01-01

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose profiles under large‐area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central‐axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ∼25% occurring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.‐x, 87.55.D‐ PMID:27074448

[Maraviroc: clinical trials results].

PubMed

Chidiac, C; Katlama, C; Yeni, P

2008-03-01

Just over a decade after identification of chemokine receptors CCR5 and CXCR4 as coreceptors for HIV, maraviroc (Celsentri), the first CCR5 antagonist, has recently obtained its Marketing Authorization in the United States and Europe, for treatment of treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable. CCR5 antagonists, after fusion inhibitor enfuvirtide available since 2003, also belong to entry inhibitors. These molecules, unlike previous antiretrovirals, do not target the virus but its target cell by blocking viral penetration. Maraviroc has shown its clinical efficacy in patients failing other antiretroviral classes. Its safety profile was similar to placebo in two large phase III trials. However, careful assessment of both hepatic and immunologic safety of this new therapeutic class is needed. Viral tropism testing has to be investigated before using maraviroc in the clinic, because CCR5 antagonists are not active against CXCR4 viruses. For the moment indicated for the treatment-experienced patient population, maraviroc could in the future benefit to other types of patients, depending on ongoing trials results.

Use of tocilizumab in systemic sclerosis: A brief literature review.

PubMed

Fernández-Codina, A; Fernández-Fernández, J; Fernández-Pantiga, A

2018-03-27

The available treatments for systemic sclerosis (SS) have limited effectiveness. Treatment with tocilizumab (TCZ), a biological drug that inhibits interleukin 6 (IL-6), has recently been proposed. In this study, we conducted a literature review to assess the safety and efficacy of TCZ in SS. We found 52 articles, 10 of which we selected after evaluating the articles. In a randomised clinical trial, TCZ showed a nonsignificant improvement in the degree of skin induration, while another observational study showed neutral results. In this same clinical trial, the functional respiratory parameters showed a certain degree of stabilization. The safety profile of TCZ is acceptable; however, the current evidence regarding treatment of SS with TCZ is highly limited, although the drug could have a beneficial effect in skin disorder. New clinical trials are needed to determine the usefulness of TCZ in SS. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Osmotherapy for intracranial hypertension: mannitol versus hypertonic saline.

PubMed

Fink, Matthew E

2012-06-01

Hyperosmolar therapy is one of the core medical treatments for brain edema and intracranial hypertension, but controversy exists regarding the use of the most common agents, mannitol, and hypertonic saline. This article describes the relative merits and adverse effects of these agents using the best available clinical evidence. Mannitol is effective and has been used for decades in the treatment of traumatic brain injury, but it may precipitate acute renal failure if serum osmolarity exceeds 320 mOsm/L. Hypertonic saline appears to be safe, and serum sodium has been elevated to as high as 180 mEq/L in clinical settings without significant neurologic, cardiac, or renal injury. In small comparative trials both agents are effective and no clinically significant difference has been noted, but a properly powered trial has not yet been performed. Both mannitol and hypertonic saline are effective and have an acceptable risk profile for use in the treatment of elevated intracranial pressure secondary to brain edema.

Investigational Notch and Hedgehog Inhibitors – Therapies for Cardiovascular disease

PubMed Central

Redmond, EM; Guha, S; Walls, D; Cahill, PA

2011-01-01

Importance to the field During the past decade a variety of Notch and Hedgehog pathway inhibitors have been developed for the treatment of several cancers. An emerging paradigm suggests that these same gene regulatory networks are often recapitulated in the context of cardiovascular disease and may now offer an attractive target for therapeutic intervention. Areas Covered This article briefly reviews the profile of Notch and Hedgehog inhibitors that have reached the pre-clinic and clinic for cancer treatment and discusses the clinical issues surrounding targeted use of these inhibitors in the treatment of vascular disorders. Expert Opinion Pre-clinical and clinical data using pan-Notch inhibitors (γ-secretase inhibitors) and selective antibodies to preferentially target notch receptors and ligands has proven successful but concerns remain over normal organ homeostasis and significant pathology in multiple organs. In contrast, the Hedgehog based drug pipeline is rich with more than a dozen Smoothened (SMO) inhibitors at various stages of development. Overall, refined strategies will be necessary to harness these pathways safely as a powerful tool to disrupt angiogenesis and vascular proliferative phenomena without causing prohibitive side effects already seen with cancer models and patients. PMID:22007748

FUNCTIONAL SUBCLONE PROFILING FOR PREDICTION OF TREATMENT-INDUCED INTRA-TUMOR POPULATION SHIFTS AND DISCOVERY OF RATIONAL DRUG COMBINATIONS IN HUMAN GLIOBLASTOMA

PubMed Central

Reinartz, Roman; Wang, Shanshan; Kebir, Sied; Silver, Daniel J.; Wieland, Anja; Zheng, Tong; Küpper, Marius; Rauschenbach, Laurèl; Fimmers, Rolf; Shepherd, Timothy M.; Trageser, Daniel; Till, Andreas; Schäfer, Niklas; Glas, Martin; Hillmer, Axel M.; Cichon, Sven; Smith, Amy A.; Pietsch, Torsten; Liu, Ying; Reynolds, Brent A.; Yachnis, Anthony; Pincus, David W.; Simon, Matthias; Brüstle, Oliver; Steindler, Dennis A.; Scheffler, Björn

2016-01-01

Purpose Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. Experimental Design Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and inter-individual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacological sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. Results Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential anti-glioblastoma compounds. A more comprehensive intra-tumoral analysis revealed that stable genetic and phenotypic characteristics of co-existing subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacological profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. Conclusions Our data provide a previously unrecognized strategy for revealing functional consequences of intra-tumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. PMID:27521447

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PubMed

Uthman, Basim M; Bazil, Carl W; Beydoun, Ahmad; Schulze-Bonhage, Andreas; Benabou, Reina; Whalen, Ed; Emir, Birol; Griesing, Teresa; Leon, Teresa

2010-06-01

To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study.

PubMed

Schneider, Carolina; Papachristou, Efstathios; Wimberley, Theresa; Gasse, Christiane; Dima, Danai; MacCabe, James H; Mortensen, Preben Bo; Frangou, Sophia

2015-06-01

Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Autoimmune hepatitis in children: progression of 20 cases in northern Mexico.

PubMed

Nares-Cisneros, J; Jaramillo-Rodríguez, Y

2014-01-01

Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver with nonspecific clinical manifestations that causes greater liver damage in children than in adults. To analyze the clinical progression, biochemical profiles, histopathologic changes, and treatment response in 20 children with AIH. A retrospective study was carried out on the variables associated with clinical progression, diagnosis, and treatment response in children seen at the the Unidad Médica de Alta Especialidad (UMAE) No. 71 IMSS in Torreón, Coahuila, Mexico, from 1992 to 2012. Twenty patients were analyzed, 75% with type 1 AIH (AIH-1) and 25% with type 2 AIH (AIH-2). Girls predominated with a 3:1 ratio of girls to boys. The mean age was 10.07 ± 6.53 years for the AIH-1 cases and 6.75 ± 3.77 years for the AIH-2 cases. There was an association with immunologic diseases in 40% of the patients. The patients in the AIH-2 group had greater biochemical profile alterations and IgA deficiency. Anti-nuclear antibody and anti-smooth muscle antibody were positive in 100% of the patients with AIH-1, and anti-liver kidney microsomal type 1 antibody was positive in 100% of the AIH-2 patients. Liver biopsy revealed interface hepatitis in both groups. The AIH-2 group responded more quickly to treatment, but had a higher recurrence rate. Autoimmune hepatitis in the pediatric patient should be suspected in order to make an early diagnosis and thereby establish opportune treatment. Determining the type of AIH is necessary for making adequate diagnosis and for achieving a better outcome in relation to recurrence and complication rates. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Splenic myeloid metaplasia in warm autoimmune hemolytic anemia (wAIHA): a retrospective study.

PubMed

Anguiano-Álvarez, Víctor Manuel; Hernández-Company, Alonso; Hamdan-Pérez, Nashla; Montante-M, Daniel; Zúñiga-Tamayo, Diego A; Rodríguez-Rodríguez, Sergio; Pomerantz, Alan; Tuna-Aguilar, Elena J

2018-03-01

Splenic myeloid metaplasia (SMM) is a kind of extramedullary hematopoiesis, whereas its clinical significance in wAIHA remains unclear. The aim of this study is evaluating the frequency and clinical characteristics of SMM, compared with splenic-congestion (SC). We included patients with wAIHA treated in a Mexican tertiary hospital between January 1992 and December 2015. All patients received steroids as first-line treatment and splenectomy as second-line treatment. Among the thirty-six splenectomized patients, 15 (41.6%) and 21 (58.4%) were diagnosed as SMM and SC, respectively. No differences were found in clinical characteristics between two groups. SMM patients showed lower platelet count (147×10 9 /L vs. 240×10 9 /L, P =0.02) and higher presence of anti-dsDNA antibodies (40% vs. 4.7%, P =0.01) than SC patients. Although the complete response (CR) rate with first-line treatment was lower in SMM patients (13.3% vs. 47.6%; P =0.04), post-splenectomy median disease-free-survival (DFS) was longer (16.2 mo vs. 5.1 mo; P =0.19). Univariate/multivariate analysis showed that achieving CR during first-line treatment (OR 0.3, 95% CI: 0.03-0.94, P =0.03) and higher platelet count (OR 0.99, 95% CI: 0.98-0.99, P =0.03) were protective factors for SMM; and anti-dsDNA titer higher than 9.6 IU/dL was a risk factor for SMM (OR 2.76, 95% CI: 1.48-5.14, P <0.001). The wAIHA patients with SMM have different biological profiles with those without SMM. This study is the first trial evaluating the significance of histopathological spleen findings and their association with rheumatologic profile.

Current stage in inflammatory bowel disease: What is next?

PubMed Central

Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

2015-01-01

In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

Premenstrual Dysphoric Disorder: Epidemiology and Treatment.

PubMed

Hantsoo, Liisa; Epperson, C Neill

2015-11-01

Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive-affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets.

Premenstrual Dysphoric Disorder: Epidemiology and Treatment

PubMed Central

Hantsoo, Liisa; Epperson, C. Neill

2016-01-01

Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive–affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets. PMID:26377947

Discovery of AZD2716: A Novel Secreted Phospholipase A2 (sPLA2) Inhibitor for the Treatment of Coronary Artery Disease

PubMed Central

2016-01-01

Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A2 (sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease. PMID:27774123

Liposomal bupivacaine for regional anesthesia.

PubMed

Uskova, Anna; O'Connor, Jessica E

2015-10-01

Using a regional block in a multimodal approach to postoperative analgesia management involves addressing, which local anesthetic and how much should be used to ensure adequate pain relief to reduce related morbidity and mortality. This article will review literature surrounding the recently approved formulation of slow release liposomal bupivacaine, define its proven benefits, and identify ongoing studies to further examine the utility of this novel formulation by various routes. Recent Phase II and III clinical trials have demonstrated the ability of liposomal bupivacaine to provide prolonged analgesia, maintain a high safety profile in therapeutic doses, and decrease opioid requirements when compared with placebo in local infiltration applications for up to 24 h. Between 24 and 72 h after study drug administration, there was minimal to no difference between EXPAREL and placebo treatments on mean pain intensity. Conventional bupivacaine or ropivacaine groups (current standard practice in many hospitals in the USA) were not compared. In addition, the analgesic efficacy, cost-effectiveness, and safety profile of liposomal bupivacaine has not thoroughly been studied in various standard clinical settings such as perineural, intrathecal, and epidural administration. Current published data do not provide superior clinical results for EXPAREL over conventional bupivacaine based upon the lack of adequately powered multicentered clinical trials with comparison groups. Further investigation is necessary to identify the analgesic efficacy and safety profile of liposomal bupivacaine versus standard local anesthetics and to define the optimal clinical indication for liposomal bupivacaine administration in regional anesthesia.

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

The efficacy of two adolescent substance abuse treatments and the impact of comorbid depression: results of a small randomized controlled trial.

PubMed

Santisteban, Daniel A; Mena, Maite P; Muir, Joan; McCabe, Brian E; Abalo, Clara; Cummings, Amanda M

2015-03-01

The purpose of this randomized trial was to investigate the efficacy of 2 behavioral treatments focusing on different change mechanisms in ameliorating a borderline personality disorder constellation of behaviors and substance use in adolescents referred by juvenile diversion programs. Forty adolescents 14-17 years of age and meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for borderline personality disorder and substance use disorders were randomized to integrative borderline personality disorder-oriented adolescent family therapy (I-BAFT) or individual drug counseling. This design allowed a comparison of 2 manualized interventions, 1 family based and 1 individually oriented. Profiles of clinical change were used to detect impact and estimate treatment effect sizes. Primary analyses showed that both interventions had a clinically significant impact on borderline personality disorder behaviors 12 months after baseline but with no differential treatment effects. The impact on substance use was more complex. Subgroup analyses revealed that adolescents with depression had significantly more severe profiles of borderline personality disorder and substance use. These youths were the only group to show reductions in substance use, but they only did so if they received the I-BAFT intervention. Study data also documented the high dosage of intensive residential treatment needed by this population. Results highlight the intensive treatment needs of juvenile justice-involved youths with co-occurring substance use and borderline personality disorder including depression, the hybrid outpatient and residential treatment often required by this population, and the promise of a family-oriented approach, particularly for youths with severe symptoms and co-occurring depression. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

PubMed

Lorente Fernández, L; Monte Boquet, E; Pérez-Miralles, F; Gil Gómez, I; Escutia Roig, M; Boscá Blasco, I; Poveda Andrés, J L; Casanova-Estruch, B

2014-06-01

Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

[Profile of the informal carer associated with the clinical management of the Alzheimer's disease patient refractory to symptomatic treatment of the disease].

PubMed

Molinuevo, J L; Hernández, B

2011-11-01

Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as, time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers' quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (p<.0001) and final visit (p=.0001). Caregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p=.021). Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Nonsteroidal antagonists of the mineralocorticoid receptor.

PubMed

Kolkhof, Peter; Nowack, Christina; Eitner, Frank

2015-09-01

The broad clinical use of steroidal mineralocorticoid receptor antagonists (MRAs) is limited by the potential risk of inducing hyperkalemia when given on top of renin-angiotensin system blockade. Drug discovery campaigns have been launched aiming for the identification of nonsteroidal MRAs with an improved safety profile. This review analyses the evidence for the potential of improved safety profiles of nonsteroidal MRAs and the current landscape of clinical trials with nonsteroidal MRAs. At least three novel nonsteroidal MRAs have reportedly demonstrated an improved therapeutic index (i.e. less risk for hyperkalemia) in comparison to steroidal antagonists in preclinical models. Five pharmaceutical companies have nonsteroidal MRAs in clinical development with a clear focus on the treatment of chronic kidney diseases. No clinical data have been published so far for MT-3995 (Mitsubishi), SC-3150 (Daiichi-Sankyo), LY2623091 (Eli Lilly) and PF-03882845 (Pfizer). In contrast, data from two clinical phase II trials are available for finerenone (Bayer) which demonstrated safety and efficacy in patients with heart failure and additional chronic kidney diseases, and significantly reduced albuminuria in patients with diabetic nephropathy. Neither hyperkalemia nor reductions in kidney function were limiting factors to its use. Novel, nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.

Effect of Aripiprazole Lauroxil on Metabolic and Endocrine Profiles and Related Safety Considerations Among Patients With Acute Schizophrenia.

PubMed

Nasrallah, Henry A; Newcomer, John W; Risinger, Robert; Du, Yangchun; Zummo, Jacqueline; Bose, Anjana; Stankovic, Srdjan; Silverman, Bernard L; Ehrich, Elliot W

2016-11-01

Aripiprazole lauroxil, a long-acting injectable antipsychotic, demonstrated safety and efficacy in treating symptoms of schizophrenia in a double-blind, placebo-controlled trial. Because the metabolic profile of antipsychotics is an important safety feature, the effects of aripiprazole lauroxil on body weight, endocrine and metabolic profiles, and safety were examined in a secondary analysis. Patients with schizophrenia (DSM-IV-TR criteria) were randomly assigned to aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or placebo intramuscularly once monthly between December 2011 and March 2014. Changes in body weight, body mass index, fasting blood glucose and serum lipids, glycosylated hemoglobin (HbA1c), and prolactin over 12 weeks were assessed. The incidence of treatment-emergent adverse events (AEs) was evaluated. Among 622 randomized patients, no clinically relevant changes from baseline to week 12 were observed for any serum lipid, lipoprotein, plasma glucose, or HbA1c value with placebo or either dose of aripiprazole lauroxil. Both doses of aripiprazole lauroxil were associated with reductions in mean prolactin levels, whereas placebo treatment was not. The mean (standard deviation) change from baseline for body weight was 0.74 (3.9) kg, 0.86 (3.7) kg, and 0.01 (3.6) kg for aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. AEs related to metabolic parameters were reported in 2.4%, 1.4%, and 2.4% of patients in the aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. Aripiprazole lauroxil was well tolerated, with a low-risk metabolic profile relative to published data for other antipsychotics. Changes similar to those observed with placebo were observed in the aripiprazole lauroxil groups for metabolic parameters, with modest weight gain in the active treatment groups over the 12-week course. ClinicalTrials.gov identifier: NCT01469039. © Copyright 2016 Physicians Postgraduate Press, Inc.

Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update.

PubMed

Sohal, Davendra P S; Kennedy, Erin B; Khorana, Alok; Copur, Mehmet S; Crane, Christopher H; Garrido-Laguna, Ignacio; Krishnamurthi, Smitha; Moravek, Cassadie; O'Reilly, Eileen M; Philip, Philip A; Ramanathan, Ramesh K; Ruggiero, Joseph T; Shah, Manish A; Urba, Susan; Uronis, Hope E; Lau, Michelle W; Laheru, Daniel

2018-05-23

Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Does Classification of Chronic Musculoskeletal Disorder Patients Into Psychosocial Subgroups Predict Differential Treatment Responsiveness and 1-Year Outcomes After a Functional Restoration Program?

PubMed

Asih, Sali; Mayer, Tom G; Williams, Mark; Choi, Yun Hee; Gatchel, Robert J

2015-12-01

The objectives of this study: (1) to assess whether Multidimensional Pain Inventory (MPI) profiles predicted differential responses to a functional restoration program (FRP) in chronic disabling occupational musculoskeletal disorder (CDOMD) patients; (2) to examine whether coping style improves following FRP; and (3) to determine whether discharge MPI profiles predict discharge psychosocial and 1-year socioeconomic outcomes. Consecutive CDOMD patients (N=716) were classified into Adaptive Coper (AC, n=209), Interpersonally Distressed (ID, n=154), Dysfunctional (DYS, n=310), and Anomalous (n=43) using the MPI, and reclassified at discharge. Profiles were compared on psychosocial measures and 1-year socioeconomic outcomes. An intent-to-treat sample analyzed the effect of drop-outs on treatment responsiveness. The MPI classification significantly predicted program completion (P=0.001), although the intent-to-treat analyses found no significant effects of drop-out on treatment responsiveness. There was a significant increase in the number of patients who became AC or Anomalous at FRP discharge and a decrease in those who were ID or DYS. Patients who changed or remained as DYS at FRP discharge reported the highest levels of pain, disability, and depression. No significant interaction effect was found between MPI group and time for pain intensity or disability. All groups improved on psychosocial measures at discharge. DYS patients had decreased work retention and a greater health care utilization at 1 year. An FRP was clinically effective for CDOMD patients regardless of initial MPI profiles. The FRP modified profiles, with patients changing from negative to positive profiles. Discharge DYS were more likely to have poor 1-year outcomes. Those classified as Anomalous had a good prognosis for functional recovery similar to ACs.

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options

PubMed Central

Bornhauser, Beat; Gombert, Michael; Kratsch, Christina; Stütz, Adrian M.; Sultan, Marc; Tchinda, Joelle; Worth, Catherine L.; Amstislavskiy, Vyacheslav; Badarinarayan, Nandini; Baruchel, André; Bartram, Thies; Basso, Giuseppe; Canpolat, Cengiz; Cario, Gunnar; Cavé, Hélène; Dakaj, Dardane; Delorenzi, Mauro; Dobay, Maria Pamela; Eckert, Cornelia; Ellinghaus, Eva; Eugster, Sabrina; Frismantas, Viktoras; Ginzel, Sebastian; Haas, Oskar A.; Heidenreich, Olaf; Hemmrich-Stanisak, Georg; Hezaveh, Kebria; Höll, Jessica I.; Hornhardt, Sabine; Husemann, Peter; Kachroo, Priyadarshini; Kratz, Christian P.; te Kronnie, Geertruy; Marovca, Blerim; Niggli, Felix; McHardy, Alice C.; Moorman, Anthony V.; Panzer-Grümayer, Renate; Petersen, Britt S.; Raeder, Benjamin; Ralser, Meryem; Rosenstiel, Philip; Schäfer, Daniel; Schrappe, Martin; Schreiber, Stefan; Schütte, Moritz; Stade, Björn; Thiele, Ralf; von der Weid, Nicolas; Vora, Ajay; Zaliova, Marketa; Zhang, Langhui; Zichner, Thomas; Zimmermann, Martin; Lehrach, Hans; Borkhardt, Arndt; Bourquin, Jean-Pierre; Franke, Andre; Korbel, Jan O.; Stanulla, Martin; Yaspo, Marie-Laure

2015-01-01

TCF3-HLF-fusion positive acute lymphoblastic leukemia (ALL) is currently incurable. Employing an integrated approach, we uncovered distinct mutation, gene expression, and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. Recurrent intragenic deletions of PAX5 or VPREB1 were identified in constellation with TCF3-HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin towards a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics, but sensitivity towards glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease. PMID:26214592

Selective estrogen receptor modulators in clinical practice: a safety overview.

PubMed

Ellis, Amanda J; Hendrick, Vicky M; Williams, Robert; Komm, Barry S

2015-06-01

Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks. This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs. Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

PubMed

Baues, C; Semrau, R; Gaipl, U S; Bröckelmann, P J; Rosenbrock, J; Engert, A; Marnitz, S

2017-02-01

Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

New approaches for identifying and testing potential new anti-asthma agents.

PubMed

Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

2018-01-01

Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

Clinical Development of VEGF Signaling Pathway Inhibitors in Childhood Solid Tumors

PubMed Central

Yamashiro, Darrell J.; Fox, Elizabeth

2011-01-01

Angiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early-phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed. Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers. PMID:22042784

High-dose levofloxacin in community-acquired pneumonia: a randomized, open-label study.

PubMed

Lee, Jin Hwa; Kim, Seo Woo; Kim, Ji Hye; Ryu, Yon Ju; Chang, Jung Hyun

2012-09-01

The conventional treatment for community-acquired pneumonia (CAP) involves combination therapy consisting of a β-lactam penicillin or a cephalosporin with a macrolide. Alternatively, high-dose levofloxacin treatment has been used as single-agent therapy for treating CAP, covering atypical pathogens. This study compared the clinical efficacy and safety of high-dose levofloxacin with combined ceftriaxone and azithromycin for the treatment of CAP. This phase IV, prospective, randomized, open-label trial enrolled patients admitted to a tertiary referral hospital for CAP treatment from 2010 to 2011. Hospital admission was decided based on clinical judgement and the pneumonia severity index. Forty subjects were enrolled and assigned to two treatment arms using a random numbers table. The 20 subjects in the experimental group were given levofloxacin 750 mg intravenously once daily, followed by the same dose of oral levofloxacin at discharge when clinically improved and the 20 subjects in the control group were given ceftriaxone 2.0 g intravenously once daily plus oral azithromycin 500 mg for 3 consecutive days, followed by oral cefpodoxime 200 mg per day at discharge after clinical improvement. The primary outcome was the clinical success rate. Secondary outcomes were the microbiological success rate and adverse events during the study. Of the 40 subjects enrolled, 36 completed the study: 17 in the experimental group and 19 in the control group. The groups did not differ in terms of demographic factors or clinical findings at baseline. The clinical success rate (cured + improved) was 94% in the experimental (levofloxacin) group and 84% in the control group (p > 0.05). The microbiological success rate and overall adverse events were also similar in both groups. Single-agent, high-dose levofloxacin treatment exhibited excellent clinical and microbiological efficacy with a safety profile comparable to that of ceftriaxone plus azithromycin therapy. Large-scale clinical trials are required to verify these results. WHO International Clinical Trials Registry: KCT0000374; Daiichi-Sankyo Korea study code: T11-13-V1.

The role of ctDNA detection and the potential of the liquid biopsy for breast cancer monitoring.

PubMed

Openshaw, Mark Robert; Page, Karen; Fernandez-Garcia, Daniel; Guttery, David; Shaw, Jacqueline Amanda

2016-07-01

Recent advances in deep amplicon sequencing have enabled rapid assessment of somatic mutations and structural changes in multiple cancer genes in DNA isolated from tumour tissues and circulating cell-free DNA (cfDNA). This cfDNA is under investigation as a 'liquid biopsy' for the real time monitoring of patients with cancer in a growing number of research studies and clinical trials. Here we will provide a brief overview of the potential clinical utility of cfDNA profiling for detection and monitoring of patients with breast cancer. The review was conducted in English using PubMed and search terms including 'breast cancer', 'plasma DNA', 'circulating cell free DNA' and 'circulating tumour DNA'. Expert commentary: Liquid biopsies through circulating tumor DNA (ctDNA) enable monitoring of patients with breast cancer. The challenge ahead will be to incorporate cfDNA mutation profiling into routine clinical practice to provide patients with the most appropriate and timely treatment.

Provision of legal services to persons with HIV or AIDS: barriers and trends.

PubMed

Carey, R

Canadian HIV/AIDS legal clinics address their agendas, funding, activities, and observed trends. The HIV & AIDS Legal Clinic (Ontario) (HALCO) is profiled in the first of a series. HALCO is a poverty law clinic for HIV-positive people with limited financial means in Ontario. The profile of legal problems handled by HALCO includes government assistance payments, inadequate or too-expensive housing, wills and substitute decision making, bankruptcy, human rights, prison health issues, employment concerns, immigration issues, and family law. HALCO has a limited budget, and can only afford one full-time lawyer and one full-time community worker on staff. HALCO is tracking a trend of diminishing legal protections for HIV-positive employees. They have also recorded increased opposition in the insurance industry to cover HIV drug treatment. Medical malpractice litigations are also increasing due to the doctors failing to inform patients of their HIV status or to treat them adequately once they have been notified.

Does obsessive-compulsive personality disorder belong within the obsessive-compulsive spectrum?

PubMed

Fineberg, Naomi A; Sharma, Punita; Sivakumaran, Thanusha; Sahakian, Barbara; Chamberlain, Sam R; Chamberlain, Sam

2007-06-01

It has been proposed that certain Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders share overlapping clinical features, genetic contributions, and treatment response and fall within an "obsessive-compulsive" spectrum. Obsessive-compulsive personality disorder (OCPD) resembles obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of phenomenology, comorbidity, neurocognition, and treatment response. This article critically examines the nosological profile of OCPD with special reference to OCD and related disorders. By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, we gain a fresh approach to understanding its neurobiology, etiology, and potential treatments.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical Factors and Outcomes of Dialysis-Dependent End-Stage Renal Disease Patients with Emergency Department Septic Shock.

PubMed

Lowe, Kevin M; Heffner, Alan C; Karvetski, Colleen H

2018-01-01

Infection is the second leading cause of death in end-stage renal disease (ESRD) patients. Prior investigations of acute septic shock in this specific population are limited. We aimed to evaluate the clinical presentation and factors associated with outcome among ESRD patients with acute septic shock. We reviewed patients prospectively enrolled in an emergency department (ED) septic shock treatment pathway registry between January 2014 and May 2016. Clinical and treatment variables for ESRD patients were compared with non-ESRD patients. A second analysis focused on ESRD septic shock survivors and nonsurvivors. Among 4126 registry enrollees, 3564 (86.4%) met inclusion for the study. End-stage renal disease was present in 3.8% (n = 137) of ED septic shock patients. Hospital mortality was 20.4% and 17.1% for the ESRD and non-ESRD septic shock patient groups (p = 0.31). Septic shock patients with ESRD had a higher burden of chronic illness, but similar admission clinical profiles to non-ESRD patients. End-stage renal disease status was independently associated with lower fluid resuscitation dose, even when controlling for severity of illness. Age and admission lactate were independently associated with mortality in ESRD septic shock patients. ESRD patients comprise a small but important portion of patients with ED septic shock. Although presentation clinical profiles are similar to patients without ESRD, ESRD status is independently associated with lower fluid dose and compliance with the 30-mL/kg fluid goal. Hyperlactatemia is a marker of mortality in ESRD septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical potential of aclidinium bromide in chronic obstructive pulmonary disease.

PubMed

Jones, Paul W

2015-01-01

Three long-acting muscarinic antagonists (LAMAs) are now available in Europe, providing clinicians and patients with a choice of interventions, which is important in COPD, which is clinically a heterogeneous disease. The first LAMA, tiotropium, has been widely used over the last decade as a once-daily maintenance therapy in stable COPD to improve patients' health-related quality of life and to reduce the risk of exacerbations. Administered via the HandiHaler(®) device, it is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also been shown to improve health status and reduce exacerbations, and is well tolerated. The subject of this review is a third LAMA, aclidinium bromide, which was approved as a twice-daily maintenance bronchodilator treatment. In the pivotal Phase III clinical trials, patients receiving aclidinium achieved significantly greater improvements in lung function, reductions in breathlessness, and improvements in health status compared with placebo, for up to 24 weeks. In continuation studies, these improvements were sustained for up to 52 weeks. Pooled data showed exacerbation frequency was significantly reduced with aclidinium versus placebo. Preclinical and pharmacological studies demonstrating low systemic bioavailability and a low propensity to induce cardiac arrhythmias were translated into a favorable tolerability profile in the clinical trial program - the adverse event profile of aclidinium was similar to placebo, with a low incidence of anticholinergic and cardiac adverse events. While additional studies are needed to evaluate its full clinical potential, aclidinium is an important part of this recent expansion of LAMA therapeutic options, providing clinicians and patients with an effective and well-tolerated COPD treatment.

Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes.

PubMed

Kristensen, P L; Tarnow, L; Bay, C; Nørgaard, K; Jensen, T; Parving, H-H; Perrild, H; Beck-Nielsen, H; Christiansen, J S; Thorsteinsson, B; Pedersen-Bjergaard, U

2017-05-01

To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. A total of 72 people [46 men, mean ± sd age 54 ± 12 years, mean ± sd HbA 1c 65 ± 12 mmol/mol (8.1 ± 1.1%), mean ± sd duration of diabetes 30 ± 14 years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn hourly during sleep. Primary endpoints were nocturnal glucose profiles and occurrence of hypoglycaemia (blood glucose ≤ 3.9 mmol/l). During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue. Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia. © 2017 Diabetes UK.

Reaction of facial soft tissues to treatment with a Herbst appliance.

PubMed

Meyer-Marcotty, P; Kochel, J; Richter, U; Richter, F; Stellzig-Eisenhauer, Angelika

2012-04-01

The objective of this prospective longitudinal study was to investigate the reaction of facial soft tissues to treatment with a Herbst appliance. We aimed to quantify three-dimensionally (3D) the isolated effect of the Herbst appliance and volume changes in the lip profile. The 3D data of the facial soft tissues of 34 patients with skeletal Class II (17 female and 17 male, mean age 13.5 ± 1.8 years) were prepared in a standardized manner immediately before (T1) and after (T2) treatment with a Herbst appliance. Anthropometric evaluation was carried out in sagittal and vertical dimensions. To quantify volume changes, pretherapeutic and posttherapeutic images were superimposed three-dimensionally and the difference volumes calculated. Following testing for normal distribution, a statistical analysis was carried out using the paired t test. We observed ventral development of the soft tissues of the lower jaw with flattening of the profile curvature and anterior displacement of the sublabial region in a total of 27 patients. Anterior facial height was lengthened and the facial depth at the lower jaw increased. The largest percentage changes were noted in the lip profile, with a reduction in the red margin of the upper lip and an increase in lower lip height. We also observed a reduction of the sublabial fold in conjunction with a simultaneous increase in volume. The influence of the Herbst appliance on the facial soft tissues is expected to result in a positive treatment outcome, particularly in patients with a convex profile, a retrusive lower lip, and a marked sublabial fold. We observed a broad clinical spectrum of individual reactions in the facial soft tissues. It is, thus, not possible to detect a linear relationship between the Herbst treatment and soft tissue changes, making soft tissue changes difficult to predict.

SGLT2 inhibitor-induced changes in body composition and simultaneous changes in metabolic profile: 52-week prospective LIGHT Study with luseogliflozin.

PubMed

Sasaki, Takashi; Sugawara, Masahiro; Fukuda, Masahiro

2018-04-16

It is unclear how changes in body composition induced by sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment correlate with metabolic profile changes. We aimed to clarify how metabolic profile changes correlate with body component changes, and if SGLT2 inhibitor treatment causes sarcopenia and bone mineral content (BMC) loss. Moderately obese Japanese type 2 diabetes (T2D) patients, treated with luseogliflozin for a year, were observed prospectively and evaluated for body composition changes. We analyzed the changes in the individual body components during treatment, and their correlation with other clinical variables. The efficacy analysis set comprised 37 of 43 enrolled patients. The total fat mass significantly decreased early in the treatment at and after Week 4, with a mean decrease of -1.97 kg [95% CI: -2.66 to -1.28] at Week 24. The visceral fat area at Week 24 showed an average downward trend, although this was not significant. The changes in visceral fat area in individual patients demonstrated a significant negative correlation with the extent of the baseline visceral fat area (r=-0.399, p=0.023). The skeletal muscle mass index exhibited a significant but small change at and after Week 36. The BMC profile showed a transient significant decrease only at Week 12. No significant change in BMC was noted at other time points. Luseogliflozin treatment brought about favorable changes in body composition and metabolism of moderately obese Japanese T2D patients, accompanied by body fat reduction and minimal muscle and BMC reduction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Risk profile, management, and outcomes of patients with venous thromboembolism attended in Spanish Emergency Departments: The ESPHERIA registry.

PubMed

Jimenez, Sonia; Ruiz-Artacho, Pedro; Merlo, Marta; Suero, Coral; Antolin, Albert; Casal, José Ramón; Sanchez, Marta; Ortega-Duarte, Alejandra; Genis, Mar; Piñera, Pascual

2017-12-01

The objective of this study was to determine the clinical profile of and diagnostic and therapeutic approach to patients with venous thromboembolism (VTE) in Spanish Emergency Departments (EDs). Risk factors, adherence to clinical practice guidelines, and outcomes were also evaluated.Patients with VTE diagnosed in 53 Spanish EDs were prospectively and consecutively included. Demographic data, comorbidities, risk factors for VTE, index event characteristics, hemorrhagic risk, and mortality were evaluated. Adherence to clinical practice guidelines was assessed based on clinical probability scales, requests for determination of D-dimer, use of anticoagulant treatment before confirmation of diagnosis, and assessment of bleeding and prognostic risk. Recurrence, bleeding, and death during admission and at 30, 90, and 180 days after diagnosis in the EDs were recorded.From 549,840 ED visits made over a mean period of 40 days, 905 patients were diagnosed with VTE (incidence 1.6 diagnoses per 1000 visits). The final analysis included 801 patients, of whom 49.8% had pulmonary embolism. The most frequent risk factors for VTE were age (≥70 years), obesity, and new immobility. Clinical probability, prognosis, and bleeding risk scales were recorded in only 7.6%, 7.5%, and 1% of cases, respectively. D-dimer was determined in 87.2% of patients with a high clinical probability of VTE, and treatment was initiated before confirmation in only 35.9% of these patients. In patients with pulmonary embolism, 31.3% had a low risk of VTE. Overall, 98.7% of patients with pulmonary embolism and 50.2% of patients with deep venous thrombosis were admitted. During follow-up, total bleeding was more frequent than recurrences: the rates of any bleeding event were 4.4%, 3.9%, 5.3%, and 3.5% at admission and at 30 and 90, and 180 days, respectively; the rates of VTE recurrence were 2.3%, 1.3%, 1.7%, and 0.6%, respectively. Mortality rates were 3.4%, 3.1%, 4.1%, and 2.6% during hospitalization and at 30, 90, and 180 days, respectively.VTE had a substantial impact on Spanish EDs. The clinical presentation and risk profile for the development of VTE in patients diagnosed in the EDs was similar to that recorded in previous studies. During follow-up, bleeding (overall) was more frequent than recurrences. Adherence to clinical practice guidelines could improve significantly.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

Clinical Reasoning in Massage Therapy

PubMed Central

LeMoon, Kim

2008-01-01

Background: Clinical reasoning has long been a valuable tool for health care practitioners, but it has been under-researched in the field of massage therapy. Case reports have been a useful method for exploring the clinical reasoning process in various fields of manual therapy and can provide a model for similar research in the field of massage therapy. A diagnostically challenging case concerning a client with low back pain serves as a guideline for examining the clinical reasoning process of a massage therapist. Methods: A two-part methodology was employed: Client profileReflective inquiry The inquiry included questions pertaining to beliefs about health problems; beliefs about the mechanisms of pain; medical conditions that could explain the client’s symptoms; knowledge of the client’s anatomy, assessment, and treatment choices; observations made during treatment; extent of experience in treating similar problems; and ability to recognize clinical patterns. Results: The clinical reasoning process of a massage therapist contributed to a differential diagnosis, which provided an explanation for the client’s symptoms and led to a satisfactory treatment resolution. Conclusion: The present report serves as an example of the value of clinical reasoning in the field of massage therapy, and the need for expanded research into its methods and applications. The results of such research could be beneficial in teaching the clinical reasoning process at both the introductory and the advanced levels of massage therapy education. PMID:21589814

ISONIAZID AND RIFAMPIN PHARMACOKINETICS IN TWO ASIAN ELEPHANTS (ELEPHAS MAXIMUS) INFECTED WITH MYCOBACTERIUM TUBERCULOSIS.

PubMed

Egelund, Eric F; Isaza, Ramiro; Alsultan, Abdullah; Peloquin, Charles A

2016-09-01

This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species. The altered pharmacokinetics of both drugs in repeated-dosing clinical situations underscores the need for individual therapeutic drug monitoring for tuberculosis treatment.

The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome.

PubMed

Minozzi, Massimo; Costantino, Demetrio; Guaraldi, Claudia; Unfer, Vittorio

2011-11-01

Compare the effects of a combined contraceptive pill (OCP) in combination with myo-inositol (MI) on endocrine, metabolic, and clinical parameters in patients with polycystic ovary syndrome (PCOS). One hundred fifty-five patients with PCOS were enrolled in this prospective, open-label clinical study. Patients were assigned to receive oral treatment with OCP alone (estradiol (EE) 30 μg/gestodene 75 μg) or in combination with myo-inositol 4 g/die, for 12 months. OCP plus MI therapy resulted in a higher reduction of FG score compared with OCP alone therapy. The combined therapy (OCP plus MI) significantly decreased hyperinsulinaemia, by positively affecting the fasting insulin and glucose levels and homeostasis model assessment-insulin resistance parameters, while no significant changes were observed in the OCP group. Androgens serum levels decreased in both groups, but significantly more in the combined therapy group. The lipid profile was improved in the combined therapy group, by reducing low-density lipoprotein cholesterol levels and enhancing high-density lipoprotein cholesterol levels. Our data show that a combination of combined contraceptive pill and MI may be more effective in controlling endocrine, metabolic, and clinical profile in patients with PCOS than OCP alone, and may reduce insulin levels and insulin resistance. Hence, combined treatment may become a more effective long-term therapeutic choice for controlling PCOS symptoms.

Two decades of change in European general practice service profiles: conditions associated with the developments in 28 countries between 1993 and 2012.

PubMed

Schäfer, Willemijn L A; Boerma, Wienke G W; Spreeuwenberg, Peter; Schellevis, François G; Groenewegen, Peter P

2016-01-01

Evidence regarding the benefits of strong primary care has influenced health policy and practice. This study focuses on changes in the breadth of services provided by general practitioners (GPs) in Europe between 1993 and 2012 and offers possible explanations for these changes. Data on the breadth of service profiles were used from two cross-sectional surveys in 28 countries: the 1993 European GP Task Profile study (6321 GPs) and the 2012 QUALICOPC study (6044 GPs). GPs' involvement in four areas of clinical activity (first contact care, treatment of diseases, medical procedures, and prevention) was established using ecometric analyses. The changes were measured by the relative increase in the breadth of service profiles. Associations between changes and national-level conditions were examined though regression analyses. Data on the national conditions were used from various other public databases including the World Databank and the PHAMEU (Primary Health care Activity Monitor) database. A total of 28 European countries. GPs. Changes in the breadth of GP service profiles. A general trend of increased involvement of European GPs in treatment of diseases and decreased involvement in preventive activities was observed. Conditions at the national level were associated with changes in the involvement of GPs in first contact care, treatment of diseases and, to a limited extent, prevention. Especially in countries with stronger growth of health care expenditures between 1993 and 2012 the service profiles have expanded. In countries where family values are more dominant the breadth in service profiles decreased. A stronger professional status of GPs was positively associated with the change in first contact care. GPs in former communist countries and Turkey have increased their involvement in the provision of services. Developments in Western Europe were less evident. The developments in the service profiles could only to a very limited extent be explained by national conditions. A main driver of reform seems to be the changes in health care expenditure, which may indicate a notion of urgency because there may be a pressure to curb the rising expenditures. Broad GP service profiles are an indicator of strong primary care in a country. It is expected that developments in the breadth of GP service profiles are influenced by various national conditions related to the urgency to reform, politics, and means. Between 1993 and 2012 the involvement of GPs in European countries in treatment of diseases increased and their involvement preventive activities decreased. The national conditions were found to be associated with changes in GPs' involvement as first contact of care, treatment of diseases, and, to a limited extent, prevention. More specifically, in countries with a stronger growth in health care expenditures, service profiles of European GPs have expanded more in the past decades.

Radiation treatment in older patients: a framework for clinical decision making.

PubMed

Smith, Grace L; Smith, Benjamin D

2014-08-20

In older patients, radiation treatment plays a vital role in curative and palliative cancer therapy. Radiation treatment recommendations should be informed by a comprehensive, personalized risk-benefit assessment that evaluates treatment efficacy and toxicity. We review several clinical factors that distinctly affect efficacy and toxicity of radiation treatment in older patients. First, locoregional tumor behavior may be more indolent in older patients for some disease sites but more aggressive for other sites. Assessment of expected locoregional relapse risk informs the magnitude and timeframe of expected radiation treatment benefits. Second, assessment of the competing cancer versus noncancer mortality and morbidity risks contextualizes cancer treatment priorities holistically within patients' entire spectrum and time course of health needs. Third, assessment of functional reserve helps predict patients' acute treatment tolerance, differentiating those patients who are unlikely to benefit from treatment or who are at high risk for treatment complications. Potential radiation treatment options include immediate curative treatment, delayed curative treatment, and no treatment, with additional consideration given to altered radiation target, dose, or sequencing with chemotherapy and/or surgery. Finally, when cure is not feasible, palliative radiation therapy remains valuable for managing symptoms and achieving meaningful quality-of-life improvements. Our proposed decision-making framework integrates these factors to help radiation oncologists formulate strategic treatment recommendations within a multidisciplinary context. Future research is still needed to identify how advanced technologies can be judiciously applied in curative and palliative settings to enhance risk-benefit profiles of radiation treatment in older patients and more accurately quantify treatment efficacy in this group. © 2014 by American Society of Clinical Oncology.

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Clinical profile of responders to buprenorphine as a substitution treatment in heroin addicts: results of a multicenter study of 73 patients.

PubMed

Poirier, Marie-France; Laqueille, Xavier; Jalfre, Valérie; Willard, Dominique; Bourdel, Marie Chantal; Fermanian, Jacques; Olié, Jean Pierre

2004-03-01

In France, high-dosage buprenorphine (HDB) is the main substitution treatment for narcotic addiction. Few data have been published concerning clinical factors predicting a good response to this treatment in a daily practice. A hospital-based multicenter clinical research program (PHRC) was undertaken in heroin-addicted patients, diagnosed according to DSM-III-R, to detect clinical criteria susceptible of predicting a good response to HDB administered during a 3-month treatment period. At the inclusion time in the study, a diagnostic structured interview (DIGS) was performed, and the Addiction Severity Index (ASI), Zuckerman scale, depression scale from Jouvent, and CGI were scored. MMPI was also administered. Good response was defined as an ongoing participation in the study, with absence of opiate detected in 75% of urine collected during the last month of treatment. Only subjects treated for at least 1 month were eligible for analyses. One hundred fifteen patients were recruited and 73 were analyzed. Patients received 8.5+/-2.6 mg (m+/-S.D.) of buprenorphine for 1 to 3 months. A forward stepwise logistic regression showed that six clinical parameters may predict a good response to treatment: probability to respond to buprenorphine was higher in subjects having a high psychopathology (ASI) subscore, low disinhibition and boredom susceptibility factor scores (Zuckerman scale), no alcohol dependence, no family history of addiction or mood disorder, and duration of opiate dependence less than 10 years. Only the MMPI D subscale was a psychological pattern correlated to a good response to substitution treatment. These findings are important to consider when making the decision to prescribe HDB substitution treatment in opiate addiction.

Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

PubMed Central

2013-01-01

Background This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. Methods We included 71 critical incidents in primary midwifery care and subsequent hospital care in case of referral after 36 weeks of pregnancy that were related to substandard care and for that reason were reported to the Health Care Inspectorate in The Netherlands in 36 months (n = 357). We performed a case-by-case analysis, using a previously validated instrument which covered five broad domains: healthcare organization, communication between healthcare providers, patient risk factors, clinical management, and clinical outcomes. Results Determinants that were associated with risk concerned healthcare organization (n = 20 incidents), communication about treatment procedures (n = 39), referral processes (n = 19), risk assessment by telephone triage (n = 10), and clinical management in an out of hours setting (n = 19). The 71 critical incidents included three cases of maternal death, eight cases of severe maternal morbidity, 42 perinatal deaths and 12 critical incidents with severe morbidity for the child. Suboptimal prenatal risk assessment, a delay in availability of health care providers in urgent situations, miscommunication about treatment between care providers, and miscommunication with patients in situations with a language barrier were associated with safety risks. Conclusions Systematic analysis of critical incidents improves insight in determinants of safety risk. The wide variety of determinants of risk of critical incidents implies that there is no single intervention to improve patient safety in the care for pregnant women with initially a low risk profile. PMID:24286376

Characteristics, resource utilization and safety profile of patients prescribed with neuropathic pain treatments: a real-world evidence study on general practices in Europe - the role of the lidocaine 5% medicated plaster.

PubMed

Katz, Pablo; Pegoraro, Valeria; Liedgens, Hiltrud

2017-08-01

To identify characteristics, resource utilization, and safety profile of patients prescribed with lidocaine 5% medicated plaster, pregabalin, gabapentin, amitriptyline and duloxetine when experiencing pain in the real-world setting of general practitioners (GPs) in Europe. Retrospective analysis on real world data from IMS Health Longitudinal Patient Database. Patients with at least one prescription of the drugs of interest during 2014 were selected and those with a non-neuropathic pain-related diagnosis were excluded. Patients' demographic and clinical characteristics, resource utilization data and adverse drug reactions (ADRs) as described in the leaflet were extracted. The association between treatments and ADR occurrence was evaluated applying multivariate logistic models. A total of 70,515 patients were selected from Italy, Germany, the UK, Spain and Belgium. Lidocaine 5% medicated plaster patients were the oldest in Italy, the UK and Spain and the most health impaired in Italy, Spain and Belgium. No relevant differences in the number of co-prescriptions, specialist visits, examinations and hospitalizations were found. Significantly less lidocaine 5% plasters patients experienced ADRs, with odds ratios in favor of lidocaine 5% medicated plasters ranging from 3.41 (p = .036) to 52.33 (p < .001). Evidence from daily clinical practice in GP settings agrees with the findings from more controlled clinical-trial settings, with lidocaine 5% medicated plaster patients showing a better safety profile, but also a comparable level of resource utilization. A possible re-evaluation of the scientific value coming from this retrospective study in building up a diagnostic as well as a therapeutic algorithm is suggested.

The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

PubMed Central

Men, Xin; Ma, Jun; Wu, Tong; Pu, Junyi; Wen, Shaojia; Shen, Jianfeng; Wang, Xun; Wang, Yamin; Chen, Chao; Dai, Penggao

2018-01-01

Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options. PMID:29423105

Impulsivity profiles in pathological slot machine gamblers.

PubMed

Aragay, Núria; Barrios, Maite; Ramirez-Gendrau, Isabel; Garcia-Caballero, Anna; Garrido, Gemma; Ramos-Grille, Irene; Galindo, Yésika; Martin-Dombrowski, Jonatan; Vallès, Vicenç

2018-05-01

In gambling disorder (GD), impulsivity has been related with severity, treatment outcome and a greater dropout rate. The aim of the study is to obtain an empirical classification of GD patients based on their impulsivity and compare the resulting groups in terms of sociodemographic, clinical and gambling behavior variables. 126 patients with slot machine GD attending the Pathological Gambling Unit between 2013 and 2016 were included. The UPPS-P Impulsive Behavior Scale was used to assess impulsivity, and the severity of past-year gambling behavior was established with the Screen for Gambling problems questionnaire (NODS). Depression and anxiety symptoms and executive function were also assessed. A two-step cluster analysis was carried out to determine impulsivity profiles. According to the UPPS-P data, two clusters were generated. Cluster 1 showed the highest scores on all the UPPS-P subscales, whereas patients from cluster 2 exhibited only high scores on two UPPS-P subscales: Negative Urgency and Lack of premeditation. Additionally, patients on cluster 1 were younger and showed significantly higher scores on the Beck Depression Inventory and on the State-Trait Anxiety Inventory questionnaires, worse emotional regulation and executive functioning, and reported more psychiatric comorbidity compared to patients in cluster 2. With regard to gambling behavior, cluster 1 patients had significantly higher NODS scores and a higher percentage presented active gambling behavior at treatment start than in cluster 2. We found two impulsivity subtypes of slot machine gamblers. Patients with high impulsivity showed more severe gambling behavior, more clinical psychopathology and worse emotional regulation and executive functioning than those with lower levels of impulsivity. These two different clinical profiles may require different therapeutic approaches. Copyright © 2018 Elsevier Inc. All rights reserved.

A Brazilian report using serological and molecular diagnosis to monitoring acute ocular toxoplasmosis.

PubMed

Previato, Mariana; Frederico, Fábio Batista; Murata, Fernando Henrique Antunes; Siqueira, Rubens Camargo; Barbosa, Amanda Pires; Silveira-Carvalho, Aparecida Perpétuo; Meira, Cristina da Silva; Pereira-Chioccola, Vera Lúcia; Gava, Ricardo; Martins Neto, Plínio Pereira; de Mattos, Luiz Carlos; de Mattos, Cinara Cássia Brandão

2015-12-07

Toxoplasmosis was recently included as a neglected disease by the Center for Disease Control. Ocular toxoplasmosis is one clinical presentation of congenital or acquired infection. The laboratory diagnosis is being used worldwide to support the clinical diagnosis and imaging. The aim of this study was to evaluate the use of serology and molecular methods to monitor acute OT in immunocompetent patients during treatment. Five immunocompetent patients were clinically diagnosed with acute OT. The clinical evaluation was performed by ophthalmologic examination using the Early Treatment Diabetic Retinopathy Study, best-corrected visual acuity, slit lamp biomicroscopy, fundoscopic examination with indirect binocular ophthalmoscopy color fundus photography, fluorescein angiography and spectral optical coherence tomography (OCT). Serology were performed by ELISA (IgA, IgM, IgG) and confirmed by ELFA (IgG, IgM). Molecular diagnoses were performed in peripheral blood by cPCR using the Toxoplasma gondii B1 gene as the marker. Follow-up exams were performed on day +15 and day +45. Only five non-immunocompromised male patients completed the follow up and their data were used for analysis. The mean age was 41.2 ± 11.3 years (median: 35; range 31-54 years). All of them were positive for IgG antibodies but with different profiles for IgM and IgA, as well as PCR. For all patients the OCT exam showed active lesions with the inner retinal layers being abnormally hyper-reflective with full-thickness disorganization of the retinal reflective layers, which assumed a blurred reflective appearance and the retina was thickened. The presence of IgA and IgM confirmed the acute infection and thus was in agreement with the clinical evaluation. Our results show the adopted treatment modified the serological profile of IgM antibodies and the PCR results, but not the IgG and IgA antibodies and that imaging is a good tool to follow-up patients.

Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib.

PubMed

Oztan, A; Fischer, S; Schrock, A B; Erlich, R L; Lovly, C M; Stephens, P J; Ross, J S; Miller, V; Ali, S M; Ou, S-H I; Raez, L E

2017-09-01

Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

New approaches to hyperkalemia in patients with indications for renin angiotensin aldosterone inhibitors: Considerations for trial design and regulatory approval.

PubMed

Zannad, Faiez; Rossignol, Patrick; Stough, Wendy Gattis; Epstein, Murray; Alonso Garcia, Maria de Los Angeles; Bakris, George L; Butler, Javed; Kosiborod, Mikhail; Berman, Lance; Mebazaa, Alexandre; Rasmussen, Henrik S; Ruilope, Luis M; Stockbridge, Norman; Thompson, Aliza; Wittes, Janet; Pitt, Bertram

2016-08-01

Hyperkalemia is a common clinical problem, especially in patients with chronic kidney disease, diabetes mellitus, or heart failure. Treatment with renin angiotensin aldosterone system inhibitors exacerbates the risk of hyperkalemia in these patients. Concern about hyperkalemia can result in the failure to initiate, suboptimal dosing, or discontinuation of renin angiotensin aldosterone system inhibitor therapy in patients; effective treatments for hyperkalemia might mitigate such undertreatment. New treatments for hyperkalemia in development may offer better efficacy, tolerability and safety profiles than do existing approved treatments. These compounds might enable more eligible patients to receive renin angiotensin aldosterone system inhibitor therapy or to receive renin angiotensin aldosterone system inhibitors at target doses. The evidence needed to support a treatment claim (reduction in serum potassium) differs from that needed to support a prevention claim (preventing hyperkalemia to allow renin angiotensin aldosterone system inhibitor treatment). Thus, several issues related to clinical trial design and drug development need to be considered. This paper summarizes and expands upon a discussion at the Global Cardiovascular Clinical Trialists 2014 Forum and examines methodologic considerations for trials of new potassium binders for the prevention and management of hyperkalemia in patients with renin angiotensin aldosterone system inhibitor indications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior.

PubMed

Thanos, Panayotis K; Robison, Lisa S; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M; Komatsu, David E; Hadjiargyrou, Michael; Volkow, Nora D

2015-04-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (quicker and higher peak concentrations). We evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic clinical drug delivery. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60mg/kg/day; as well as dual-dosages of 4 and 10mg/kg/day, 20 and 30mg/kg/day, or 30 and 60mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30ng/mL), while the 4/10mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8ng/mL). Treatment with the higher dual-dosage (HD: 30/60mg/kg) resulted in hyperactivity, while the lower (LD: 4/10mg/kg) had no effect. Chronic effects of these dual-dosages were assessed throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle, decreased exploratory behavior, and increased anxiolytic behavior. Findings suggest that these dual-dosage-drinking-paradigms can be used to examine the effects of clinically relevant pharmacokinetic doses of MP and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Perspectives on the evolving state of the art management of gastrointestinal stromal tumours

PubMed Central

Szucs, Zoltan

2018-01-01

Gastrointestinal stromal tumours (GISTs) represent a very exciting tumour entity for the medical oncologist. There has been extensive clinical and preclinical research dissecting the natural behaviour, molecular landscape and therapeutic responsiveness of this rare mesenchymal tumour. Various molecular subtypes of GIST have a differing prognostic and predictive relevance in the state of the art management of the disease. Emerging mature clinical trial data gathered over the last one and half decade provided substantial molecular profiling information in understanding the success and eventual failure of treatment. In our review of the most relevant literature we aim to guide the clinician in tailoring neoadjuvant, adjuvant and palliative treatment of GIST alongside the different, now well established molecular subgroups of GISTs. PMID:29780899

Agmatine improves locomotor function and reduces tissue damage following spinal cord injury.

PubMed

Yu, C G; Marcillo, A E; Fairbanks, C A; Wilcox, G L; Yezierski, R P

2000-09-28

Clinically effective drug treatments for spinal cord injury (SCI) remain unavailable. Agmatine, an NMDA receptor antagonist and inhibitor of nitric oxide synthase (NOS), is an endogenous neuromodulator found in the brain and spinal cord. Evidence is presented that agmatine significantly improves locomotor function and reduces tissue damage following traumatic SCI in rats. The results suggest the importance of future therapeutic strategies encompassing the use of single drugs with multiple targets for the treatment of acute SCI. The therapeutic targets of agmatine (NMDA receptor and NOS) have been shown to be critically linked to the pathophysiological sequelae of CNS injury and this, combined with the non-toxic profile, lends support to agmatine being considered as a potential candidate for future clinical applications.

Design of oral agents for the management of multiple sclerosis: benefit and risk assessment for dimethyl fumarate

PubMed Central

Nicholas, Jacqueline Ann; Boster, Aaron Lee; Imitola, Jaime; O’Connell, Colleen; Racke, Michael Karl

2014-01-01

Dimethyl fumarate (DMF) is the most recent oral disease-modifying therapy approved by the US Food and Drug Administration and is indicated for the treatment of relapsing forms of multiple sclerosis (MS). Prior to approval for use in MS, DMF and its active metabolite, monomethyl fumarate, had been used for decades as two of the fumaric acid esters in Fumaderm®, a medication used in Europe for the treatment of psoriasis. The unique mechanism of action of DMF remains under evaluation; however, it has been shown to act through multiple pathways leading to shifts away from the Th1 proinflammatory response to the less inflammatory Th2 response. Preliminary data suggest that DMF may induce neuroprotective effects in central nervous system white matter, although further studies are needed to demonstrate these effects on inflammatory demyelination. The DMF Phase III clinical trials demonstrated its efficacy with regard to a reduction in the annualized relapse rate and reductions in new or enlarging T2 lesions and numbers of gadolinium-enhancing lesions on magnetic resonance imaging. DMF has a well-defined safety profile, given the experience with its use in the treatment of psoriasis, and more recently from the DMF clinical trials program and post-marketing era for treatment of MS. The safety profile and oral mode of administration of DMF place it as an attractive first-line therapy option for the treatment of relapsing forms of MS. Long-term observational studies will be needed to determine the effects of DMF on progression of disability in MS. PMID:25045248

Preventing and Treating Peri-Implantitis: A Cost-Effectiveness Analysis.

PubMed

Schwendicke, Falk; Tu, Yu-Kang; Stolpe, Michael

2015-09-01

A large number of treatments for peri-implantitis are available, but their cost-effectiveness remains uncertain. This study evaluates the cost-effectiveness of preventing and treating peri-implantitis. A Markov model was constructed that followed each implant over 20 years. Supportive implant therapy (SIT) for managing peri-implant mucositis and preventing development of peri-implantitis was either provided or not. Risk of peri-implantitis was assumed to be affected by SIT and the patient's risk profile. If peri-implantitis occurred, 11 treatment strategies (non-surgical or surgical debridement alone or combined with adjunct therapies) were compared. Treatments and risk profiles determined disease progression. Modeling was performed based on systematically collected data. Primary outcomes were costs and proportion of lost implants, as assessed via Monte Carlo microsimulations. Not providing SIT and performing only non-surgical debridement was both least costly and least effective. The next best (more costly and effective) option was to provide SIT and perform surgical debridement (additional 0.89 euros per 1% fewer implants lost). The most effective option included bone grafts, membranes, and laser treatment (56 euros per 1%). For patients at high risk, the cost-effectiveness of SIT increased, whereas in low-risk groups, a cost-optimized strategy was cost-effective. Although clinical decision-making will be guided mainly by clinical condition, cost-effectiveness analyses might add another perspective. Based on these findings, an unambiguous comparative effectiveness ranking was not established. However, cost-effectiveness was predominantly determined by provision of SIT and initial treatment costs. Transferability of these findings to other healthcare systems needs further confirmation.

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

PubMed

Rubin, David T; Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Sale, Mark E; Rolleri, Robert L; Golden, Pamela L; Barrett, Andrew C; Bortey, Enoch; Forbes, William P

2015-11-01

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

PubMed Central

Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-01-01

Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

PubMed

Li, Dian-Jeng; Wang, Fu-Chiang; Chu, Che-Sheng; Chen, Tien-Yu; Tang, Chia-Hung; Yang, Wei-Cheng; Chow, Philip Chik-Keung; Wu, Ching-Kuan; Tseng, Ping-Tao; Lin, Pao-Yen

2017-01-01

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

The European Society for Medical Oncology Magnitude of Clinical Benefit Scale in daily practice: a single institution, real-life experience at the Medical University of Vienna.

PubMed

Kiesewetter, Barbara; Raderer, Markus; Steger, Günther G; Bartsch, Rupert; Pirker, Robert; Zöchbauer-Müller, Sabine; Prager, Gerald; Krainer, Michael; Preusser, Matthias; Schmidinger, Manuela; Zielinski, Christoph C

2016-01-01

The European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) has been designed to stratify the therapeutic benefit of a certain drug registered for the treatment of cancer. However, though internally validated, this tool has not yet been evaluated for its feasibility in the daily practice of a major center of medical oncology. The practicability of the MCBS for advanced oncological diseases at the Clinical Division of Oncology, Medical University of Vienna, which constitutes one of the largest oncological centres in Europe, was analysed in a three-step approach. First, retrospectively collected data were analysed to gain an overview of treatments in regular use. Second, data were scored by using the MCBS. Third, the ensuing results were evaluated within corresponding programme directorships to assess feasibility in a real-life clinical context. In the majority of tumour entities, the MCBS results reported earlier are consistent with daily clinical practice. Thus, in metastatic breast cancer or advanced lung cancer, there was a high level of clinical benefit for first-line treatment standards, and these results reflected well real-life experience. However, analyses based on the first version of the MCBS are limited if it comes to salvage treatment in tumour entities in which optimal sequencing of potential treatment options is of major importance, as in metastatic colorectal or renal cell cancer. In contrast to this, it is remarkable that certain novel therapies such as nivolumab assessed for heavily pretreated advanced renal cancer reached the highest level of clinical benefit due to prolongation in survival and a favourable toxicity profile. The MCBS clearly underlines the potential benefit of these compounds. The MCBS is an excellent tool for daily clinical practice of a tertiary referral centre. It supports treatment decisions based on the clinical benefit to be expected from a novel approach such as immunotherapy in as yet untested indications.

Target biomarker profile for the clinical management of paracetamol overdose

PubMed Central

Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy.

PubMed

Xie, Yunhe; Bentefour, El Hassane; Janssens, Guillaume; Smeets, Julien; Vander Stappen, François; Hotoiu, Lucian; Yin, Lingshu; Dolney, Derek; Avery, Stephen; O'Grady, Fionnbarr; Prieels, Damien; McDonough, James; Solberg, Timothy D; Lustig, Robert A; Lin, Alexander; Teo, Boon-Keng K

2017-09-01

To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode. A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were -0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and -0.4 ± 0.9 mm for the vertex field. This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties. Copyright © 2017 Elsevier Inc. All rights reserved.

Medical-attention injuries in community Australian football: a review of 30 years of surveillance data from treatment sources.

PubMed

Ekegren, Christina L; Gabbe, Belinda J; Finch, Caroline F

2015-03-01

In recent reports, Australian football has outranked other team sports in the frequency of hospitalizations and emergency department (ED) presentations. Understanding the profile of these and other "medical-attention" injuries is vital for developing preventive strategies that can reduce health costs. The objective of this review was to describe the frequency and profile of Australian football injuries presenting for medical attention. A systematic search was carried out to identify peer-reviewed articles and reports presenting original data about Australian football injuries from treatment sources (hospitals, EDs, and health-care clinics). Data extracted included injury frequency and rate, body region, and nature and mechanism of injury. Following literature search and review, 12 publications were included. In most studies, Australian football contributed the greatest number of injuries out of any sport or recreation activity. Hospitals and EDs reported a higher proportion of upper limb than lower limb injuries, whereas the opposite was true for sports medicine clinics. In hospitals, fractures and dislocations were most prevalent out of all injuries. In EDs and clinics, sprains/strains were most common in adults and superficial injuries were predominant in children. Most injuries resulted from contact with other players or falling. The upper limb was the most commonly injured body region for Australian football presentations to hospitals and EDs. Strategies to prevent upper limb injuries could reduce associated public health costs. However, to understand the full extent of the injury problem in football, treatment source surveillance systems should be supplemented with other datasets, including community club-based collections.

Clinical Profile of Scrub Typhus in Pregnancy in Sub-Himalayan Region.

PubMed

Kumar, Ritesh; Thakur, Surinder; Bhawani, Rajesh; Kanga, Anil; Ranjan, Asha

2016-10-01

Scrub typhus is rare in pregnancy, but it has now become an important cause of febrile illness in pregnancy in sub-Himalayan region of India. Only a few case reports have been published so far, and they show adverse maternal and fetal outcomes. No consensus has been reached till now regarding treatment. All the pregnant patients irrespective of period of gestation admitted with febrile illness with positive IgM ELISA for scrub typhus with or without eschar were included. The clinical profile was observed using a detailed history of symptoms, travel, recreation, agricultural activities, treatment record prior to admission, and a detailed examination, and the treatment outcome was noted. Fever workup including cultures, CXR, CSF analysis, serology for scrub was done. IgM scrub typhus was done by kit method manufactured by InBios Intertational, Inc. We observed in total 14 pregnant patients out of which eight were in the the second trimester and six were in the third trimester. The clinical features of the disease observed for pregnant females were the same as for nonpregnant females. There was no difference in the severity of scrub typhus between pregnant and nonpregnant women. No mortality was found in these patients. On follow-up, they had normal peripartum and postpartum periods. All were treated with azithromycin 500 mg once a day for 5 days. Although rare, scrub typhus should be considered in differential diagnosis of fever in pregnant patients especially in scrub season. Azithromycin should be the drug of choice in pregnancy as it has no adverse effect on fetus and pregnancy outcome.

Monoamine Oxidase B Inhibitors in Parkinson's Disease.

PubMed

Dezsi, Livia; Vecsei, Laszlo

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Chen, I-Ju; Liu, Chia-Yu; Chiu, Jung-Peng; Hsu, Chung-Hua

2016-06-01

To examine the effect and safety of high-dose green tea extract (Epigallocatechin gallate, EGCG) at a daily dosage of 856.8 mg on weight reduction and changes of lipid profile and obesity-related hormone peptides in women with central obesity. We conducted a randomized, double-blind trial registered under ClinicalTrials.gov Identifier no. NCT02147041. A total of 115 women with central obesity were screened at our clinic. 102 of them with a body mass index (BMI) ≥ 27 kg/m(2) and a waist circumference (WC) ≥ 80 cm were eligible for the study. These women were randomly assigned to either a high-dose green tea group or placebo group. The total treatment time was 12 weeks. The main outcome measures were anthropometric measurements, lipid profiles, and obesity related hormone peptides including leptin, adiponectin, ghrelin, and insulin. Significant weight loss, from 76.8 ± 11.3 kg to 75.7 ± 11.5 kg (p = 0.025), as well as decreases in BMI (p = 0.018) and waist circumference (p = 0.023) were observed in the treatment group after 12 weeks of high-dose EGCG treatment. This study also demonstrated a consistent trend of decreased total cholesterol, reaching 5.33%, and decreased LDL plasma levels. There was good tolerance of the treatment among subjects without any side effects or adverse events. Significantly lower ghrelin levels and elevated adiponectin levels were detected in the study group than in the placebo group. 12 weeks of treatment with high-dose green tea extract resulted in significant weight loss, reduced waist circumference, and a consistent decrease in total cholesterol and LDL plasma levels without any side effects or adverse effects in women with central obesity. The antiobestic mechanism of high-dose green tea extract might be associated in part with ghrelin secretion inhibition, leading to increased adiponectin levels. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Clinical profile, level of affection and therapeutic management of patients with osteoarthritis in primary care: The Spanish multicenter study EVALÚA.

PubMed

Castaño Carou, Ana; Pita Fernández, Salvador; Pértega Díaz, Sonia; de Toro Santos, Francisco Javier

2015-01-01

To determine the clinical profile, degree of involvement and management in patients with knee, hip or hand osteoarthritis. Observational study (health centers from 14 autonomous regions, n=363 primary care physicians), involving patients with clinical and/or radiological criteria for osteoarthritis from the American College of Rheumatology, consecutively selected (n=1,258). Sociodemographic variables, clinical and radiological findings, comorbidity and therapeutic management were analyzed. Mean age was 68.0±9.5 years old; 77.8% were women and 47.6% obese. Distribution by location was: 84.3% knee, 23.4% hip, 14.7% hands. All patients reported pain. The most frequent radiographic Kellgren-Lawrence grade was stage 3 for knee and hip (42.9% and 51.9%, respectively), and 3 (37.2%) and 2 (34.5%) for hip. Time since onset of osteoarthritis symptoms was 9.4±7.5 years, with a mean age at onset of around 60 years old and a family history of osteoarthritis in 66.0%. The most frequent comorbidities were: hypertension (55.1%), depression/anxiety (24.7%) and gastroduodenal diseases (22.9%). A total of 97.6% of the patients received pharmacological treatment, with oral analgesics (paracetamol) (70.5%) and oral NSAIDs (67.9%) being the most frequent drugs. Bilateral osteoarthritis was present in 76.9% of patients with knee osteoarthritis, 59.3% in hip and 94.7% in hands. Female gender and time since onset were associated with bilateral knee and hip osteoarthritis. The profile of the osteoarthritis patient is female, >65 years old, overweight/obese, with comorbidity, frequent symptoms and moderate radiologic involvement. Most of patients had bilateral osteoarthritis, associated with female gender and time since onset of disease. Paracetamol was the most common pharmacological treatment. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Balancing efficacy against safety in sublingual immunotherapy with inhalant allergens: what is the best approach?

PubMed

Caminati, Marco; Dama, Annarita; Schiappoli, Michele; Senna, Gianenrico

2013-10-01

Over the last 20 years, studies and clinical trials have demonstrated efficacy, safety and cost-effectiveness of sublingual immunotherapy (SLIT) for respiratory allergic diseases. Nevertheless, it seems to be mostly used as a second-line therapeutic option, and adherence to treatment is not always optimal. Selective literature research was done in Medline and PubMed, including guidelines, position papers and Cochrane meta-analyses concerning SLIT in adult patients. The most recent reviews confirm SLIT as viable and efficacious treatment especially for allergic rhinitis, even if the optimal dosage, duration, schedule are not clearly established for most of the products. Despite an optimal safety profile, tolerability and patient-reported outcomes concerning SLIT have received poor attention until now. Recently, new tools have been specifically developed in order to investigate these aspects. Regular assessment of tolerability profile and SLIT-related patient-reported outcomes will allow balancing efficacy with tolerability and all the other patient-related variables that may affect treatment effectiveness beyond its efficacy.

Personality traits in patients with Parkinson's disease: assessment and clinical implications.

PubMed

Poletti, Michele; Bonuccelli, Ubaldo

2012-06-01

This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.

"Clinical brain profiling": a neuroscientific diagnostic approach for mental disorders.

PubMed

Peled, Abraham; Geva, Amir B

2014-10-01

Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain profiling (CBP) and presents some provisional validation using clinical assessments and meta-analyses of neuroscientific publications. The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling. This involves a description of the key aspects of functional anatomy that can lead to psychopathology. These features constitute the dimensions or categories for a profile of brain disorders based upon pathophysiology. The second section describes a mapping or translation matrix that maps from symptoms and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation. We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and figures. The third section addresses the construct validity of clinical brain profiling by establishing correlations between profiles based on clinical ratings of symptoms and signs under classical diagnostic categories with the corresponding profiles generated automatically using archetypal diagnoses. We then provide further validation by performing a cluster analysis on the symptoms and signs and showing how they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis. In the fourth section, we address the construct validity of clinical brain profiling by looking for associations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in the first section, we test some particular hypotheses about double dissociations using a meta-analysis of PubMed searches. The final section concludes with perspectives for the future and outstanding validation issues for clinical brain profiling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictors of multidisciplinary treatment outcome in fibromyalgia:a systematic review.

PubMed

de Rooij, Aleid; Roorda, Leo D; Otten, René H J; van der Leeden, Marike; Dekker, Joost; Steultjens, Martijn P M

2013-03-01

To identify outcome predictors for multidisciplinary treatment in patients with chronic widespread pain (CWP) or fibromyalgia (FM). A systematic literature search in PubMed, PsycINFO, CINAHL, Cochrane Library, EMBASE and Pedro. Selection criteria included: age over 18; diagnosis CWP or FM; multidisciplinary treatment; longitudinal study design; original research report. Outcome domains: pain, physical functioning, emotional functioning, global treatment effect and 'others'. Methodological quality of the selected articles was assessed and a qualitative data synthesis was performed to identify the level of evidence. Fourteen studies (all with FM patients) fulfilled the selection criteria. Six were of high quality. Poorer outcome (pain, moderate evidence; physical functioning and quality of life, weak evidence) was predicted by depression. Similarly, poorer outcome was predicted by the disturbance and pain profile of the Minnesota Multiphasic Personality Inventory (MMPI), strong beliefs in fate and high disability (weak evidence). A better outcome was predicted by a worse baseline status, the dysfunctional and the adaptive copers profile of the Multidimensional Pain Inventory (MPI), and high levels of pain (weak evidence). Some predictors were related to specific multidisciplinary treatment (weak evidence). Inconclusive evidence was found for other demographic and clinical factors, cognitive and emotional factors, symptoms and physical functioning as predictors of outcome. It was found that a higher level of depression was a predictor of poor outcome in FM (moderate evidence). In addition, it was found that the baseline status, specific patient profiles, belief in fate, disability, and pain were predictors of the outcome of multidisciplinary treatment. Our results highlight the lack of high quality studies for evaluating predictors of the outcome of multidisciplinary treatment in FM. Further research on predictors of multidisciplinary treatment outcome is needed.

A Cluster Analytic Approach to Identifying Predictors and Moderators of Psychosocial Treatment for Bipolar Depression: Results from STEP-BD

PubMed Central

Deckersbach, Thilo; Peters, Amy T.; Sylvia, Louisa G.; Gold, Alexandra K.; da Silva Magalhaes, Pedro Vieira; Henry, David B.; Frank, Ellen; Otto, Michael W.; Berk, Michael; Dougherty, Darin D.; Nierenberg, Andrew A.; Miklowitz, David J.

2016-01-01

Background We sought to address how predictors and moderators of psychotherapy for bipolar depression – identified individually in prior analyses – can inform the development of a metric for prospectively classifying treatment outcome in intensive psychotherapy (IP) versus collaborative care (CC) adjunctive to pharmacotherapy in the Systematic Treatment Enhancement Program (STEP-BD) study. Methods We conducted post-hoc analyses on 135 STEP-BD participants using cluster analysis to identify subsets of participants with similar clinical profiles and investigated this combined metric as a moderator and predictor of response to IP. We used agglomerative hierarchical cluster analyses and k-means clustering to determine the content of the clinical profiles. Logistic regression and Cox proportional hazard models were used to evaluate whether the resulting clusters predicted or moderated likelihood of recovery or time until recovery. Results The cluster analysis yielded a two-cluster solution: 1) “less-recurrent/severe” and 2) “chronic/recurrent.” Rates of recovery in IP were similar for less-recurrent/severe and chronic/recurrent participants. Less-recurrent/severe patients were more likely than chronic/recurrent patients to achieve recovery in CC (p = .040, OR = 4.56). IP yielded a faster recovery for chronic/recurrent participants, whereas CC led to recovery sooner in the less-recurrent/severe cluster (p = .034, OR = 2.62). Limitations Cluster analyses require list-wise deletion of cases with missing data so we were unable to conduct analyses on all STEP-BD participants. Conclusions A well-powered, parametric approach can distinguish patients based on illness history and provide clinicians with symptom profiles of patients that confer differential prognosis in CC vs. IP. PMID:27289316

Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults

PubMed Central

2014-01-01

Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair® mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18–55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration–time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00–125.00%: 92.2% (90% CI: 87.42–97.30%) for Cmax, 98.1% (90% CI: 94.49–101.81%) for AUC0–t and 97.6% (90% CI: 94.14–101.27%) for AUC0–∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair® 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice. PMID:25250173

Lung function and long-term safety of tiotropium/olodaterol in East Asian patients with chronic obstructive pulmonary disease.

PubMed

Bai, Chunxue; Ichinose, Masakazu; Lee, Sang Haak; Lee, Kwan Ho; Jöns, Olaf; Bothner, Ulrich; Zhao, Yihua; Buhl, Roland

2017-01-01

While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO ® trials. In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV 1 ) area under the curve from 0 to 3 hours (AUC 0-3 ) response and trough FEV 1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication. In the East Asian population, 1,152 patients were randomized (5,163 overall). After 24 weeks, FEV 1 AUC 0-3 and trough FEV 1 responses were greater ( P <0.0001) with tiotropium/olodaterol 5/5 μg in both populations versus tiotropium or olodaterol. The East Asian population showed slightly greater trough FEV 1 treatment differences between tiotropium/olodaterol 5/5 μg and tiotropium compared to the overall population. Generally, no increase in adverse events was seen with tiotropium/olodaterol 5/5 μg compared to tiotropium and olodaterol in either population. The efficacy and safety profile of tiotropium/olodaterol 5/5 μg has been demonstrated for both East Asian and global populations.