Systematic review of disease-modifying antirheumatic drugs for juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Treatment of juvenile idiopathic arthritis (JIA) with disease-modifying antirheumatic drugs (DMARDs) may improve outcomes compared to conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra-articular corticosteroids). The purpose of this systematic review was to evaluate the comparative effectiveness and safety of DMARDs versus conventional therapy and versus other DMARDs.</p> <p>Results</p> <p>A systematic evidence review of 156 reports identified in MEDLINE^®, EMBASE^®, and by hand searches. There is some evidence that methotrexate is superior to conventional therapy. Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. However, these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying comparators and follow-up periods. Rates of serious adverse events are similar between DMARDs and placebo in published trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD.</p> <p>Conclusions</p> <p>Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve JIA-associated symptoms. Limited data suggest that short-term risk of cancer is low.</p

Craniosacral therapy for migraine: Protocol development for an exploratory controlled clinical trial

Abstract Background Migraine affects approximately 20% of the population. Conventional care for migraine is suboptimal; overuse of medications for the treatment of episodic migraines is a risk factor for developing chronic daily headache. The study of non-pharmaceutical approaches for prevention of migraine headaches is therefore warranted. Craniosacral therapy (CST) is a popular non-pharmacological approach to the treatment or prevention of migraine headaches for which there is limited evidence of safety and efficacy. In this paper, we describe an ongoing feasibility study to assess the safety and efficacy of CST in the treatment of migraine, using a rigorous and innovative randomized controlled study design involving low-strength static magnets (LSSM) as an attention control intervention. Methods The trial is designed to test the hypothesis that, compared to those receiving usual care plus a treatment with low-strength static magnets (attention-control complementary therapy), subjects receiving usual medical care plus CST will demonstrate significant improvement in: quality-of-life as measured by the Headache Impact Test (HIT-6); reduced frequency of migraine; and a perception of clinical benefit. Criteria for inclusion are either gender, age > 11, English or Spanish speaking, meeting the International Classification of Headache Disorders (ICHD) criteria for migraine with or without aura, a headache frequency of 5 to 15 per month over at least two years. After an 8 week baseline phase, eligible subjects are randomized to either CST or an attention control intervention, low strength static magnets (LSSM). To evaluate possible therapist bias, videotaped encounters are analyzed to assess for any systematic group differences in interactions with subjects. Results 169 individuals have been screened for eligibility, of which 109 were eligible for the study. Five did not qualify during the baseline phase because of inadequate headache frequency. Nineteen have withdrawn from the study after giving consent. Conclusion This report endorses the feasibility of undertaking a rigorous randomized clinical trial of CST for migraine using a standardized CST protocol and an innovative control protocol developed for the study. Subjects are able and willing to complete detailed headache diaries during an 8-week baseline period, with few dropouts during the study period, indicating the acceptability of both interventions. Trial Registration ClinicalTrials.gov NCT0066523

Incorporating Acupuncture Into American Healthcare: Initiating a Discussion on Implementation Science, the Status of the Field, and Stakeholder Considerations

Introduction: The field of implementation science is the study of methods that promote the uptake of evidence-based interventions into healthcare policy and practice. While acupuncture has gained significant traction in the American healthcare landscape, its journey has been somewhat haphazard and non-linear. Methods: In June 2019, a group of thirty diverse stakeholders was convened by the Society for Acupuncture Research with the support of a Patient Centered Outcomes Research Institute, Eugene Washington Engagement Award. This group of stakeholders represented a diverse mix of patients, providers, academicians, researchers, funders, allied health professionals, insurers, association leaders, certification experts, and military program developers. The collective engaged in discussion that explored acupuncture\u27s status in healthcare, including reflections on its safety, effectiveness, best practices, and the actual implementation of acupuncture as seen from diverse stakeholder viewpoints. Objectives: A primary goal was to consider how to utilize knowledge from the field of implementation science more systematically and intentionally to disseminate information about acupuncture and its research base, through application of methods known to implementation science. The group also considered novel challenges that acupuncture may present to known implementation processes. Findings: This article summarizes the initial findings of this in-person meeting of stakeholders and the ongoing discussion among the subject matter experts who authored this report. The goal of this report is to catalyze greater conversation about how the field of implementation science might intersect with practice, access, research, and policymaking pertaining to acupuncture. Core concepts of implementation science and its relationship to acupuncture are introduced, and the case for acupuncture as an Evidence Based Practice (EBP) is established. The status of the field and current environment of acupuncture is examined, and the perspectives of four stakeholder groups--patients, two types of professional practitioners, and researchers--are explored in more detail

Randomized Trial of Partial Gland Ablation with Vascular Targeted Phototherapy versus Active Surveillance for Low Risk Prostate Cancer: Extended Followup and Analyses of Effectiveness

PURPOSE: The prospective PCM301 trial randomized 413 men with low risk prostate cancer to partial gland ablation with vascular targeted photodynamic therapy in 207 and active surveillance in 206. Two-year outcomes were reported previously. We report 4-year rates of intervention with radical therapy and further assess efficacy with biopsy results. MATERIALS AND METHODS: Prostate biopsies were mandated at 12 and 24 months. Thereafter patients were monitored for radical therapy with periodic biopsies performed according to the standard of care at each institution. Ablation efficacy was assessed by biopsy results overall and in field in the treated lobe or the lobe with index cancer. RESULTS: Conversion to radical therapy was less likely in the ablation cohort than in the surveillance cohort, including 7% vs 32% at 2 years, 15% vs 44% at 3 years and 24% vs 53% at 4 years (HR 0.31, 95% CI 0.21-0.46). Radical therapy triggers were similar in the 2 arms. Cancer progression rates overall and by grade were significantly lower in the ablation cohort (HR 0.42, 95% CI 0.29-0.59). End of study biopsy results were negative throughout the prostate in 50% of patients after ablation vs 14% after surveillance (risk difference 36%, 95% CI 28-44). Gleason 7 or higher cancer was less likely for ablation than for surveillance (16% vs 41%). Of the in field biopsies 10% contained Gleason 7 cancer after ablation vs 34% after surveillance. CONCLUSIONS: In this randomized trial of partial ablation of low risk prostate cancer photodynamic therapy significantly reduced the subsequent finding of higher grade cancer on biopsy. Consequently fewer cases were converted to radical therapy, a clinically meaningful benefit that lowered treatment related morbidity

Credibility of Low-Strength Static Magnet Therapy as an Attention Control Intervention for a Randomized Controlled Study of CranioSacral Therapy for Migraine Headaches

Developing valid control groups that generate similar perceptions and expectations to experimental complementary and alternative (CAM) treatments can be challenging. The perceived credibility of treatment and outcome expectancy often contributes to positive clinical responses to CAM therapies, thereby confounding efficacy data. As part of a clinical feasibility study, credibility and expectancy data were obtained from subjects suffering from migraine who received either CranioSacral therapy (CST) or an attention-control, sham, and low-strength magnet (LSSM) intervention

Unanticipated Insights into Biomedicine from the Study of Acupuncture

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies

Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with Chronic Tension Type Headache (CTTH) report functional and emotional impairments (loss of workdays, sleep disturbances, emotional well-being) and are at risk for overuse of medication. Manual therapy may improve symptoms through mobilisation of the spine, correction of posture, and training of cervical muscles.</p> <p>We present the design of a randomised clinical trial (RCT) evaluating the effectiveness of manual therapy (MT) compared to usual care by the general practitioner (GP) in patients with CTTH.</p> <p>Methods and design</p> <p>Patients are eligible for participation if they present in general practice with CTTH according to the classification of the International Headache Society (IHS).</p> <p>Participants are randomised to either usual GP care according to the national Dutch general practice guidelines for headache, or manual therapy, consisting of mobilisations (high- and low velocity techniques), exercise therapy for the cervical and thoracic spine and postural correction. The primary outcome measures are the number of headache days and use of medication. Secondary outcome measures are severity of headache, functional status, sickness absence, use of other healthcare resources, active cervical range of motion, algometry, endurance of the neckflexor muscles and head posture. Follow-up assessments are conducted after 8 and 26 weeks.</p> <p>Discussion</p> <p>This is a pragmatic trial in which interventions are offered as they are carried out in everyday practice. This increases generalisability of results, but blinding of patients, GPs and therapists is not possible.</p> <p>The results of this trial will contribute to clinical decision making of the GP regarding referral to manual therapy in patients with chronic tension headache.</p

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432