Primary Clinical Outcome Measure Research Articles

PCN329 - OUTCOMES-BASED ARRANGEMENTS IN ONCOLOGY: A LANDSCAPE ANALYSIS

Outcomes-based payment arrangements (OBA) for cancer drugs are used internationally with more limited use in the U.S. These arrangements seek to increase the realized value of pharmaceuticals and decrease value uncertainty for payers. Our objective was to identify and characterize OBAs involving oncology products. OBAs were defined as arrangements between a payer and a pharmaceutical developer where the price or reimbursement level is related to its performance in clinical practice. We used a systematic search, leveraging the University of Washington’s Performance Based Risk Sharing Database that contains information obtained by searching Google, PubMed, and government websites from 1993 to 2018. Included arrangements had a financial or health outcomes related component linked to reimbursement. We collected data on product name, year, country, tumor type, payer, arrangement structure, and outcome measure. We summarized the findings using descriptive statistics. The search yielded 117 oncology-related arrangements for 55 drugs in 12 countries. The majority were from Italy (56%) followed by the United Kingdom and Australia. The U.S. had 3 cases. The most common tumor types were lung (13%), breast (11%), and kidney (9%). The distribution of outcome measures used was clinical (44%), financial/utilization (41%), cost-effectiveness (3%), hybrid (5%) and unknown (16%). 60% were first-in-therapeutic-class molecules in the US and 27% had an orphan designation. The primary clinical outcome measures included tumor response, disease progression, and toxicity. The primary financial/utilization measures included the number of treatment cycles and treatment duration. Arrangement structures primarily used rebates (41%), manufacturer funded treatment initiation (40%), and refunds (24%). 17 drugs in 19 tumor types had OBAs in multiple countries. Outcomes-based oncology arrangements are used in many countries. Arrangements have employed a variety of endpoints, outcomes measures and contract structures. U.S. stakeholders can learn from global experiences to inform further implementation and research moving forward.

Optimizing psychotherapy dosage for comorbid depression and personality disorders (PsyDos): a pragmatic randomized factorial trial using schema therapy and short-term psychodynamic psychotherapy

BackgroundPatients with comorbid depression and personality disorders suffer from a heavy disease burden while tailored treatment options are limited, accounting for a high psychological and economic burden. Little is known about the effect of treatment dosage and type of psychotherapy for this specific co-morbid patient population, in terms of treatment-effect and cost-effectiveness. This study aims to compare treatment outcome of 25 versus 50 individual therapy sessions in a year. We expect the 50-session condition to be more effective in treating depression and maintaining the effect. Secondary objectives will be addressed in order to find therapy-specific and non-specific mechanisms of change.MethodsIn a mono-center pragmatic randomized controlled trial with a 2 × 2 factorial design, 200 patients with a depressive disorder and personality disorder(s) will be included. Patients will be recruited from a Dutch mental health care institute for personality disorders. They will be randomized over therapy dosage (25 vs 50 sessions in a year) and type of therapy (schema therapy vs short-term psychodynamic supportive psychotherapy). The primary clinical outcome measure will be depression severity and remission. Changes in personality functioning and quality of life will be investigated as secondary outcomes. A priori postulated effect moderators and mediators will be collected as well. All patients are assessed at baseline and at 1, 2, 3, 6, 9–12 months (end of therapy) and at follow up (6 and 12 months after end of treatment). Alongside the trial, an economic evaluation will be conducted. Costs will be collected from a societal perspective.DiscussionThis trial will be the first to compare two psychotherapy dosages in patients with both depression and personality disorders. Insight in the effect of treatment dosage for this patient group will contribute to both higher treatment effectiveness and lower costs. In addition, this study will contribute to the limited evidence base on treating patients with both depression and personality disorders. Understanding the processes that account for the therapeutic changes could help to gain insight in what works for whom.Trial registrationThis trial has been registered on July 20th 2016, Netherlands Trial Register, part of the Dutch Cochrane Centre (NTR5941).

Arthroscopic-assisted balloon tibioplasty versus open reduction internal fixation (ORIF) for treatment of Schatzker II–IV tibial plateau fractures: study protocol of a randomised controlled trial

IntroductionArthroscopic-assisted balloon tibioplasty is an emerging technology that has shown advantages in recovering depression of the articular surface. However, studies evaluating clinical outcomes between arthroscopic-assisted balloon tibioplasty and traditional open...

Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability.

Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission. This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement. The study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement. Although the results are negative, they are an important addition to the literature in this rapidly changing field.

Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren's Syndrome: Post Hoc Analyses From the EMBODY Trials.

Objective EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22‐targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell–specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS).MethodsThe efficacy and safety of epratuzumab were compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE patients with and those without a diagnosis of associated SS. British Isles Lupus Assessment Group (BILAG) total score, BILAG‐based Combined Lupus Assessment (BICLA) clinical response to treatment, biologic markers (including B cells, IgG, IgM, and IgA), and safety were assessed.ResultsA total of 1,584 patients were randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti‐SSA positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no diagnosis of associated SS (918 patients were randomized to receive epratuzumab and 457 to receive placebo). For patients with associated SS, but not those without associated SS, a higher proportion of patients receiving epratuzumab achieved a BICLA response and a reduction from baseline in BILAG total score. B cell reduction was faster in patients with associated SS. The sensitivity of B cells to epratuzumab as measured by the mean concentration producing 50% of the maximum B cell count depletion was lower for patients with associated SS (9.5 μg/ml) versus the total EMBODY population (87.1 μg/ml). No difference in the frequency of adverse events in those receiving placebo was reported.ConclusionPatients with SLE and associated SS treated with epratuzumab showed improvement in SLE disease activity, which was associated with bioactivity, such as decreases in B cell number and IgM level.

Pharmacy Diabetes Screening Trial: protocol for a pragmatic cluster-randomised controlled trial to compare three screening methods for undiagnosed type 2 diabetes in Australian community pharmacy

IntroductionWith the rising prevalence of type 2 diabetes in Australia, screening and earlier diagnosis is needed to provide opportunities to intervene with evidence-based lifestyle and treatment options to reduce the...

The impact of maintaining serum potassium \u22653.6 mEq/L vs \u22654.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting \u2013 study protocol for a randomised feasibility trial for the proposed Tight K randomized non-inferiority trial

BackgroundAtrial fibrillation (AF) occurs in approximately one in three patients after cardiac surgery, and is associated with increased short-term and long-term mortality, intensive care unit (ICU) and hospital stay, and increased cost of care. In an attempt to reduce AF incidence in these patients, serum potassium (K+) levels are commonly maintained at the high end of normal (4.5–5.5 mEq/L). However, such potassium supplementation is without proven benefit, and is not without negative consequences. It carries clinical risk, negatively impacts patient experience and is both time-consuming and costly. This protocol describes a randomised controlled pilot trial to assess the feasibility of a proposed randomised non-inferiority trial to investigate the impact of maintaining serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting.MethodsDesign: this is a randomized feasibility trial as a pilot for a randomized non-inferiority trial. Participants: are 160 patients undergoing isolated coronary artery bypass grafting at two centres. Allocation: patients will be randomized (1:1) to protocols aiming to maintain serum potassium at either ≥ 3.6 mEq/L (“relaxed control”) or ≥ 4.5 mEq/L (“tight control”). Primary analytic aim: was to assess the feasibility and acceptability of planning and delivering the intervention and trial methods to inform a full-scale non-inferiority trial. Outcome: the primary indicative efficacy outcome measures being field-tested are feasibility of participant recruitment and randomization, maintaining a protocol violation rate < 10%, and retaining 90% patient follow up 28 days after surgery. The primary clinical outcome measure of the future full “Tight K Study” will be incidence of AF after cardiac surgery.DiscussionThe Tight K Pilot will assess the feasibility of conducting the full trial, which is intended to confirm or refute the efficacy of current potassium management in preventing AF after cardiac surgery.Trial registrationClinicalTrials.gov, NCT03195647. Registered on 23 May 2017. Last updated 19June 2017.

Is routine distal clavicle resection necessary in rotator cuff repair surgery? A systematic review and meta-analysis.

The objective of the present study was to perform a systematic review and meta-analysis of randomized controlled trials looking at the effect of distal clavicle resection in patients undergoing rotator cuff repair (RCR). A systematic literature search was undertaken to identify randomized controlled trials looking at RCR +/- distal clavicle resection. Primary clinical outcome measures included in the meta-analysis were American Shoulder Elbow Society (ASES) score, pain on visual analogue scale and range of motion in forward elevation. The systematic review identified three studies with a total of 203 participants. Those who underwent distal clavicle resection in conjunction with RCR had worse pain and acromioclavicular joint tenderness at 3-month follow-up. This difference, however, was not observed at the 24-month follow-up. The mean difference (95% confidence interval) for the ASES score was 0.45 (-3.67 to 4.58) and pain on visual analogue scale was - 0.27 (-0.70 to 0.16). Routine distal clavicle resection in the setting of rotator cuff repair does not result in improved outcomes for patients with no difference being observed at 24 months post surgery. The results of our systematic review and meta-analysis do not support routine distal clavicle resection when performing RCR.

Transforaminal lumbar interbody fusion with cortical bone trajectory screws versus traditional pedicle screws fixation: a study protocol of randomised controlled trial

IntroductionTransforaminal lumbar interbody fusion (TLIF) has been widely used in the treatment of lumbar degenerative disc disorders and shows favourable clinical results. Recently, cortical bone trajectory (CBT) has become a...

AExaCTT - Aerobic Exercise and Consecutive Task-specific Training for the upper limb after stroke: Protocol for a randomised controlled pilot study.

Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70–85%HRmax) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.

Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes

Survival rates for head and neck cancer have been relatively stable for several decades. Individualized prognostic indicators are needed to identify patients at risk for poorer outcomes. To determine whether biomarker levels in surgical drain fluid of patients with head and neck cancer are associated with poor cancer outcomes. This prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx who required surgical treatment from April 1, 2011, to February 1, 2016, at a tertiary or academic care center. Twenty patients, including 14 with stage IV disease, had complete specimen collection. Differences in cytokine and MMP levels by disease outcomes were evaluated. Patients underwent surgical treatment with drain placement as dictated by the standard of care. Drain fluid samples were collected every 8 hours postoperatively until drains were removed because of clinical criteria. Levels of cytokines and matrix metalloproteinases (MMPs) were measured using electrochemiluminescent, patterned array, multiplex technology. The primary clinical outcome measures were survival outcome and recurrence. The biomarkers measured included the cytokines basic fibroblastic growth factor, vascular endothelial growth factor isoform A, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3, and MMP-9. Other clinical and pathologic cancer characteristics were recorded. In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD] age, 63.5 [9.9] years), a significant association with recurrence was found for levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29), MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1 (relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were associated with disease outcome. Vascular endothelial growth factor isoform A was associated with nodal metastasis (relative difference between groups, 1.98; 95% CI, 1.12-3.51), and basic fibroblastic growth factor was associated with lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02-2.97). In this pilot sample of patients with SCC of the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid were associated with poor clinical cancer outcomes in the form of recurrence. This finding is consistent with the literature of tumor microenvironment in saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the first of such findings in surgical drain fluid, an easily accessible means of cytokine measurement. Measurement of these biomarkers in surgical fluid potentially represents a novel means of assessing cancer prognosis in this population.

Return to duty following combat-related multi-ligamentous knee injury

IntroductionThis retrospective cohort study characterized injury patterns, treatment practices, and identified the return to duty (RTD) rate following combat-related multi-ligament knee injuries (MLKI). Patients and methodsWe evaluated injury characteristics and treatment methods of 46 military service members who had sustained a MLKI during combat activity. The primary clinical outcome measure was ability to return to active military duty. Secondary outcomes included subjective pain score, knee motion, knee instability, and use of ambulatory assistive device. ResultsThe RTD rate was 41% (19/46). High-energy mechanism, neurovascular injury, compartment syndrome, traumatic knee arthrotomy, and intra-articular femur fracture (Orthopedic Trauma Association Classification (OTA) 33-B/C) were all more prevalent in subjects who were unable to return to duty (p<0.05). Acute external fixator application and poor knee range of motion (ROM) were also associated with military separation (p=0.041 and p=0.016, respectively). The most common ligament injury pattern (n=9; 20%) was combined disruption of the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), posterolateral corner (PLC), and medial collateral ligament (MCL). However, number of ligaments injured was not associated with RTD status. ConclusionMLKIs sustained in a combat setting have a high incidence of associated lower extremity injuries. Certain associated injuries, such as intra-articular femur fracture, knee arthrotomy, neurovascular injury, and compartment syndrome may be more important than the severity of the knee ligamentous injury in determining RTD outcome.

Outcome Measures in Clinical Trials for Multiple Sclerosis.

Due to the heterogeneous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. Therefore, it can be difficult to assess the true efficacy of interventions in clinical trials. In phase III trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale and the relapse rate. Secondary outcome measures in these trials are the number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) of the brain. These secondary outcome measures are often primary outcome measures in phase II trials in MS. Despite several limitations, the traditional clinical measures are still the mainstay for assessing treatment efficacy. Newer and potentially valuable outcome measures increasingly used or explored in MS trials are, clinically, the MS Functional Composite and patient-reported outcome measures, and on MRI, brain atrophy and the formation of persisting black holes. Several limitations of these measures have been addressed and further improvements will probably be proposed. Major improvements are the coverage of additional functional domains such as cognitive functioning and assessment of the ability to carry out activities of daily living. The development of multidimensional measures is promising because these measures have the potential to cover the full extent of MS activity and progression. In this review, we provide an overview of the historical background and recent developments of outcome measures in MS trials. We discuss the advantages and limitations of various measures, including newer assessments such as optical coherence tomography, biomarkers in body fluids and the concept of ‘no evidence of disease activity’.

Long-term (8–10 years) outcomes after biodegradable polymer-coated biolimus-eluting stent implantation

ObjectiveEfficacy and safety data on biodegradable polymer-coated biolimus-eluting stent (BP-BES) are currently limited to 5 years. We evaluated longer term (8–10 years) clinical and angiographic outcomes after BP-BES implantation.MethodsBetween 2005...

Efficacy and mechanisms of imagery rescripting and imaginal exposure for nightmares: study protocol for a randomized controlled trial.

BackgroundRecurrent nightmares can effectively be treated with cognitive-behavioral techniques such as imagery rehearsal therapy, which involves imagery rescripting (IR) of nightmares, and imaginal exposure (IE) therapy. However, the underlying mechanisms of these treatments remain largely unknown. To investigate this, we identified a number of variables that might mediate the therapeutic effect of rescripting-based and/or exposure-based therapies. Also, to control for the possible confounding influence of (other) treatment components, we designed two stripped-down treatment protocols, which primarily consist of either (1) rescripting of, or (2) exposure to, the nightmare content. In a randomized controlled trial, we aim to investigate the therapeutic efficacy of these stripped-down IR and IE treatments, and explore their working mechanisms.MethodThree weekly sessions of either IR or IE will be compared to a waiting-list control group. Ninety participants suffering from nightmare disorder will be included and randomly allocated to one of the three groups. The primary clinical outcome measures are nightmare frequency and distress caused by nightmares. Secondary clinical outcome measures include sleep complaints, dysfunctional beliefs about nightmares, and posttraumatic stress symptom severity. Outcomes will be assessed weekly from week 1 (pre-assessment) to week 5 (post-assessment). Online follow-up assessments will take place at 3 and 6 months after post-assessment. In order to investigate temporal relationships between mediators and outcome, we will measure the proposed mediators of the treatment effect 1 day after each outcome assessment (but not after the follow-ups). Mediators include nightmare distress and valence, mastery of the nightmare content, predictability, controllability, and tolerability of emotions elicited by nightmares, as well as sleep quality.DiscussionThe proposed trial allows us to investigate the efficacy of IR and IE as intervention techniques for the treatment of nightmares, and to explore mediators of their respective therapeutic effects. The results may advance our understanding of nightmare therapies by identifying possible mechanisms of psychological treatments for chronic nightmares. Moreover, the results of the proposed study might provide useful knowledge about the working mechanism of rescripting-based and exposure-based treatments in general.Trial registrationNetherlands Trial Register (NTR4951), registered on 14 December 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1570-3) contains supplementary material, which is available to authorized users.

Behavioural Activation Therapy for Depression after Stroke (BEADS): a study protocol for a feasibility randomised controlled pilot trial of a psychological intervention for post-stroke depression

BackgroundThere is currently insufficient evidence for the clinical and cost-effectiveness of psychological therapies for treating post-stroke depression.Methods/DesignBEADS is a parallel group feasibility multicentre randomised controlled trial with nested qualitative research and economic evaluation. The aim is to evaluate the feasibility of undertaking a full trial comparing behavioural activation (BA) to usual stroke care for 4 months for patients with post-stroke depression. We aim to recruit 72 patients with post-stroke depression over 12 months at three centres, with patients identified from the National Health Service (NHS) community and acute services and from the voluntary sector. They will be randomly allocated to receive behavioural activation in addition to usual care or usual care alone. Outcomes will be measured at 6 months after randomisation for both participants and their carers, to determine their effectiveness. The primary clinical outcome measure for the full trial will be the Patient Health Questionnaire-9 (PHQ-9). Rates of consent, recruitment and follow-up by centre and randomised group will be reported. The acceptability of the intervention to patients, their carers and therapists will also be assessed using qualitative interviews. The economic evaluation will be undertaken from the National Health Service and personal social service perspective, with a supplementary analysis from the societal perspective. A value of information analysis will be completed to identify the areas in which future research will be most valuable.DiscussionThe feasibility outcomes from this trial will provide the data needed to inform the design of a definitive multicentre randomised controlled trial evaluating the clinical and cost-effectiveness of behavioural activation for treating post-stroke depression.Trial registrationCurrent controlled trials ISRCTN12715175

Effects of a novel foot-ankle orthosis in the non-operative treatment of unicompartmental knee osteoarthritis.

IntroductionUnloader braces are non-surgical treatment options for patients with unicompartmental knee osteoarthritis (OA). However, many patients do not adhere to brace treatment because of complications related to discomfort and poor fit. An alternative to knee bracing is an ankle–foot orthosis (AFO) with a lever arm that presses the lower leg into valgus or varus. The aim of this study is to evaluate the clinical benefits of this AFO for patients with unicompartmental knee OA.Materials and methodsTwenty-three patients with knee OA were enrolled in this observational study. The primary clinical outcome measure was the Western Ontario and McMasters Universities Arthritis Index (WOMAC) total score. Secondary outcome measures included WOMAC subscores, visual analogue pain scale, activity restriction and complication rate. Clinical scores were collected at start and 3, 6, 9, and 12 months after enrollment. Statistical evaluation was performed using the Student’s t test.ResultsOf the patients enrolled, 83 % suffered from medial compartment OA. Most patients had Grade II OA according to the Kellgren and Lawrence classification. WOMAC total score, both subscores and visual analogue pain scale were significantly improved over time. Patients also noted a reduction in restrictions to activities of daily living and sport-related activities while using the AFO. No patients discontinued orthosis use because of adverse effects. Two types of complications were noted: discomfort or light pressure sores around the ankle (7 patients), and wear and tear of the shoe in which the AFO was worn (14 patients).ConclusionsThis observational study suggests that this AFO is effective at significantly reducing pain and stiffness as well as improving the physical function of patients with mild to moderate unicompartmental osteoarthritis of the knee.

High-Convexity Tightness Predicts the Shunt Response in Idiopathic Normal Pressure Hydrocephalus.

Although neuroimaging plays an important role in the diagnosis of idiopathic normal pressure hydrocephalus, its predictive value for response to shunt surgery has not been established. The purpose of the current study was to identify neuroimaging markers that predict the shunt response of idiopathic normal pressure hydrocephalus. Sixty patients with idiopathic normal pressure hydrocephalus underwent presurgical brain MR imaging and clinical evaluation before and 1 year after shunt surgery. The assessed MR imaging features included the Evans index, high-convexity tightness, Sylvian fissure dilation, callosal angle, focal enlargement of the cortical sulci, bumps in the lateral ventricular roof, and deep white matter and periventricular hyperintensities. The idiopathic normal pressure hydrocephalus grading scale total score was used as a primary clinical outcome measure. We used measures for individual symptoms (ie, the idiopathic normal pressure hydrocephalus grading scale subdomain scores, such as gait, cognitive, and urinary scores), the Timed Up and Go test, and the Mini-Mental State Examination as secondary clinical outcome measures. The relationships between presurgical neuroimaging features and postoperative clinical changes were investigated by using simple linear regression analysis. To identify the set of presurgical MR imaging features that best predict surgical outcomes, we performed multiple linear regression analysis by using a bidirectional stepwise method. Simple linear regression analyses demonstrated that presurgical high-convexity tightness, callosal angle, and Sylvian fissure dilation were significantly associated with the 1-year changes in the clinical symptoms. A multiple linear regression analysis demonstrated that presurgical high-convexity tightness alone predicted the improvement of the clinical symptoms 1 year after surgery. High-convexity tightness is a neuroimaging feature predictive of shunt response in idiopathic normal pressure hydrocephalus.

Protocol of randomized controlled trial of potentized estrogen in homeopathic treatment of chronic pelvic pain associated with endometriosis

Endometriosis is a chronic inflammatory disease that causes difficult-to-treat pelvic pain. Thus being, many patients seek help in complementary and alternative medicine, including homeopathy. The effectiveness of homeopathic treatment for endometriosis is controversial due to the lack of evidences in the literature. The aim of the present randomized controlled trial is to assess the efficacy of potentized estrogen compared to placebo in the treatment of chronic pelvic pain associated with endometriosis. The present is a randomized, double-blind, placebo-controlled trial of a homeopathic medicine individualized according to program 'New Homeopathic Medicines: use of modern drugs according to the principle of similitude' (http://newhomeopathicmedicines.com). Women with endometriosis, chronic pelvic pain and a set of signs and symptoms similar to the adverse events caused by estrogen were recruited at the Endometriosis Unit of Division of Clinical Gynecology, Clinical Hospital, School of Medicine, University of São Paulo (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP). The participants were selected based on the analysis of their medical records and the application of self-report structured questionnaires. A total of 50 women meeting the eligibility criteria will be randomly allocated to receive potentized estrogen or placebo. The primary clinical outcome measure will be severity of chronic pelvic pain. Statistical analysis will be performed on the intention-to-treat and per-protocol approaches comparing the effect of the homeopathic medicine versus placebo after 24 weeks of intervention. The present study was approved by the research ethics committee of HCFMUSP and the results are expected in 2016. ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT02427386.

Clinical and Radiologic Outcome of a Less Invasive, Low-Cost Surgical Technique of Osteoplastic Decompressive Craniectomy.

Decompressive craniectomy (DC) has many technical details with significant constraining logistic/economic considerations in low-resource practice areas. We present a less invasive, cost-saving, and evidence-based technique of DC evolving in our practice. Earlier, we reported a technique of hinge decompressive craniectomy (hDC), in which the frontotemporoparietal skull flap is hinged on the temporal muscle. In this article we describe further refinements of this temporal muscle hDC : The scalp flap is raised in a galeal-skeletonizing plane preserving the subgaleal fascia on the pericranium, ready for use for duraplasty after durotomy. We performed a descriptive analysis of the clinical outcome of this surgical technique in a prospective consecutive cohort of patients with traumatic brain injury (TBI). The primary and secondary clinical outcome measures were in-hospital mortality and survival, respectively, and the immediate as well as long-term surgical wound issues. There were 40 cases, 38 men (95%) and 2 women over a 40-month period with a mild (n = 8), moderate (n = 17), or severe TBI (n = 15). As assessed by the computed tomography Rotterdam score, life-threatening significant brain injury was present in 90%. Poor clinical outcome occurred in about a third of cases (32.5%) mainly in the severe TBI group (77% of poor outcome) and not in the mild TBI group. Surgical site complications occurred in four patients (10%) The presented modified temporal muscle hDC technique offers significant economic advantages over the traditional surgical method of DC without added complications. Analysis of the clinical data in a consecutive prospective cohort of patients with potentially fatal TBI who underwent this surgical procedure showed a good outcome in at least two thirds.