Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study.

BACKGROUND: ANCHOVY was a global, multicenter, chart-review study that aimed to describe the natural history of Type 1 spinal muscular atrophy (SMA) from a broad geographical area and provide further contextualization of results from the FIREFISH (NCT02913482) interventional study of risdiplam treatment in Type 1 SMA. METHODS: Data were extracted from medical records of patients with first symptoms attributable to Type 1 SMA between 28 days and 3 months of age, genetic confirmation of SMA, and confirmed survival of motor neuron 2 copy number of two or unknown. The study period started on 1 January 2008 for all sites; study end dates were site-specific due to local treatment availabilities. Primary endpoints were time to death and/or permanent ventilation and proportion of patients achieving motor milestones. Secondary endpoints included time to initiation of respiratory and feeding support. RESULTS: Data for 60 patients from nine countries across Asia, Europe and North and South America were analyzed. The median age (interquartile range [IQR]) for reaching death or permanent ventilation was ~ 7.3 (5.9-10.5) months. The median age (IQR) at permanent ventilation was ~ 12.7 (6.9-16.4) months and at death was ~ 41.2 (7.3-not applicable) months. No patients were able to sit without support or achieved any level of crawling, standing or walking. INTERPRETATION: Findings from ANCHOVY were consistent with published natural history data on Type 1 SMA demonstrating the disease's devastating course, which markedly differed from risdiplam-treated infants (FIREFISH Part 2). The results provide meaningful additions to the literature, including a broader geographical representation.

Distribution of weight, stature, and growth status in children and adolescents with spinal muscular atrophy: An observational retrospective study in the United States.

INTRODUCTION/AIMS: Data regarding weight, height/length, and growth status of patients with spinal muscular atrophy (SMA) who have received only supportive care are limited. This cross-sectional study describes these measurements in patients with Type 1 and Types 2/3 SMA and compares them with reference values from typically developing children. METHODS: Retrospective baseline data from three sites in the Pediatric Neuromuscular Clinical Research Network (Boston, New York, Philadelphia) were used. Descriptive statistics for weight, height/length, body mass index-for-age, as well as weight-for-length and absolute and relative deviations from reference values (ie, 50th percentile from World Health Organization/Centers for Disease Control growth charts) were calculated. Furthermore, growth status was reported. RESULTS: A total of 91 genetically confirmed patients with SMA receiving optimal supportive care and without any disease-modifying treatment were stratified into Types 1 (n = 28) and 2/3 SMA (n = 63). Patients with Type 1 SMA weighed significantly less (median = -7.5%) compared with reference values and patients with Types 2/3 SMA were significantly shorter (mean = -3.0%) compared with reference values. The median weight was considerably below the 50th percentile in both groups of patients, even if they received a high standard of care and proactive feeding support. DISCUSSION: More research is needed to understand which factors influence growth longitudinally, and how to accurately capture growth in patients with SMA. Further research should investigate the best time to provide feeding support to avoid underweight, especially in patients with Type 1, and how to avoid the risk of overfeeding, especially in patients with Types 2/3 SMA.

Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.

Long-term Results After Surgical or Nonsurgical Treatment in Patients With Degenerative Lumbar Spinal Stenosis: A Prospective Multicenter Study.

STUDY DESIGN: Prospective, multicenter cohort study. OBJECTIVE: The aim of our study was to assess the course of patients over a period of 3 years undergoing surgical or nonsurgical treatments for degenerative lumbar spinal stenoses (DLSS) based on data from the Lumbar Stenosis Outcome Study (LSOS), prospectively performed in eight hospitals. SUMMARY OF BACKGROUND DATA: The optimal treatment strategy for patients with DLSS is still debated. METHODS: The outcomes of patients with verified DLSS were quantified by Spinal Stenosis Measure (SSM) symptoms- and SSM function-scores, and EQ-5D-3L (quality of life) summary index (SI) over time (up to 36-month follow-up), and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and EQ-5D-3L SI from baseline to 36-month follow-up. RESULTS: For this study, 601 patients met the inclusion criteria; 430 underwent surgery, 18 of them only after more than a year after enrolment, 171 received nonsurgical treatment only. At baseline, patients in the surgical and nonsurgical groups had similar values for the SSM symptoms and SSM function scores, but patients in the surgical group suffered significantly more from buttocks pain and reported more worsening symptoms over the last 3 months before enrollment in the study. Surgically treated patients (except changers) performed significantly better in all clinical outcome measures (P < 0.001) with a plateau at 12-month follow-up staying constant until the follow-up ended. Further, two-thirds of patients in the surgical group had a relevant improvement in function, symptoms, and quality of life, compared with only about half of those in terms of symptoms and even less in terms of function and quality of life with nonsurgical treatment. CONCLUSIONS: Surgical treatment of DLSS results in more favorable clinical outcomes with a sustained effect over time, compared to nonsurgical treatment. LEVEL OF EVIDENCE: 3.

Two-year outcome comparison of decompression in 14 lipomatosis cases with 169 degenerative lumbar spinal stenosis cases: a Swiss prospective multicenter cohort study.

PURPOSE: Spinal epidural lipomatosis (SEL) is defined as an abnormal and extensive accumulation of unencapsulated adipose tissue within the spinal epidural space. To date, there is a lack of high-level evidence studies reporting the outcome of surgical treatment of symptomatic SEL in patients with lumbar spinal stenosis (LSS). The aim was to compare clinical outcomes in patients with symptomatic LSS with and without SEL who underwent decompression surgery alone at the 12- and 24-month follow-up. METHODS: One hundred and eighty-three patients met the inclusion criteria, of which 14 had mainly SEL on at least one level operated in addition to possible degenerative changes on other levels and 169 degenerative LSS only. The main outcomes were pain (Spinal Stenosis Measure (SSM) symptoms), disability (SSM function), and quality of life [EQ-5D-3L summary index (SI)] at 24-month follow-up, and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and EQ-5D-3L SI. RESULTS: The multiple regression linear models showed that SEL was associated with worse SSM symptoms (p = 0.045) and EQ-5D-3L SI scores (p = 0.026) at 24-month follow-up, but not with worse SSM function scores. Further, depression (in all models) was negatively associated with better clinical outcomes at 24-month follow-up. In the outcomes SSM symptoms and EQ-5D-3L SI, distinctly more patients in the classical LSS group reached MCID than in the SEL group (71.3% and 62.3% vs. 50.0% and 42.9%). CONCLUSIONS: Our study demonstrated that decompression alone surgery was associated with significant improvement in disability in both groups at 2 years, but not in pain and quality of life in patients with SEL.

Datasets describing the introduction of the high-sensitive troponin in the emergency department.

Chest pain is a common clinical condition in the emergency department. A high sensitive (hs) troponin test assay may help to identify patients with acute coronary syndrome earlier compared to conventional tests but also entails the risk of a high proportion of positive test results in patients without cardiac disease. We assessed the impact of the introduction of the hs-troponin test in clinical practice in an emergency department. We compared December 1, 2009 until November 30, 2010 (standard test period) to December 1, 2010 - the date of the introduction of the hs-troponin assay - until December 31, 2011 (hs troponin test period) of patients presenting with chest pain to one of the ten largest hospitals in Switzerland. We identified electronic health records using the following ICD-10 codes: R06.4 (hyperventilation), R07.1 (chest pain when breathing), R07.2 (precordial pain), R07.3 (other chest pain), and R07.4 (chest pain not specified), I20 (angina pectoris), I21 (acute MI), I22 (recurrent MI), I23 (complications after acute MI), and I24 (other acute ischemic heart disease). Included were all medical records of adult patients (≥18 years) presenting to the ED with chest pain and with ≥1 troponin test. Excluded were records without troponin test, pregnancy, trauma patients/life-threatening conditions, malignant disease, current fracture, renal replacement therapy/severe kidney failure (creatinine clearance <30ml/min/1.73m2), patients with disability, or patients disagreeing that their data will be used for scientific purposes. Two researchers screened all records for in-/exclusion. The first presentation for chest pain to the ED and all presentations within the following three months extracted. Presentations after >3 months due to chest pain were defined as a new index visit of a second episode. The extraction form with predefined variables was pilot-tested in 20 records. Additional diagnostic tests were ECG, treadmill test, coronary angiography, MIBI scintigraphy, echocardiography, chest X-ray, computer tomography (CT) of the chest or abdomen, sonography of the abdomen or pleura, gastroscopy, and lung function tests. We compared the number of non-invasive / invasive cardiac diagnostic tests in troponin positive and negative patients and the number of diagnostic tests after the exclusion of patients with STEMI diagnosis. Non-invasive / invasive cardiac tests included treadmill test, coronary angiography, MIBI scintigraphy, and echocardiography. We calculated average monthly tests per patient and compared mean tests per patient between groups. We used a t-test to quantify the evidence for differential number of diagnostic tests per patient in each period. Between-group differences were estimated with 95% confidence intervals. All analyses were performed with the statistical software R for windows [1]. Interpretation of this data can be found in a research article titled Impact of the introduction of high-sensitive troponin assay on the evaluation of chest pain patients in the emergency department: a retrospective study [2]).

The influence of endplate (Modic) changes on clinical outcomes in lumbar spinal stenosis surgery: a Swiss prospective multicenter cohort study.

PURPOSE: To investigate if the presence or absence of preoperative endplate Modic changes (MC) is predictive for clinical outcomes in degenerative lumbar spinal stenosis (DLSS) patients undergoing decompression-alone or decompression with instrumented fusion surgery. METHODS: Two hundred five patients were included and categorized into four groups; 102 patients into the decompression-alone group with MCs, 41 patients into the fusion group with MCs, 46 patients into the decompression-alone group without MCs, and 16 patients into the fusion group without MCs. Clinical outcome was quantified with changes in spinal stenosis measure (SSM) symptoms, SSM function, NRS pain, and EQ-5D-3L sum score over time (measured at baseline, 12-, 24-, and 36-month follow-up) and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and NRS pain from baseline to 36-month follow-up. To investigate if possible effects of MCs had been modified or hidden by confounding variables, we used the group LASSO method to search for good prognostic models. RESULTS: There were no obvious differences in any of the clinical outcome measures between groups at baseline. At 12 months, most patients have improved in all outcomes and maintained improved conditions over time (no significant group differences). Between 70 and 90 percent of the patients maintained a clinically important improvement up to 36 months. CONCLUSIONS: Endplate MCs have no significant influence on clinical outcome parameters in patients with lumbar spinal stenosis compared to patients without MCs, independent of the chosen surgical strategy. All patients benefitted from surgical therapy up to 36-month follow-up. These slides can be retrieved under Electronic Supplementary Material.

Evaluating the Minimal Clinically Important Difference of EQ-5D-3L in Patients With Degenerative Lumbar Spinal Stenosis: A Swiss Prospective Multicenter Cohort Study.

STUDY DESIGN: Analysis of a prospective, multicenter cohort study. OBJECTIVE: The aim of our study was to compare thresholds of published minimal clinically important differences (MCID) for the three-level EuroQol-5D health survey (EQ-5D-3L) summary index (range -0.53 to 1.00) with our anchor-based estimate and evaluate how useful these thresholds are in determining treatment success in patients undergoing surgery for degenerative lumbar spinal stenosis (DLSS). SUMMARY OF BACKGROUND DATA: MCID values for EQ-5D-3L are specific to the underlying disease and only three studies have been published for DLSS patients reporting different values. METHODS: Patients of the multicenter Lumbar Stenosis Outcome Study with confirmed DLSS undergoing first-time decompression or fusion surgery with 12-month follow-up were enrolled in this study. To calculate MCID we used the Spinal Stenosis Measure satisfaction subscale as anchor. RESULTS: For this study, 364 patients met the inclusion criteria; of these, 196 were very satisfied, 72 moderately satisfied, 43 somewhat satisfied, and 53 unsatisfied 12 months after surgery. The MCID calculation estimated for EQ-5D-3L a value of 0.19. Compared with published MCID values (ranging from 0.30 to 0.52), our estimation is less restrictive. CONCLUSIONS: In patients with LSS undergoing surgery, we estimated an MCID value for EQ-5D-3L summary index of 0.19 with the help of the average change anchor-based method, which we find to be the most suitable method for assessing patient change scores. LEVEL OF EVIDENCE: 3.

Impact of the Introduction of High-Sensitive Troponin Assay in the Emergency Department: A Retrospective Study.

BACKGROUND: Compared with troponin T/I test, the introduction of a high-sensitive (hs) troponin test may result in a higher proportion of positive test results in patients with chest pain and over-testing in patients without acute coronary syndrome. We assessed the impact of the introduction of the hs-troponin assay on the discharge diagnoses and the number of diagnostic tests in patients presenting with chest pain in a real-life setting in an emergency department. METHODS: Retrospective chart review of patients presenting with chest pain to one of the largest hospitals in Switzerland. We compared the standard troponin period (December 2009 to November 2010) with the hs-troponin period (December 2010 to December 2011). RESULTS: Data from 1274 patients (standard 597 [46.9%], hs-troponin 677 [53.1%]) were analyzed. The proportion of patients with non-ST-segment elevation myocardial infarction increased (hs-troponin 14.9%, compared with 9.7%); the proportion in unstable angina (1.5% to 4.0%) and other cardiac illnesses (8.1% to 11.7%) decreased. Although the proportion of noncardiac chest pain illnesses (67%) remained unchanged, the proportion of positive hs-troponin was higher (6.1% vs 2.0%). The average number of additional tests/person decreased in troponin-positive patients (2.0 to 1.7 test per patient; P = .02) and troponin-negative patients (3.1 to 2.8 tests; P < .0001). CONCLUSION: Although the introduction of the hs-troponin test resulted in a higher proportion of positive hs-troponin tests in patients with noncardiac chest pain, the average number of diagnostic tests decreased in patients with chest pain presenting to an emergency department, indicating an increased confidence of clinicians in their diagnosis.

Appetite-Suppressing and Satiety-Increasing Bioactive Phytochemicals: A Systematic Review.

The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.

Serious adverse events in patients with target-oriented blood pressure management: a systematic review.

: On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets. Seven original studies and eight post hoc analyses (derived from two original studies) met the inclusion criteria. Compared with moderate blood pressure treatment, intensive treatment was associated with a significant increase in treatment-related SAEs (Sign-test: P = 0.0002, Wilcoxon signed-rank test: P = 0.001). However, comparability between studies was limited, due to unclear determinations about the treatment-relatedness of adverse events, missing definitions of SAEs and variations in recording methods. Thus, a meta-analysis was not justified. The definitions of serious adverse events and methods of recording and reporting need to be improved and standardized to facilitate the comparison of results.

Outcome of unilateral versus standard open midline approach for bilateral decompression in lumbar spinal stenosis: is "over the top" really better? A Swiss prospective multicenter cohort study.

OBJECTIVEIn this retrospective analysis of a prospective multicenter cohort study, the authors assessed which surgical approach, 1) the unilateral laminotomy with bilateral spinal canal decompression (ULBD; also called "over the top") or 2) the standard open bilateral decompression (SOBD), achieves better clinical outcomes in the long-term follow-up. The optimal surgical approach (ULBD vs SOBD) to treat lumbar spinal stenosis remains controversial.METHODSThe main outcomes of this study were changes in a spinal stenosis measure (SSM) symptoms score, SSM function score, and quality of life (sum score of the 3-level version of the EQ-5D tool [EQ-5D-3L]) over time. These outcome parameters were measured at baseline and at 12-, 24-, and 36-month follow-ups. To obtain an unbiased result on the effect of ULBD compared to SOBD the authors used matching techniques relying on propensity scores. The latter were calculated based on a logistic regression model including relevant confounders. Additional outcomes of interest were raw changes in main outcomes and in the Roland and Morris Disability Questionnaire from baseline to 12, 24, and 36 months.RESULTSFor this study, 277 patients met the inclusion criteria. One hundred forty-nine patients were treated by ULBD, and 128 were treated by SOBD. After propensity score matching, 128 patients were left in each group. In the matched cohort, the mean (95% CI) estimated differences between ULBD and SOBD for change in SSM symptoms score from baseline to 12 months were -0.04 (-0.25 to 0.17), to 24 months -0.07 (-0.29 to 0.15), and to 36 months -0.04 (-0.28 to 0.21). For change in SSM function score, the estimated differences from baseline to 12 months were 0.06 (-0.08 to 0.21), to 24 months 0.08 (-0.07 to 0.22), and to 36 months 0.01 (-0.16 to 0.17). Differences in changes between groups in EQ-5D-3L sum scores were estimated to be -0.32 (-4.04 to 3.40), -0.89 (-4.76 to 2.98), and -2.71 (-7.16 to 1.74) from baseline to 12, 24, and 36 months, respectively. None of the group differences between ULBD and SOBD were statistically significant.CONCLUSIONSBoth surgical techniques, ULBD and SOBD, may provide effective treatment options for DLSS patients. The authors further determined that the patient outcome results for the technically more challenging ULBD seem not to be superior to those for the SOBD even after 3 years of follow-up.

What is the treatment effect of surgery compared with nonoperative treatment in patients with lumbar spinal stenosis at 1-year follow-up?

Objective: The aim of this study was to obtain an unbiased causal treatment estimate of the between-group difference of surgery versus nonoperative treatment with respect to outcomes on quality of life, pain, and disability in patients with degenerative lumbar spinal stenosis (DLSS) 12 months after baseline. Methods: The authors included DLSS patients from a large prospective multicenter observational cohort study. Propensity score matching was used, including 15 demographic, clinical, and MRI variables. Linear and logistic mixed-effects regression models were applied to quantify the between-group treatment effect. Unmeasured confounding was addressed in a sensitivity analysis, assessing the robustness of the results. Results: A total of 408 patients were included in this study, 222 patients after matching, with 111 in each treatment group. Patients with nonoperative treatment had lower quality of life at the 12-month follow-up (−6.21 points, 95% CI −9.93 to −2.49) as well as lower chances of reaching a minimal clinically important difference in Spinal Stenosis Measure (SSM) symptoms (OR 0.26, 95% CI 0.13 to 0.53) and SSM function (OR 0.26, 95% CI 0.14 to 0.49), than patients undergoing surgery. These results were very robust in case of unmeasured confounding. The surgical complication rate was low; 5 (4.5%) patients experienced a durotomy during intervention, and 5 (4.5%) patients underwent re-decompression. Conclusions: The authors used propensity score matching to assess the difference in treatment efficacy of surgery compared with nonoperative treatment in elderly patients with DLSS. This study delivers strong evidence that surgical treatment is superior to nonoperative treatment. It helps in clinical decision-making, especially when patients suffer for a long time, sometimes over many years, hoping for a spontaneous improvement of their symptoms. In light of these new results, the number of years with disability can hopefully be reduced by providing adequate treatment at the right time for this ever-growing elderly and frail population. Abbreviations: DLSS = degenerative lumbar spinal stenosis; HADS = Hospital Anxiety and Depression Scale; ITT = intention-to-treat; LSOS = Lumbar Stenosis Outcome Study; MCID = minimal clinically important difference; RCT = randomized controlled trial; SMD = standardized mean difference; SSM = Spinal Stenosis Measure.

A systemic review and meta-analysis: Bentall versus David procedure in acute type A aortic dissection.

This systemic review of the literature and meta-analysis examined the current state of the evidence in long-term outcomes for and/or against aortic valve reimplantation (RAV) versus composite valve graft (CVG) intervention in patients with an acute type A dissection. Descriptive statistics were used to summarize the baseline characteristics of patients across studies. A random-effects metaregression was performed across study arms with logit-transformed proportions weighted by the study size for each of these outcomes. The results are presented as odds ratios with the RAV procedure as compared to the CVG procedure, including 95% confidence intervals (CIs) and P-values. Further outcomes are summarized with medians, interquartile ranges and the range and number of patients at risk. A total of 27 retrospective studies that included a combined 3058 patients were analysed. In-hospital mortality was in favour of the RAV procedure, which was 2% vs 8% for the CVG procedure. Survival rate at midterm was 98.8% (95% CI 91.7-100%) for RAV and 81.3% (CI 78.5-83.9%) for CVG. Freedom from valve-related reintervention was 100% (CI 93.7-100%) for RAV and 94.6% (CI 86.7-99.1%) for CVG. For an acute type A aortic dissection in the mid-term period, RAV provides a superior outcome over CVG, both in terms of aortic-valve-related reintervention and survival rate.

Power priors based on multiple historical studies for binary outcomes.

Incorporating historical information into the design and analysis of a new clinical trial has been the subject of much recent discussion. For example, in the context of clinical trials of antibiotics for drug resistant infections, where patients with specific infections can be difficult to recruit, there is often only limited and heterogeneous information available from the historical trials. To make the best use of the combined information at hand, we consider an approach based on the multiple power prior that allows the prior weight of each historical study to be chosen adaptively by empirical Bayes. This choice of weight has advantages in that it varies commensurably with differences in the historical and current data and can choose weights near 1 if the data from the corresponding historical study are similar enough to the data from the current study. Fully Bayesian approaches are also considered. The methods are applied to data from antibiotics trials. An analysis of the operating characteristics in a binomial setting shows that the proposed empirical Bayes adaptive method works well, compared to several alternative approaches, including the meta-analytic prior.

Benefits of Mobile Apps in Pain Management: Systematic Review.

BACKGROUND: Pain is a common condition with a significant physical, psychosocial, and economic impact. Due to enormous progress in mobile device technology as well as the increase in smartphone ownership in the general population, mobile apps can be used to monitor patients with pain and support them in pain management. OBJECTIVE: The aim of this review was to assess the efficacy of smartphone or computer tablet apps in the management of patients with pain. METHODS: In December 2017, a literature search was performed in the following databases: MEDLINE, EMBASE, CINAHL, Cochrane, and PsycINFO. In addition, a bibliography search was conducted. We included studies with at least 20 participants per arm that evaluated the effects of apps on smartphones or computer tablets on improvement in pain. RESULTS: A total of 15 studies with 1962 patients met the inclusion criteria. Of these, 4 studies examined the effect of mobile apps on pain management in an in-clinic setting and 11 in an out-clinic setting. The majority of the original studies reported beneficial effects of the use of a pain app. Severity of pain decreased in most studies where patients were using an app compared with patients not using an app. Other outcomes, such as worst pain or quality of life showed improvements in patients using an app. Due to heterogeneity between the original studies-patient characteristics, app content, and study setting-a synthesis of the results by statistical methods was not performed. CONCLUSIONS: Apps for pain management may be beneficial for patients, particularly in an out-clinic setting. Studies have shown that pain apps are workable and well liked by patients and health care professionals. There is no doubt that in the near future, mobile technologies will develop further. Medicine could profit from this development as indicated by our results, but there is a need for more scientific inputs. It is desirable to know which elements of apps or additional devices and tools may improve usability and help patients in pain management.

Optimizing the Design and Analysis of Clinical Trials for Antibacterials Against Multidrug-resistant Organisms: A White Paper From COMBACTE's STAT-Net.

Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical trials, which has resulted in 8 recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic modeling, emphasizing the pertinence of population-based pharmacokinetic models, regulatory procedures for the reassessment of old antibiotics, and rigorous quality improvement. Recommendations 4 and 5 address the need for more sensitive primary end points through the use of rank-based or time-dependent composite end points. Recommendation 6 relates to the applicability of hierarchical nested-trial designs, and the last 2 recommendations propose the incorporation of historical or concomitant trial data through Bayesian methods and/or platform trials. Although not all of these recommendations are directly applicable, they provide a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge.

Does Preoperative Degenerative Spondylolisthesis Influence Outcome in Degenerative Lumbar Spinal Stenosis? Three-Year Results of a Swiss Prospective Multicenter Cohort Study.

BACKGROUND: Decompression alone to treat degenerative lumbar stenosis with and without concomitant degenerative spondylolisthesis (DS; non-DS) has shown ambiguous results in the literature. OBJECTIVE: The aim is to compare clinical outcomes in DS and non-DS patients with lumbar stenosis who underwent decompression alone surgery without fusion on 1-3 adjacent levels after 6-month, 12-month, 24-month, and 36-month follow-up. METHODS: We conducted a prospective cohort study at 8 medical centers. The main outcomes of this study are changes in Spinal Stenosis Measure (SSM) symptoms score, SSM function score, and quality of life (EQ-5D-3L sum score) over time. Propensity score matching for DS versus non-DS was applied. RESULTS: One hundred seventy-seven patients met the inclusion criteria, 68 of whom had DS. In the matched cohort (n = 136), the estimated difference in SSM symptoms score of DS versus non-DS for changes from baseline to 36 months was 0.21 (95% CI, -0.15 to 0.57). For SSM function score, the estimated difference from baseline to 36 months was 0.05 (-0.21 to 0.31). Differences in changes between groups in EQ-5D-3L sum score were estimated to be -3.66 (-10.63 to 3.31) from baseline to 36 months. None of the group differences between the non-DS and the DS group was statistically significant. All matched patients improved over time in all additional outcomes. CONCLUSIONS: Even after 3 years of follow-up, we show that among patients with degenerative lumbar spinal stenosis, both groups (DS and non-DS) distinctively take advantage of decompression alone without fusion.

Adaptive power priors with empirical Bayes for clinical trials.

Incorporating historical information into the design and analysis of a new clinical trial has been the subject of much discussion as a way to increase the feasibility of trials in situations where patients are difficult to recruit. The best method to include this data is not yet clear, especially in the case when few historical studies are available. This paper looks at the power prior technique afresh in a binomial setting and examines some previously unexamined properties, such as Box P values, bias, and coverage. Additionally, it proposes an empirical Bayes-type approach to estimating the prior weight parameter by marginal likelihood. This estimate has advantages over previously criticised methods in that it varies commensurably with differences in the historical and current data and can choose weights near 1 when the data are similar enough. Fully Bayesian approaches are also considered. An analysis of the operating characteristics shows that the adaptive methods work well and that the various approaches have different strengths and weaknesses.

Objective Bayesian model selection for Cox regression.

There is now a large literature on objective Bayesian model selection in the linear model based on the g-prior. The methodology has been recently extended to generalized linear models using test-based Bayes factors. In this paper, we show that test-based Bayes factors can also be applied to the Cox proportional hazards model. If the goal is to select a single model, then both the maximum a posteriori and the median probability model can be calculated. For clinical prediction of survival, we shrink the model-specific log hazard ratio estimates with subsequent calculation of the Breslow estimate of the cumulative baseline hazard function. A Bayesian model average can also be employed. We illustrate the proposed methodology with the analysis of survival data on primary biliary cirrhosis patients and the development of a clinical prediction model for future cardiovascular events based on data from the Second Manifestations of ARTerial disease (SMART) cohort study. Cross-validation is applied to compare the predictive performance with alternative model selection approaches based on Harrell's c-Index, the calibration slope and the integrated Brier score. Finally, a novel application of Bayesian variable selection to optimal conditional prediction via landmarking is described. Copyright © 2016 John Wiley & Sons, Ltd.