Impact of the matching algorithm on the treatment effect estimate: A neutral comparison study

Propensity score matching is increasingly being used in the medical literature. Choice of matching algorithms, reporting quality, and estimands are oftentimes not discussed. We evaluated the impact of propensity score matching algorithms, based on a recent clinical dataset, with three commonly used outcomes. The resulting estimands for different strengths of treatment effects were compared in a neutral comparison study and based on a thoroughly designed simulation study. Different algorithms yielded different levels of balance after matching. Along with full matching and genetic matching with replacement, good balance was achieved with nearest neighbor matching with caliper but thereby more than one fifth of the treated units were discarded. Average marginal treatment effect estimates were least biased with genetic or nearest neighbor matching, both with replacement and full matching. Double adjustment yielded conditional treatment effects that were closer to the true values, throughout. The choice of the matching algorithm had an impact on covariate balance after matching as well as treatment effect estimates. In comparison, genetic matching with replacement yielded better covariate balance than all other matching algorithms. A literature review in the British Medical Journal including its subjournals revealed frequent use of propensity score matching; however, the use of different matching algorithms before treatment effect estimation was only reported in one out of 21 studies. Propensity score matching is a methodology for causal treatment effect estimation from observational data; however, the methodological difficulties and low reporting quality in applied medical research need to be addressed

Reducing the Probability of False Positive Research Findings by Pre-Publication Validation - Experience with a Large Multiple Sclerosis Database

*Objective*
We have assessed the utility of a pre-publication validation policy in reducing the probability of publishing false positive research findings. 
*Study design and setting*
The large database of the Sylvia Lawry Centre for Multiple Sclerosis Research was split in two parts: one for hypothesis generation and a validation part for confirmation of selected results. We present case studies from 5 finalized projects that have used the validation policy and results from a simulation study.
*Results*
In one project, the "relapse and disability" project as described in section II (example 3), findings could not be confirmed in the validation part of the database. The simulation study showed that the percentage of false positive findings can exceed 20% depending on variable selection. 
*Conclusion*
We conclude that the validation policy has prevented the publication of at least one research finding that could not be validated in an independent data set (and probably would have been a "true" false-positive finding) over the past three years, and has led to improved data analysis, statistical programming, and selection of hypotheses. The advantages outweigh the lost statistical power inherent in the process

Sex hormones and cortisol during experimental trauma memory consolidation: Prospective association with intrusive memories

Background: Trauma- and stress-related disorders, such as post-traumatic stress disorder (PTSD), are more common in females than in males. Sex hormones affect learning and emotional memory formation and may be associated with the development of PTSD. Most previous studies have indexed these hormones in isolation. Objectives: To investigate associations of sex hormones and cortisol during memory consolidation on the development of intrusive memories. Methods: We employed an experimental trauma film paradigm in 61 healthy women and indexed salivary testosterone, progesterone, estradiol, and cortisol on day one and day two post experimental trauma exposure and their effects on intrusion frequency, distress, and vividness. Intrusive trauma memories were indexed by means of a diary in which participants documented intrusion frequency, distress, and vividness. Results and conclusion: Participants reported an average of 5.3 intrusions over the course of seven days (SD = 4.6, range 0-26). Progesterone, and estradiol indexed on day one predicted intrusion frequency, with higher progesterone and lower estradiol predicting more intrusive memories (p-values AUC progesterone 0.01 and estradiol 0.02). There was no evidence for associations between hormone concentration indices on day two and intrusion outcomes. Further research on the roles of gonadal and adrenal hormones in trauma memory formation is needed to advance our efforts to understand their influence on PTSD development

Obesity is Associated with More Disability at Presentation and After Treatment in Low Back Pain but Not in Neck Pain: Findings from the OIOC Registry

Background: The influence on the treatment response in patients with low back pain (LBP) and neck pain (NP) is unknown. The aim of the study was to investigate the influence of body weight in patients with low back pain (LBP) and neck pain (NP) on baseline and end of treatment disability. Methods: Cross-sectional analysis of baseline factors. Longitudinal analysis of prospectively collected patient information at an outpatient physical therapy registry (data from June 2010 to December 2012). WHO-BMI classification was used: underweight, lean, overweight, obesity class I, obesity class II and III. The influence of body weight and a predefined set of confounders was analyzed by multiple regression models. Results: In LBP, disability increased with increasing BMI [lean = reference, obesity class I Beta 5.41 (95 % CI 0.75; 10.07), obesity class II-III Beta 7.58 (95 % CI 2.13; 13.03)]. Compared to lean patients, disability after treatment improved in overweight subjects [Beta −3.90 (95 % CI −7.4; −0.41)] but not in subjects with obesity class II–III [Beta 3.43 (95 % CI −3.81; 10.68)]. There were insufficient patients in the sample with severe obesity and therefore this trend has to be confirmed. The likelihood for meaningful important change (MID) was similar in all BMI subgroups. For patients with NP, BMI was not associated with baseline disability, and did not predict end of treatment disability or the likelihood of a MID. These findings must be interpreted with caution as BMI subgroups did not meet the required sample size. Conclusion: Overweight and obesity are associated with higher levels of disability before treatment in LBP patients, but not in NP. In severely obese patients class II–III with LBP the rate of MID was lowest indicating that these patients experienced the least treatment response compared to the other groups. Further studies should address the impact of severe obesity on the prognosis of LBP. In patients with LBP, severe obesity may be an important factor to consider during the physical therapy treatment. In particular, combined treatment strategies combining weight management, cardiovascular fitness, and low back pain rehabilitation should be investigated

Prevalence and predictors of fatigue in glioblastoma: a prospective study

Background The main goal of this study was to assess frequency, clinical correlates, and independent predictors of fatigue in a homogeneous cohort of well-defined glioblastoma patients at baseline prior to combined radio-chemotherapy. Methods We prospectively included 65 glioblastoma patients at postsurgical baseline and assessed fatigue, sleepiness, mean bedtimes, mood disturbances, and clinical characteristics such as clinical performance status, presenting symptomatology, details on neurosurgical procedure, and tumor location and diameter as well as pharmacological treatment including antiepileptic drugs, antidepressants, and use of corticosteroids. Data on fatigue and sleepiness were measured with the Fatigue Severity Scale and the Epworth Sleepiness Scale, respectively, and compared with 130 age- and sex-matched healthy controls. Results We observed a significant correlation between fatigue and sleepiness scores in both patients (r = 0.26; P = .04) and controls (r = 0.36; P < .001). Only fatigue appeared to be more common in glioblastoma patients than in healthy controls (48% vs 11%; P < .001) but not the frequency of sleepiness (22% vs 19%; P = .43). Female sex was associated with increased fatigue frequency among glioblastoma patients but not among control participants. Multiple linear regression analyses identified depression, left-sided tumor location, and female sex as strongest associates of baseline fatigue severity. Conclusions Our findings indicate that glioblastoma patients are frequently affected by fatigue at baseline, suggesting that factors other than those related to radio- or chemotherapy have significant impact, particularly depression and tumor localizatio

Neurovascular disease in Switzerland: 10-year trends show non-traditional risk factors on the rise and higher exposure in women

BACKGROUND AND PURPOSE Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed. METHODS Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design. RESULTS Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]). CONCLUSIONS A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease

Development and internal validation of a prediction model for long-term opioid use-an analysis of insurance claims data.

In the United States, a public-health crisis of opioid overuse has been observed, and in Europe, prescriptions of opioids are strongly increasing over time. The objective was to develop and validate a multivariable prognostic model to be used at the beginning of an opioid prescription episode, aiming to identify individual patients at high risk for long-term opioid use based on routinely collected data. Predictors including demographics, comorbid diseases, comedication, morphine dose at episode initiation, and prescription practice were collected. The primary outcome was long-term opioid use, defined as opioid use of either >90 days duration and ≥10 claims or >120 days, independent of the number of claims. Traditional generalized linear statistical regression models and machine learning approaches were applied. The area under the curve, calibration plots, and the scaled Brier score assessed model performance. More than four hundred thousand opioid episodes were included. The final risk prediction model had an area under the curve of 0.927 (95% confidence interval 0.924-0.931) in the validation set, and this model had a scaled Brier score of 48.5%. Using a threshold of 10% predicted probability to identify patients at high risk, the overall accuracy of this risk prediction model was 81.6% (95% confidence interval 81.2% to 82.0%). Our study demonstrated that long-term opioid use can be predicted at the initiation of an opioid prescription episode, with satisfactory accuracy using data routinely collected at a large health insurance company. Traditional statistical methods resulted in higher discriminative ability and similarly good calibration as compared with machine learning approaches

The Chronic CARe for diAbeTes study (CARAT): a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Diabetes is a major challenge for the health care system and especially for the primary care provider. The Chronic Care Model represents an evidence-based framework for the care for chronically ill. An increasing number of studies showed that implementing elements of the Chronic Care Model improves patient relevant outcomes and process parameters. However, most of these findings have been performed in settings different from the Swiss health care system which is dominated by single handed practices.</p> <p>Methods/Design</p> <p>CARAT is a cluster randomized controlled trial with general practitioners as the unit of randomization (trial registration: ISRCTN05947538). The study challenges the hypothesis that implementing several elements of the Chronic Care Model via a specially trained practice nurse improves the HbA1c level of diabetes type II patients significantly after one year (primary outcome). Furthermore, we assume that the intervention increases the proportion of patients who achieve the recommended targets regarding blood pressure (<130/80), HbA1c (=<6.5%) and low-density lipoprotein-cholesterol (<2.6 mmol/l), increases patients' quality of life (SF-36) and several evidence-based quality indicators for diabetes care. These improvements in care will be experienced by the patients (PACIC-5A) as well as by the practice team (ACIC). According to the power calculation, 28 general practitioners will be randomized either to the intervention group or to the control group. Each general practitioner will include 12 patients suffering from diabetes type II. In the intervention group the general practitioner as well as the practice nurse will be trained to perform care for diabetes patients according to the Chronic Care Model in teamwork. In the control group no intervention will be applied at all and patients will be treated as usual. Measurements (pre-data-collection) will take place in months II-IV, starting in February 2010. Follow-up data will be collected after 1 year.</p> <p>Discussion</p> <p>This study challenges the hypothesis that the Chronic Care Model can be easily implemented by a practice nurse focused approach. If our results will confirm this hypothesis the suggestion arises whether this approach should be implemented in other chronic diseases and multimorbid patients and how to redesign care in Switzerland.</p