Psychopathology in bariatric surgery candidates: A review of studies using structured diagnostic interviews

Psychiatric disorders are not uncommon among severely obese patients who present for bariatric surgery. This paper (1) reviews the results of the published studies using the structured interviews to assess psychopathology in bariatric surgery candidates; (2) compares the prevalence rates of psychiatric disorders across these studies with the data from other population samples; and (3) assesses whether sociodemographic variables appear to affect these prevalence rates. We searched online resources, PubMed, PsychINFO and reference lists of all the relevant articles to provide an overview of evidence so far and highlight some details in the assessment and comparisons of different samples in different countries. The prevalence estimates in the non-treatment obese group did not appear to differ substantially from the general population group in the US or the Italian population samples, although they were relatively higher for the German population. However, the rates of psychopathology in the bariatric surgery candidates were considerably higher than the other two population groups in all the samples. Overall, the most common category of lifetime Axis I disorders in all the studies was affective disorders, with anxiety disorders being the most common category of current Axis I disorders. Certain demographic characteristics are also associated with higher rates of psychopathology, such as, female gender, low socioeconomic status, higher BMI. Overall, methodological and sociodemographic differences make these studies difficult to compare and these differences should be taken into account when interpreting the results.     

Factors Associated with Poor Mental Health Status Among Homeless Women With and Without Dependent Children

The purpose of this study was to estimate the prevalence of mental health problems among a representative sample of homeless women with and without dependent children and determine if the effects of risk factors for mental health are modified by the presence of dependent children. Homeless women (n = 522) were recruited in 2004–2005 from shelters and meal programs in Toronto, Canada. Linear and logistic regression was performed to identify factors associated with mental health status. Poor mental health was associated with low perceived access to social support, physical/sexual assault in the past 12 months, presence of a chronic health condition, and presence of a drug use problem in the past month. Efforts to improve mental health in this population will need to address the associated problems of victimization, substance abuse, and lack of social supports.     

Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz–type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor

Introduction

A humanised monoclonal antibody, concizumab, that binds with high affinity to the Kunitz-type protease inhibitor (KPI) 2 domain of human tissue factor pathway inhibitor (TFPI) is in clinical development. It promotes coagulation by neutralising the inhibitory function of TFPI and may provide a subcutaneous prophylaxis option for patients with haemophilia. We aimed to study biodistribution and pharmacokinetics (PK) of concizumab.

Materials and Methods

Blockage of cellular TFPI by concizumab was measured by tissue factor/Factor VIIa-mediated Factor X activation on human EA.hy926 cells. Biodistribution of concizumab was analysed in rabbits by immunohistology, and the PK was measured in rabbits and rats.

Results and Conclusions

Concizumab bound to cell surface TFPI on EA.hy926 cells and neutralised TFPI inhibition of Factor X activation. The antibody cross-reacted with rabbit TFPI, but not with rat TFPI, allowing for comparative PK studies. PK data in rats described a log-linear profile typical for a non-binding antibody, whereas PK data in rabbits revealed a non-linear, dose-dependent profile, consistent with a target-mediated clearance mechanism. Immunohistology in rabbits during target-saturation showed localisation of the antibody on the endothelium of the microvasculature in several organs. We observed a marked co-localisation with endogenous rabbit TFPI, but a negligible sub-endothelial build-up. Concizumab binds and neutralises the inhibitory effect of cell surface-bound TFPI. The PK profile observed in rabbits is consistent with a TFPI-mediated drug disposition. Double immunofluorescence shows co-localisation of the antibody with TFPI on the endothelium of the microvasculature and points to this TFPI as a putative target involved in the clearance mechanism.     

Nonvolitional assessment of muscle endurance in idiopathic inflammatory myopathies: There is no relationship between patient‐reported fatigue and muscle fatigability

Introduction: We investigated whether muscle endurance differs between IIM patients and controls and if a relationship exists between perceived fatigue and poor muscle endurance. Methods: Quadriceps contractility, measured using femoral nerve stimulation (TwQ), and strength, measured using maximal voluntary contraction (MVCQ), were assessed in 20 IIM patients and matched controls. Quadriceps endurance was assessed using repetitive electrical stimulation (3 minutes). Time for force to fall to 70% initial force was determined (T70). Reported fatigue was measured using the FACIT‐F/Fatigue Severity Scales. Results: TwQ and MVCQ were lower and perceived fatigue greater for patients. There was no difference in T70 between groups. No relationships were observed between perceived fatigue and endurance (T70). Conclusions: IIM patients reported more fatigue and were weaker than controls, but there was no difference in muscle endurance. Endurance and strength were unrelated to reported fatigue measures. Mechanisms driving perceived IIM fatigue are likely to be multifactorial. Muscle Nerve 50 : 401–406, 2014     

Can Motor Measures Tell Us If Someone Is Trying? An Assessment of Sincerity of Effort in Simulated Malingering

Several studies have focused on detection of simulated injury or submaximal effort using forced-choice measures of memory. However, few studies have examined the role of motor performance in patient effort, and no studies have examined motor functioning in an injury simulation. In this study, we administered measures of motor strength, motor speed, and attention and a forced-choice memory measure to 30 participants instructed to simulate brain injury and 30 participants instructed to perform to the best of their abilities. Simulators' level of performance and variability were significantly different from those of participants instructed to give maximal performance. Variables derived from motor measures may serve as useful supplemental indicators of incomplete effort.     

Postapproval clinical experience in the treatment of Dupuytren’s contracture with collagenase clostridium histolyticum (CCH): the first 1,000 days

Dupuytren’s contracture is a benign fibromatosis of the palmar and digital fascia of the hand of uncertain etiology, resulting in nodules and cords beneath the skin of the palm of the hands that may lead to the development of contractures. Surgical intervention is often considered when metacarpophalangeal (MP) joint contracture is 30° or more, or when there is any degree of proximal interphalangeal (PIP) joint contracture. Collagenase clostridium histolyticum (CCH) is a nonsurgical, minimally invasive enzymatic drug indicated for the treatment of adult patients with Dupuytren’s contracture (DC) and palpable cord. CCH has been available for approximately 3.5 years, and postapproval experience indicates that the effectiveness of CCH is equivalent to or better than efficacy observed in clinical trials, as seen by lower injection rates to achieve clinical success. Postapproval experience has shown a risk-benefit profile that favors CCH for patients not indicated for surgery based on current recommendations and shows also that treating earlier-stage vs later-stage joint contracture results in significantly better outcomes on average. Postapproval surveillance reveals a safety profile similar to that observed in clinical trials. Nonserious adverse events are mainly local reactions; tendon rupture, a serious adverse event, is reported rarely in the clinical practice setting and at a lower rate than in clinical trials. Risk Evaluation and Mitigation Strategy (REMS) training is designed to mitigate benefit vs risk to achieve safe and effective use of CCH.     

Accurately measuring the quality and effectiveness of lumbar surgery in registry efforts: determining the most valid and responsive instruments

Background contextProspective registries have emerged as a feasible way to capture real-world care across large patient populations. However, the proven validity of more robust and cumbersome patient-reported outcomes instruments (PROis) must be balanced with what is feasible to apply in large-scale registry efforts.PurposeTo determine the relative validity and responsiveness of common PROis in accurately determining effectiveness of lumbar fusion for degenerative lumbar spondylolisthesis in registry efforts.Study designProspective cohort study.Patient sampleFifty-eight patients undergoing transforaminal lumbar interbody fusion (TLIF) for degenerative lumbar spondylolisthesisOutcome measuresPatient-reported outcome measures for pain (numeric rating scale for back and leg pain [NRS-BP, NRS-LP]), disability (Oswestry Disability Index [ODI]), general health (Short Form [SF]-12), quality of life (QOL) (EuroQol five dimensions [EQ-5D]), and depression (Zung depression scale [ZDS]) were assessed.MethodsFifty-eight patients undergoing primary TLIF for lumbar spondylolisthesis were entered into an institutional registry and prospectively followed for 2 years. Baseline and 2-year patient-reported outcomes were assessed. To assess the validity of PROis to discriminate between effective and noneffective improvements, receiver operating characteristic curves were generated for each outcomes instrument. An area under the curve (AUC) of ≥0.80 was considered an accurate discriminator. The difference between standardized response means (SRMs) in patients reporting meaningful improvement versus not was calculated to determine the relative responsiveness of each instrument.ResultsFor pain and disability, ODI had AUC=0.94, suggesting it as an accurate discriminator of meaningful improvement. Oswestry Disability Index was most responsive to postoperative improvement (SRM difference: 2.18), followed by NRS-BP and NRS-LP. For general health and QOL, SF-12 physical component score (AUC: 0.90), ZDS (AUC: 0.89), and SF-12 mental component score (AUC: 0.85) were all accurate discriminators of meaningful improvement, however, EQ-5D was most accurate (AUC: 0.97). EuroQol five dimensions was also most responsive (SRM difference: 2.83).ConclusionsFor pain and disability, ODI was the most valid and responsive measure of effectiveness of lumbar fusion. Numeric rating scale-BP and NRS-LP should not be used as substitutes for ODI in measuring effectiveness of care in registry efforts. For health-related QOL, EQ-5D was the most valid and responsive measure of improvement, however, SF-12 and ZDS are valid alternatives with less responsiveness.