Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report

Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirement for substantial immunosuppressive therapy. Calcineurin inhibitors have served as the centerpiece agent in all reported cases, and CNI‐associated complications associated with the broad therapeutic effects and side effects of calcineurin inhibitors have been similarly common. Recently, belatacept has been approved as a calcineurin inhibitor replacement in kidney transplantation, but to date, its use in VCA has not been reported. Herein, we report on the case of a hand transplant recipient who developed recurrent acute rejection with alloantibody formation and concomitant calcineurin inhibitor nephrotoxicity, all of which resolved upon conversion from a maintenance regimen of tacrolimus, mycophenolate mofetil and steroids to belatacept and sirolimus. This case indicates that belatacept may be a reasonable maintenance immunosuppressive alternative for use in VCA, providing sufficient prophylaxis from rejection with a reduced side effect profile, the latter being particularly relevant for nonlife threatening conditions typically treated by VCA.     

PCSK7 Genotype Modifies Effect of a Weight-Loss Diet on 2-Year Changes of Insulin Resistance: The POUNDS LOST Trial

OBJECTIVEA common variant rs236918 in the PCSK7 gene has the strongest association with iron homeostasis and is related to insulin resistance. Dietary carbohydrate (CHO) modulates the genetic effect on insulin resistance. We examined whether 2-year weight-loss diets modify the effect of PCSK7 genetic variants on changes in fasting insulin levels and insulin resistance in a randomized, controlled trial.RESULTSDuring the 6-month weight-loss phase, the PCSK7 rs236918 G allele was significantly associated with greater decreases in fasting insulin levels in the high–dietary CHO group (P for interaction = 0.04), while the interaction for changes in HOMA-insulin resistance (HOMA-IR) (P for interaction = 0.06) did not reach significant levels in white subjects. The G allele was significantly associated with a greater decrease in fasting insulin levels and HOMA-IR in response to high dietary CHO levels (P = 0.02 and P = 0.03, respectively). From 6 months to 2 years (weight-regain phase), the interactions became attenuated due to the regaining of weight (P for interactions = 0.08 and 0.06, respectively). In addition, we observed similar and even stronger results in the whole-study samples from the trial.CONCLUSIONSOur data suggest that PCSK7 genotypes may interact with dietary CHO intake on changes in insulin sensitivity in the white Americans.     

Weight changes in obese adults 6‐months after discontinuation of double‐blind zonisamide or placebo treatment

We evaluated weight changes in obese patients at 6‐months after they ended participation in a 12‐month randomised controlled trial in which they received daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle counselling. Of the originally randomised 225 patients, 218 completed month‐12 when study interventions were discontinued. For the 154 patients who returned for 6‐month follow‐up off‐treatment, weight changes between month‐12 and month‐18 for placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n = 52) were 0.5 kg [95% confidence interval (CI), ?0.8 to 1.8; 0.7%], 1.5 kg (0.2–2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1–3.7; 2.6%; p = 0.04 vs. placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12‐months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group.     

American indians with substance use disorders: treatment needs and comorbid conditions

Background: American Indians and Alaska Natives (AI/ANs) experience significant disparities in health status and access to care. Furthermore, only limited data are available on substance use, mental health disorders, and treatment needs for this population. Addressing such disparities and developing culturally relevant, effective interventions for AI/AN communities require participatory research. Objectives and Methods: The Western States Node of the National Institute on Drug Abuse Clinical Trials Network partnered with two American Indian substance abuse treatment programs: an urban health center and a reservation-based program to assess client characteristics, drug use patterns, and treatment needs. Data collected by staff members at the respective programs from urban (n = 74) and reservation (n = 121) clients were compared. Additional sub-analysis examined patients reporting regular opioid use and mood disorders. Results: Findings indicate that urban clients were more likely to report employment problems, polysubstance use, and a history of abuse. Reservation-based clients reported having more severe medical problems and a greater prevalence of psychiatric problems. Clients who were regular opioid users were more likely to report having a chronic medical condition, suicidal thoughts, suicide attempts, polysubstance abuse, and IV drug use. Clients who reported a history of depression had twice as many lifetime hospitalizations and more than five times as many days with medical problems. Conclusions: Findings from this project provide information about the patterns of substance abuse and the importance of comprehensive assessments of trauma and comorbid conditions. Results point to the need for integrative coordinated care and auxiliary services for AI/AN clients seeking treatment for substance use disorders.     

Do we need cardiac arrest centres in Australia?

The mortality rate post admission to hospital after successful resuscitation from out‐of‐hospital cardiac arrest is high, with significant variation between regions and individual institutions. While prehospital factors such as age, bystander cardiopulmonary resuscitation and total cardiac arrest time are known to influence outcome, several aspects of post‐resuscitative care including therapeutic hypothermia, coronary intervention and goal‐directed therapy may also influence patient survival. Regional systems of care have improved provider experience and patient outcomes for those with ST elevation myocardial infarction and life‐threatening traumatic injury. In particular, hospital factors such as hospital size and interventional cardiac care capabilities have been found to influence patient mortality. This paper reviews the evidence supporting the possible development and implementation of Australian cardiac arrest centres.     

Depressive Symptoms Among Children and Adolescents in Iran: A Confirmatory Factor Analytic Study of the Centre for Epidemiological Studies Depression Scale for Children

This study investigated the psychometric properties of the Iranian translation of the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) in school children and adolescents in Iran. The CES-DC is a 20-item self-report scale designed to measure depressive symptoms in children and adolescents. A total of 1,984 children and adolescents, aged 12–17 years, participated in this research. In addition to the CES-DC, all participants completed the Spence Children’s Anxiety Scale (SCAS) and the Strength and Difficulties Questionnaire (SDQ). The CES-DC demonstrated high internal consistency (Cronbach Alpha = .87). Confirmatory factor analyses revealed the same four factor structure as proposed by Radloff. Invariance tests showed an equivalent structure among boys and girls and younger and older adolescents. The CES-DC total scores correlated significantly with the SCAS total scores and the SDQ emotional symptoms subscale, providing support of its convergent validity. To conclude, the CES-DC proved to be a reliable and valid measure of depressive symptoms in the Iranian context.     

Host odor synergizes attraction of virgin female Lutzomyia longipalpis (Diptera: Psychodidae)

The sand fly Lutzomyia longipalpis Lutz & Neiva (Diptera: Psychodidae) is the principle vector of Leishmania chagasi/infantum Cunha and Chagas, the causative agent of visceral leishmaniasis. The disease is transmitted by blood-feeding females, which seek aggregations of males above potential hosts both to mate and blood-feed. Pheromones produced by male sand flies could potentially be used as lures in L. longipalpis control programs. We investigated whether attraction of male and female sand flies to pheromone could be increased by addition of host odor. Pheromone was attractive to females in the absence of host odor, although a 10-fold increase in concentration did not increase numbers attracted or reduce the proportion of flies not responding during trials. Odors from Syrian hamsters, Mesocricetus auratus, were more attractive to females than air when presented without sex pheromone, but this effect was masked by hexane, suggesting attraction to host odor alone may be relatively weak. Addition of hamster odor both increased the number of virgin female L. longipalpis attracted to sex pheromone (relative to a solvent control) and reduced the number of nonresponders, indicating that host odor may have both a synergistic and activating effect. Male sand flies were not attracted to pheromone with or without host odor, although addition of pheromone did counteract an apparent avoidance of host odor combined with a hexane control. These results indicate L. longipalpis pheromones function primarily to attract females and that their efficacy as lures may be increased through addition of host odor, or by deploying traps in the vicinity of host animals.     

An Exploratory Cost-Effectiveness Analysis of the Connected Health Intervention to Improve Care for People with Dementia: A Simulation Analysis

Many people with dementia live in the community; thus, supporting informal caregivers is critical. The Connected Health intervention facilitates collection and sharing of patient data among informal caregivers and providers to identify emerging patient needs and support rapid decision-making. This study estimates the costs of care of dementia using time-driven activity based costing of an exemplar patient. Intervention costs and health utility values were derived from a feasibility study of the intervention. A Markov model produced estimates of the cost-effectiveness of the intervention under four scenarios: (1) a minimal effect of the intervention on disease progression; (2) moderate effects on disease progression, and minimal effects on quality of life (QOL) and cost; (3) minimal effects on disease progression and QOL, and a moderate effect on cost; (4) moderate effects on disease progression and cost, with minimal effects on QOL. Cost estimates of formal and informal care ranged from €3713 to €7614 per month. Intervention costs were €484 per month. Under scenarios 2, 3 and 4, the cost per quality-adjusted life year of the intervention falls below €45,000, the threshold below which the Health Information and Quality Authority in Ireland generally accepts interventions as cost-effective. The results suggest that the intervention would be cost-effective with limited reductions in rates of disease progression and cost of care, and with minimal improvements in quality of life. Future research should consider the specific experiences of intervention patients.