Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.     

Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center

Tobacco use remains the leading cause of preventable disease and death in the US. The number of tobacco products has grown over the past decade. E-cigarette use has increased rapidly in recent years, but patterns and correlates of use have not been thoroughly assessed. We examined relationships among demographic factors, e-cigarette and conventional cigarette use in a large sample (N?=?12,409) of adult patients at a community health center in the Northeastern US. Overall, 13% (N?=?1675) of the sample reported ever using e-cigarettes. In logistic regression models, ever having used e-cigarettes was associated with younger age (ages 18–25; OR?=?3.5, p?<?0.001). Being transgender (OR?=?1.8, p?<?0.001), bisexual (OR?=?1.5, p?<?0.001), un-partnered (OR?=?1.5, p?<?0.001), having a lower income (OR?=?1.6, p?<?0.001) or a high BMI (OR?=?1.4, p?=?0.009) were associated with increased odds of use, whereas being a woman (OR?=?0.7, p?<?0.001) or Black/African American (OR?=?0.7, p?=?0.007) were associated with lower odds of use. Of the participants who reported e-cigarette use, a majority also endorsed current or former use of conventional cigarettes. Individuals who formerly used conventional cigarettes were nearly three times more likely to report daily e-cigarette use than current users. Among primary care patients at a community health center, e-cigarette use was reported by a sizeable portion of the sample. Overall, odds of use were higher in certain patient populations, and individuals who formally used cigarettes were more likely to report e-cigarette use than individuals who currently smoke, suggesting that e-cigarettes may be functioning as a cessation aid or a strategy to reduce conventional cigarette use.

     

Evaluation of the 2016–2020 regional tuberculosis response framework,WHO Western Pacific Region

ObjectiveTo assess the implementation of the Regional framework for action on implementation of the End TB Strategy in the Western Pacific, 2016–2020 in countries and areas in the World Health Organization Western Pacific Region.MethodsWe used a mixed methods approach to assess the framework’s measurable and perceived impact. We conducted an analysis of national tuberculosis strategic plans, a cross-sectional survey of senior staff of tuberculosis programmes, key informant interviews and some country case studies.FindingsOf the 37 countries and areas of the Western Pacific Region, 14 had a national tuberculosis strategic plan, including all countries and areas with a high incidence of tuberculosis. Most senior tuberculosis programme staff who responded to the survey (16/23) found the regional framework useful when developing their national targets and grant applications. Programmatic challenges identified included financing, human resources, public–private mix, active case finding, and paediatric and drug-resistant tuberculosis. Most of the 17 key informants thought that the regional framework’s categorization of actions (for all settings, for specific settings and for pre-elimination settings) was useful, but that the added value of the regional framework over other relevant documents was not obvious because of overlap in content.ConclusionThe regional framework influenced national level tuberculosis control planning and implementation in a positive way. A future regional framework should provide a longer-term strategic horizon and specifically address emerging trends and persistent problems faced by countries or areas of the region.     

Depression,anxiety, and loneliness among adolescents and young adults with IBD in the UK: the role of disease severity,age of onset,and embarrassment of the condition

Quality of Life Research - Adolescents and young adults (AYA) with Inflammatory Bowel Disease (IBD) report higher depressive symptoms and anxiety compared to healthy controls, with disease severity...     

Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord

ZC4H2 (MIM# 300897) is a nuclear factor involved in various cellular processes including proliferation and differentiation of neural stem cells, ventral spinal patterning and osteogenic and myogenic processes. Pathogenic variants in ZC4H2 have been associated with Wieacker-Wolff syndrome (MIM# 314580), an X-linked neurodevelopmental disorder characterized by arthrogryposis, development delay, hypotonia, feeding difficulties, poor growth, skeletal abnormalities, and dysmorphic features. Zebrafish zc4h2 null mutants recapitulated the human phenotype, showed complete loss of vsx2 expression in brain, and exhibited abnormal swimming and balance problems. Here we report 7 new patients (four males and three females) with ZC4H2-related disorder from six unrelated families. Four of the 6 ZC4H2 variants are novel: three missense variants, designated as c.142T>A (p.Tyr48Asn), c.558G>A (p.Met186Ile) and c.602C>T (p.Pro201Leu), and a nonsense variant, c.618C>A (p.Cys206*). Two variants were previously reported : a nonsense variant c.199C>T (p.Arg67*) and a splice site variant (c.225+5G>A). Five patients were on the severe spectrum of clinical findings, two of whom had early death. The male patient harboring the p.Met186Ile variant and the female patient that carries the p.Pro201Leu variant have a relatively mild phenotype. Of note, 4/7 patients had a tethered cord that required a surgical repair. We also demonstrate and discuss previously under-recognized phenotypic features including sleep apnea, arrhythmia, hypoglycemia, and unexpected early death. To study the effect of the missense variants, we performed microinjection of human ZC4H2 wild-type or variant mRNAs into zc4h2 null mutant zebrafish embryos. The p.Met186Ile mRNA variant was able to partially rescue vsx2 expression while p.Tyr48Asn and p.Pro201Leu mRNA variants were not. However, swimming and balance problems could not be rescued by any of these variants. These results suggest that the p.Met186Ile is a hypomorphic allele. Our work expands the genotypes and phenotypes associated with ZC4H2-related disorder and demonstrates that the zebrafish system is a reliable method to determine the pathogenicity of ZC4H2 variants.     

Use of refractometry to identify opioid-containing solutions

The purpose of this laboratory study was to assess the value of refractometry in identifying the contents of a variety of opioid-containing solutions. A hand-held refractometer was used to document the refraction produced by the undiluted contents of alfentanil, fentanyl, morphine, sufentanil ampoules and by solutions of Ringer’s lactate, 0.9% saline, 3.3% dextrose in 0.3% saline, and distilled water. Each opioid was then serially diluted in serial 1:2, 1:4, and 1:8 dilutions in each of these solutions and the refractions of each determined. Based on this information, blinded identification of various diluted opioid solutions was attempted. Refractometer values for undiluted fentanyl and sufentanil were identical with those for distilled water. Those for undiluted alfentanil and morphine were almost identical with each other and with 1:2 and 1:4 dilutions of either drug in Ringer’s lactate or 0.9% saline. We conclude that refractometry is an unreliable screening method to detect tampering with opioid solutions.     

Anaesthetic management of a patient with a descending thoracic aortic aneurysm and severe bilateral bullous pulmonary parenchymal disease

The anaesthetic management of the surgical repair of a descending aortic aneurysm in a patient with large, bilateral, pulmonary bullae is described. Anaesthesia for descending aortic surgery normally involves unilateral, positive-pressure ventilation, an option which poses some risk of barotrauma in the presence of bilateral bullae. Patients with bullous disease commonly have severe lung disease and thorough preoperative assessment and preparation are necessary. Intraoperatively, bilateral rupture of the bullae could be catastrophic and preparations should be made for this possibility. In order to diminish this risk, a surgical technique including preemptive collapse of the bulla by minithoracotomy and tube drainage, with use of a bronchial blocker to the affected part of the lung may be used. If rupture occurs, then high frequency jet ventilation may be effective. Use of a double lumen endobronchial tube may be advantageous for patients with either unilateral and bilateral bullae. Anaesthesia for patients with bullae should avoid positive-pressure ventilation and nitrous oxide in order to limit the risk of barotrauma from a ball valve mechanism. In this case, the risk of barotrauma was reduced by performing an inhalational induction of anaesthesia and limiting peak inflation pressures during thoracotomy. It was elected to use positivepressure ventilation through a double lumen endobronchial tube following chest incision. A high frequency jet ventilator was available but not employed. Anaesthetic management was complicated by the presence of pleural adhesions, surgical approach directly through a bulla, and the requirement for one lung ventilation. The de i’aone descendante aecouverte cnez un pattent porde grosses bulles bilatérales d’emphysème est discutée, esthésie habituelle pour une chirurgie de l’aorte descendante site une ventilation mécanique unilatérale et constitue ainsi sque additionnel pour le porteur de bulles emphysémas bilatérales. Ces patients ont ordinairement des affections onaires graves et l’évaluation et la préparation préopéraprennent une importance spéciale. Pendant l’intervention, pture de bulles bilatérales peut être catastrophique et il se préparer à cette éventualité. Pour minimiser ce risque, technique chirurgicale qui inclut le collapsus préventif de lle par minithoracotomie et drainage, avec installation d’un ieur bronchique sur la partie atteinte du poumon. Si une re survient, le passage à la ventilation par jet à haute tence peut être salutaire. Le tube endobronchique à double ère peut présenter des avantages aussi bien dans les cas ulles unilatérales que bilatérales. Chez ces patients, il vaut x s’abstenir de ventiler avec une pression positive et du xyde d’azote afin de limiter le risque de barotraumisme soupape. Dans ce cas-ci, on a réussi à limiter le risque arotraumatisme en réalisant une induction par inhalation réduisant la pression d’inflation de pointe pendant la cotomie. Après l’incision thoracique, on a choisi d’utiliser tilation mécanique avec un tube endobronchique à double ère. Un ventilateur à jet à haute fréquence était prêt mais as été utilisé. La gestion de l’anesthésie a été compliquée par dhérences pleurales, par la rencontre d’une bulle d’emphysà l’incision et par l’obligation de ventiler un seul poumon.