Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Relationship between depression,weight, and patient satisfaction 2 years after bariatric surgery

BackgroundFindings regarding longer term symptoms of depression and the impact of depression on outcomes such as weight loss and patient satisfaction, are mixed or lacking.ObjectivesThis study sought to understand the relationship between depression, weight loss, and patient satisfaction in the two years after bariatric surgery.SettingThis study used data from a multi-institutional, statewide quality improvement collaborative of 45 different bariatric surgery sites.MethodsParticipants included patients (N = 1991) who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2015–2018. Participants self-reported symptoms of depression (Patient Health Questionnaire-8 [PHQ-8]), satisfaction with surgery, and weight presurgery and 1 year and 2 years postsurgery.ResultsCompared to presurgery, fewer patients’ PHQ-8 scores indicated clinically significant depression (PHQ-8≥10) at 1 year (P < .001; 14.3% versus 5.1%) and 2 years postsurgery (P < .0001; 8.7%). There was a significant increase in the prevalence of clinical depression from the first to second year postsurgery (P < .0001; 5.1% versus 8.7%). Higher PHQ-8 at baseline was related to less weight loss (%Total Weight Loss [%TWL] and %Excess Weight Loss [%EWL]) at 1 year postsurgery (P < .001), with a trend toward statistical significance at 2 years (P = .06). Postoperative depression was related to lower %TWL and %EWL, and less reduction in body mass index (BMI) at 1 year (P < .001) and 2 years (P < .0001). Baseline and postoperative depression were associated with lower patient satisfaction at both postoperative time points.ConclusionsThis study suggests improvements in depression up to 2 years postbariatric surgery, although it appears that the prevalence of depression increases after the first year. Depression, both pre- and postbariatric surgery, may impact weight loss and patient satisfaction.     

Factors associated with completion of patient surveys 1 year after bariatric surgery

BackgroundPatient-reported outcomes (PRO) obtained from follow-up survey data are essential to understanding the longitudinal effects of bariatric surgery. However, capturing data among patients who are well beyond the recovery period of surgery remains a challenge, and little is known about what factors may influence follow-up rates for PRO.ObjectivesTo assess the effect of hospital practices and surgical outcomes on patient survey completion rates at 1 year after bariatric surgery.SettingProspective, statewide, bariatric-specific clinical registry.MethodsPatients at hospitals participating in the Michigan Bariatric Surgery Collaborative are surveyed annually to obtain information on weight loss, medication use, satisfaction, body image, and quality of life following bariatric surgery. Hospital program coordinators were surveyed in June 2017 about their practices for ensuring survey completion among their patients. Hospitals were ranked based on 1-year patient survey completion rates between 2011 and 2015. Multivariable regression analyses were used to identify associations between hospital practices, as well as 30-day outcomes, on hospital survey completion rankings.ResultsOverall, patient survey completion rates at 1 year improved from 2011 (33.9% ± 14.5%) to 2015 (51.0% ± 13.0%), although there was wide variability between hospitals (21.1% versus 77.3% in 2015). Hospitals in the bottom quartile for survey completion rates had higher adjusted rates of 30-day severe complications (2.6% versus 1.7%, respectively; P = .0481), readmissions (5.0% versus 3.9%, respectively; P = .0157), and reoperations (1.5% versus .7%, respectively; P = .0216) than those in the top quartile. While most hospital practices did not significantly impact survey completion at 1 year, physically handing out surveys during clinic visits was independently associated with higher completion rates (odds ratio, 13.60; 95% confidence interval, 1.99?93.03; P =.0078).ConclusionsHospitals vary considerably in completion rates of patient surveys at 1 year after bariatric surgery, and lower rates were associated with hospitals that had higher complication rates. Hospitals with the highest completion rates were more likely to physically hand surveys to patients during clinic visits. Given the value of PRO on longitudinal outcomes of bariatric surgery, improving data collection across multiple hospital systems is imperative.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Gay Community Involvement and Condomless Anal Sex Among Sexual Minority Men in the USA

Archives of Sexual Behavior - Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective...     

Psycholinguistic features,design attributes,and respondent-reported cognition predict response time to patient-reported outcome measure items

Purpose

Patient-reported outcome measures (PROMs) vary in their psycholinguistic complexity. This study examined whether response time to PROM items is related to psycholinguistic attributes of the item and/or the self-reported cognitive ability of the respondent.

Methods

Baseline data from Wave 2 of the Quality of Life in Neurological Disorders (Neuro-QoL) development study were reanalyzed. That sample contained 581 adults with neurological disorders and whose self-reported cognitive abilities were quantified by the Neuro-QoL v2.0 Cognitive Function Item Bank. 185 Neuro-QoL items were coded for several psycholinguistic variables and design attributes: number of words and syllables, mean imageability of words, mean word frequency, mean age of word acquisition, and response format (e.g., about symptom frequency or task difficulty). Data were analyzed with linear and generalized linear mixed models.

Results

Main effects models revealed that slower response times were associated with respondents with lower self-reported cognitive abilities and with PROM items that contained more syllables, less imageable (e.g., more abstract) words, and that asked about task difficulty rather than symptom frequency. Interaction effects were found between self-reported cognition and those same PROM attributes such that people with worse self-reported cognitive abilities were disproportionately slow when responding to items that were longer (more syllables), contained less imageable words, and asked about task difficulty.

Conclusion

Completing a PROM requires multiple cognitive skills (e.g., memory, executive functioning) and appraisal processes. Response time is a means of operationalizing the amount or difficulty of cognitive processing, and this report indicates several aspects of PROM design that relate to a measure’s cognitive burden. However, future research with better experimental control is needed.

     

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).