Validation of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) chronic kidney disease risk score in HIV-infected patients in the USA.

OBJECTIVES: The aim of the study was to assess the validity of an easy-to-calculate chronic kidney disease (CKD) risk score developed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group in a longitudinal observational study of people living with HIV (PLWH) in the USA. METHODS: PLWH (2002-2016) without prior exposure to potentially nephrotoxic antiretroviral agents and with at least three estimated glomerular filtration rate (eGFR) test results were identified in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA® ) cohort. Three samples were drawn independently using the same eligibility criteria but each using a different eGFR equation, specifically the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR estimation method. Full and short D:A:D risk scores were applied. CKD was defined as a confirmed decrease in eGFR to < 60 mL/min/1.73 m2 (stages 3-5). Poisson models estimated the association between CKD incidence and a one-point increase in the continuous risk score. The incidence rate ratio (IRR), adjusted IRR (aIRR), and Harrell's discrimination statistic were used to assess validity. RESULTS: There were 19 444, 22 727 and 22 748 PLWH in the OPERA C-G, CKD-EPI and MDRD samples, respectively. The median (minimum-maximum) follow-up duration was 6.1 (0.3-9.1) years in the D:A:D cohort and ranged from 3.2 to 3.5 (0.2-15.5) years in the OPERA validation samples. The observation time for the majority of PLWH in the D:A:D cohort began prior to 2006, in stark contrast to the OPERA validation samples, where the majority of PLWH were observed after 2011. The CKD incidence ranged from 7.3 per 1000 person-years [95% confidence interval (CI) 6.8, 7.9 per 1000 person-years] in OPERA C-G to 11.0 (95% CI 10.4, 11.6 per 1000 person-years) in OPERA MDRD. In OPERA samples, IRRs by risk group and adjusted IRRs (full risk score) were similar to those in the D:A:D derivation cohort (adjusted IRR 1.3; 95% CI 1.3, 1.3). Harrell's c-statistic ranged from 0.87 to 0.92 in the OPERA samples, comparable to that in the derivation cohort (0.92). Results for short scores were similar. CONCLUSIONS: The findings support the validity of the D:A:D risk scoring method for assessing CKD (stages 3-5) probability in an exclusively USA-based sample regardless of eGFR method.

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment-naïve, HIV-1-infected patients at 48 weeks.

OBJECTIVES: The aim of the study was to compare the neuropsychiatric safety and tolerability of rilpivirine (TMC278) vs. efavirenz in a preplanned pooled analysis of data from the ECHO and THRIVE studies which compared the safety and efficacy of the two drugs in HIV-1 infected treatment naïve adults. METHODS: ECHO and THRIVE were randomized, double-blind, double-dummy, 96-week, international, phase 3 trials comparing the efficacy, safety and tolerability of rilpivirine 25 mg vs. efavirenz 600 mg once daily in combination with two background nucleoside/tide reverse transcriptase inhibitors. Safety and tolerability analyses were conducted when all patients had received at least 48 weeks of treatment or discontinued earlier. Differences between treatments in the incidence of neurological and psychiatric adverse events (AEs) of interest were assessed in preplanned statistical analyses using Fisher's exact test. RESULTS: At the time of the week 48 analysis, the cumulative incidences in the rilpivirine vs. efavirenz groups of any grade 2-4 treatment-related AEs and of discontinuation because of AEs were 16% vs. 31% (P<0.0001) and 3% vs. 8% (P=0.0005), respectively. The incidence of treatment-related neuropsychiatric AEs was 27% vs. 48%, respectively (P<0.0001). The incidence of treatment-related neurological AEs of interest was 17% vs. 38% (P<0.0001), and that of treatment-related psychiatric AEs of interest was 15% vs. 23% (P=0.0002). Dizziness and abnormal dreams/nightmares occurred significantly less frequently with rilpivirine vs. efavirenz (P<0.01). In both groups, patients with prior neuropsychiatric history tended to report more neuropsychiatric AEs but rates remained lower for rilpivirine than for efavirenz. CONCLUSIONS: Rilpivirine was associated with fewer neurological and psychiatric AEs of interest than efavirenz over 48 weeks in treatment-naïve, HIV-1-infected adults.

Effect of insurance status on patients admitted for acute diverticulitis.

AIM: The study aimed to evaluate the relationship between insurance status and the management and outcome of acute diverticulitis in a nationally representative sample. METHOD: A retrospective cohort analysis of a nationally representative sample of 1 031 665 hospital discharges of patients admitted for acute diverticulitis in the 2006-2009 Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project data set. The main outcome measures included state at presentation (complicated/uncomplicated), management (medical/surgical), time to surgical intervention, type of operation and inpatient death. RESULTS: In total, 207 838 discharges were identified (including 37.0% with private insurance, 49.3% in Medicare, 5.6% in Medicaid and 5.8% uninsured) representing 1 031 665 total discharges nationally. Medicare patients were more likely to present with complicated diverticulitis compared with private insurance patients (23.8% vs 15.1%). Time to surgical intervention differed by insurance status. After adjusting for patient, hospital and treatment factors, Medicare patients were less likely than those with private insurance to undergo a procedure (Medicare OR = 0.86, 95% CI: 0.82-0.91), while the uninsured were more likely to undergo drainage (OR = 1.30, 95% CI: 1.16-1.46) or a colostomy only (OR = 1.70, 95% CI: 1.24-2.33). All patients without private insurance were more likely to die in hospital (Medicare OR = 1.29, 95% CI: 1.09-1.52; Medicaid OR = 1.55, 95% CI: 1.22-1.97; uninsured OR = 1.41, 95% CI: 1.07-1.87). CONCLUSION: In a nationally representative sample of patients with acute diverticulitis, patient management and outcome varied significantly by insurance status, despite adjustment for potential confounders. Providers might need to heighten surveillance for complications when treating patients without private insurance to improve outcome.

Layered rare-earth gallium antimonides REGaSb(2) (RE = La--Nd, Sm).

The ternary rare-earth gallium antimonides, REGaSb(2) (RE = La--Nd, Sm), have been synthesized through reaction of the elements. The structures of SmGaSb(2) (orthorhombic, space group D(5)(2)-C222(1), Z = 4, a = 4.3087(5) A, b = 22.093(4) A, c = 4.3319(4) A) and NdGaSb(2) (tetragonal, space group D(19)(4h)-I4(1)/amd, Z = 8, a = 4.3486(3) A, c = 44.579(8) A) have been determined by single-crystal X-ray diffraction. The SmGaSb(2)-type structure is adopted for RE = La and Sm, whereas the NdGaSb(2)-type structure is adopted for RE = Ce--Nd. The layered SmGaSb(2) and NdGaSb(2) structures are stacking variants of each other. In both structures, two-dimensional layers of composition (2)(infinity)[GaSb] are separated from square nets of Sb atoms [Sb] by RE atoms. Alternatively, the structures may be considered as resulting from the insertion of zigzag Ga chains between (2)(infinity)[RE Sb(2)] slabs. In SmGaSb(2), all of the Ga chains are parallel and the (2)(infinity)[SmSb(2)] layers are stacked in a ZrSi(2)-type arrangement. In NdGaSb(2), the Ga chains alternate in direction, resulting in a doubling of the long axis relative to SmGaSb(2), and the (2)(infinity)[NdSb(2)] layers are stacked in a Zr(3)Al(4)Si(5)-type arrangement. Extended Hückel band structure calculations are used to explain the bonding in the [GaSb(2)](3-) substructure.

Calpain activity in the rat brain after transient forebrain ischemia.

Activity of the Ca(2+)-dependent protease calpain is increased in neurons after global and focal brain ischemia, and may contribute to postischemic injury cascades. Understanding the time course and location of calpain activity in the post-ischemic brain is essential to establishing causality and optimizing therapeutic interventions. This study examined the temporal and spatial characteristics of brain calpain activity after transient forebrain ischemia (TFI) in rats. Male Long Evans rats underwent 10 min of normothermic TFI induced by bilateral carotid occlusion with hypovolemic hypotension (MABP 30 mm Hg). Brain calpain activity was examined between 1 and 72 h after reperfusion. Western blot analysis of regional brain homogenates demonstrated a bimodal pattern of calpain-mediated alpha-spectrin degradation in the hippocampus, cortex, and striatum with an initial increase at 1 h followed by a more prominent secondary increase at 36 h after reperfusion. Immunohistochemical analysis revealed that calpain activity was primarily localized to dendritic fields of selectively vulnerable neurons at one hour after reperfusion. Between 24 and 48 h after reperfusion neuronal calpain activity progressed from the dorsal to ventral striatum, medial to lateral CA1 hippocampus, and centripetally expanded from watershed foci in the cerebral cortex. This progression was associated with fragmentation of dendritic processes, calpain activation in the neuronal soma and subsequent neuronal degeneration. These observations demonstrate a clear association between calpain activation and subsequent delayed neuronal death and suggest broad therapeutic window for interventions aimed at preventing delayed intracellular Ca(2+) overload and pathologic calpain activation.

Ovarian function and the return of potential fertility in lactating women.

OBJECTIVE: Indices of ovarian function and potential fertility have been studied in fully lactating women from the sixth week post-partum to the start of the second menstrual period. PATIENTS: Thirty-four women entered the study and 17 (50%) continued until the first menses. Of these, 16 continued until the second menses. The median time from delivery to day 1 of the first menses was 202 days (range, 85 to 668 days). METHODS: The concentrations of estrone glucuronide (EG) and pregnanediol glucuronide in daily samples of early morning urine were measured by time-resolved fluoroimmunoassay and LH by an immunoradiometric assay. Algorithms were used retrospectively to determine the rise and peak days of all three metabolites. RESULTS: Three cycles were studied relative to day 1 of first menses: (1) premenstrual (days -60 to -31), (2) menstrual (days -30 to -1), and (3) postmenstrual (days 1 to 56). Follicular development occurred in 53%, 100% and 100% of the dated cycles respectively. A peak of LH occurred in 6%, 75% and 80% of cycles, respectively. A period of potential fertility occurred in 11/17 (65%) and 13/16 (81%) of cycles (2) and (3), respectively. The proportion of potentially fertile cycles was higher after the first menses, and after 6 months had elapsed postpartum. CONCLUSION: A test based on the measurement of EG and used prospectively predicted 13/15 (85%) of the periods of potential fertility during the postmenstrual cycle.

An assessment of pre-operative microbial screening on the prevention of post-abortion pelvic inflammatory disease.

Five hundred women were examined for lower genital tract infection before vaginal termination of pregnancy. Pre-operatively, Neisseria gonorrhoeae was isolated from nine women (1.8%); five of eight male partners also had gonorrhoea. All the women with gonorrhoea were treated at least 48 h pre-operatively with ampicillin and probenicid; three of them had symptoms of pelvic infection pre-operatively and one had symptoms postoperatively. Of these women, 120 (24%) had a follow-up examination within 47 days of abortion; 15 (3%) required an evacuation of retained products of conception and only 12 (2%) had mild suspected pelvic infection. Screening for Neisseria gonorrhoeae and treatment pre-operatively prevented pelvic infection in a further eight patients.

Use of the nitrazine yellow swab test in the diagnosis of ruptured membranes.

Throat swabs impregnated with nitrazine yellow have been used to detect pH change in the vagina before and after amniotomy. The effect of infection on the test has been examined. A negative result is of use in excluding the diagnosis of ruptured membranes. A positive result is highly suggestive of the presence of amniotic fluid.