Introduction: Water exchange (WE) and caP-assisted colonoscopy independently reduced insertion pain in unsedated colonoscopy. In pilot investigation, WE combined with cap (WECAC) lowered insertion pain. We hypothesize that real-time maximum insertion pain (RTMIP) is significantly lower in unsedated Veterans in a randomized controlled trial (RCT) of WECAC vs. WE. Methods: Veterans across 3 sites presenting for unsedated colonoscopy were recruited, randomized and examined by 9 colonoscopists. Demographic and patient characteristics were recorded. Subjects were blinded to method. The highest segmental pain (0=no pain, 9=worst pain) during insertion yielded the RTMIP. RTMIP was analyzed with logistic regression using binarized (0 or 1) RTMIP score with a threshold of 0.5 (“no pain” vs. “some pain”) and 7.5 (“no or manageable pain” vs. “severe pain”) as the dependent variable. p < 0.05 was significant. Results: Screening (84), surveillance (180) and FIT+ (13) cases were included. WE (135) and WECAC (142) were successful in 93% and 92%, respectively. Failure was due to poor preparation (9), stricture (1), technical difficulty (3) and other (2). Table 1A shows racial/ethnic distributions. The mean RTMIP was low in both groups and did not differ (Table 1B). Logistic regression revealed LA & SAC site (P=0.0058), high volume of water infused (P=0.0111) and suctioned (P=0.0241) were significantly associated with no pain. Low body mass index (P=0.0124), poor self-reported health (P=0.0165), and low weight (P=0.0176) were significantly associated with “severe pain”. Colonoscopy method was not significant for any RTMIP cutoff. Adenoma detection rates and adenomas per colonoscopy were satisfactorily high in both groups (Table 1B). Conclusion: In a single (patient) blinded multicenter RCT, WE and WECAC similarly yielded high success and low RTMIP in a racially diverse group of male and female Veterans. This study attests to both the feasibility of unsedated colonoscopy in those without escort and its utility in providing alternative option and access to Veterans who would otherwise have to forgo colonoscopy, including for urgent indications (e.g., FIT+). Intention-to-treat analysis showed high success rates and high adenoma detection rates ( >45%), consistent with quality examinations. Suction of all infused water during insertion (as original WE) is associated with pain reduction and addition of a cap does not further reduce it. Inadequate water exchange and patient specific factors contribute to high RTMIP. Table 1. - A. Racial/Ethnic Distribution. B: Real Time Maximum Insertion Pain and Adenoma Detection A. LA PA SAC Count 126 101 50 Age 67.7 (7.02) 68.5 (7.03) 64.5 (11.43) Male 119 (94.4%) 97 (96%) 50 (100%) Female 7 (5.6%) 4 (4%) 0 (0%) White 84 (66.7%) 73 (72.3%) 30 (62.5%) African American 33 (26.2%) 15 (14.9%) 13 (27.1%) Asian 4 (3.2%) 5 (5%) 5 (10.4%) Native American / Alaska Native 0 (0%) 1 (1%) 0 (0%) Hawaiian / Pacific Islander 0 (0%) 6 (5.9%) 0 (0%) Other 5 (4%) 1 (1%) 0 (0%) Hispanic 22 (17.5%) 8 (7.9%) 2 (4.1%) Non-Hispanic 104 (82.5%) 93 (92.1%) 47 (95.9%) B. WE n=135 WECAC n=142 p Overall RTMIP mean (SD) 2.6 (2.4) 2.9 (2.5) 0.890* Binarized RTMIP Method was not significant predictor for any cutoff* Overall adenoma detection rate, n (%) 76 (55.1%) 69 (48.3%) 0.2527** Adenoma per colonoscopy, mean (SD) 0.9 (1.03) 0.8 (0.98) 0.1867*** WE, water exchange; WECAC, water exchange plus cap; LA, Los Angeles; PA, Palo Alto; SAC, Sacramento. Data mean (SD). RTMIP (0=no pain; 9=worst pain).*p, logistic regression of the binarized RTMIP, Kolmogorov-Smirnov (KS) test. **Chi square; ***t test. (Supported by VA Merit Review Research Funds).

Background: Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD. Study aims and design: We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: Thirty clinical studies (n = 1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I2 = 99.8%) and 0.09 (95% CI, 0.05; 0.13, I2 = 84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I2 = 73.3%) (P < 0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, −0.01; 0.04, I2 = 16.1%). Common serious adverse events were anemia (n = 26, 38%) and reduced eGFR (n = 14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I2 = 80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I2 = 95.8%). Six studies (n = 69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found. Conclusions: SOF-based regimens appear safe and effective in patients with stage 4–5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way. Resumen: Antecedentes: La hepatitis C es un importante agente de daño hepático en los pacientes con enfermedad renal crónica. La aparición de los antivíricos de acción directa (AAD) ha cambiado espectacularmente el tratamiento de los pacientes con positividad para el virus de hepatitis C (VHC), incluidos los que presentan enfermedad renal crónica (ERC) avanzada. El sofosbuvir es la piedra angular de muchos tratamientos contra la infección por el VHC basados en AAD, pero sigue habiendo dudas sobre si es apropiado en los pacientes con infección por el VHC y ERC en estadio 4-5. Objetivos y diseño del estudio: Realizamos una revisión sistemática de la literatura médica con un metaanálisis de estudios clínicos para evaluar la eficacia y la seguridad de tratamientos con AAD basados en el sofosbuvir en pacientes con ERC en estadio 4-5. El criterio principal de valoración fue la respuesta virológica sostenida (como indicador de la eficacia); los criterios secundarios de valoración fueron la frecuencia de acontecimientos adversos graves (AAG) y los abandonos por acontecimientos adversos (AA) (como indicadores de la tolerabilidad). Se adoptó el modelo de efectos aleatorios de DerSimonian y Laird, con análisis estratificados y de heterogeneidad. Resultados: Se recuperaron 30 estudios clínicos (n = 1.537 pacientes individuales). La tasa agrupada de respuesta virológica sostenida a las 12 semanas (RVS12) y de AAG fue de 0,99 (intervalos de confianza del 95%, 0,97; 1,0, I2 = 99,8%) y 0,09 (IC del 95%, 0,05; 0,13, I2= 84,3%), respectivamente. La tasa agrupada de RVS12 en estudios con niveles altos de ARN del VHC al inicio fue menor, 0,87 (IC del 95%, 0,75; 1,0, I2 = 73,3%) (p < 0,001). La tasa agrupada de abandonos por AA fue 0,02 (IC del 95%, –0,01; 0,04, I2 = 16,1%). Los acontecimientos adversos graves frecuentes fueron anemia (n = 26, 38%) y filtración glomerular estimada (FGe) reducida (n = 14, 19%). Los AAG fueron más frecuentes en los estudios que administraron sofosbuvir en la dosis completa (tasa agrupada de AAG 0,15, IC del 95%, 0,06; 0,25; I2 = 80,1%) y en los que se administró ribavirina (0,15, IC del 95%, 0,07; 0,23, I2 = 95,8%). En seis estudios (n = 69 pacientes) se notificaron niveles de FGe al inicio/después del tratamiento antivírico; no se observaron variaciones sistemáticas. Conclusiones: Los tratamientos basados en SOF parecen seguros y eficaces en los pacientes con ERC en estadio 4-5. La creatinina sérica debe vigilarse atentamente durante el tratamiento con SOF en los pacientes con ERC. Se están llevando a cabo estudios controlados aleatorizados para ampliar nuestros conocimientos al respecto.

Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine. We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD. The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40 mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%. We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (<10 IU/mL) during the follow-up are appropriate. The patho-physiologic mechanisms responsible for the poor immunogenicity of HBV vaccine in CKD patients are under active investigation. La hepatitis B es un importante agente de la enfermedad hepática en pacientes con nefropatía crónica (NC) y la infección crónica por el virus de la hepatitis B (VHB), promueve el desarrollo de la NC en la población general adulta. Los pacientes con NC tienen una respuesta subóptima a varias vacunas, y no está claro cómo podemos aumentar la respuesta inmunológica de estos pacientes a la vacuna contra el VHB. Realizamos una revisión narrativa para evaluar los mecanismos de menor inmunogenicidad de la vacuna contra el VHB en la población con NC; se han documentado varios enfoques para mejorar la tasa de respuesta de los pacientes con NC a la vacuna contra el VHB. Este es un tema muy importante para los nefrólogos, que a menudo atienden como médicos de atención primaria a pacientes con NC. El programa de vacunación recomendado para los pacientes con NC, incluidos los que están en diálisis de mantenimiento, se basa en una vacuna recombinante de cuatro dosis (meses 0, 1, 2 y 6; 40 mcg cada dosis), administrada por vía intramuscular (músculo deltoides). Según los ECA, o estudios observacionales, algunas vacunas recombinantes con adyuvantes (es decir, HBV-AS02 y HBV-AS04) parecen prometedoras. La HBV-AS04 demostró ofrecer mejores tasas de seroprotección y una respuesta inmunitaria duradera durante los seguimientos prolongados, en comparación con la vacuna autorizada contra el VHB en pacientes con NC. La tasa de seroprotección fue del 95% (97/102) y del 82% (202/248), en pacientes en prediálisis y diálisis, respectivamente, un mes después de completar el programa de vacunación con HBV-AS04. La HBV-AS02 fue superior a la vacuna autorizada con respecto a la tasa de seroprotección, 76,9 vs. a 37,6%. Sugerimos una vacuna recombinante con adyuvante (HBV-AS04) (meses 0, 1, 2 y 3, 20 mcg cada dosis) y pruebas de anticuerpos anti-HB después de la vacunación. Se consideran adecuadas las dosis de refuerzo para los pacientes cuyos títulos de anticuerpos anti-HB sean inferiores al nivel de seroprotección (< 10 UI/mL) durante el seguimiento. Los mecanismos fisiopatológicos responsables de una inmunogenicidad deficiente de la vacuna contra el VHB en pacientes con NC son objeto de investigaciones exhaustivas.

Background and aims: The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a ‘real-world’ cohort of patients with CKD. Methods: We performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1–3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities. Results: The average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m2; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures – eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%). Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a ‘real–world’ clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population. Resumen: Antecedentes y objetivos: La aparición de los antivíricos de acción directa (AAD) promete cambiar el tratamiento de la infección por el virus de la hepatitis C (VHC) en los pacientes con nefropatía crónica (NC), un grupo de pacientes en el que el tratamiento de la hepatitis C siempre supuso una dificultad. Se investiga la seguridad y la eficacia de los antivíricos de acción directa, sin interferones orales, en todos los casos para el tratamiento de la hepatitis C en una cohorte en condiciones reales de pacientes con NC. Métodos: Se llevó a cabo un estudio multicéntrico, de un solo grupo y observacional en una cohorte amplia (n = 198) de pacientes con NC en estadio 1-3 a los que se administró tratamiento antivírico con AAD para el VHC. El criterio principal de valoración fue la respuesta virológica sostenida (ARN sérico del VHC < 15 UI/ml, 12 semanas después de la finalización del tratamiento) (RVS12). Se recogieron los datos sobre acontecimientos adversos (AA) surgidos durante el tratamiento, AA graves y anomalías analíticas. Resultados: La FGe inicial media (ecuación de CKD-EPI) fue de 70,06 ± 20,1 ml/min/1,72 m2; el genotipo más frecuente fue VHC 1b (n = 93; 51%). Se observó cicatrización hepática avanzada en 58 (46%) pacientes mediante elastografía transitoria. Se adoptaron 5 pautas: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), pauta de paritaprevir/ombitasvir/dasabuvir (PrOD) potenciada con ritonavir (n = 40), simeprevir ± daclatasvir (n = 2) y combinaciones basadas en sofosbuvir (n = 147). La tasa de RVS12 fue del 95,4% (IC del 95%: 93,8; 96,8%). Hubo 9 fracasos virológicos, 8 de ellos recidivantes. Se produjeron acontecimientos adversos en el 30% (51/168) de los pacientes, que se trataron clínicamente sin suspensión del tratamiento ni hospitalización. Uno de los AA más frecuentes fue la anemia (n = 12), que precisó la suspensión o la reducción de la dosis de ribavirina en algunos casos (n = 6); se produjo deterioro de la función renal en 3 casos (1,7%). Conclusiones: El tratamiento sin interferón oral en todos los casos con AAD para el VHC crónico en la NC de leve a moderada fue eficaz y bien tolerado en un contexto de la práctica clínica real. Hay estudios en curso para abordar si la respuesta viral sostenida se traduce en una mejor supervivencia en esta población. Keywords: Adverse effects, Antiviral agents, Hepatitis C, Kidney failure, Sustained virologic response, Palabras clave: Efectos adversos, Antivíricos, Hepatitis C, Insuficiencia renal, Respuesta virológica sostenida

Background: Controversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease. Study Aims and Design: A systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out. Results: Fifteen studies were eligible (n = 356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n = 7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p = 0.0016) and between-study heterogeneity was found (p-value by Q test = 0.004). Aggregation of studies comparing treated vs untreated cohorts (n = 8, n = 333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p = 0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p = 0.02) and HBV infection (p = 0.0001) increase among HCV-infected individuals. Conclusions: Antiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing. Resumen: Antecedentes: Sigue existiendo controversia acerca del rol de la hepatitis C como factor de riesgo de desarrollo de enfermedades renales en la población general. Algunos autores han evaluado el efecto de la terapia antiviral para el VHC en el riesgo de enfermedad renal. Objetivos y diseño del estudio: Se realizó una revisión sistemática de la literatura médica publicada, para evaluar si la terapia antiviral para el VHC tenía un impacto independiente en la supervivencia renal en la población adulta general. Se utilizó un modelo de efectos aleatorios para generar una estimación general del riesgo de enfermedad renal tras la terapia anti-VHC, entre los estudios publicados. También se realizaron análisis de meta-regresión y estratificados. Resultados: Quince estudios resultaron elegibles (n = 356, 285 pacientes), realizándose meta-análisis separados con arreglo al resultado. Los estudios agrupados basados en las respuestas virales (n = 7; 34.763 pacientes individuales) demostraron una relación entre la respuesta viral sostenida y la menor frecuencia de enfermedad renal; la estimación general para el riesgo ajustado de enfermedad renal fue de 2,5 (95% IC, 1,41; 4,41) (p = 0,0016), encontrándose una heterogeneidad entre estudios (valor p con prueba Q = 0,004). La suma de estudios comparativos de cohortes tratadas vs no tratadas (n = 8, n = 333.312 pacientes) reveló una asociación entre la terapia anti-VHC y el menor riesgo de enfermedad renal. La estimación general para el riesgo ajustado de enfermedad renal entre ocho estudios fue de 0,39 (95% IC, 0,25; 0,612) (p = 0,0001). La meta-regresión reflejó que la efectividad de la terapia antiviral para reducir la frecuencia de enfermedad renal disminuye a medida que aumentan los casos de cirrosis (p = 0,02) e infección por VHB (p = 0,0001) entre los individuos infectados de VHC. Conclusiones: La terapia antiviral para el VHC disminuye el riesgo de enfermedad renal entre los individuos infectados de VHC. Son continuos los estudios para comprender los mecanismos subyacentes a esta asociación.

Background and rationale: The rote of hepatitis C virus (HCV) as an independent risk factor for death in dialysis population is unclear. Design: A systematic review of the published medical literature was performed to evaluate the impact of positive anti-HCV serologic status on all-cause and disease-specific mortality in patients on regular dialysis. The risk of all-cause, cardiovascular and liver disease-related mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. Results: Twenty-three observational studies (n=574,081 patients on long-term dialysis) were identified. Pooling of study results demonstrated that HCV positive status was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted death risk (all-cause mortality) with HCV was 1.26 (95% CI: 1.18; 1.34) (P<0.0001). Between-study heterogeneity was found (Q value 52.8, P= 0.001). The overall estimate for adjusted death risk (liver disease-related mortality) was 5.05 (95% CI: 2.53; 10.0) (P<0.0001); heterogeneity statistics, Q value 8.2, P= 0.04. The overall estimate for adjusted death risk (cardiovascular mortality) was 1.18 (95% CI: 1.085; 1.29) (P < 0.0001) (no heterogeneity). Metaregression showed that the effect of HCV on all-cause mortality was more evident in those studies provided with a greater size (P=0.0001), a higher prevalence of diabetics (P=0.0005) and HCV-infected individuals (P=0.001). Conclusions: An association between HCV positive serologic status and increased risk of either liver or cardiovascular disease-related mortality exists among dialysis patients. (C) 2018 Published by Elsevier Masson SAS.

Background: Ulcerative colitis (UC) is a chronic, debilitating disease localized in the colon with no known medical cure.Active inflammation can result in significant morbidity and mortality which current medical therapies aim to manage; however, medical therapies for UC are not without their own risks including lymphoma and serious infections.While colectomy has traditionally been utilized after failure of medical therapies, earlier, elective surgery has not been assessed.We employed Markov Modeling to determine the optimal position of colectomy in the current treatment paradigm of UC.Methods: A Markov Model was designed to assess the optimal placement of colectomy in the treatment paradigm of UC.The base case was a 50-year old male with steroid-dependent UC with moderate to severely active disease who had not previously used immunomodulators or biologic therapies.Medical therapy was modeled after step-up therapy, starting initially with azathioprine (AZA), followed by infliximab (IFX) monotherapy, combination therapy with IFX+AZA, and lastly adalimumab.We then developed 4 separate algorithms incorporating elective colectomy:(1) colectomy prior to biologic therapy, (2) colectomy after infliximab monotherapy failure, (3) colectomy after infliximab and azathioprine combination therapy failure (4) colectomy after failure of all medical therapy including ADA (Figure 1).For each medical therapy, patients could experience clinical remission, response, or a serious adverse event.Transition probabilities were derived from published clinical trials including ULTRA, ACT and SUC-CESS.The time horizon was 3 years with a cycle length of 12 weeks.First order Monte Carlo simulation of 100 trials of 100,000 individuals was used to calculate the mean quality adjusted life years (QALYs) for each algorithm.1-way sensitivity analyses were conducted for all variables.Results: In this simulation, colectomy following combination therapy with IFX+AZA (3) is the preferred strategy, yielding 0.0095 to 0.0177 greater QALYs at 3 years than other treatment algorithms (Table 1).However, the model was sensitive to QALY estimates for medical remission and response and post-operative remission; If the quality of life for medical remission and response were decreased by 4.03% and 2.87% respectively or the post-operative quality of life was increased by 1.56%, earlier colectomy was preferred.Conclusions: This simulation suggests that incorporating colectomy earlier within the traditional treatment algorithm, particularly after failure of IFX+AZA but prior to a second anti-TNF, may yield greater quality of life for patients with steroid-dependent UC.These findings suggest avenues for more patient-centered preference work and a combined medical-surgical approach to UC.

This study shows a high 25-hydroxyvitamin D deficiency among postmenopausal women accompanying secondary hyperparathyroidism. However, a sizable number of subjects did not have secondary hyperparathyroidism despite having low 25-hydroxyvitamin D levels. This condition arises a research question in clinical practice needed to be addressed in the future.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct‐acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African‐Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non‐CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA‐treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single‐center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African‐American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non‐SVR. African‐Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5‐4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26‐0.68) was also a significant predictor of non‐SVR. In a single‐center VA population on DAAs, African‐Americans were less likely than White people to reach SVR12 when adjusting for covariates.

Treating vitamin D deficiency is of key importance in preventing stress fractures. The importance of nutrition in athletes is essential, especially in the female athlete. Both inadequate intake of calcium, vitamin D or inadequate caloric intake, are associated with reduced bone mass. Vitamin D deficiency leads to the pathogenesis of osteoporosis, which further increases the risk of fragility fractures. The article describes numerous risk factors that also increase the risk of tibial stress fractures, with previous stress fracture consistently the strongest predictor of subsequent stress fractures in both sexes. Assessment and management of tibial stress fractures depends on whether the anterior or posterior cortex is involved. Rehabilitation and management options are discussed to help rehabilitate this complex pathology. Ongoing studies are encouraged to improve the knowledge, awareness and attitude towards vitamin D. There is a need for a public health initiative to reduce the risk of stress fractures.

Vitamin D (25-dihydroxy Vitamin D [25(OH)D]) is both a nutrient and hormone which provides a wide variety of health benefits to human health; hence, makes it unique. Vitamin D deficiency prevails all over Indian subcontinent including both urban and rural population with a prevalence rate 70-100% in general Indian population [1]. Vitamin D deficiency leads to rickets, osteomalacia, and osteoporosis. Vitamin D also plays an important role in cardiovascular diseases, diabetes, cancer, and infectious disease such as tuberculosis.

Kidney disease has become an important co‐morbidity among human immunodeficiency virus‐infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co‐infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV‐infected patients. To evaluate the effect of co‐infection with HCV on the risk of kidney disease in HIV‐infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co‐infection is associated with increased likelihood of chronic kidney disease in HIV‐positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta‐regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta‐analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV‐infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P < 0.001) in HIV‐HCV co‐infected individuals compared with those having HIV mono‐infection. No between‐studies heterogeneity was noted (P‐value by Q test = 0.08). HCV positive serology was an independent risk factor for proteinuria; adjusted effect estimate, 1.23 (95% confidence interval, 1.18; 1.28, P = 0.001) (n = 6 studies; 26,835 unique patients). In meta‐regression, we noted the impact of ageing (P = 0.0001) upon the adjusted hazard ratio of incidence of reduced glomerular filtration rate among HCV‐HIV co‐infected patients; a negative association between frequency of males (P = 0.001) and the adjusted hazard ratio of prevalence of low glomerular filtration rate was found. Hepatitis C co‐infection is associated with a significant increase in the risk of reduced glomerular filtration rate and/or detectable proteinuria among HIV‐infected individuals. J. Med. Virol. 88:487–497, 2016. © 2015 Wiley Periodicals, Inc.

To investigate the role of Sirtuin1 in osteoporosis, Sirtuin1 was determined at the femoral neck in female patients undergoing hip operation for fractured hip or osteoarthritis. Reduced Sirtuin1 was found in osteoporotic patients. Pharmacologic activation of Sirtuin1 reduced sclerostin, an inhibitor of bone formation. Activation of Sirtuin1 may be a new direction to generate therapies for osteoporosis.