Hepatitis C virus increases the risk of kidney disease among HIV-positive patients: Systematic review and meta-analysis.

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.

The pathophysiology, diagnosis, and management of foot stress fractures.

INTRODUCTION: There is an increasing prevalence of osteoporosis, and with it a rise in the diagnosis of stress fractures. Postmenopausal women are particularly at risk of stress fractures. This review article describes the pathophysiology of foot stress fractures and the latest diagnostic and treatment strategies for these common injuries. DISCUSSION: There are numerous risk factors for stress fractures that have been identified in the literature. Reduced bone mineral density is an independent risk factor for delayed union. Prevention of stress fractures with training periodization and nutritional assessment is essential, especially in females. Diagnosis of stress fractures of the foot is based on history and diagnostic imaging, which include radiographs, ultrasound, therapeutic ultrasound, computed tomography, and bone scans; however, magnetic resonance imaging is still the gold standard. Treatment depends on the bone involved and the risk of nonunion, with high-risk fractures requiring immobilization or surgical intervention. Patients presenting with underlying bone mineral deficiency treated without surgery require a longer period of activity modification. Training rehabilitation protocols are described for those with low-risk stress fractures. RESULTS: A useful algorithm is presented to guide the clinician in the diagnosis and management of such injuries.

Surveillance of mosquitoes harnessing their buzzing sound.

Mosquito surveillance for vector-borne disease management relies on traditional morphological and molecular techniques, which are tedious, time-consuming, and costly. The present study describes a simple and efficient recording device that analyzes mosquito sound to estimate species composition, male-female ratio, fed-unfed status, and harmonic convergence interaction using fundamental frequency (F0) bandwidth, harmonics, amplitude, and combinations of these parameters. The study examined a total of 19 mosquito species, including 3 species of Aedes, 7 species of Anopheles, 1 species of Armigeres, 5 species of Culex, 1 species of Hulecoetomyia, and 2 species of Mansonia. Among them, the F0 ranges between 269.09 ± 2.96 Hz (Anopheles culiciformis) to 567.51 ± 3.82 Hz (Aedes vittatus) and the harmonic band (hb) number ranges from 5 (An. culiciformis) to 12 (Ae. albopictus). In terms of species identification, the success rate was 95.32 % with F0, 84.79 % with F0-bandwidth, 84.79 % with harmonic band (hb) diversity, and 49.7 % with amplitude (dB). The species identification rate has gone up to 96.50 % and 97.66 % with the ratio and multiplication of F0 and hb, respectively. This is because of the matrices that combine multiple sound attributes. Comparatively, combinations of the amplitude of the F0 and the higher harmonic frequency band were non-significant for species identification (60.82 %). The fed females have shown a considerable increase in F0 in comparison to the unfed. The males of all the species possessed significantly higher frequencies with respect to the females. Interestingly, the presence of male-female of Ae. vittatus together showed harmonic convergence between the 2nd and 3rd harmonic bands. In conclusion, the sound-based technology is simple, precise, and cost-effective and provides better resolution for species, sex, and fed-unfed status detection in comparison to conventional methods. Real-time surveillance of mosquitoes could potentially utilize this technology.

Antiviral therapy of symptomatic HCV-associated mixed cryoglobulinemia: meta-analysis of clinical studies.

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia. Evidence on HCV-related mixed cryoglobulinemia in the non-transplantation setting exists even if its appropriate management remains unclear. The cornerstone of treatment for symptomatic HCV-associated mixed cryoglobulinemia is antiviral therapy but little is known about its activity. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to assess efficacy and safety of combination antiviral therapy for symptomatic HCV-associated mixed cryoglobulinemia in non-immunosuppressed individuals. The random effects model of DerSimonian and Laird was used, with heterogeneity and sensitivity analyses. The primary outcome was sustained virological response (as a measure of efficacy), and the secondary outcome was the rate of patients stopping (or dose reducing) antiviral agents (as a measure of tolerability). Ten clinical studies (300 unique patients) were identified; the rate of baseline kidney involvement ranged between 4% and 39%. The summary estimate of frequency of sustained viral response was 0.42 with a 95% confidence interval (CI) of 0.31; 0.54 (random effects model). Significant heterogeneity occurred (P = 0.00001; I(2) = 77.6%). Stratified analysis showed higher efficacy in those studies using combination therapy with pegylated-than conventional IFN; the summary estimate of sustained viral response being 0.52 (95% CI, 0.40; 0.63) and 0.32 (95% CI, 0.15; 0.49), respectively. There was good association between viral and clinical response, weighted K 0.634 (95% CI, 0.455; 0.814), by a meta-analysis at individual level on a subset of reports (n = 3; 74 unique patients). The summary estimate of frequency of patients stopping (or dose reducing) antiviral agents was 0.15 (95% CI, 0.08; 0.21); no heterogeneity occurred (P = 0.05; I(2) = 51%). In summary, combination antiviral therapy (pegylated IFN plus ribavirin) gives satisfactory response in more than the half of patients with symptomatic mixed cryoglobulinemia associated with HCV. HCV-related mixed cryoglobulinemia is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed to evaluate efficacy and safety of antiviral therapy in non-immunosuppressed individuals.

The Third Gender in a Third World Country: Major Concerns and the "AIIMS Initiative".

With a population dividend of around 1.3 billion, India is the largest democracy in the world that encompasses "unity in diversity". The kaleidoscope of the socio-cultural fabric comprises the transgender population too, which has a historical context dating back millennia and also plays a vital role as described in Hindu scriptures. The Indian transgender person's community shows a variety of gender identities and sexual orientations, which is unlikely from the West, forming a culturally unique gender group. In India, transgender persons were recognised as the 'third gender' in 2014. The third gender population of India is marginalised to a great extent in every sector. Often, transgender persons have been the subjects of sociology, psychology, and health issues. There was a dearth of data regarding their major health problems including bone health, which has not been reported in India and elsewhere before this study. Through a prospective cross-sectional study design, we aimed to determine the current health status of transgender persons with a special emphasis on bone health. Descriptive statistics were used for data analysis. The preliminary results of the study show poor bone health in the transgender population of India. The majority of transgender persons have low bone mineral density (BMD) at a much young age, even before the achievement of their peak bone mass. The health status of the transgender population in India is poor overall. Transgender persons have many impediments to optimal healthcare that requires holistic care. This study presents the current health challenges of the transgender population with a special emphasis on their bone health status as 'AIIMS initiative'. This study also shows transgender persons human rights needs to be explicitly discussed. The stakeholders of social policies require an urgent attention to unfold the major concerns encompassing transgender persons.

Erythropoietin use and immunogenicity of hepatitis B virus vaccine in chronic kidney disease patients: a meta-analysis.

BACKGROUND: It is known that the immunogenicity of hepatitis B virus (HBV) vaccine is lower in uremic patients than healthy subjects. Numerous inherited or acquired factors have been implicated in this lowered response, and the high frequency of recombinant human erythropoietin use among patients on maintenance dialysis has been suggested to play a pivotal role. However, the impact of therapy with recombinant erythropoietin on the immune response to HBV vaccine in patients with chronic kidney disease (CKD) is not appropriately detailed. AIM: To evaluate the influence of human recombinant erythropoietin therapy on the immunological response to HBV vaccine in CKD patients by performing a systematic review of the literature with a meta-analysis of clinical studies. METHODS: We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titers at completion of a hepatitis B vaccine schedule among human erythropoietin users versus those who did not receive the drug in a CKD population. RESULTS: We identified 11 studies involving 862 unique patients with CKD. Aggregation of study results did not show a significant increase in response rates among erythropoietin user versus non-user patients (pooled odds ratio = 1.431; 95% CI 0.954; 2.146), according to a random-effects model. No heterogeneity was found, the p value was 0.1 for our test of study heterogeneity (Q = 14.147). Stratified analysis in various subgroups of interest did not significantly change these findings. CONCLUSIONS: Our meta-analysis showed no link between immunological response to HBV vaccine and therapy with human recombinant erythropoietin among individuals on long-term dialysis. We suggest the use of recombinant vaccine towards hepatitis B in patients on regular dialysis irrespective of erythropoietin treatment.

Meta-analysis: the impact of nutritional status on the immune response to hepatitis B virus vaccine in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) typically show a diminished immune response to hepatitis B virus (HBV) vaccine compared with individuals with intact kidney function. A number of inherited or acquired factors have been implicated in this suboptimal response. Patients with chronic kidney disease frequently have a compromised nutritional status; however, the impact of malnutrition on the immune response to hepatitis B virus vaccine in chronic kidney disease patients remains unclear. AIM: To evaluate the influence of nutrition status on the immune response to HBV vaccine in CKD population by performing a systematic review of the literature with a meta-analysis of clinical studies. METHODS: Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates of impaired vaccine response across the published studies. The risk of poor serological response to HBV vaccine in chronic kidney disease population according to nutritional parameters was regarded as the most reliable outcome end-point. Only studies performing multivariate analysis in order to make adjustments for potential confounders were included. RESULTS: We identified seven studies (15,172 unique patients with CKD). The serum protection rate after a full course of recombinant or plasma-derived vaccine towards HBV ranged between 40 and 86%. Aggregation of study results showed an independent and adverse effect of poor nutrition status, as mostly detected by serum albumin levels, on the protection rate after HBV vaccine course; the summary estimate for adjusted RR was 1.50 with a 95% confidence interval (CI) of 1.02, 2.21; R( i ) = 0.01 (random-effects model). The P value for study heterogeneity was significant (Q = 0.0001). In the subgroup of patients who received HBV recombinant vaccine, the relative risk of impaired serological response after HBV vaccination was 1.63 (95% CI, 1.08, 2.45), R( i ) = 0.90, Q = 0.00001, with poor nutritional parameters at baseline. CONCLUSIONS: An increased risk exists of impaired serologic response to HBV vaccine response among chronic kidney disease patients having poor nutrition status. Additional studies are needed to understand better the mechanisms underlying the relationship between nutritional status and serological response to HBV vaccine among patients with CKD.

Lack of secondary hyperparathyroidism in sub-group of vitamin D deficient postmenopausal women: Is VDR gene polymorphism behind this mystery?

BACKGROUND AND AIMS: We aimed to determine the cause of non-secondary hyperparathyroidism (Non-SHPT) in Indian postmenopausal women. MATERIALS & METHODS: 334 apparently healthy postmenopausal women were assessed for bone mineral homeostaisis including Vitamin D, PTH and VDR polymorphism. RESULTS: 83% of the subjects had vitamin D deficiency further associated with VDR gene polymorphism (P 0.000). A sizable number of subjects (N = 83) did evoke SHPT despite low vitamin D levels. We observe that VDR gene polymorphism was strongly associated in the sub-group of non-SHPT. CONCLUSION: lack of SHPT warrants researchers to study the pathophysiology of non-SHPT in detail to substantiate our findings.

A high speed electro-optic phase shifter based on a polymer-infiltrated P-S-N diode capacitor.

A polymer-infiltrated P-S-N diode capacitor configuration is proposed and a high speed electro-optic phase shifter based on a silicon organic hybrid platform is designed and modeled. The structure enables fast carrier depletion in addition to the second order nonlinearity so that a large electro-optic overlapped volume is achievable. Moreover, the device speed can be significantly improved with the introduction of free carriers due to a reduced experienced transient capacitance. The advantages of the diode capacitor structure are highly suitable for application to a class of low aspect ratio slot waveguides where the RC limitation of the radio frequency response is minimized. According to our numerical results, by optimizing both the waveguide geometry and polarization mode, at least 269 GHz 3-dB bandwidth with high efficiency of 5.5 V-cm is achievable. More importantly, the device does not rely on strong optical confinement within the nano-slot, a feature that gives considerable tolerance in the use of nano-fabrication techniques. Finally, the high overlap and energy efficiency of the device can be applied to slow light or optical resonance media for realizing photonic integrated circuits-based green photonics.

Pre-transplant kidney function predicts chronic kidney disease after liver transplant: meta-analysis of observational studies.

BACKGROUND: Chronic kidney disease is a common problem in long-term survivors after liver transplantation. Several studies to clarify the risk factors for incidence of chronic kidney disease among liver transplant recipients, including preoperative kidney function, have yielded conflicting results. AIM: The aim of this study was to conduct a systematic review of the published medical literature on the impact of pre-transplant kidney function on the occurrence of chronic kidney disease after liver transplantation. METHODS: Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for incidence of chronic kidney disease across the published studies. The relative risk of chronic kidney disease after liver transplantation according to pre-transplant glomerular filtration rate was regarded as the most reliable outcome end-point. RESULTS: We identified seven studies (38,036 unique liver transplant recipients). A stratified analysis including only studies provided with glomerular filtration rate at transplant reported that the summary estimate of relative risk and 95% confidence intervals (CIs) for developing chronic renal failure among liver transplant recipients with diminished renal function at transplant was 2.12 (95% CI, 1.01; 4.46) (random-effects model). The p value for study heterogeneity was significant (p = 0.0001). Post-transplant chronic kidney disease shows impact on survival; the summary estimate for the adjusted relative risk of all-cause mortality with chronic kidney disease after liver transplant was 4.35 (95% confidence Intervals, 3.34; 5.66), p = 0.0001 (random-effects model). CONCLUSIONS: An increased risk of chronic kidney disease frequently exists among liver transplant recipients with reduced renal function at transplant. The occurrence of chronic kidney disease after liver transplantation has a major impact on mortality. Additional studies are needed to understand better the natural history of chronic kidney disease among liver transplant recipients.

Sofosbuvir-based regimens for HCV in stage 4-stage 5 chronic kidney disease. A systematic review with meta-analysis.

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.

Hepatitis B virus vaccine and chronic kidney disease. The advances.

BACKGROUND: 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. STUDY AIMS AND DESIGN: 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. RESULTS: 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; 40mcg 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%. CONCLUSIONS: 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 (<10IU/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.

Hepatitis B virus vaccine and chronic kidney disease. The advances.

BACKGROUND: 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. STUDY AIMS AND DESIGN: 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. RESULTS: 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; 40mcg 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%. CONCLUSIONS: 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 (<10IU/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.

Prime factorization using quantum variational imaginary time evolution.

The road to computing on quantum devices has been accelerated by the promises that come from using Shor's algorithm to reduce the complexity of prime factorization. However, this promise hast not yet been realized due to noisy qubits and lack of robust error correction schemes. Here we explore a promising, alternative method for prime factorization that uses well-established techniques from variational imaginary time evolution. We create a Hamiltonian whose ground state encodes the solution to the problem and use variational techniques to evolve a state iteratively towards these prime factors. We show that the number of circuits evaluated in each iteration scales as [Formula: see text], where n is the bit-length of the number to be factorized and d is the depth of the circuit. We use a single layer of entangling gates to factorize 36 numbers represented using 7, 8, and 9-qubit Hamiltonians. We also verify the method's performance by implementing it on the IBMQ Lima hardware to factorize 55, 65, 77 and 91 which are greater than the largest number (21) to have been factorized on IBMQ hardware.

Impact of COVID-19 outbreak on lifestyle behaviour: A review of studies published in India.

BACKGROUND AND AIMS: The entire globe is undergoing an unprecedented challenge of COVID-19 which has affected the lifestyle behaviour of individuals. The present review is an attempt to summarize the effect of pandemic COVID-19 on lifestyle behaviour among the Indian population. METHODS: A review was carried out to summarize the effect of pandemic COVID-19 on lifestyle behaviour focusing on changes in dietary or eating behaviour, stress, sleep pattern, and level of physical activity among the Indian population. Literature searches were conducted in PubMed and Google Scholar from inception till October 2020 to identify all relevant studies. RESULTS: A total of 11 studies (n = 5957, age group 18-70 years, comprising both genders) consisting of 1 hospital and 10 community based, were included in the present review. A change in lifestyle behaviour was observed due to COVID-19. Psychosocial or any kind of mental stress among the participants was found to be prevalent. Weight gain and decline in physical activity were also observed. Not only sleep quantity but sleep quality was also found to be affected due to COVID-19. CONCLUSION: The present review indicates the need for lifestyle behaviour programmes via using the platform of E-media and also for the dissemination of health education.

COVID-19 infection, inception and immunity: Observations and recommendations in the light of vitamin D?

Responsive immunity plays an important role fighting against infections. Worldwide, Vitamin D deficiency is a major concern not only for musculoskeletal health but also affecting the immunity status in population. Amidst COVID-19 pandemic, it is imperative to establish the role of vitamin D in destruction of pathogens. Vitamin D awareness program at school level might be an effective health governance policy to educate populations for the importance of vitamin D in overall health.

"Association of Leptin with Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis".

BACKGROUND: Serum leptin has been considered as an important measurable diagnostic and prognostic biomarker for polycystic ovarian syndrome (PCOS), although its evidence for use in clinical practice is limited. We aim to synthesize the available evidence on the clinical use of serum leptin values in PCOS by doing a systematic review and meta-analysis of studies. OBJECTIVE: To conduct a meta-analysis to determine the pooled effect size of the association of leptin levels in patients with PCOS. METHODS: We searched electronic databases, i.e., PubMed, Google Scholar, Web of Science, ClinicalTrials.gov, and Medline from inception to September 2020, keeping filters for human studies and published in the English language. We used the random-effects model if heterogeneity between the studies was > 50%; otherwise, a fixed-effect model was applied to determine the standardized mean difference with 95% CI for comparison of leptin level between cases and controls. All the statistical analyses were completed using software STATA version 13. RESULTS: The meta-analysis included a total of 35 studies involving 2015 cases and 1767 controls that suggested statistically significantly higher leptin levels in the women with PCOS as compared to controls (SMD, 1.76, 95% CI 1.28 to 2.23, P < 0.001). In the stratified analysis when only high methodological quality studies were included, we did not observe a statistically significant difference in the leptin level between PCOS and controls (SMD 0.68, 95% CI -0.09 to 1.46). Analysis restricted to low methodological quality studies observed statistically significant high leptin levels in PCOS women as compared to controls (SMD 2.24, 95% CI 1.65 to 2.83). CONCLUSION: The available evidence suggests that elevated leptin levels may be associated with risk of PCOS as compared to controls; however, failure to observe the similar association in high methodological quality studies demands further well-designed adequately powered studies to validate the findings.

Pegylated interferon monotherapy of chronic hepatitis C in dialysis patients: Meta-analysis of clinical trials.

The efficacy and safety of pegylated interferon monotherapy in patients with chronic renal failure and chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. A systematic review of the literature with a meta-analysis of clinical trials was performed in order to assess efficacy and safety of initial pegylated interferon monotherapy in chronic renal failure patients with chronic hepatitis C. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). The random effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen clinical trials (254 unique patients) were identified, five (31%) being controlled studies; the majority (15/16 = 94%) regarded patients on long-term dialysis. The summary estimate for sustained virological response and drop-out rate was 33% [95% Confidence Intervals (95%CI) 24-43] and 23% (95%CI, 14-33), respectively. The most frequent side-effects requiring interruption of treatment were haematological (18%) and gastrointestinal (14%). In the group of controlled clinical trials, the summary estimate for sustained viral response and drop-out rate was 38% (95% CI, 18-59), and 15% (95% CI, 3-26), respectively. The studies were heterogeneous with regard to sustained virological response and drop-out rate. Pegylated IFN does not provide an added benefit in terms of virological response in comparison with standard IFN monotherapy. Tolerance to pegylated-IFN monotherapy was unsatisfactory. Prospective trials are in progress to assess the optimal antiviral therapy for chronic hepatitis C in dialysis patients.

Therapy with nucleos(t)ide analogues: current role in dialysis patients.

Hepatitis B virus (HBV) infection persists among patients undergoing maintenance dialysis in the industrialized world. Knowledge of the epidemiology and the natural history of HBV infection in dialysis patients has markedly improved but antiviral therapy for hepatitis B remains a significant challenge in this population. A variety of therapeutic options are now available for the treatment of chronic hepatitis B, including potent new nucleos(t)ide analogues, along with standard and pegylated interferon. The most extensive experience in the dialysis population has been with lamivudine. Although several questions about lamivudine use in dialysis patients remain unanswered, it has shown potent antiviral activity: the range of clearance of HBV viremia (HBV DNA) from serum is between 56% and 100% in dialysis patients with chronic hepatitis B. Its major limitation is emergence of resistance. Tolerance to conventional or pegylated interferon monotherapy is poor in the dialysis population. There is limited data regarding adefovir dipivoxil (ADV) therapy in the dialysis population, while very little information is available about the use of the newer agents, tenofovir and entecavir, in patients with renal failure. It is recommended that dialysis patients with persistent HBsAg seropositive status be evaluated for antiviral treatment and that the decision to treat be based on the potential benefits and risks of therapy including life expectancy, candidacy for kidney transplantation, and comorbidities. Hepatitis B is relatively uncommon among patients undergoing dialysis in developed countries and this clearly hampers prospective clinical trials aimed to evaluate the efficacy and safety of therapy with nucleos(t)ide analogues for chronic hepatitis B in this population.

The impact of antiviral therapy for HCV on kidney disease: a systematic review and meta-analysis.

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.