Corrigendum: Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

[This corrects the article DOI: 10.3389/ti.2022.10528.][This corrects the article DOI: 10.3389/ti.2023.12367.].

Burden of neutropenia and leukopenia among adult kidney transplant recipients: A systematic literature review of observational studies.

BACKGROUND: Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT. METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs. RESULTS: Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/µl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/µl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/µl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N. CONCLUSION: Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Outcomes among CMV-mismatched and highly sensitized kidney transplants recipients who develop neutropenia.

Limited data exist on the incidence and clinical outcomes of neutropenia among kidney transplant recipients. Our study included 572 adults who received a kidney transplant at the University of California, San Francisco Medical Center between 2012 and 2018, and were CMV-mismatched or had a PRA ≥ 80%. Recipients with HIV, Hepatitis B and C, and primary non-function were excluded. Participants were followed for at least 1 year after transplantation. Neutropenia was defined as absolute neutrophil count < 1000 cells/µl. Cox proportional hazards regression models using neutropenia as a time-varying predictor were used to determine the risk of mycophenolic acid and valganciclovir changes, rejection, hospitalizations and use of granulocyte colony stimulating factor. Models were adjusted for demographics and transplant characteristics. Mean follow-up was 3.7 (SD, 1.8) years. The mean age of the cohort was 50.4 (13.1) years, and 57.5% were female. A total of 208 (36.3%) participants had neutropenia. Neutropenia was associated with an increased risk of valganciclovir or MPA dose reductions or discontinuations [adjusted hazard ratio, aHR: 7.78, 95% CI: 4.73-12.81], rejection [aHR 2.00, 95% CI: 1.10-3.64] and hospitalizations [aHR 3.32, 95% CI: 2.12-5.19]. Neutropenia occurs frequently after kidney transplantation and leads to more medication changes and adverse clinical outcomes.

Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

Limited data exist on cytomegalovirus (CMV) antiviral treatment patterns among kidney transplant recipients (KTRs). Using United States Renal Database System registry data and Medicare claims (1 January 2011-31 December 2017), we examined CMV antiviral use in 22,878 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (85.8% of high-, 82.4% of intermediate-, and 32.1% of low-risk KTRs). Median time to prophylaxis discontinuation was 98, 65, and 61 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were high-risk status, diabetes, receipt of a well-functioning kidney graft, greater time on dialysis before KT, panel reactive antibodies ≥80%, and use of antithymocyte globulin, alemtuzumab, and tacrolimus. KTRs were more likely to discontinue CMV prophylaxis if they developed leukopenia/neutropenia, had cardiovascular disease, or received their kidney from a deceased donor. These findings suggest that adherence to the recommended duration of CMV-prophylaxis for high and intermediate-risk patients is suboptimal, and CMV prophylaxis is overused in low-risk patients.

The changing impact of cytomegalovirus among hematopoietic cell transplant recipients during the past decade: A single institutional cohort study.

BACKGROUND: With advancements in allogeneic hematopoietic cell transplantation (alloHCT), the need for cytomegalovirus (CMV) surveillance persists. METHODS: We present a retrospective analysis on the impact of CMV with preemptive therapy in 1065 alloHCT patients with donor and/or recipient CMV seropositivity from 2009 to 2019. RESULTS: Fifty-one percent developed clinically significant CMV infection (CMV-CSI); 6.5% had CMV disease. In multivariate analysis stratified by serostatus and preparative regimen, the use of anti-thymocyte globulin (hazard ratios 2.97, 95% confidence interval 2.00-4.42, p < .001) was associated with development of CMV-CSI. Median length of stay for index hospitalization was longer in patients with CMV-CSI (27 vs. 25 days, respectively; p = .002), as were rates (32.9% vs. 17.7%; p < .001) and duration (9 d vs. 6 d; p < .001) of rehospitalization, and median total inpatient days (28 d vs. 26 d; p < .001). Patients with CMV-CSI had higher rates of neutropenia (47% vs. 20%; p < .001) and transfusion support (packed red blood cell, median 5 vs. 3; p < .001; platelets, median 3 vs. 3; p < .001). CONCLUSION: Preemptive therapy does not negate the impact of CMV-CSI on peri-engraftment toxicity and healthcare utilization. This cohort represents a large single center study on the impact of CMV in the preletermovir era and serves as a real-world comparator for assessing the impact of future prophylaxis.

Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real-world evidence.

Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A comprehensive review of published literature reporting real-world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real-world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R- and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one-fourth of KTR developed CMV infection. Age and D+/R- CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management.

Impact of Preemptive Therapy for Cytomegalovirus on Hospitalizations and Cost after Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management. We examined the impact of clinically significant CMV treated with PET on inpatient length of stay (LOS), number of readmissions, and associated costs from day 0 through day 180 post-HCT. This was a retrospective study of R+ adults who underwent peripheral blood or marrow allogeneic HCT at Memorial Sloan Kettering Cancer Center between March 2013 and December 2017. Patients were routinely screened for CMV by qPCR and received PET according to institutional standards of care. Data were extracted from electronic medical records and hospital databases. Itemized cost data per patient were obtained from the Vizient database, adjusted to 2017 dollars using inflation indices. Study outcomes included HCRU evaluated by inpatient LOS and inpatient cost in patients who received PET for clinically significant CMV (PET group) compared with those who did not receive PET (no PET group) and the frequency and cost of CMV-related readmissions compared with non CMV-related readmissions. We used generalized linear models to examine the incremental HCRU and costs associated with PET controlling for other potential factors. Of 357 patients, PET was initiated in 208 (58.3%), at a median of 35 days after HCT. By day 180, 23 patients (6.4%) had developed CMV EOD and 3 (.8%) had died of CMV. Compared with the no PET group, the PET group had a longer LOS for HCT admission (P = .0276), longer total LOS by day 180 (P = .0001), a higher number of readmissions (P = .0001), a higher mean inpatient cost for HCT admission ($189,389 versus $151,646; P = .0133), and a higher total inpatient cost ($297,563 versus $205,815; P < .0001). Among PET recipients, CMV-related readmissions were associated with higher mean cost per episode compared with non CMV-related readmissions ($165,455 versus $89,419; P = .005). CMV-related readmissions comprised 40.6% of total all-cause readmissions and incurred 55.9% of total all-cause readmission costs in PET recipients. Our data show that patients treated with currently available PET had greater inpatient HCRU and cost, by day 180 compared with patients who did not receive PET. The cost of CMV-related readmissions accounted for 56% of total readmission cost among PET recipients. Future studies are needed to examine the cost-effectiveness of alternative strategies for CMV management.

The impact of intra-abdominal pressure on perioperative outcomes in laparoscopic cholecystectomy: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic cholecystectomy involves using intra-abdominal pressure (IAP) to facilitate adequate surgical conditions. However, there is no consensus on optimal IAP levels to improve surgical outcomes. Therefore, we conducted a systematic literature review (SLR) to examine outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. METHODS: An electronic database search was performed to identify randomized controlled trials (RCTs) that compared outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. A Bayesian network meta-analysis (NMA) was used to conduct pairwise meta-analyses and indirect treatment comparisons of the levels of IAP assessed across trials. RESULTS: The SLR and NMA included 22 studies. Compared with standard IAP, on a scale of 0 (no pain at all) to 10 (worst imaginable pain), low IAP was associated with significantly lower overall pain scores at 24 h (mean difference [MD]: - 0.70; 95% credible interval [CrI]: - 1.26, - 0.13) and reduced risk of shoulder pain 24 h (odds ratio [OR] 0.24; 95% CrI 0.12, 0.48) and 72 h post-surgery (OR 0.22; 95% CrI 0.07, 0.65). Hospital stay was shorter with low IAP (MD: - 0.14 days; 95% CrI - 0.30, - 0.01). High IAP was not associated with a significant difference for these outcomes when compared with standard or low IAP. No significant differences were found between the IAP levels regarding need for conversion to open surgery; post-operative acute bleeding, pain at 72 h, nausea, and vomiting; and duration of surgery. CONCLUSIONS: Our study of published trials indicates that using low, as opposed to standard, IAP during laparoscopic cholecystectomy may reduce patients' post-operative pain, including shoulder pain, and length of hospital stay. Heterogeneity in the pooled estimates and high risk of bias of the included trials suggest the need for high-quality, adequately powered RCTs to confirm these findings.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Non-adherence to basal insulin among patients with type 2 diabetes in a US managed care population: Results from a patient survey.

The aim of this study was to assess insulin non-adherence among patients with type 2 diabetes (T2DM) to better understand relationships between adherence, basal insulin (BI) usage, and patient experiences. A cross-sectional survey of patients with T2DM using BI was conducted. Adherence was measured by the Morisky Medication Adherence Scale 8-Items (MMAS-8). Low adherence (LA) was defined as MMAS-8 score < 6, high adherence (HA) as MMAS-8 score = 8, and medium adherence as MMAS-8 score = 6 to < 8. Patients with MMAS-8 scores = 6 to < 8 were excluded from the analysis. Of 400 completed surveys, 395 patients (98.8%) completed all MMAS-8 items, 112 with LA, 134 with HA. Compared with HA patients, greater proportions of LA patients followed more complex BI dosing patterns (57.1% vs. 39.5%, P = 0.014), had some difficulty calculating their correct BI dose (40.2% vs. 6.8%, P < 0.001), reported having missed ≥1 dose per month (79.3% vs. 12.6%, P < 0.001), and temporarily stopped BI in the past year (23.2% vs. 0.7%, P < 0.001). In conclusion, understanding patients' experiences with BI therapy can help formulate strategies to improve adherence.

Impact of Prostate Cancer Diagnosis on Noncancer Hospitalizations Among Elderly Medicare Beneficiaries With Incident Prostate Cancer.

OBJECTIVES: The purpose of this study was to analyze the impact of cancer diagnosis on noncancer hospitalizations (NCHs) by comparing these hospitalizations between the precancer and postcancer periods in a cohort of fee-for-service Medicare beneficiaries with incident prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the SEER-Medicare linked database for 2000 through 2010. The study cohort consisted of 57,489 elderly men (aged ≥ 67 years) with incident prostate cancer. NCHs were identified in 6 periods (t1-t6) before and after the incidence of prostate cancer. Each period consisted of 120 days. For each period, NCHs were defined as inpatient admissions with primary diagnosis codes not related to prostate cancer, prostate cancer-related procedures, or bowel, sexual, and urinary dysfunction. Bivariate and multivariate comparisons on rates of NCHs between the precancer and postcancer periods accounted for the repeated measures design. RESULTS: The rate of NCHs was higher during the postcancer period (5.1%) compared with the precancer period (3.2%). In both unadjusted and adjusted models, elderly men were 37% (odds ratio [OR], 1.37; 95% CI, 1.32, 1.41) and 38% (adjusted OR, 1.38; 95% CI, 1.33, 1.46) more likely to have any NCHs during the postcancer period compared with the precancer period. CONCLUSIONS: Elderly men with prostate cancer had a significant increase in the risk of NCHs after the diagnosis of prostate cancer. This study highlights the need to design interventions for reducing the excess NCHs after prostate cancer diagnosis among elderly men.

Vitamin B and its derivatives for diabetic kidney disease.

BACKGROUND: Diabetes is a leading cause of end-stage kidney disease (ESKD) mainly due to development and progression of diabetic kidney disease (DKD). In absence of definitive treatments of DKD, small studies showed that vitamin B may help in delaying progression of DKD by inhibiting vascular inflammation and endothelial cell damage. Hence, it could be beneficial as a treatment option for DKD. OBJECTIVES: To assess the benefits and harms of vitamin B and its derivatives in patients with DKD. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 29 October 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials comparing vitamin B or its derivatives, or both with placebo, no treatment or active treatment in patients with DKD. We excluded studies comparing vitamin B or its derivatives, or both among patients with pre-existing ESKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model. MAIN RESULTS: Nine studies compared 1354 participants randomised to either vitamin B or its derivatives with placebo or active control were identified. A total of 1102 participants were randomised to single vitamin B derivatives, placebo or active control in eight studies, and 252 participants randomised to multiple vitamin B derivatives or placebo. Monotherapy included different dose of pyridoxamine (four studies), benfotiamine (1), folic acid (1), thiamine (1), and vitamin B12 (1) while combination therapy included folic acid, vitamin B6, and vitamin B12 in one study. Treatment duration ranged from two to 36 months. Selection bias was unclear in three studies and low in the remaining six studies. Two studies reported blinding of patient, caregiver and observer and were at low risk of performance and detection bias, two studies were at high risk bias, and five studies were unclear. Attrition bias was high in one study, unclear in one study and low in seven studies. Reporting bias was high in one study, unclear in one study, and low in the remaining seven studies. Four studies funded by pharmaceutical companies were judged to be at high risk bias, three were at low risk of bias, and two were unclear.Only a single study reported a reduction in albuminuria with thiamine compared to placebo, while second study reported reduction in glomerular filtration rate (GFR) following use of combination therapy. No significant difference in the risk of all-cause mortality with pyridoxamine or combination therapy was reported. None of the vitamin B derivatives used either alone or in combination improved kidney function: increased in creatinine clearance, improved the GFR; neither were effective in controlling blood pressure significantly compared to placebo or active control. One study reported a significant median reduction in urinary albumin excretion with thiamine treatment compared to placebo. No significant difference was found between vitamin B combination therapy and control group for serious adverse events, or one or more adverse event per patient. Vitamin B therapy was reported to well-tolerated with mild side effects in studies with treatment duration of more than six months. Studies of less than six months duration did not explicitly report adverse events; they reported that the drugs were well-tolerated without any serious drug related adverse events. None of the included studies reported cardiovascular death, progression from macroalbuminuria to ESKD, progression from microalbuminuria to macroalbuminuria, regression from microalbuminuria to normoalbuminuria, doubling of SCr, and quality of life. We were not able to perform subgroup or sensitivity analyses or assess publication bias due to insufficient data. AUTHORS' CONCLUSIONS: There is an absence of evidence to recommend the use of vitamin B therapy alone or combination for delaying progression of DKD. Thiamine was found to be beneficial for reduction in albuminuria in a single study; however, there was lack of any improvement in kidney function or blood pressure following the use of vitamin B preparations used alone or in combination. These findings require further confirmation given the limitations of the small number and poor quality of the available studies.

Chronic condition combinations and health care expenditures and out-of-pocket spending burden among adults, Medical Expenditure Panel Survey, 2009 and 2011.

INTRODUCTION: Little is known about how combinations of chronic conditions in adults affect total health care expenditures. Our objective was to estimate the annual average total expenditures and out-of-pocket spending burden among US adults by combinations of conditions. METHODS: We conducted a cross-sectional study using 2009 and 2011 data from the Medical Expenditure Panel Survey. The sample consisted of 9,296 adults aged 21 years or older with at least 2 of the following 4 highly prevalent chronic conditions: arthritis, diabetes mellitus, heart disease, and hypertension. Unadjusted and adjusted regression techniques were used to examine the association between chronic condition combinations and log-transformed total expenditures. Logistic regressions were used to analyze the relationship between chronic condition combinations and high out-of-pocket spending burden. RESULTS: Among adults with chronic conditions, adults with all 4 conditions had the highest average total expenditures ($20,016), whereas adults with diabetes/hypertension had the lowest annual total expenditures ($7,116). In adjusted models, adults with diabetes/hypertension and hypertension/arthritis had lower health care expenditures than adults with diabetes/heart disease (P < .001). In adjusted models, adults with all 4 conditions had higher expenditures compared with those with diabetes and heart disease. However, the difference was only marginally significant (P = .04). CONCLUSION: Among adults with arthritis, diabetes, heart disease, and hypertension, total health care expenditures differed by type of chronic condition combinations. For individuals with multiple chronic conditions, such as heart disease and diabetes, new models of care management are needed to reduce the cost burden on the payers.

Presence of depression and its risk factors in patients with chronic obstructive pulmonary disease.

BACKGROUND & OBJECTIVES: Although depression is a significant co-morbid condition in chronic illnesses, little is known about the prevalence or risk factors for depressive symptoms in patients with chronic obstructive pulmonary disease (COPD) in India. This study was undertaken to investigate the presence and risk factors of depression in the COPD patients attending a tertiary care health facility in north India. METHODS: COPD was classified according to GOLD stages based on forced expiratory volume in one second (FEV 1 ) in 126 stable patients. Depression was examined by administering the nine-item Hindi version of Patient Health Questionnaire-9 (PHQ-9). Linear regression model was used to examine association between predictor variables and risk of depression with adjustment of age and sex. Cronbach alpha was calculated to assess internal consistency of PHQ-9. RESULTS: In the study population as whole, 33.3 per cent patients showed moderate to severe depressive symptoms whereas 20.6 per cent patients had major depressive disorder on PHQ-9 Scale. Educational and occupational status, body mass index, FEV 1, respiratory symptoms, physical impairment and dyspnoea were found to be potential predictors of depression in COPD patients. INTERPRETATION & CONCLUSIONS: One fifth of the patients with COPD had severe symptoms of related to depression, which was especially higher with severity of COPD. Hence, the patients with COPD should focus on management of these two conditions. Further, future studies should be conducted to assess the role of depression management and timely treatment of it in patients with COPD.

Real-World Outcomes Associated With Letermovir Use for Cytomegalovirus Primary Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Systematic Review and Meta-analysis of Observational Studies.

Background: A systematic review and meta-analysis of real-world observational studies was conducted to summarize the impact of letermovir cytomegalovirus (CMV) primary prophylaxis (PP) among adult allogeneic hematopoietic cell transplant (allo-HCT) recipients. Methods: Systematic searches in Medline/PubMed, Embase, and conferences (from database inception to October 2021) were conducted to identify studies for inclusion. Random-effects models were used to derive pooled estimates on the relative effectiveness of letermovir PP compared to controls. Results: Forty-eight unique studies (N = 7104 patients) were included, most of which were comparative, single-center, and conducted in the United States. Letermovir PP was associated with statistically significant reduction in odds of CMV reactivation (pooled odds ratio [pOR], 0.13 and 0.24; P < .05), clinically significant CMV infection (pOR, 0.09 and 0.19; P < .05), and CMV disease (pOR, 0.31 and 0.35; P < .05) by day +100 and day +200 after allo-HCT, respectively. Letermovir PP was associated with significantly lower odds of all-cause (pOR, 0.73; P < .01) and nonrelapse mortality (pOR, 0.65; P = .01) beyond day 200 after allo-HCT. Conclusions: Letermovir for CMV PP was effective in reducing the risk of CMV-related complications overall and mortality beyond day 200 among adult allo-HCT recipients.

Drug-induced Stevens-Johnson syndrome: case series from tertiary care centre in Gujarat.

PURPOSE: The aims of the present article were to study clinical features and to analyse them in different drug class associated with Stevens-Johnson syndrome (SJS) in a tertiary care hospital in Gujarat, India. MATERIALS AND METHODS: A prospective hospital-based study was carried out over a period of 3 years (June 2007 to September 2009) at Sheth Vadilal Hospital, Ahmedabad, India. The diagnosis of SJS was made mainly on the basis of the clinical findings, which included extensive erythema multiforme, purpuric lesions with bullae and detachment of skin involving at least two mucous membranes. Further, in each patient suspected with SJS, various laboratory tests such as complete blood count, liver function tests, metabolic panel, chest X-ray and other serological test were carried out. SJS was confirmed on the basis of most widely accepted Bastuji-Garin definition. Causality assessment was performed using the Naranjo scale. Only 'probable' and 'definite' reactions were included. RESULTS: Antibacterials for systemic use, anti-inflammatory and antirheumatic products and antiepileptics were the drug classes most commonly associated (8 of 29 cases, each) with SJS. Individually, ibuprofen was involved in the highest number of cases (five cases, 17.2%), followed by carbamazepine (four cases, 13.8%) . The mean duration of developing SJS symptoms was 15.9 days (SD = 8.7 days) and improvement after treatment was 14.2 days (SD = 4.6 days). The duration of appearing SJS symptoms varied significantly between different classes of drugs (p < 0.001). The appearance of SJS symptom started within 10 days for anti-inflammatory and antibacterial compared with 24 days of antiepileptic agents. All the patients with antiepileptic agent-induced SJS had 7% to 9% of detached body surface area. In two patients, SJS progressed to toxic epidermal necrolysis and of which one led to death and the other developed long-term complication of conjunctival xerosis. A total of six patients developed long-term complications: four patients had conjunctival synechia, one patient had conjunctival xerosis and one patient had urethral stricture. CONCLUSION: More than 80% of the SJS events were induced by antibacterial, anti-inflammatory and antiepileptic agents with same frequency. The duration of the appearance of SJS symptoms significantly varied between different drug classes and started within 10 days for anti-inflammatory and antibacterial compared with 24 days of antiepileptic agents.

Statins for women with polycystic ovary syndrome not actively trying to conceive.

BACKGROUND: Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects. OBJECTIVES: To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive. SEARCH STRATEGY: We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors performed data collection and analysis independently. MAIN RESULTS: Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS: Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.

Antiviral treatment approaches for cytomegalovirus prevention in kidney transplant recipients: A systematic review of randomized controlled trials.

Various CMV anti-viral (AV) preventive strategies have been utilized in KTRs. We examined efficacy, safety and costs of CMV-AV prevention strategies in KTRs using a systematic literature review (SLR) of randomized controlled trials (RCTs) publications indexed in MEDLINE and Embase (from inception to November 2018). Thirty RCTs met inclusion criteria with 22 unique AV preventive strategies. Prophylaxis was associated with significantly lower rates of CMV infection/disease (CMVi/d) compared to no prophylaxis (pooled odds ratio, pOR with 95% confidence interval (CI): CMVi: 0.33; 0.19, 0.57; CMVd: 0.27; 0.19; 0.39). Preemptive therapy (PET) had lower rates of CMVd (0.29; 0.11, 0.77), and medical costs compared to no PET. Prophylaxis had significantly lower rates of early CMVi/d, and higher rates of late CMVi and hematological adverse events (leukopenia, 2.93; 1.22, 7.04), and similar overall medical costs compared to PET. Studies involving head-to-head comparison of different prophylaxis approaches showed mixed findings with respect to optimum dose, duration and route of administration on CMV outcomes. Although there was heterogeneity across populations and interventions, both prophylaxis and PET strategies reduced CMVi/d compared to no prophylaxis/PET and had differential safety profile in terms of hematological adverse events. For comprehensiveness we did not limit study inclusion based on date; the wide time-period may have contributed to the heterogeneity in prevention approaches which subsequently made pooling studies a challenge. Despite demonstrated efficacy of prophylaxis/PET, our findings highlight the potential need of a novel intervention with a better safety profile and perhaps improved outcomes.

National Trends in Diabetes Medication Use in the United States: 2008 to 2015.

BACKGROUND: Data on trends of diabetes medications use are sparse, outdated, and limited to prescription data. We determined trends in diabetes medication use among US individuals with diabetes during 2008-2015. METHODS: We used 2008-2015 Medical Expenditure Panel Survey to examine diabetes medication utilization among individuals aged ≥18 years with diabetes. Prescription medications were classified based on therapeutic class and subclass using Multum Lexicon database. RESULTS: From 2008 to 2015, use of any diabetes medication (81.4% vs. 87%), metformin (47.8% vs. 59.0%), and insulin (23.0% vs. 31.0%) increased, whereas, use of sulfonylurea (36.0% vs. 29.0%) and thiazolidinedione (21% vs. 9.0%) declined. A linear increase was observed in the uptake of dipeptidyl peptidase-4 (DPP-4) inhibitors from 6.2% in 2008 to 12.4% in 2015; glucagon-like peptide-1 (GLP-1) receptor agonists from 2.5% in 2008 to 4.4% in 2015 and sodium glucose transporter-2 (SGLT2) inhibitors from 0.8% in 2014 (the first SGLT2 inhibitors approval year) to 4.4% in 2015. Monotherapy use increased from 50.6% to 56.4% during 2008-2015, while triple therapy use declined. CONCLUSIONS: Metformin, insulin and sulfonylureas remained the top-three prescribed classes of diabetes medications. Increased use of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors was offset by decline in TZDs use.