Switch to a raltegravir-based antiretroviral regimen in people with HIV and non-alcoholic fatty liver disease: A randomized controlled trial.

INTRODUCTION: The effect of antiretroviral therapy (ART), particularly integrase strand transfer inhibitors (INSTIs), on non-alcoholic fatty liver disease (NAFLD) in people with HIV remains unclear. We evaluated the effect of switching non-INSTI backbone antiretroviral medications to raltegravir on NAFLD and metabolic parameters. MATERIALS AND METHODS: This was a single-centre, phase IV, open-label, randomized controlled clinical trial. People living with HIV with NAFLD and undetectable viral load while receiving a non-INSTI were randomized 1:1 to the switch arm (raltegravir 400 mg twice daily) or the control arm (continuing ART regimens not containing INSTI). NAFLD was defined as hepatic steatosis by controlled attenuation parameter ≥238 dB/m in the absence of significant alcohol use and viral hepatitis co-infections. Cytokeratin 18 was used as a biomarker of non-alcoholic steatohepatitis. Changes over time in outcomes were quantified as standardized mean differences (SMDs), and a generalized linear mixed model was used to compare outcomes between study arms. RESULTS: A total of 31 people with HIV (mean age 54 years, 74% male) were randomized and followed for 24 months. Hepatic steatosis improved between baseline and end of follow-up in both the switch (SMD -43.4 dB/m) and the control arm (-26.6 dB/m); the difference between arms was not significant. At the end of follow-up, aspartate aminotransferase significantly decreased in the switch arm compared with the control arm (SMD -9.4 vs. 5.5 IU/L). No changes in cytokeratin 18, body mass index, or lipids were observed between study arms. DISCUSSION: Switching to a raltegravir-based regimen improved aspartate aminotransferase but seemed to have no effect on NAFLD, body weight, and lipids compared with remaining on any other ART.

Sex differences in the perception of cardiovascular risk in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH), a common genetic condition, is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Recent data indicate an undertreatment of females with FH. OBJECTIVE: To characterize the role of sex in the perception of FH, its associated ASCVD risk and treatment. METHODS: A survey investigating for sex differences in the perception of FH was sent to 1073 patients with FH using a cross sectional study design. RESULTS: A total of 412 patients (51.9 % male) responded to the survey; mean age was 56.2 ± 14.4 years. There was a higher proportion of males with ASCVD than females (41.5 % vs. 16.5 %, respectively, p<0.001). Analyses of the survey responses showed that a majority of both males and females agreed that their risk of ASCVD is higher than healthy individuals of same age (70.8 % vs. 74.7 %, respectively, p = 0.434). Females were more concerned about having high LDL-C levels (67.5 % vs. 56.5 % in males, p = 0.024), especially those in secondary prevention programs. As for treatment of FH, approximately 75 % of both sex groups considered statins to be efficient in reducing the risk of myocardial infarction, but less than half of the females considered statins to be safe (44.8 % vs. 60.0 % in males, p = 0.003). No major sex differences were noted regarding the influence of the doctor in their understanding of FH as a disease. CONCLUSION: Overall, both males and females with FH were well informed about FH, although females were more concerned about having high LDL-C levels and they feared the safety of statins.

Increased Serum Fibroblast Growth Factor 23 Predicts Mortality in People With HIV/HCV Coinfection.

BACKGROUND: People with HIV and hepatitis C virus (HCV) coinfection experience excess mortality because of multiple causes. Identification of biomarkers associated with mortality beyond that attributable to liver fibrosis may be relevant for prognostication. Fibroblast growth factor 23 (FGF23), a phosphotropic hormone, predicts adverse outcomes in several chronic conditions. We aimed to investigate whether elevated FGF23 predicts all-cause mortality in patients with HIV/HCV coinfection. METHODS: We included patients with HIV/HCV coinfection from the Canadian Coinfection Cohort with available serum FGF23, fibrosis biomarker fibrosis-4 (FIB-4), and at least 1-year follow-up. Elevated FGF23 and advanced liver fibrosis were defined as FGF23 > 241 reference unit/mL and FIB-4 > 3.25, respectively. All-cause mortality was analyzed using survival analysis. The effect of advanced liver fibrosis as a mediator on mortality was estimated by mediation analysis. RESULTS: Three hundred twenty-one patients were included (24% with elevated FGF23, 19% with advanced liver fibrosis). During a mean follow-up period of 8.4 years, 34% of the cohort died. The incidence rate of all-cause mortality was higher in patients with elevated FGF23 (66.1 per 1000 person-years, 95% confidence interval 45.8 to 92.3) relative to patients without elevated FGF23 (37.5 per 1000 person-years, 95% confidence interval 29.6 to 46.9). After adjusting for potential confounders, elevated FGF23 was associated with significant direct and indirect effects (mediated through advanced liver fibrosis) on all-cause mortality, with 57% of deaths not mediated through advanced fibrosis. CONCLUSIONS: In patients with HIV/HCV coinfection, FGF23 may be used as prognostic biomarker for risk stratification accounting also for death causes other than those attributable to liver fibrosis.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

Fibroscan-Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. METHODS: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. RESULTS: Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14-1.29]), hypertension (aOR, 2.24 [95% CI, 1.16-4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20-2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02-4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5-4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2-77.7] vs 5.0 [95% CI, 2.9-8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97-12.51]). Conversely, FAST did not predict extrahepatic events. CONCLUSIONS: A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.

Fear of cancer recurrence therapy (FORT): A randomized controlled trial.

OBJECTIVE: Most fear of cancer recurrence (FCR) interventions have small effects, and few target FCR. This randomized controlled trial (RCT) with breast and gynecological cancer survivors evaluated the efficacy of a cognitive-existential fear of recurrence therapy (FORT) compared to an attention placebo control group (living well with cancer [LWWC]) on FCR. METHOD: One hundred and sixty-four women with clinical levels of FCR and cancer distress were randomly assigned to 6-weekly, 120 min FORT (n = 80) or LWWC (n = 84) group sessions. They completed questionnaires at baseline (T1), posttreatment (T2; primary endpoint), 3 (T3), and 6 months (T4) posttreatment. Generalized linear models were used to compare group differences in the fear of cancer recurrence inventory (FCRI) total score and secondary outcomes. RESULTS: FORT participants experienced greater reductions from T1 to T2 on FCRI total with a between-group difference of -9.48 points (p = .0393), resulting in a medium effect of -0.530, with a maintained effect at T3 (p = .0330) but not at T4. For the secondary outcomes, improvements were in favor of FORT, including FCRI triggers (p = .0208), FCRI coping (p = .0351), cognitive avoidance (p = .0155), need for reassurance from physicians (p = .0117), and quality of life (mental health; p = .0147). CONCLUSIONS: This RCT demonstrated that FORT, compared to an attention placebo control group, resulted in a greater reduction in FCR posttreatment and at 3 months posttreatment in women with breast and gynecological cancer, indicating its potential as a new treatment strategy. We recommend a booster session to sustain gains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Usefulness of MRI-Based Local Surveillance After Surgical Treatment of Musculoskeletal Soft-Tissue Sarcomas: A Systematic Review and Meta-Analysis.

BACKGROUND. The value of routine MRI follow-up after surgical treatment of musculoskeletal soft-tissue sarcoma (STS) is controversial. OBJECTIVE. The purpose of this study was to evaluate the usefulness of MRI-based surveillance for musculoskeletal STS represented by the proportion of local recurrences (LRs) discovered by MRI versus clinically, stratified by imaging surveillance intensity; the characteristics of LRs detected on imaging versus clinically; and the impact of imaging surveillance on survival. EVIDENCE ACQUISITION. Multiple electronic databases were searched systematically for articles published through November 28, 2022, about controlled trials and cohort studies on the usefulness of MRI-based surveillance for musculoskeletal STS. The risk of bias was assessed using an adapted Newcastle-Ottawa scale. Random-effects meta-analyses of the proportion of LRs discovered by MRI as opposed to clinically were conducted. The association of low- versus high-intensity surveillance with the proportion of LR detected on MRI was assessed with a chi-square test of subgroup differences; for this latter assessment, high intensity was defined as at least one local surveillance imaging examination for low-risk tumors and at least three imaging examinations for high-risk tumors during the first 2 posttreatment years. EVIDENCE SYNTHESIS. A total of 4821 titles and abstracts were identified, and 19 studies were included. All studies were retrospective cohorts. There was substantial variability in follow-up approaches. The risk of bias was moderate in 32% and high in 68% of studies. The pooled proportion of LRs detected on MRI was 53% (95% CI, 36-71%) with high-intensity surveillance and 6% (95% CI, 3-9%) with low-intensity surveillance (p < .01). Comparison of LR characteristics (LR size, depth, grade, location, resection margins) detected on imaging versus clinically identified inconsistent results between studies. Trends toward better survival for imaging-detected LRs or more frequent imaging use were noted in four studies. CONCLUSION. When used at a high intensity, MRI-based surveillance can detect many clinically occult LRs, although the studies are small, occasionally yielded conflicting results, and are often of poor quality. A survival benefit could be associated with imaging use, but further research is needed to evaluate the causality of any observed survival differences. CLINICAL IMPACT. MRI-based surveillance after surgical treatment of musculoskeletal STS is useful to detect clinically occult LRs and could improve patient outcomes.

Evaluating the impact of COVID-19 on cancer declarations in Quebec, Canada.

BACKGROUND: COVID-19 affected healthcare worldwide, limited access to healthcare, and delayed cancer screening and diagnosis. In this study, the effect of the first year of COVID-19 was determined on cancer diagnoses in the province of Quebec, Canada. METHODS: Data were collected from the 13 Quebec Cancer Registry health institutions. Newly diagnosed cancer declarations in the first year of the COVID-19 (April 2020-March 2021) were compared with the reference periods (averages of 3 previous years). The main focus was on four leading cancers: lung, prostate, colorectal, and breast cancers. Generalized regression models with a poisson approximation and interrupted time series (ITS) analysis were used. Underestimated cases were presented in terms of relative risk (RR) and 95% confidence intervals (CI). The changes in the stage-specific counts were also assessed in each of the four cancers. Results were illustrated separately for the first 4 months of the pandemic (first wave). FINDINGS: This study estimated an overall under-reporting of 15.3% (29,019 vs. 24,584) of declarations. This under-reporting was evident across all age groups above 35 years (p < 0.0001), four primary cancers (p < 0.0001), all stages of cancers (p < 0.0001), and both sexes (p < 0.0001). Based on the relative risks, stage-specific lung cancer counts were underestimated by 5%-34% in the first wave (0%-11% in the first year), prostate cancer by 16%-46% in the first wave (0%-25% in the first year), colorectal cancer 15%-45% in the first wave (0%-24% in the first year), and breast cancer 3%-45% in the first wave and (0%-28% in the first year). However, no stage-IV cancers were statically under-reported compared to the pre-pandemic era and not even in the first wave. INTERPRETATION: Cancer diagnosis was underestimated due to the COVID-19 pandemic in the first year; this effect was more evident in the first phase of the pandemic in Quebec. Further research is required to determine the accurate burden of the disease in the long term.

Impact of robotic surgery on patient flow and resource use intensity in ovarian cancer.

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.

Opioid versus opioid-free analgesia after surgical discharge: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Excessive opioid prescribing after surgery has contributed to the current opioid crisis; however, the value of prescribing opioids at surgical discharge remains uncertain. We aimed to estimate the extent to which opioid prescribing after discharge affects self-reported pain intensity and adverse events in comparison with an opioid-free analgesic regimen. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, Scopus, AMED, Biosis, and CINAHL from Jan 1, 1990, until July 8, 2021. We included multidose randomised controlled trials comparing opioid versus opioid-free analgesia in patients aged 15 years or older, discharged after undergoing a surgical procedure according to the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity definition (minor, moderate, major, and major complex). We screened articles, extracted data, and assessed risk of bias (Cochrane's risk-of-bias tool for randomised trials) in duplicate. The primary outcomes of interest were self-reported pain intensity on day 1 after discharge (standardised to 0-10 cm visual analogue scale) and vomiting up to 30 days. Pain intensity at further timepoints, pain interference, other adverse events, risk of dissatisfaction, and health-care reutilisation were also assessed. We did random-effects meta-analyses and appraised evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluations scoring system. The review was registered with PROSPERO (ID CRD42020153050). FINDINGS: 47 trials (n=6607 patients) were included. 30 (64%) trials involved elective minor procedures (63% dental procedures) and 17 (36%) trials involved procedures of moderate extent (47% orthopaedic and 29% general surgery procedures). Compared with opioid-free analgesia, opioid prescribing did not reduce pain on the first day after discharge (weighted mean difference 0·01cm, 95% CI -0·26 to 0·27; moderate certainty) or at other postoperative timepoints (moderate-to-very-low certainty). Opioid prescribing was associated with increased risk of vomiting (relative risk 4·50, 95% CI 1·93 to 10·51; high certainty) and other adverse events, including nausea, constipation, dizziness, and drowsiness (high-to-moderate certainty). Opioids did not affect other outcomes. INTERPRETATION: Findings from this meta-analysis support that opioid prescribing at surgical discharge does not reduce pain intensity but does increase adverse events. Evidence relied on trials focused on elective surgeries of minor and moderate extent, suggesting that clinicians can consider prescribing opioid-free analgesia in these surgical settings. Data were largely derived from low-quality trials, and none involved patients having major or major-complex procedures. Given these limitations, there is a great need to advance the quality and scope of research in this field. FUNDING: The Canadian Institutes of Health Research.

Role of Human Leukocyte Antigen Allele Sharing in Human Papillomavirus Infection Transmission Among Heterosexual Couples: Findings From the HITCH Cohort Study.

BACKGROUND: Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners' infections with the same human papillomavirus (HPV) type. METHODS: We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive. RESULTS: We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3-5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio, 1.1 [95% confidence interval, .5-2.1], for 3-5 vs none). CONCLUSIONS: We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

OBJECTIVE: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

Development and evaluation of a new non-competitive Luminex immunoassay detecting antibodies against human papillomavirus types 6, 11, 16 and 18.

Serum antibody levels can be used to measure the humoral immune response against human papillomaviruses (HPV). We developed and validated a rapid, technically simple and relatively inexpensive multiplex non-competitive Luminex-based immunoassay (ncLIA) to measure total IgG antibody levels against four HPV types. For the assay's solid phase, virus-like particles (VLPs) of HPV6, 11, 16 and 18 were bound to heparin-coated beads. HPV serum antibody levels binding to the VLPs were quantified using a phycoerithrin-conjugated secondary polyclonal donkey anti-human IgG antibody. Standardization and validation of the ncLIA were performed using 96 paired serum and genital samples from participants in the HITCH cohort study, including young women (aged 18-24 years) and their male sexual partners (aged 18+) in Montreal, Canada. Results from the ncLIA were compared to a validated Luminex immunoassay from PPD laboratories using Pearson's correlation coefficients, receiver operating characteristic curves and logistic regression. Our assay had good inter- and intra-assay variability. The correlation of serum antibody levels between the ncLIA and validation assay was highest for HPV16 and HPV11 (r=0.90), followed by HPV6 (r=0.86) and HPV18 (r=0.67). The ncLIA was better able to predict HPV DNA positivity in genital samples than the validation assay for HPV16 [area under the curve (AUC) 0.65 versus 0.52, P=0.001] and HPV18 [AUC 0.71 versus 0.57, P=0.024]. AUCs for HPV6 and HPV11 were similar between the two assays (0.70 versus 0.71, P=0.59, and 0.88 versus 0.96, P=0.08, respectively). The developed ncLIA is useful for measuring total IgG antibody response following natural infection or vaccination against four HPV VLPs included in the quadrivalent vaccine.

Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta-analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. METHODS: Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random-effect model, and heterogeneity was addressed through I 2. Subgroup analyses and meta-regression for various covariates were performed. RESULTS: Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5-fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20-2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27-5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85-2.67) and Asia (OR 2.63, 95% CI 2.20-3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44-2.71 and OR 3.39, 95% CI 2.42-4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta-regression, with a regression coefficient of -2.219 (95% CI -3.927 to -0.511) and -1.929 (95% CI -3.776 to -0.0826), respectively. CONCLUSIONS: This meta-analysis indicates that premenopausal PCOS patients are associated with 2.5-fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.

Relative decrease in hemoglobin and outcomes in patients undergoing kidney transplantation surgery: A retrospective cohort study.

BACKGROUND: Recent surgical literature suggests that a relative decrease in hemoglobin (ΔHb) is predictive of adverse outcomes regardless of the absolute level. We aimed to examine the association between perioperative ΔHb and kidney transplantation (KT) outcomes. METHODS: This was a retrospective cohort study of transplant recipients, where ΔHb = [Hb0- Hb1Hb0]x 100 (Hb0 = hemoglobin pre-KT and Hb1 = lowest hemoglobin 24-h post-KT). The main outcome of interest was immediate graft function (IGF). RESULTS: Of the 899 eligible patients, 38% experienced IGF, and ΔHb was associated with 36% lower odds of IGF. Also, ΔHb was associated with higher all-cause graft failure and longer length of stay but not death-censored graft failure or mortality. ΔHb ≥30% was the threshold beyond which the odds of IGF were significantly lower even if Hb1 was ≥7 g/dL. CONCLUSION: ΔHb is associated with inferior outcomes independent of Hb1; whether it can be used to guide transfusion practices should be explored.

The impact of excluding or including Death Certificate Initiated (DCI) cases on estimated cancer survival: A simulation study.

BACKGROUND: Population-based cancer registries strive to cover all cancer cases diagnosed within the population, but some cases will always be missed and no register is 100 % complete. Many cancer registries use death certificates to identify additional cases not captured through other routine sources, to hopefully add a large proportion of the missed cases. Cases notified through this route, who would not have been captured without death certificate information, are referred to as Death Certificate Initiated (DCI) cases. Inclusion of DCI cases in cancer registries increases completeness and is important for estimating cancer incidence. However, inclusion of DCI cases will generally lead to biased estimates of cancer survival, but the same is often also true if excluding DCI cases. Missed cases are probably not a random sample of all cancer cases, but rather cases with poor prognosis. Further, DCI cases have poorer prognosis than missed cases in general, since they have all died with cancer mentioned on the death certificates. METHODS: We performed a simulation study to estimate the impact of including or excluding DCI cases on cancer survival estimates, under different scenarios. RESULTS: We demonstrated that including DCI cases underestimates survival. The exclusion of DCI cases gives unbiased survival estimates if missed cases are a random sample of all cancer cases, while survival is overestimated if these have poorer prognosis. CONCLUSION: In our most extreme scenarios, with 25 % of cases initially missed, the usual practice of including DCI cases underestimated 5-year survival by at most 3 percentage points.

Exploring the impact of cancer registry completeness on international cancer survival differences: a simulation study.

BACKGROUND: Data from population-based cancer registries are often used to compare cancer survival between countries or regions. The ICBP SURVMARK-2 study is an international partnership aiming to quantify and explore the reasons behind survival differences across high-income countries. However, the magnitude and relevance of differences in cancer survival between countries have been questioned, as it is argued that observed survival variations may be explained, at least in part, by differences in cancer registration practice, completeness and the availability and quality of the respective data sources. METHODS: As part of the ICBP SURVMARK-2 study, we used a simulation approach to better understand how differences in completeness, the characteristics of those missed and inclusion of cases found from death certificates can impact on cancer survival estimates. RESULTS: Bias in 1- and 5-year net survival estimates for 216 simulated scenarios is presented. Out of the investigated factors, the proportion of cases not registered through sources other than death certificates, had the largest impact on survival estimates. CONCLUSION: Our results show that the differences in registration practice between participating countries could in our most extreme scenarios explain only a part of the largest observed differences in cancer survival.

Clinical utility of therapeutic drug monitoring of antiepileptic drugs: Systematic review.

OBJECTIVE: To systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: We searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925. RESULTS: Sixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line. CONCLUSIONS: If optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

Real-world direct healthcare costs of treating recurrent high-grade serous ovarian cancer with cytotoxic chemotherapy.

Aim: To describe the direct healthcare costs associated with repeated cytotoxic chemotherapy treatments for recurrent high-grade serous cancer (HGSC) of the ovaries. Patients & methods: Retrospective review of 66 women with recurrent stage III/IV HGSC ovarian cancer treated with repeated lines of cytotoxic chemotherapy in a Canadian University Tertiary Center. Results: Mean cost of treatment of first relapse was CAD$52,227 increasing by 38% for two, and 86% for three or more relapses with median overall survival of 36.0, 50.7 and 42.8 months, respectively. In-hospital care accounted for 71% and chemotherapy drugs accounted for 17% of the total costs. Conclusion: After the third relapse of HGSC, cytotoxic chemotherapy did not prolong survival but was associated with substantially increased healthcare costs.