The impact of body mass index on robotic surgery outcomes in endometrial cancer.

OBJECTIVES: To compare surgical outcomes of patients with endometrial cancer who underwent robotic surgery across different BMI categories. METHODS: A retrospective study including all consecutive patients with endometrial cancer who underwent robotic surgery at a tertiary cancer center between December 2007 and December 2022. The study analyzed outcome measures, including blood loss, surgical times, length of hospitalization, perioperative complications, and conversion rates with the Kruskal-Wallis test for BMI group differences and the Chi-squared test for associations between categorical variables. RESULTS: A total of 1329 patients with endometrial cancer were included in the study. Patients were stratified by BMI: <30.0 (n = 576; 43.3%), 30.0-39.9 (n = 449; 33.8%), and ≥ 40.0 (n = 304; 22.9%). There were no significant differences in post-anesthesia care unit (PACU) stay (p = 0.105) and hospital stay (p = 0.497) between the groups. The rate of post-op complications was similar across the groups, ranging from 8.0% to 9.5% (p = 0.761). The rate of conversion to laparotomy was also similar across the groups, ranging from 0.7% to 1.0% (p = 0.885). Women with a BMI ≥40.0 had a non-clinically relevant but greater median estimated blood loss (30 mL vs. 20 mL; p < 0.001) and longer median operating room (OR) time (288 min vs. 270 min; p < 0.001). Within the OR time, the median set-up time was longer for those with a higher BMI (58 min vs. 50 min; p < 0.001). However, skin-to-skin time (209 min vs. 203 min; p = 0.202) and post-op time (14 min vs. 13 min; p = 0.094) were comparable between groups. CONCLUSION: BMI does not affect the peri-operative outcome of patients undergoing robotic staging procedures for endometrial cancer.

Characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy and/or effectiveness of influenza vaccines: an overview of reviews.

BACKGROUND: While systematic reviews (SR) generally suggest that vaccination is an effective way to prevent influenza infection, it is not clear if these conclusions are based on high quality SR methods. As such, we systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza vaccines. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 11, 2022. We summarised the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From 11,193 retrieved citations, we included 48 publications (47 SRs). Seventy-five percent were of a critically low quality, 19% of a low quality, 2% of a moderate quality, and 4% of a high quality. Thirteen percent were industry-funded, about 13% co-authored by industry employee(s), and 4% commissioned by an organisation or authority. Only 45% percent reported protocol registration, 6% reported collaboration with a knowledge synthesis librarian/information specialist, and 60% utilised a reporting checklist (e.g. PRISMA). CONCLUSIONS AND RELEVANCE: SRs with meta-analysis of efficacy/effectiveness of influenza vaccines are mostly of critically low quality and even the more recent reviews did not follow current best SR practices. These findings are significant in view of the controversies that surround influenza vaccines, and the use of SRs in informed decision-making. However, the findings do not justify curtailment or cessation of influenza vaccine use as vaccines continue to offer substantial net public health benefit.HighlightsWe systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in 47 systematic reviews with meta-analysis of efficacy/effectiveness of influenza vaccines.13% of the reviews were industry-funded.About 13% of the reviews were co-authored by industry employee(s).4% of the reviews were commissioned by an organisation/authority.45% of the reviews reported protocol registration.6% of the reviews reported collaborating with a knowledge synthesis librarian/information specialist to prepare the search strategy.60% of the reviews reported using the PRISMA (or similar) checklist.75% of the reviews were judged to be of critically low quality; 19% of low quality; 2% of moderate quality; 4% of high quality.

An overview of the characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy/effectiveness of influenza antiviral drugs.

BACKGROUND: Influenza antiviral drugs remain controversial and it is not clear if conclusions on their efficacy/effectiveness are based on high quality systematic reviews (SRs). We systematically identified, critically appraised, and summarized the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza antiviral drugs for prevention and/or treatment of influenza. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 2020. We summarized the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From a total 3,898 citations after removal of duplicates from all identified citations, we included 24 SRs. Seventy-five percent (n = 18) were of a critically low quality, 8% (n = 2) of a low quality, 17% (n = 4) of a moderate quality, and none were of a high quality. Seventeen percent (n = 4) were industry-funded, 4% (n = 1) coauthored by industry employee(s), and 33% (n = 8) commissioned by an organization or authority. Only 33% percent (n = 8) reported protocol registration, 4% (n = 1) reported collaboration with a knowledge synthesis librarian/information specialist, and 17% (n = 4) utilized a systematic review reporting checklist. CONCLUSIONS: The evidence suggests that SRs of efficacy/effectiveness of influenza antiviral drugs are mostly of critically low quality and do not follow current best SR practices. These findings are significant in view of the important role of SRs in decision-making and the controversies that surround the use of the influenza antiviral drugs. However, the findings should not be interpreted to mean curtailment/cessation of use of antiviral drugs for influenza.

Mandate to evaluate robotic surgery implementation: a 12-year retrospective analysis of impact and future implications.

The introduction of robotic surgery in hospitals has raised much debate given the various effects on care, costs, education and medical advancement. Purchasing discussions are often approached with more questions than answers and there is a need for reports that provide a case for whether or not such technologies are advantageous from multiple perspectives, and offer insights into ways such devices can be introduced into a hospital setting. This report provides an evidence-based review of a university-affiliated tertiary care hospital's 12-year experience with robotic surgery in gynecologic oncology and delves into the various takeaways and challenges of implementing robotic surgery. Key findings were that robotic surgery significantly reduced complication rates, lengths of hospital stays for patients and overall hospital costs. Key obstacles were large upfront costs and the need for significant leadership and collaboration. Ongoing challenges to evaluating robotics include assessing long-term survival data, making comparisons with concurrently changing hospital conditions and determining how data can be generalized to other departments and institutions.

Inhibition of Poly ADP-Ribose Glycohydrolase Sensitizes Ovarian Cancer Cells to Poly ADP-Ribose Polymerase Inhibitors and Platinum Agents.

BACKGROUND: Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin. METHODS: PARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle. RESULTS: PARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction. CONCLUSIONS: PARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects.

Sentinel Lymph Node Sampling as an Alternative to Lymphadenectomy in Patients With Endometrial Cancer and Obesity.

OBJECTIVE: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes. METHODS: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease. RESULTS: Out of 223 patients with a median BMI of 40.6 kg/m2, 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively). CONCLUSIONS: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years.

Interim seasonal influenza vaccine effectiveness estimates as proxy for final estimates: analysis of systematically identified matched pairs of interim/final estimates from test-negative design studies in outpatient settings from 2010/11 to 2018/19.

OBJECTIVES: Limited time for seasonal influenza vaccine development means that the World Health Organization has to consider interim (early) rather than final vaccine effectiveness (VE) estimates in deciding influenza vaccine composition. We assessed agreement between interim and final VE estimates, and factors that may determine a substantial difference (≥10%) between point estimates. METHODS: This was a mixed methods study. We systematically searched, identified, and matched interim/final VE studies of test-negative design (TND) type in outpatient settings after the 2009/10 influenza pandemic. The chi-square statistic (χ2) was used to assess the statistical significance of the difference between paired interim/final VE estimates. We calculated the difference between point estimates and used multivariable logistic regression to assess factors that may determine a substantial difference. RESULTS: We identified 68 interim/final VE pairs. There was no statistically significant difference between almost all compared pairs. An inconsistent statistical model for interim/final VE estimation and interim VE estimation before the epidemic peak increased the odds of having a substantial difference between estimates. CONCLUSION: : Interim influenza VE appears to be sufficient for vaccine composition decision-making. Consistency in interim/final VE estimation, and interim VE estimation during/after epidemic peak may increase agreement between the VE estimates.

Decline in Seasonal Influenza Vaccine Effectiveness With Vaccination Program Maturation: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence suggests that repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (PM; number of years since program inception) as a proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies. METHODS: We systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles and calculated pooled VE using an inverse-variance random-effects model. The primary outcome was pooled VE against all influenza. RESULTS: We included 72 articles from 11 931 citations. Across the 3 categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2), and influenza B. CONCLUSIONS: The evidence suggests that influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE.

Integration of geriatric assessment into clinical oncology practice: A scoping review.

Sixty percent of newly diagnosed cancers occur in older adults and more complex planning is required to sustain quality care for older populations. Individualized care incorporating geriatric assessment can predict early mortality and treatment toxicity for older cancer patients. We mapped and summarized the available evidence on the integration of geriatric assessment into clinical oncology practice, and ascertained which domains have been implemented. We systematically searched bibliographic databases and trial registries for reports of clinical studies, clinical practice guidelines, systematic and non-systematic reviews, and grey literature published in English. We gathered data on study characteristics, geriatric domains and strategies evaluated, and relevant study objectives and findings. From a total of 10,124 identified citations, 38 articles met our eligibility criteria, 3 of which were clinical practice guidelines. Nearly half of these articles came from the United States. Domains of the geriatric assessment implemented in studies ranged from 1 to 12, with varied combinations. We identified 27 studies on strategies for implementing geriatric assessment and 24 studies on feasibility of implementing geriatric assessment, into clinical oncology practice. We also identified 3 main geriatric assessment models: 2 from the United States and 1 from Australia. Furthermore, we identified 2 reviews that reported varied components of geriatric assessment models. There is increasingly robust evidence to implement formal geriatric assessment in oncology practice. There remains a great deal of variation in the tools recommended to address each of the domains in a geriatric assessment, with only 1 guideline (American Society of Clinical Oncology guideline) settling on a specific best practice. Protocol registration: Open Science Framework osf.io/mec93.

Variations in Seasonal Influenza Vaccine Effectiveness due to Study Characteristics: A Systematic Review and Meta-analysis of Test-Negative Design Studies.

BACKGROUND: Study characteristics influence vaccine effectiveness (VE) estimation. We examined the influence of some of these on seasonal influenza VE estimates from test-negative design (TND) studies. METHODS: We systematically searched bibliographic databases and websites for full-text publications of TND studies on VE against laboratory-confirmed seasonal influenza in outpatients after the 2009 pandemic influenza. We followed the Cochrane Handbook for Systematic Reviews of Interventions guidelines. We examined influence of source of vaccination information, respiratory specimen swab time, and covariate adjustment on VE. We calculated pooled adjusted VE against H1N1 and H3N2 influenza subtypes, influenza B, and all influenza using an inverse-variance random-effects model. RESULTS: We included 70 full-text articles. Pooled VE against H1N1 and H3N2 influenza subtypes, influenza B, and all influenza was higher for studies that used self-reported vaccination than for those that used medical records. Pooled VE was higher with respiratory specimen collection within ≤7 days vs ≤4 days of symptom onset, but the opposite was observed for H1N1. Pooled VE was higher for studies that adjusted for age but not for medical conditions compared with those that adjusted for both. There was, however, a lack of statistical significance in almost all differences in pooled VE between compared groups. CONCLUSIONS: The available evidence is not strong enough to conclude that influenza VE from TND studies varies by source of vaccination information, respiratory specimen swab time, or adjustment for age/medical conditions. The evidence is, however, indicative that these factors ought to be considered while designing or evaluating TND studies of influenza VE.

Seasonal influenza vaccination in older people: A systematic review and meta-analysis of the determining factors.

BACKGROUND/OBJECTIVES: Despite influenza vaccination programs in various jurisdictions, seasonal influenza vaccine (SIV) uptake remains suboptimal among older people (≥65years old), an important subpopulation for influenza vaccination. We sought to summarize determinants of SIV uptake (any vaccine receipt) and vaccination adherence (receipt of vaccine in two or more seasons in sequence) among older people. METHODS: We searched for population-based studies conducted in community-dwelling older people (irrespective of their health status) from 2000-2019. Two reviewers independently selected publications for inclusion. One reviewer extracted data from the included studies; a second checked the extracted data for errors. Disagreements were resolved by discussion and consensus, or a third reviewer. We were interested in the determinants of SIV uptake and vaccination adherence. Where appropriate, we pooled adjusted results using the inverse variance, random-effects method and reported the odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: Out of 11,570 citations screened, we included 34 cross-sectional studies. The following were associated with increased SIV uptake: being older (OR 1.52, 95%CI 1.38-1.67 [21 studies]), white (1.30, 1.14-1.49 [10 studies]), married (1.23, 1.17-1.28 [9 studies]), non-smoker (1.28, 1.11-1.47 [7 studies]), of a higher social class (1.20, 1.06-1.36 [2 studies]), having a higher education (1.12, 1.04-1.21 [14 studies]), having a higher household income (1.11, 1.05-1.18 [8 studies]), having a chronic illness (1.53, 1.44-1.63 [16 studies]), having poor self-assessed health (1.23, 1.02-1.40 [9 studies]), having a family doctor (2.94, 1.79-4.76 [2 studies]), and having health insurance (1.58, 1.13-2.21 [6 studies]). The influence of these factors varied across geographical regions. Being older (1.26, 1.11-1.44 [2 studies]) was also associated with increased vaccination adherence. CONCLUSIONS: Several factors may determine SIV uptake and vaccination adherence among older people. More studies are needed to provide a stronger evidence base for planning more effective influenza vaccination programs.