Assessing the long-term priorities of pancreaticoduodenectomy survivors.

BACKGROUND: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors. METHODS: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed. RESULTS: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors. CONCLUSION: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence.

Validating biologic age in selecting elderly patients with pancreatic cancer for surgical resection.

BACKGROUND AND OBJECTIVES: Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes. METHODS: The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health-related quality-of-life data. The characteristics of frail and nonfrail patients were compared. RESULTS: Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65-10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47-34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3-79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3-52.4, p = 0.10). In the no-surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85-16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34-7.03, p = 0.02). CONCLUSIONS: The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.

Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.

Influenza Vaccination During COVID-19 in a Rural Community: A Cross-sectional Survey.

Vaccination behavior is an informative metric for assessing flu seasons and is especially important to understand for the 2020-2021 flu season, which coincided with the COVID-19 pandemic. This study aimed to estimate flu vaccine behavior and assess vaccine perceptions during the pandemic season. Using a cross-sectional descriptive study design, we conducted an online survey to assess vaccination behavior and perceptions of both COVID-19 and the flu. Patients were identified as recently seen by providers in an academic internal medicine practice (n = 827) and surveys were distributed as messages in the Epic electronic medical record system. We found that 88.3% of respondents (188/206) had received their flu vaccination for the season at the time of their survey response in December 2020-February 2021. Of those that had not yet received the flu vaccine, only 13.6% indicated they planned on getting one. 12.5% of respondents said they had changed their flu vaccine plans due to the COVID-19 pandemic. Looking at differences from past season's behavior, more individuals switched to getting the flu vaccine than those that switched to not getting the vaccine this season. The most frequently cited reasons for not receiving the flu vaccination were concerns about side effects and not being in a priority group. Changes in flu vaccination behavior from previous seasons represent a net positive in the direction of vaccine acceptance. Barriers to vaccination were identified and results from this study provide more information on vaccine perceptions, beliefs, and behavior, which can benefit future vaccination programs.

Prognostic indicators for undifferentiated carcinoma with/without osteoclast-like giant cells of the pancreas.

BACKGROUND: Undifferentiated carcinoma of the pancreas (UPC) is a rare malignancy. There are no standardized guidelines for treatment. Current management has been extrapolated from smaller reviews. METHODS: 858 patients with UPC were identified in the 2004-2017 NCDB. Kaplan-Meier method followed by Cox proportional-hazards regression examined independent prognostic factors associated with overall survival (OS). Logistic regression analyses were performed to determine independent predictors of surgical intervention and the status of surgical resection by histologic subtype. RESULTS: Patients with osteoclast-like giant cells (OCLGC) had a longer median OS compared to those without (aHR 0.52: 95% CI 0.41-0.67). Of the non-OCLGC subtypes, pleomorphic large cell demonstrated the shortest median OS (2.4 months). Surgical resection was associated with improved survival in all histologies except for pleomorphic cell carcinoma. R0 resection and negative lymph nodes were independently associated with an improved OS. CONCLUSION: This is the largest database review published to date on UCP. OCLGC histology is associated with an improved survival compared to those without OCLGC. Of the non-OCLGC subtypes, pleomorphic large cell is associated with the shortest overall survival. Surgical resection is associated with a significant survival advantage for all histologies except for pleomorphic cell carcinoma.

Community perspectives of South African adolescents' experiences seeking treatment at local HIV clinics and how such clinics may influence engagement in the HIV treatment cascade: a qualitative study.

Despite having the largest antiretroviral treatment (ART) program in the world, only 14% of South African adolescents living with HIV (ALWH) are on ART. The purpose of this study was to identify aspects of the clinic environment that either improve or inhibit ALWH's ability to engage in HIV care. We conducted fifty-nine semi-structured, in-depth interviews with ALWH (n = 20; 13-19 years of age), their caregivers (n = 19), and local stakeholders (n = 20) in Cape Town, South Africa. Data were coded and analyzed using inductive and deductive approaches to content analyses. Codes were grouped into positive and negative aspects of the HIV clinic environment, and into suggestions on how clinic practices could be improved to facilitate ALWH treatment retention and ART adherence. Positive clinic factors included: community co-location; familiarity with clinic staff; and adolescent only/adolescent-friendly clinic spaces. Negative clinic factors included: clinic visit frequency; overcrowding and long wait times; discrimination and stigma; lack of confidentiality; inflexible appointment-scheduling; and staff attitudes. ALWHs' clinic experiences affect their ability to remain in care and adhere to their treatment regimens. These findings support a call for innovative approaches that improve ALWH's clinic experiences and support them as they progress along the HIV treatment cascade.

An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well.

Healthcare retention and clinical outcomes among adolescents living with HIV after transition from pediatric to adult care: a systematic review.

BACKGROUND: Adolescents living with HIV (ALWH) who transition from pediatric to adult care face several challenges that increase their risk of experiencing treatment interruptions and being lost to HIV care with resultant increased morbidity and mortality. To date, few studies have examined their outcomes post-healthcare transition (HCT), precluding the development and dissemination of evidence-based interventions aimed at retaining ALWH in HIV care both during and after HCT. We conducted a systematic review to synthesize the outcomes of ALWH post-HCT to provide suggestions for future directions. METHODS: We systematically searched several electronic databases through October 2019 using keywords for HIV, HCT and ALWH. We categorized studies by target population, country (i.e., upper-high income and low-middle income), study design (i.e., descriptive, mixed methods, quantitative), outcomes measured, and follow-up period. RESULTS: A total of 24 studies met inclusion criteria. Studies were categorized according to the following HCT outcomes: retention in HIV care post-HCT (n = 13), changes in CD4+ count and viral load post-HCT (n = 16), and mortality among ALWH post-HCT (n = 7). Most studies (n = 11) examining retention in HIV care indicated that more than 70% of ALWH were retained in care 1-2 years post-HCT while the remaining studies (n = 2) reported retention rates less than 55%. While studies indicated that CD4+ counts and viral loads tended to worsen during the first few years post-HCT, these differences were often not statistically significant. Among all ALWH who transitioned to adult care, a small proportion died within their first seven years post-HCT. Among qualitative studies, common themes included transition readiness (n = 6), provider-patient relationship in the adult clinic setting (n = 6), and concern about the adult clinic setting (n = 4). CONCLUSIONS: Transition outcomes were poorest for ALWH with unsuppressed viremia pre-HCT, suggesting that this subgroup of ALWH may need greater support from their treatment teams and caregivers during and post-HCT to improve clinical outcomes.

Facilitation of Surgical Innovation: Is It Possible to Speed the Introduction of New Technology While Simultaneously Improving Patient Safety?

OBJECTIVE: To review efficiency metrics and patient safety data before and after implementation of a structured review process for surgical innovations. SUMMARY BACKGROUND DATA: Surgical innovation ranges from minor incremental improvement to radical experimentation. Although innovation paradigms have been described, these are not widely adopted or enforced in the surgical community. METHODS: A Continuous Quality Improvement Team (CQIT) of surgical quality officers and perioperative nurses was organized to perform structured reviews of proposed new surgical devices and procedures at a large quaternary cancer care center. The CQIT process was placed to precede an established Value Analysis Team business evaluation. Pre- and post-CQIT implementation metrics of approval process efficiency and patient safety data were compared. Seven novel procedures were also vetted by the CQIT. RESULTS: Forty-six product requests were evaluated after CQIT implementation. Compared with 34 products evaluated prior to CQIT establishment, the total mean evaluation time decreased from 124 to 51 days (P= 0.007). For new devices requiring intraoperative trial, the time between product proposal and trial decreased from a mean of 260 to 99 days (P= 0.014). The rate of device-related complications in the pre-CQIT group was 10% compared with 0% post-CQIT. Two devices, which administratively bypassed CQIT review, had both minor and major complications, including a mortality. Five novel procedures approved by CQIT with simulation were performed without complications. CONCLUSIONS: Using novel algorithms, the addition of a dedicated team of surgical quality officers to the surgical innovation evaluation process improved both the efficiency and the safety associated with introducing new devices and procedures into practice.

Severe Preoperative Symptoms Delay Readiness to Return to Intended Oncologic Therapy (RIOT) After Liver Resection.

BACKGROUND: Symptom burden, as measured by patient-reported outcome (PRO) metrics, may have prognostic value in various cancer populations, but remains underreported. The aim of this project was to determine the predictive impact of preoperative patient-reported symptom burden on readiness to return to intended oncologic therapy (RIOT) after oncologic liver resection. METHODS: Preoperative factors, including anthropometric analysis of sarcopenia, were collected for patients undergoing oncologic liver resection from 2015 to 2018. All patients reported their preoperative symptom burden using the MD Anderson Symptom Inventory, Gastrointestinal version (MDASI-GI). Time to RIOT readiness was compared using standard statistics. RESULTS: Preoperative symptom burden was measured in 107 consecutive patients; 52% had at least one moderate symptom score and 21% reported at least one severe score. Highest rated symptoms were fatigue, disturbed sleep, and distress. For patients reporting a severe preoperative symptom burden, the median time to RIOT readiness was 35 days (interquartile range [IQR] 28-42), compared with 21 days (IQR 21-28) for those without severe symptoms (p < 0.001). On multivariable analysis, severe preoperative symptom burden was independently associated with longer time to RIOT readiness (estimate +7.5 days, 95% confidence interval 2.6-12.3; p = 0.002). CONCLUSIONS: Preoperative symptom burden has a substantial impact on time to RIOT readiness, leading to, on average, a 7-day delay in RIOT readiness compared with patients without severe preoperative symptoms. Identifying and targeting severe preoperative symptoms may hasten recovery and improve time to necessary adjuvant therapies.

Determining the Safety and Efficacy of Enhanced Recovery Protocols in Major Oncologic Surgery: An Institutional NSQIP Analysis.

BACKGROUND: Enhanced-recovery (ER) protocols are increasingly being utilized in surgical practice. Outside of colorectal surgery, however, their feasibility, safety, and efficacy in major oncologic surgery have not been proven. This study compared patient outcomes before and after multispecialty implementation of ER protocols at a large, comprehensive cancer center. METHODS: Surgical cases performed from 2011 to 2016 and captured by an institutional NSQIP database were reviewed. Following exclusion of outpatient and emergent surgeries, 2747 cases were included in the analyses. Cases were stratified by presence or absence of ER compliance, defined by preoperative patient education and electronic medical record order set-driven opioid-sparing analgesia, goal-directed fluid therapy, and early postoperative diet advancement and ambulation. RESULTS: Approximately half of patients were treated on ER protocols (46%) and the remaining on traditional postoperative (TP) protocols (54%). Treatment on an ER protocol was associated with decreased overall complication rates (20% vs. 33%, p < 0.0001), severe complication rates (7.4% vs. 10%, p = 0.010), and median hospital length of stay (4 vs. 5 days, p < 0.0001). There was no change in readmission rates (ER vs. TP, 8.6% vs. 9.0%, p = 0.701). Subanalyses of high magnitude cases and specialty-specific outcomes consistently demonstrated improved outcomes with ER protocol adherence, including decreased opioid use. CONCLUSIONS: This assessment of a large-scale ER implementation in multispecialty major oncologic surgery indicates its feasibility, safety, and efficacy. Future efforts should be directed toward defining the long-term oncologic benefits of these protocols.

Mobile sexual health services for adolescents: investigating the acceptability of youth-directed mobile clinic services in Cape Town, South Africa.

BACKGROUND: The Human Immunodeficiency Virus (HIV) epidemic is growing rapidly among South African adolescents and young adults (AYA). Although HIV counselling and testing, HIV prevention and treatment options are widely available, many AYA delay health-seeking until illness occurs, demonstrating a need for youth responsive, integrated sexual and reproductive health services (SRHS). While feasibility and cost-effectiveness have been evaluated, acceptability of mobile clinics among AYA has yet to be established. The objective of this study was to investigate patient acceptability of mobile AYA SRHS and compare mobile clinic usage and HIV outcomes with nearby conventional clinics. METHODS: Patients presenting to a mobile clinic in Cape Town were invited to participate in an acceptability study of a mobile clinic after using the service. A trained researcher administered an acceptability questionnaire. Mobile clinic medical records during the study period were compared with the records of AYA attending four clinics in the same community. RESULTS: Three hundred three enrolled participants (16-24 years, 246 (81.2%) female) rated mobile AYA SRHS acceptability highly (median = 4,6 out of 5), with 90% rating their experience as better or much better than conventional clinics. The mobile clinic, compared to conventional clinics, attracted more men (26% v 13%, p < 0,000), younger patients (18 v 19 years, p < 0,000), and yielded more HIV diagnoses (4% v 2%, p < 0,000). CONCLUSIONS: Given the high ratings of acceptability, and the preference for mobile clinics over conventional primary health clinics, the scalability of mobile clinics should be investigated as part of a multipronged approach to improve the uptake of SRHS diagnostic, prevention and treatment options for AYA.

Recent advances in genomic profiling of adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole-genome and -exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP. Laser capture microdissection revealed that adenocarcinoma and squamous carcinoma components of ASCP harbor similar genomic variations, indicating that the origin of tumor components is the same or similar. Although the study published by Fang et al. increases our knowledge of this rare mixed tumor type, further investigation, including RNA sequencing, will be needed to fully characterize this malignancy and to aid the development of novel treatment approaches. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Genetics and Genomics in Clinical Practice: The Views of Wisconsin Physicians.

INTRODUCTION: Decreasing costs and increased availability of genetic testing and genome sequencing mean many physicians will consider using these services over the next few years. Despite this promising future, some argue the present roadmap for translating genetics and genomics into routine clinical practice is unclear. OBJECTIVE: We conducted a pilot study to explore Wisconsin physicians' views, practices and educational desires regarding genetic and genomic testing. METHODS: Our study consists of an Internet survey (n=155) conducted in August and September 2015 and follow-up phone interviews with a portion of survey participants. Physicians of all specialties were invited to participate. Variables measured include physicians' general knowledge and experience regarding genetic and genomic testing, attitudes and perceptions toward these tests, testing intentions, and educational desires. Sociodemographic variables included gender, age, and medical specialty. RESULTS: In our exploratory survey of Wisconsin physicians, adult primary care providers (PCPs) lagged behind other providers in terms of familiarity and experience with genetic and genomic testing. PCPs in our sample were less likely than other physicians to feel their training in genetics and genomics is adequate. Physicians younger than 50 were more likely than older colleagues to feel their training is adequate. CONCLUSIONS: Our exploratory study suggests a gap in physician education and understanding regarding genomic testing, which is fast becoming part of personalized medical care. Future studies with larger samples should examine ways for physicians to close this gap, with special focus on the needs of PCPs.

Variability and Errors of Manually Digitized Goldmann Visual Fields.

PURPOSE: Goldmann visual fields (GVFs) are useful for tracking changes in areas of functional retina, including the periphery, in inherited retinal degeneration patients. Quantitative GVF analysis requires digitization of the chart coordinates for the main axes and isopter points marked by the GVF operator during testing. This study investigated inter- and intra-digitizer variability among users of a manual GVF digitization program. METHODS: Ten digitizers were trained for 1 hour, then digitized 23 different GVFs from inherited retinal degeneration patients in each of three testing blocks. Digitizers labeled each isopter as seeing or non-seeing, and its target size. Isopters with the same test target within each GVF were grouped to create isopter groups. RESULTS: The standard deviation of isopter group area showed an approximate square-root relationship with total isopter group area. Accordingly, the coefficient of variation for isopter group area decreased from 68% to 0.2% with increasing isopter group area. A bootstrap version of ANOVA did not reveal a significant effect of digitizers on isopter group area. Simulations involving random sampling of digitizers showed that five to seven digitizers would be required to catch 95% to 99% of labeling errors and isopter misses, on the basis of data discrepancies, with 99% probability. CONCLUSIONS: These data suggest that any minimally trained digitizer would be capable of reliably determining any isopter area, regardless of size. Studies using this software could either use five to seven minimally trained digitizers for each GVF, three digitizers who demonstrate low frequencies of errors on a practice set of GVFs, or two digitizers with an expert reader to adjudicate discrepancies and catch errors.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis.

BACKGROUND: Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature. METHODS: The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots. RESULTS: Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival. CONCLUSIONS: While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.

Acceptability and challenges of rapid ART initiation among pregnant women in a pilot programme, Cape Town, South Africa.

Maternal antiretroviral therapy (ART) is a critical intervention in the prevention-of-mother-to child transmission (PMTCT) of HIV. In South Africa, many HIV-infected pregnant women commence ART late in pregnancy, and as a result, the duration of ART prior to delivery is often insufficient to prevent vertical transmission. To address this, we designed an intervention for the rapid initiation of ART in pregnancy (RAP), where patient's ART preparation occurred during rather than before treatment commencement. Here we report on the acceptability and the challenges of the RAP programme. We conducted 7 key informant and 27 semi-structured interviews with RAP participants. Participants were purposefully selected based on ART-eligibility and stage in the pregnancy to post-partum continuum. Interviews were conducted in participants' home language by trained fieldworkers, with key informant interviews conducted by the study investigators. The data were analysed using a framework analysis approach. Rapid initiation in pregnancy was acceptable to the majority of programme participants and protection of the woman's unborn child was the primary motivation for starting treatment. The key barrier was the limited time to accept the dual challenges of being diagnosed HIV-positive and eligible for life-long ART. Truncated time also limited the opportunity for disclosure to others. Despite these and other barriers, most women found the benefits of rapid ART commencement outweighed the challenges, with 91% of women initiated onto ART starting the same day treatment eligibility was determined. Many participants and key informants identified the importance of counseling and the need to make an informed, independent choice on the timing of ART initiation, based on individual circumstances. Acceptance of ART-eligibility improved with time on the programme, however, as women's principal reason for initiating ART was protection of the unborn child, monitoring and supporting adherence during the post-partum period will be critical.