22 research outputs found

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

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    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

    Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

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    Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

    Mortality of emergency abdominal surgery in high-, middle- and low-income countries

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    Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

    Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

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    Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

    Cervical cancer screening in rural South Africa among HIV-infected migrant farm workers and sex workers

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    At an HIV clinic in the Limpopo province of South Africa, chart reviews revealed long delays in addressing abnormal Pap smears, difficulty in referrals, poor quality and lost results, and increasing cases of cervical cancer. To address these barriers, a “see and treat” approach to screening was proposed. The objective was to integrate this method into current HIV care offered by local providers and to obtain demographic and risk factor data for use in future educational and intervention programs in the region. A cross sectional study of HIV farm workers and at-risk sex workers attending an HIV clinic was performed with visual inspection with acetic acid (VIA). Those with positive screens were offered cryotherapy. Clinic charts were reviewed retrospectively for Pap smear results for the previous year at the time of program initiation and at 12 and 18 months post-program. A total of 403 participants consented and underwent screening with VIA (306 Farm workers and 97 sex workers participated). 83.9% of participants (32.9% sex workers and 100% farm workers) were HIV+. VIA was positive in 30.5% of participants, necessitating cryotherapy. There was no significant difference in VIA positivity between HIV+ farm workers and sex workers. There was a positive correlation between Pap smears and VIAs results. We demonstrate successful integration of cervical cancer screening using VIA for HIV+ farm workers and sex workers into an existing HIV treatment and prevention clinic in rural South Africa, addressing and treating abnormal results promptly

    Determining a Patient\u27s Comfort in Inquiring About Healthcare Providers\u27 Hand-washing Behavior

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    OBJECTIVES: To determine whether a patient\u27s level of assertiveness and other factors influences her comfort level in asking her provider to wash his or her hands. METHODS: In this pilot study, we developed a survey to gather cross-sectional information on a variety of factors that might explain patient willingness to ask her health-care provider to wash his or her hands. Three primary predictor variables are analyzed: (1) patient assertiveness; (2) patient familiarity with her healthcare provider; and (3) whether the patient has observed hand-washing behavior. Fifty patients participated from the Obstetrics and Gynecology Department of Metropolitan Hospital Center. RESULTS: Less assertive patients are much less likely than assertive patients to ask physicians to wash hands (25% versus 68%; Fisher\u27s exact test P = 0.0427). Among the 3 assertiveness questions included in the survey, the ability to ask physicians questions during visits is most strongly indicative of willingness to ask about hand washing. Familiarity with the names of regular health-care providers has a statistically significant impact on willingness to ask about hand washing. Evidence suggests that observing hand washing behavior affects willingness to ask, but differences are not statistically significant. Results by socioeconomic status such as age, education, income, and race/ethnicity are inconclusive. CONCLUSIONS: A patient\u27s level of assertiveness alone is not sufficient to determine her willingness to inquire about the hand-washing behavior of her provider. A high percentage of patients did not see their provider engaging in adequate hand washing behavior. If patients feel comfortable with their provider to inquire about their care and request hand-washing behavior, health outcomes are affected by reducing the rates of health care-associated infections

    Cervical cancer risk factors and screening preferences among Muslim women in Monrovia, Liberia

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    Cervical cancer is the most common cancer in reproductive aged women in Liberia. Lack of awareness and screening capacity are both major contributors to the prevalence of this disease. The minority Muslim population in this country is largely unscreened. The objective of the study was to assess cervical cancer risk factors and screening preferences among Muslim women living in Monrovia, Liberia and to offer self-screening with HPV testing. A multiple step implementation strategy was devised in order to outreach to the Muslim population with the engagement of community and religious leaders, about an upcoming screening program and informational session at a local clinic. Over 150 Muslim women attended the session, 120 completed the HPV screening, and 55 women completed the questionnaires. Questionnaire data revealed overall low risk factors for cervical cancer, but also low use of family planning as well as low knowledge about cervical cancer and HPV. Participants showed an interest in screening and a majority preferred self-collected tests. These preferences should be incorporated in future programming. To engage minority populations in screening programs, there may be success with targeted messages, involvement of community religious leaders, and eliciting feedback to incorporate preferred strategies and improve participation and programming. Keywords: HPV screening, Muslim, cervical cancer &nbsp; Le cancer du col de l'utérus est le cancer le plus courant chez les femmes en âge de procréer au Libéria. Le manque de sensibilisation et de capacité de dépistage sont tous deux des facteurs majeurs de la prévalence de cette maladie. La population musulmane minoritaire de ce pays est largement non filtrée. L'objectif de l'étude était d'évaluer les facteurs de risque de cancer du col de l'utérus et les préférences en matière de dépistage chez les femmes musulmanes vivant à Monrovia, au Libéria, et de proposer un auto-dépistage avec des tests HPV. Une stratégie de mise en oeuvre en plusieurs étapes a été élaborée afin de sensibiliser la population musulmane avec l'engagement des chefs communautaires et religieux, sur un programme de dépistage à venir et une séance d'information dans une clinique locale. Plus de 150 femmes musulmanes ont assisté à la session, 120 ont terminé le dépistage du VPH et 55 femmes ont rempli les questionnaires. Les données du questionnaire ont révélé des facteurs de risque globalement faibles pour le cancer du col de l'utérus, mais aussi une faible utilisation de la planification familiale ainsi qu'une faible connaissance du cancer du col de l'utérus et du VPH. Les participants ont montré un intérêt pour le dépistage et une majorité préféraient les tests auto-collectés. Ces préférences devraient être incorporées dans la programmation future. Pour impliquer les populations minoritaires dans les programmes de dépistage, il peut y avoir du succès avec des messages ciblés, la participation des chefs religieux de la communauté et l'obtention de commentaires pour intégrer les stratégies préférées et améliorer la participation et la programmation. Mots-clés: Dépistage du VPH chez les femmes musulmanes Libéri

    Postpartum mood among universally screened high and low socioeconomic status patients during COVID-19 social restrictions in New York City

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    The mental health effects of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Coronavirus Disease 2019 (COVID-19) pandemic on postpartum women are of increasing concern among mental health practitioners. To date, only a handful of studies have explored the emotional impact of the pandemic surrounding pregnancy and none have investigated the consequence of pandemic-related social restrictions on the postpartum mood of those living among different socioeconomic status (SES). All postpartum patients appearing to the Mount Sinai Health System for their postpartum appointment between January 2, 2020 and June 30, 2020, corresponding to before and during pandemic imposed social restrictions, were screened for mood symptomatology using the Edinburgh Postnatal Depression Scale (EPDS). Each patient’s socioeconomic status (high/low) was determined by their location of clinical service. A total of 516 postpartum patients were screened. While no differences in EPDS scores were observed by SES prior to social restrictions (U = 7956.0, z = − 1.05, p = .293), a significant change in mood symptomatology was observed following COVID-19 restrictions (U = 4895.0, z = − 3.48, p &lt; .001), with patients living in lower SES reporting significantly less depression symptomatology (U = 9209.0, z = − 4.56, p &lt; .001). There was no change in symptomatology among patients of higher SES (U = 4045.5, z = − 1.06, p = .288). Postpartum depression, the most common complication of childbearing, is a prevalent, cross-cultural disorder with significant morbidity. The observed differences in postpartum mood between patients of different SES in the context of temporarily imposed COVID-19-related social restrictions present a unique opportunity to better understand the specific health and social support needs of postpartum patients living in urban economic poverty. Given that maternal mental illness has negative long-term developmental implications for the offspring and that poor mental health reinforces the poverty cycle, future health policy specifically directed towards supporting postpartum women living in low SES by ameliorating some of the early maternal burdens associated with balancing employment-family-childcare demands may assist in interrupting this cycle while simultaneously improving the long-term outcomes of their offspring
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