Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

BACKGROUND: Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. METHODS AND FINDINGS: Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. CONCLUSIONS: This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

External validation of the COVID-19 4C mortality score in an urban United States cohort.

BACKGROUND: Identifying patients at risk for mortality from COVID-19 is crucial to triage, clinical decision-making, and the allocation of scarce hospital resources. The 4C Mortality Score effectively predicts COVID-19 mortality, but it has not been validated in a United States (U.S.) population. The purpose of this study is to determine whether the 4C Mortality Score accurately predicts COVID-19 mortality in an urban U.S. adult inpatient population. METHODS: This retrospective cohort study included adult patients admitted to a single-center, tertiary care hospital (Philadelphia, PA) with a positive SARS-CoV-2 PCR from 3/01/2020 to 6/06/2020. Variables were extracted through a combination of automated export and manual chart review. The outcome of interest was mortality during hospital admission or within 30 days of discharge. RESULTS: This study included 426 patients; mean age was 64.4 years, 43.4% were female, and 54.5% self-identified as Black or African American. All-cause mortality was observed in 71 patients (16.7%). The area under the receiver operator characteristic curve of the 4C Mortality Score was 0.85 (95% confidence interval, 0.79-0.89). CONCLUSIONS: Clinicians may use the 4C Mortality Score in an urban, majority Black, U.S. inpatient population. The derivation and validation cohorts were treated in the pre-vaccine era so the 4C Score may over-predict mortality in current patient populations. With stubbornly high inpatient mortality rates, however, the 4C Score remains one of the best tools available to date to inform thoughtful triage and treatment allocation.

Comparing reliability of ICD-10-based COVID-19 comorbidity data to manual chart review, a retrospective cross-sectional study.

International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD-10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. OBJECTIVE: Compare COVID-19 cohort manual-chart-review and ICD-10-based comorbidity data; characterize the accuracy of different methods of extracting ICD-10-code-based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. DESIGN: Retrospective cross-sectional study. MEASUREMENTS: ICD-10-based-data performance characteristics relative to manual-chart-review. RESULTS: Discharge billing diagnoses had a sensitivity of 0.82 (95% confidence interval [CI]: 0.79-0.85; comorbidity range: 0.35-0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69-0.76; range: 0.44-0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63-0.71; range: 0.47-0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54-0.63; range: 0.30-0.68)and past medical history table had a sensitivity of 0.48 (95% CI: 0.43-0.53; range: 0.30-0.56). CONCLUSIONS AND RELEVANCE: ICD-10-based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual-chart-review.

Association of race/ethnicity and socioeconomic status with COVID-19 30-day mortality at a Philadelphia medical center using a retrospective cohort study.

COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. This is a retrospective cohort study in a single-center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1, 2020 and June 6, 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. The study included 426 patients: 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (odds ratio [OR]: 11.01; 95% confidence interval [CI]: 1.96-61.97) and renal disease (OR: 2.78; 95% CI: 1.31-5.90) were associated with higher odds of the composite primary outcome. Living in a "very-low-income area" (OR: 0.29; 95% CI: 0.12-0.71) and body mass index (BMI) 30-35 (OR: 0.24; 95% CI: 0.08-0.69) were associated with lower odds of the primary outcome. When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, was associated with lower odds of the composite primary outcome.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

A student initiative to implement peer-led study groups for a pharmacogenomics course: Evaluation of student performance and perceptions.

INTRODUCTION: To better elucidate the impact of cooperative learning outside the classroom, a student-initiated research project was conducted to explore the effects of participating in peer-led study groups (PLSGs) on student examination scores and perceptions. METHODS: First-year pharmacy students were given the opportunity to participate in weekly PLSGs for a pharmacogenomics course during spring 2016 and spring 2017. Student exam performance was stratified by those who attended vs. those who did not. Optional pre- and post-course surveys examined student perceptions of PLSGs. RESULTS: No significant differences were seen between the attendance groups in spring 2016. In spring 2017, student attendees were significantly more likely to pass two of their six exams (p = .04, p = .0029) and to have higher exam scores on one exam (p = .02) in comparison to non-attendees. Overall exam score averages were significantly different between attendees and non-attendees during spring 2017 (p = .03) but not during spring 2016 (p = .38). Perception surveys indicated students believed participation helped them to demonstrate competency and build confidence. Additionally, students reported they felt more comfortable clarifying questions during the study groups vs. during class time. CONCLUSIONS: The impact of study group participation on student exam performance was minimal over the two years of data collection, but there were instances where exam scores were positively impacted. Students perceived value in study group participation even if it did not translate directly to improved exam performance on all exams.

Palliative Care in Undergraduate Medical Education-How Far Have We Come?

PURPOSE: There is an increasing demand for quality palliative care teaching within undergraduate medical education. Studies suggest that many junior doctors feel underprepared to perform end-of-life care. Previous systematic reviews on palliative care teaching within medical schools have identified significant variability and lack of consistency in teaching. This review aims to update the literature on the current status of palliative care teaching to undergraduates within medical schools. METHOD: A systematic review was undertaken on articles published from December 2001 to November 2015 on palliative care teaching for undergraduate medical students. In all, 650 abstract citations were obtained, of which 126 were relevant to the research questions. Thematic analysis was performed on remaining articles according to whether they discussed content and/or methodology of palliative care education, and data collated. RESULTS: There is greater consistency in the content being delivered as part of end-of-life care education within medical schools. The most frequently taught topics include attitudes to death and dying, communication skills, and pain management. Pediatric care and religious/cultural issues are less frequently addressed. Teaching institutions are also utilising a broader range of teaching modalities. CONCLUSION: There is significant progress in palliative care education within medical schools. Ongoing challenges relate to correlating our current practice in medical education to professional recommendations and the expressed needs of junior doctors to practice competent end-of-life care.

Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience.

B-cell receptor kinase inhibitor (KI) therapy represents a paradigm shift in chronic lymphocytic leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%). Overall response rate (ORR) to first KI was 62% (complete response 14%). The most common reasons for KI discontinuation were toxicity (51%), CLL progression (29%), and Richter transformation (RT) (8%). Median progression-free survival (PFS) and OS from KI initiation were 10.5 and 29 months, respectively. Notably, initial KI choice did not impact PFS or OS; however, RT portended significantly inferior OS (P = .0007). One hundred fourteen patients received subsequent salvage therapy following KI discontinuation with an ORR to subsequent KI at 50% and a median PFS of 11.9 months. Median PFS in KI-intolerant patients treated with an alternate KI was not reached vs 7 months for patients with CLL progression. In summary, these data demonstrate that toxicity was the most common reason for KI discontinuation, that patients who discontinue KI due to toxicity can respond to an alternate KI, and that these responses may be durable. This trial was registered at www.clinicaltrials.gov as #NCT02717611 and #NCT02742090.

Developing the future Indigenous health workforce: The feasibility and impact of a student-led placement programme in remote Indigenous communities.

OBJECTIVE: To describe and evaluate a programme where medical students designed and implemented Indigenous health placements for students with an interest in rural/Indigenous health. DESIGN, SETTING AND PARTICIPANTS: In 2011, a student-led programme at the University of Adelaide was set up to give medical students the opportunity to undertake outreach trips and clinical placements in remote Indigenous communities. Twenty-four medical students attended trips to remote communities between 2012 and 2014. Here we evaluate our programme using a single-arm experimental design. MAIN OUTCOME MEASURES: Responses to questionnaire items before and after attending an outreach placement, scored on 6-point Likert scales. RESULTS: Following their remote Indigenous health placement, participants expressed a significantly higher mean likelihood of working in an Indigenous community in the future (3.17 (2.69-3.64) versus 4.00 (3.65-4.35); P < 0.007). Furthermore, after their placement participants felt better prepared to work in Indigenous communities (mean 1.79 (1.44-2.14) versus 3.21 (2.88-3.54); P < 0.001). CONCLUSIONS: A placement programme initiated and run by medical students can provide meaningful exposure to Indigenous health. Implementation of this student-led model in other medical schools may encourage nationwide development of the Indigenous health workforce.

Time to breast cancer relapse predicted by primary tumour characteristics, not lymph node involvement.

INTRODUCTION: The risk of breast cancer recurrence has been linked to tumour size, grade, oestrogen (ER) receptor status, and degree of lymph node (LN) involvement. However, the role of these variables in predicting time to relapse is not well defined. This study was designed to identify patient and primary tumour characteristics that predict risk periods for breast cancer recurrence within our institution, to enable more tailored surveillance strategies. METHODS: We retrospectively studied a cohort of 473 patients who presented to The Queen Elizabeth Hospital, Adelaide, Australia, with recurrent breast cancer between 1968 and 2008. Patient and primary tumour characteristics were collected, including age, menopausal status, tumour grade, size, ER and progesterone receptor (PR) status, and LN involvement and modeled against time to relapse using Kaplan-Meier survival curves. RESULTS: High tumour grade, size ≥ 20 mm, ER negativity, and PR negativity were shown on univariate analysis to correlate significantly with earlier recurrence (P < 0.0001, P = 0.0012, P = 0.0006, and P = 0.006). Multivariate analysis identified tumour grade and size as significant predictors of timing of relapse after adjustment for other variables. LN involvement, menopausal status, and age did not significantly correlate with earlier recurrence. CONCLUSIONS: High tumour grade and larger size were shown to independently predict earlier breast cancer relapse. While LN involvement increases absolute recurrence risk, our study proposes that it does not influence timing of relapse. Use of these predictors will enable key risk periods for onset of relapse to be characterised according to tumour profile with more appropriate discharge to primary care providers for ongoing surveillance.