Ramadan fasting and pregnancy: an evidence-based guide for the obstetrician.

Pregnant Muslim women may be religiously exempt from fasting during the Islamic month of Ramadan, especially if there is concern for undue hardship or harm to maternal or fetal health. However, several studies demonstrate that most women still choose to fast during pregnancy and avoid discussing fasting with their providers. A targeted literature review of published studies on fasting during Ramadan and pregnancy or maternal and fetal outcomes was performed. We generally found little to no clinically significant effect of fasting on neonatal birthweight or preterm delivery. Conflicting data exist on fasting and mode of delivery. Fasting during Ramadan has been mainly associated with signs and symptoms of maternal fatigue and dehydration, with a minimal decrease in weight gain. There is conflicting data regarding the association with gestational diabetes mellitus and insufficient data on maternal hypertension. Fasting may affect some antenatal fetal testing indices, including nonstress tests, lower amniotic fluid levels, and lower biophysical profile scores. Current literature on the long-term effects of fasting on offspring suggests possible adverse effects, but more data are required. The quality of evidence was negatively impacted by the variation in defining "fasting during Ramadan" in pregnancy, study size and design, and potential confounders. Therefore, in counseling patients, obstetricians should be prepared to discuss the nuances in the existing data while demonstrating cultural and religious awareness and sensitivity to foster a trusting relationship between patient and provider. We provide a framework for obstetricians and other prenatal care providers to aid in that effort and supplemental materials to encourage patients to seek clinical advice on fasting. Providers should engage patients in a shared decision-making process and offer them a nuanced review of the evidence (including limitations) and individualized recommendations based on clinical experience and patient history. Finally, should certain patients choose to fast while pregnant, providers should offer medical recommendations, closer observation, and support to reduce harm and hardship while fasting.

Radiosurgery fractionation and post-treatment hemorrhage development for intact melanoma brain metastases.

PURPOSE: To assess, for intact melanoma brain metastases (MBM), whether single-fraction stereotactic radiosurgery (SRS) versus fractionated stereotactic radiotherapy (fSRT) is associated with a differential risk of post-treatment lesion hemorrhage (HA) development. METHODS: A single institution retrospective database review identified consecutive patients with previously unresected MBM treated with robotic SRS/fSRT between 2013 and 2021. The presence of lesion HA was determined by multi-disciplinary imaging review. Dosimetric variables were reported as biologically effective doses using an α/ß ratio of 2.5 (BED2.5). Statistical analysis was performed using mixed effect logistic regression for post-treatment HA and Cox frailty modeling for local control (LC). RESULTS: The cohort included 48 patients with 226 intact MBM treated with SRS/fSRT. Of lesions without prior HA, 63 of 133 lesions (47.4%) receiving SRS demonstrated evidence of post-treatment HA versus 2 of 24 lesions (8.3%) treated with fSRT (p = 0.01). A larger maximum BED2.5 was observed in lesions developing HA compared to no HA (238.3 Gy vs. 211.4 Gy; p = 0.022). 12-month LC was 65.7% (95% CI 37.2-87.3%) and 77.5% (95% CI 58.5-91.2%) for lesions demonstrating pre-treatment and post-treatment HA, respectively, with no local failure events observed within 12 months for non-hemorrhagic lesions (p < 0.001). CONCLUSION: We found an increased incidence of post-treatment HA for intact MBM receiving a larger maximum BED2.5, which was significantly higher for single fraction treatments within our cohort. The presence of lesion HA, either pre- or post-treatment, was indicative of inferior LC. Further investigations of optimal dose and fractionation schedules for treatment of MBM in the era of immunotherapy are warranted.

Stereotactic radiosurgery for melanoma brain metastases: dose-size response relationship in the era of immunotherapy.

PURPOSE/OBJECTIVE(S): To determine, for intact melanoma brain metastases (MBM) treated with single-fraction stereotactic radiosurgery (SRS), whether planning parameter peripheral dose per lesion diameter (PDLDm, Gy/mm) and lesion control (LC) differs with versus without immunotherapy (IO). MATERIALS/METHODS: We performed a retrospective analysis of patients with intact MBM treated with SRS from 2008 to 2019. Cox-frailty models were constructed to include confounders selected by penalized Cox regression models with a LASSO selector. Interaction effect testing was used to determine whether a significant effect between IO and PDLDm could be demonstrated with respect to LC. RESULTS: The study cohort comprised 67 patients with 244 MBMs treated with SRS (30 patients with 122 lesions treated with both SRS and IO) were included. The logarithm of PDLDm was selected as a predictor of LC (HR 0.307, 95% CI 0.098-0.441), adjusting for IO receipt (HR 0.363, 95% CI 0.108-1.224). Interaction effect testing demonstrated a differential effect of PDLDm by IO receipt, with respect to LC (p = 0.048). Twelve-month LC rates for a 7.5 mm lesion receiving SRS (18 Gy) with IO versus without IO were 87.8% (95% CI 69.0-98.3%) versus 79.8% (95% CI 55.1-93.8%) respectively. CONCLUSION: PDLDm predicted LC in patients with small MBMs treated with single-fraction SRS. We found a differential effect of dose per lesion size and LC by immunotherapy receipt. Future studies are needed to determine whether lower doses of single-fraction SRS afford similarly effective LC for patients with small MBMs receiving immunotherapy.

Immune Status in Merkel Cell Carcinoma: Relationships With Clinical Factors and Independent Prognostic Value.

BACKGROUND: Immunosuppression (IS) currently is not considered in staging for Merkel cell carcinoma (MCC). An analysis of the National Cancer Database (NCDB) was performed to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and to describe the relationship between immune status and other prognostic factors. METHODS: The NCDB was queried for patients with a diagnosis of MCC from 2010 to 2016 who had known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. RESULTS: The 3-year OS was lower for the patients with IS (44.6%) than for the immunocompetent (IC) patients (68.7%; p < 0.0001). Immunosuppression was associated with increased adjusted mortality hazard (hazard ratio [HR], 2.36, 95% confidence interval [CI], 2.03-2.75). The etiology of IS was associated with OS (p = 0.0015), and patients with solid-organ transplantation had the lowest 3-year OS (32.7%). Immunosuppression was associated with increased odds of greater nodal burden (odds ratio [OR], 1.70; 95% CI, 1.37-2.11) and lymphovascular invasion (OR, 1.58; 95% CI, 1.23-2.03). CONCLUSIONS: Immune status was independently prognostic for the OS of patients with localized MCC. The etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status, and potentially the etiology of IS, may be useful prognostic factors to consider for future MCC staging systems.

Patterns of care and outcomes of radiotherapy or hormone therapy in patients with medically inoperable endometrial adenocarcinoma.

OBJECTIVE: The optimal treatment for medically inoperable endometrioid endometrial adenocarcinoma is unknown. The goal of this study was to evaluate the patterns of care and efficacy of radiotherapy (RT) or hormone therapy (HT) in the treatment of these patients. METHODS: We performed a query of the National Cancer Database (NCDB) of patients with medically inoperable endometrioid adenocarcinoma of the endometrium diagnosed between 2004 and 2016 and treated with either RT or HT. A multivariate Cox regression model and propensity weighted analyses were used to evaluate overall survival after controlling for confounding variables. A multinomial logistic regression model was used to assess predictors of RT or HT use. RESULTS: A total of 1036 patients were included in this cohort, and 73% (n = 759) were treated with RT alone. Patients who received definitive HT compared to RT were more likely to be older, diagnosed in the earlier years of this analysis, treated at lower-case volume centers, diagnosed with high-grade disease, or located outside of metropolitan areas. On multivariate analysis, treatment with HT alone versus RT alone was associated with significantly worse overall survival in the multivariate Cox model but not on propensity score weighted analysis. Interaction effect testing revealed that older patients and those treated at lower-volume centers had improved survival with RT compared to HT. CONCLUSIONS: We identified factors associated with the receipt of RT or HT in medically inoperable endometrial cancer patients. Treatment with RT correlated with improved survival compared to HT in older patients and those treated at lower-volume centers.

Developing an Islamic Research Ethics Framework.

In surveying the medical literature on Islamic principles of research ethics, it is apparent that attempts to identify ethical principles are replete with issues of standards and gaps in knowledge of the uses of scriptural sources. Despite this, attempts at creating an Islamic ethical framework for research ethics may improve current practices in research in Muslim-majority countries and contribute to the growing canon of secular bioethics. This paper aims to identify principles and considerations within Islam that (1) overlap with current corpora on research ethics, and (2) further informs the current research ethics discourse.

Pediatric neurosurgical workforce, access to care, equipment and training needs worldwide.

OBJECTIVE: The presence and capability of existing pediatric neurosurgical care worldwide is unknown. The objective of this study was to solicit the expertise of specialists to quantify the geographic representation of pediatric neurosurgeons, access to specialist care, and equipment and training needs globally. METHODS: A mixed-question survey was sent to surgeon members of several international neurosurgical and general pediatric surgical societies via a web-based platform. Respondents answered questions on 5 categories: surgeon demographics and training, hospital and practice details, surgical workforce and access to neurosurgical care, training and equipment needs, and desire for international collaboration. Responses were anonymized and analyzed using Stata software. RESULTS: A total of 459 surgeons from 76 countries responded. Pediatric neurosurgeons in high-income and upper-middle-income countries underwent formal pediatric training at a greater rate than surgeons in low- and lower-middle-income countries (89.5% vs 54.4%). There are an estimated 2297 pediatric neurosurgeons in practice globally, with 85.6% operating in high-income and upper-middle-income countries. In low- and lower-middle-income countries, roughly 330 pediatric neurosurgeons care for a total child population of 1.2 billion. In low-income countries in Africa, the density of pediatric neurosurgeons is roughly 1 per 30 million children. A higher proportion of patients in low- and lower-middle-income countries must travel > 2 hours to seek emergency neurosurgical care, relative to high-income countries (75.6% vs 33.6%, p < 0.001). Vast basic and essential training and equipment needs exist, particularly low- and lower-middle-income countries within Africa, South America, the Eastern Mediterranean, and South-East Asia. Eighty-nine percent of respondents demonstrated an interest in international collaboration for the purposes of pediatric neurosurgical capacity building. CONCLUSIONS: Wide disparity in the access to pediatric neurosurgical care exists globally. In low- and lower-middle-income countries, wherein there exists the greatest burden of pediatric neurosurgical disease, there is a grossly insufficient presence of capable providers and equipped facilities. Neurosurgeons across income groups and geographic regions share a desire for collaboration and partnership.

Delayed seizures after intracerebral haemorrhage.

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ≥ 1 APOE ε4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.

What Makes Health Systems Research in Developing Countries Ethical? Application of the Emanuel Framework for Clinical Research to Health Systems Research.

The growing importance of health systems research has opened debate about appropriate ethical frameworks and guidelines for the ethical review and conduct of health systems research. In this article we consider a detailed proposal from Hyder et al. (2014) and consider it in relation to the conventional criteria for ethics review of clinical research outlined by Emanuel et al. (2004; 2008) and argue that the Emanuel criteria can be usefully applied to the review of health systems research to supplement the Hyder et al. proposals. We argue further that health systems researchers and reviewers would benefit from many of the debates that have characterized the ethics of clinical research over the past three decades.

A Scoping Study on the Ethics of Health Systems Research.

Currently, health systems research (HSR) is reviewed by the same ethical standards as clinical research, which has recently been argued in the literature to be an inappropriate standard of evaluation. The issues unique to HSR warrant a different review by research ethics committees (RECs), as it does not impose the same risks to study participants as other types of clinical or public health research. However, there are limited tools and supporting documents that clarify the ethical considerations. Therefore, there is a need for additional reflection around ethical review of HSR and their consideration by RECs. The purpose of this paper is to review, understand, and synthesize the current state of literature and practice to inform these deliberations and the larger discourse on ethics review guidelines for HSR. This paper presents a review of the literature on ethics of HSR in the biomedical, public health, and implementation research to identify ethical considerations specific to HSR; and to identify examples of commonly available guidance and/or tools for the ethical review of HSR studies. Fifteen articles were identified on HSR ethics issues, and forty-two international academic institutions were contacted (of the responses (n=29), no institution had special ethical guidelines for reviewing HSR) about their HSR ethics review guidelines. There appears to be a clear gap in the current health research ethics discourse around health systems research ethics. This review serves as a first step (to better understand the current status) towards a larger dialogue on the topic.

Ethical review of health systems research in low- and middle-income countries: a conceptual exploration.

Given that health systems research (HSR) involves different aims, approaches, and methodologies as compared to more traditional clinical trials, the ethical issues present in HSR may be unique or particularly nuanced. This article outlines eight pertinent ethical issues that are particularly salient in HSR and argues that the ethical review process should be better tailored to ensure more efficient and appropriate oversight of HSR with adequate human protections, especially in low- and middle-income countries. The eight ethical areas we discuss include the nature of intervention, types of research subjects, units of intervention and observation, informed consent, controls and comparisons, risk assessment, inclusion of vulnerable groups, and benefits of research. HSR involving human participants is necessary to ensure health systems strengthening and quality of care and to guide public policy intelligently. Health systems researchers must carefully define their intent and goals and openly clarify the values that may influence the premises and design of protocols. As new types of population-level research activities become more commonplace, it is critical that institutional review board (IRB) and research ethics committee (REC) review processes evolve to evaluate these research protocols in ways that address the nuanced features of these studies.

A systematic review of barriers to pursuing careers in medicine among Black premedical students.

Among the various etiologies of the exclusion of Black male physicians from the healthcare workforce, it is critical to identify and examine the barriers in their trajectory. Given that most medical school matriculants graduate and pursue residency training, medical school admission has been identified as the primary impediment to a career in medicine. Thus, this work aims to identify barriers in the journey of primarily Black, and secondarily underrepresented minority, premedical students. A systematic review of the medical literature was conducted for articles pertaining to the undergraduate/premedical period, Black experiences, and the medical school application process. The search yielded 5336 results, and 13 articles were included. Most papers corroborated common barriers, such as financial/socioeconomic burdens, lack of access to preparatory materials and academic enrichment programs, lack of exposure to the medical field, poor mentorship/advising experiences, systemic and interpersonal racism, and limited support systems. Common facilitators of interest and interventions included increasing academic enrichment programs, improving mentorship and career guidance quality and availability, and improving access to and availability of resources as well as exposure opportunities. No article explicitly discussed addressing racism. There is a dearth of studies exploring the premedical stage-the penultimate point of entry into medicine. Though interest in becoming a physician may be present, multiple and disparate impediments restrict Black men's participation in medicine. Addressing the barriers Black and underrepresented minority premedical students face requires an awareness of how multiple systems work together to discriminate and restrict access to careers in medicine beyond the traditional pipeline understanding.

Tailored Mentorship for the Underrepresented and Allies in Radiation Oncology: The Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Mentorship Experience.

PURPOSE: There are limited opportunities for mentorship for underrepresented in medicine (URM) trainees and physicians in radiation oncology (RO). The purpose of this study was to create and evaluate a formal mentorship program open to URMs and allies with interests in diversity, equity, and inclusion. METHODS AND MATERIALS: A mentorship program incorporating a virtual platform was designed by the Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee. It was structured to include 6 sessions over 6 months with matched mentor-mentee pairs based on responses to a publicized online interest form. A compilation of evidence-based guidelines was provided to optimize the mentorship relationship. Linked pre- and postprogram surveys were administered to collect demographic data, define baseline goals and level of support, and evaluate program satisfaction. RESULTS: Thirty-five mentor-mentee pairs were matched; 31 mentees completed the preprogram survey and 17 completed the postprogram survey. Preprogram, only 3 mentees (9.7%) reported satisfaction with current mentorship and 5 (16%) reported mechanisms or mentorship in place at their program to support URMs. On the postprogram survey, mentees reported high satisfaction with areas of mentorship, mentor attributes, and the program overall. Opportunities for improvement include implementation of mechanisms to enhance communication with mentor-mentee pairs and maintain longitudinal engagement. CONCLUSIONS: In the first tailored mentorship program in RO for URMs and those with diversity, equity, and inclusion interests, our results demonstrate that there is self-reported interest for better mentorship for URMs in RO, and that a nationwide structured mentorship program can address participants' goals with high satisfaction. Program expansion could provide URMs and allies in RO more opportunities for career development and promote a greater sense of community and inclusion within the field.

Incidence of repeat procedures and healthcare utilization following surgery, radiosurgery, and percutaneous procedures in elderly patients with trigeminal neuralgia.

OBJECTIVE: Management of trigeminal neuralgia (TN) in elderly patients poses significant challenges. The impact of different treatment modalities (surgery, radiosurgery [RS], and percutaneous techniques [PTs]) on healthcare utilization is not well defined in the management of TN in elderly patients. The aim of this study was to compare the long-term healthcare utilization metrics of different interventions in the management of elderly patients with TN. METHODS: The MarketScan database was queried using the International Classification of Diseases, Ninth Revision and Current Procedural Terminology, from 2000 to 2016. TN patients ≥ 65 years of age managed using surgery, RS, and PTs with at least 5 years of follow-up after the index procedure were included. Outcomes analyzed were hospital admissions, outpatient services, and medication refills. RESULTS: Of 993 patients, 43% (n = 430) underwent RS, 44% (n = 432) had PTs, and only 13% (n = 131) underwent surgery for TN. Overall, the median age of patients was 74 years old, 64% were females, 90% had Medicare insurance, and 17% had an Elixhauser index ≥ 3. Patients in the surgery group were younger (median age 71 years) with a higher comorbidity index (≥ 3; 24%) compared with patients undergoing RS and PTs (13% and 17%, respectively). At 1, 2, and 5 years after the index procedure, 41%, 48%, and 57% of patients in the PT cohort underwent any repeat procedure compared with 11%, 18%, and 29% for the RS cohort, and 6%, 9%, and 11% for the surgical cohort, respectively. Also, patients in the PT cohort incurred 1.8, 1.9, and 2.0 times the combined payment at 1, 2, and 5 years, respectively, compared with the surgery cohort. Similarly, patients who underwent RS for TN incurred 1.4, 1.5, and 1.5 times the combined payment at 1, 2, and 5 years, respectively, compared with the surgery cohort. At 5 years after the index procedure, combined payments for the PT cohort were $79,753 (IQR $46,013, $144,064) compared with $61,016 (IQR $27,114, $117,097) for the RS cohort and $41,074 (IQR $25,392, $87,952) for the surgery cohort (p < 0.0001). CONCLUSIONS: PTs followed by RS were the common procedures used in the majority of elderly patients with TN. However, surgery for TN resulted in durable control with the least need for reoperations up to 5 years after the index procedure, followed by RS and PTs. PTs for TN resulted in the highest utilization of healthcare resources and need for reoperations at all time points. These findings should be considered in clinical decision-making when selecting appropriate treatment modalities in elderly patients with TN.