First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema.

PURPOSE: Only a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that stereotactic ablative radiation therapy of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and secondarily explore the efficacy of stereotactic irradiation for lung volume reduction (SILVR) over 18 months after intervention in patients with severe emphysema. METHODS AND MATERIALS: We conducted a single-arm, prospective clinical trial in eligible patients with severe emphysema treated with unilateral stereotactic ablative radiation therapy (45 Gy in 3 fractions) to a target within the most emphysematous region. The primary outcome was safety in terms of incidence of grade ≥3 adverse events, and the secondary outcome was efficacy. RESULTS: Eight patients received the intervention. Median (range) baseline characteristics were age 73 years (63-78); forced expiratory volume in 1 second percent of predicted value (FEV1%) 28.5% (19.0-42.0); diffusing capacity of the lungs for carbon monoxide percent of predicted value 40% (24.0-67.0); and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index 5.5 (5-9). The incidence of grade ≥3 adverse events was 3 of 8 (37.5%). The relative change in target lobe volume was -23.1% (-1.6 to -41.5) and -26.5% (-20.6 to -40.8) at 6 and 18 months, respectively. The absolute ΔFEV1% was greater in patients with a BODE index ≤5 versus ≥6 (+12.0% vs -2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V60BED3) correlated with the absolute change in target lobe volume at 18 months. CONCLUSIONS: SILVR appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe and effective in patients with a lower BODE index and/or less parenchymal destruction.

A scoping review, mapping, and prioritisation process for emergency obstetric and neonatal quality of care indicators: Focus on provision and experience of care.

Background: Globally, approximately 800 women and 6400 newborns die around the time of childbirth each day. Many of these deaths could be prevented with high-quality emergency obstetric and newborn care (EmONC). The Monitoring Emergency Obstetric Care: A handbook guides strengthening EmONC services. However, the handbook contains limited quality of care measures. Our study identified and prioritised quality of care indicators for potential inclusion in the handbook, which is undergoing revision. Methods: We conducted a consultative scoping review, mapping, and prioritisation exercise to select a short list of indicators on facility-based maternal and newborn quality of care. Indicators were identified from literature searches and expert suggestions and organised by the categories of structure, process, and outcomes as defined in the World Health Organization's Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. We focused on process indicators, encompassing the provision of care and experience of care during the intrapartum period, and developed a priority list of indicators using the selection criteria of relevance and feasibility. Experience of care indicators were also mapped against the Person-Centered Maternity Care (PCMC) scale. Results: We extracted a total of 3023 quality of care indicators. After removing out-of-scope and duplicate indicators and applying our selection criteria, we identified 20 provision of care indicators for possible inclusion in the revised EmONC handbook. We recommend including a score for experience of care that could be measured with the 30-item or the 13-item PCMC scale. We also identified 29 experience of care items not covered by the PCMC scale that could be used. Provider experience, patient safety, and quality of abortion care were identified as areas for which no or few indicators were found through our scoping review. Conclusions: Through a rigorous, consultative, and multi-step process, we selected a short list of process-related, facility-based quality of care indicators for emergency obstetric and newborn care. This list could be included in the EmONC handbook or used for other monitoring purposes. Country consultations to assess the utility and feasibility of the proposed indicators and their adaptation to local contexts will support their refinement and uptake. Registration: https://osf.io/msxbd (Open Science Framework).

Associations between self-reported obstetric complications and experience of care: a secondary analysis of survey data from Ghana, Kenya, and India.

BACKGROUND: Although several indicators have been proposed to measure women's experience of care in health facilities during the intrapartum period, it is unknown if these indicators perform differently in the context of obstetric emergencies. We examined the relationship between experience of care indicators from the Person-Centered Maternity Care (PCMC) scale and obstetric complications. METHODS: We used data from four cross-sectional surveys conducted in Kenya (rural: N = 873; urban: N = 531), Ghana (N = 531), and India (N = 2018) between August 2016 and October 2017. The pooled sample included 3953 women aged 15-49 years who gave birth within 9 weeks prior to the survey. Experience of care was measured using the PCMC scale. Univariate, bivariate, and multivariable analyses were conducted to examine the associations between the composite and 31 individual PCMC indicators with (1) obstetric complications; (2) severity of complications; and (3) delivery by cesarean section (c-section). RESULTS: 16% (632) of women in the pooled sample reported obstetric complications; and 4% (132) reported having given birth via c-Sect. (10.5% among those with complications). The average standardized PCMC scores (range 0-100) were 63.5 (SD = 14.1) for the full scale, 43.2 (SD = 20.6) for communication and autonomy, 67.8 (SD = 14.1) for supportive care, and 80.1 (SD = 18.2) for dignity and respect sub-scales. Women with complications had higher communication and autonomy scores (45.6 [SD = 20.2]) on average compared to those without complications (42.7 [SD = 20.6]) (p < 0.001), but lower supportive care scores, and about the same scores for dignity and respect and for the overall PCMC. 18 out of 31 experience of care indicators showed statistically significant differences by complications, but the magnitudes of the differences were generally small, and the direction of the associations were inconsistent. In general, women who delivered by c-section reported better experiences. CONCLUSIONS: There is insufficient evidence based on our analysis to suggest that women with obstetric complications report consistently better or worse experiences of care than women without. Women with complications appear to experience better care on some indicators and worse care on others. More studies are needed to understand the relationship between obstetric complications and women's experience of care and to explore why women who deliver by c-section may report better experience of care.

In several studies and reports, women have described mistreatment by health providers during childbirth in health facilities. Particularly in low- and middle-income countries, such mistreatment has negative effects on women's decisions to seek maternity care in health facilities. It is unclear if women with complications are more or less likely to experience some forms of mistreatment compared to women without complications. In this study, we examined 31 experience of care indicators in three domains: (1) Supportive Care; (2) Respect and Dignity; and (3) Communication and Autonomy from the validated Person-Centered Maternity Care (PCMC) questionnaire. We compare these experience of care indicators between women who report obstetric complications and those who don't report complications, by the reported severity of the complications, and by their mode of delivery. The study included data from three countries: Ghana, Kenya, and India. The results showed that the experience of care among women who reported obstetric complications was not consistently better or worse than that of those who did not have complications. Therefore, efforts should be made to improve the experience of care in health facilities for every birthing woman. Additionally, women who delivered via c-section had consistently better experiences than women who delivered vaginally. More studies are needed to understand the relationship between mode of delivery and women's experience of care.

Comparison of failure to rescue in younger versus elderly patients following lung cancer resection.

Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients. Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80 years) cohort. Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n = 139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n = 39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P < .001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P = .01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P = .028). Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer.

Background: Radiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3 decades to quantify this risk over time as modern oncologic treatment continues to evolve. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9 years, 10 to 15 years, and >15 years after breast cancer diagnosis. Results: Of the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P = .036) after 5 to 9 years of follow-up, 1.28 (P = .002) after 10 to 15 years of follow-up, and 1.30 (P = .014) after >15 years of follow-up. The HR of contralateral lung cancer was not increased at any time interval. Conclusions: The increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

Examining socioeconomic status disparities in facility-based childbirth in Kenya: role of perceived need, accessibility, and quality of care.

BACKGROUND: Giving birth in health facilities with skilled birth attendants (SBAs) is one of the key efforts promoted to reduce preventable maternal deaths in sub-Saharan Africa. However, research has revealed large socioeconomic status (SES) disparities in facility-based childbirth. We seek to extend the literature on the factors underlying these SES disparities. Drawing on the Disparities in Skilled Birth Attendance (DiSBA) framework, we examined the contribution of three proximal factors-perceived need, accessibility, and quality of care-that influence the use of SBAs. METHODS: We used data from a survey conducted in Migori County, Kenya in 2016, among women aged 15-49 years who gave birth nine weeks before the survey (N = 1020). The primary outcome is facility-based childbirth. The primary predictors are wealth, measured in quintiles calculated from a wealth index based on principal component analysis of household assets, and highest education level attained. Proposed mediating variables include maternal perceptions of need, accessibility (physical and financial), and quality of care (antenatal services received and experience of care). Logistic regression with mediation analysis was used to investigate the mediating effects. RESULTS: Overall, 85% of women in the sample gave birth in a health facility. Women in the highest wealth quintile were more likely to give birth in a facility than women in the lowest quintile, controlling for demographic factors (adjusted odds ratio [aOR]: 2.97, 95% CI: 1.69-5.22). College-educated women were five times more likely than women with no formal education or primary education to give birth in a health facility (aOR: 4.96; 95% CI: 1.43-17.3). Women who gave birth in health facilities had higher perceived accessibility and quality of care than those who gave birth at home. The five mediators were estimated to account for between 15% and 48% of the differences in facility births between women in the lowest and higher wealth quintiles. CONCLUSION: Our results confirm SES disparities in facility-based childbirth, with the proximal factors accounting for some of these differences. These proximal factors - particularly perceived accessibility and quality of care - warrant attention due to their relationship with facility-birth overall, and their impact on inequities in this care.

Biological changes in the pregnancy-postpartum period and subsequent cardiometabolic risk-UPSIDE MOMS: A research protocol.

Multiple physiological changes occur in pregnancy as a woman's body adapts to support the growing fetus. These pregnancy-induced changes are essential for fetal growth, but the extent to which they reverse after pregnancy remains in question. For some women, physiological changes persist after pregnancy and may increase long-term cardiometabolic disease risk. The National Institutes of Health-funded study described in this protocol addresses a scientific gap by characterizing weight and biological changes during pregnancy and an extended postpartum period in relation to cardiometabolic risk. We use a longitudinal repeated measures design to prospectively examine maternal health from early pregnancy until 3 years postpartum. The aims are: (1) identify maternal weight profiles in the pregnancy-postpartum period that predict adverse cardiometabolic risk profiles three years postpartum; (2) describe immune, endocrine, and metabolic biomarker profiles in the pregnancy-postpartum period, and determine their associations with cardiometabolic risk; and (3) determine how modifiable postpartum health behaviors (diet, physical activity, breastfeeding, sleep, stress) (a) predict weight and cardiometabolic risk in the postpartum period; and (b) moderate associations between postpartum weight retention and downstream cardiometabolic risk. The proposed sample is 250 women. This study of mothers is conducted in conjunction with the Understanding Pregnancy Signals and Infant Development study, which examines child health outcomes. Biological and behavioral data are collected in each trimester and at 6, 12, 24, and 36 months postpartum. Findings will inform targeted health strategies that promote health and reduce cardiometabolic risk in childbearing women.

Cohort profile: Understanding Pregnancy Signals and Infant Development (UPSIDE): a pregnancy cohort study on prenatal exposure mechanisms for child health.

PURPOSE: Extensive research suggests that maternal prenatal distress is reliably related to perinatal and child health outcomes-which may persist into adulthood. However, basic questions remain regarding mechanisms involved. To better understand these mechanisms, we developed the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort study, which has several distinguishing features, including repeated assessments across trimesters, analysis of multiple biological pathways of interest, and incorporation of placental structure and function as mediators of child health outcomes. PARTICIPANTS: Women with normal risk pregnancies were recruited at <14 weeks gestation. Study visits occurred in each trimester and included extensive psychological, sociodemographic, health behaviour and biospecimen collection. Placenta and cord blood were collected at birth. Child visits (ongoing) occur at birth and 1, 6, 12, 24, 36 and 48 months of age and use standard anthropometric, clinical, behavioural, biological and neuroimaging methods to assess child physical and neurodevelopment. FINDINGS TO DATE: We recruited 326 pregnancies; 294 (90%) were retained through birth. Success rates for prenatal biospecimen collection were high across all trimesters (96%-99% for blood, 94%-97% for urine, 96%-99% for saliva, 96% of placentas, 88% for cord blood and 93% for buccal swab). Ninety-four per cent of eligible babies (n=277) participated in a birth examination; postnatal visits are ongoing. FUTURE PLANS: The current phase of the study follows children through age 4 to examine child neurodevelopment and physical development. In addition, the cohort participates in the National Institutes of Health's Environmental influences on Child Health Outcomes programme, a national study of 50 000 families examining early environmental influences on perinatal outcomes, neurodevelopment, obesity and airway disease. Future research will leverage the rich repository of biological samples and clinical data to expand research on the mechanisms of child health outcomes in relation to environmental chemical exposures, genetics and the microbiome.