The full cohort of 512 patients and the nested controlled trial in 93 patients in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study raise doubts about the effective size at present claimed

A comparison of the relative merits of video-assisted pulmonary metastasectomy versus thoracotomy is predicated on the assumption that removal of asymptomatic lung metastases favourably influences survival and that it does so by a large degree. Recently published but long-awaited evidence from a prospective cohort study and a randomised trial of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) challenges that assumption.

Prevalence and determinants of oral and cervicogenital HPV infection: baseline analysis of the MHOC cohort study

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older-adult participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection among those reporting no recent sexual partners compared to those with a single recent sexual partner, but prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and older-adult populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: A nationwide register-based study with family-based designs

Objectives: Maternal smoking during pregnancy is associated with a reduced risk of type 1 diabetes (T1D) in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. Design: A nationwide, prospective cohort study and a nested case-control study (quasi-experiment) comparing children with T1D to their age-matched siblings (or cousins). Setting: Swedish national registers. Participants: We included 2,995,321 children born in Sweden between 1983 and 2014. Exposure: Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Main outcome measures: Children were followed for a diagnosis of T1D until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Results: A total of 18,617 children developed T1D, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7,988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring T1D in the full cohort (hazard ratio: 0.78, 95% confidence interval [CI]: 0.75 to 0.82) in the multivariable-adjusted model. The corresponding odds ratio was 0.78 (95% CI: 0.69 to 0.88) in the sibling and 0.72 (95% CI: 0.66 to 0.79) in the cousin comparison analysis. Conclusions: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring T1D. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Risk of drug-related upper gastrointestinal bleeding in the total population of the Netherlands: a time-trend analysis

ObjectiveMany prescribed and over-the-counter medications, for example, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with upper gastrointestinal bleeding (UGIB). Recently, a decrease in prescribing of NSAIDs was observed in the Netherlands, but whether a similar decreasing trend could be observed in the incidence of severe UGIB (either fatal or requiring hospitalisation), contingent on medication prescription, is unknown.DesignWe conducted a cohort study using Dutch national statistics on pharmacy claims, hospitalisation and mortality between 2013 and 2018. We explored the incidence of sex-specific and age-specific severe UGIB in four (sub)populations: (A) total population, (B) without a filled prescrption for NSAIDs, (C) without filled prescriptions for NSAIDs and antithrombotic agents, (D) without any risk factors for UGIB.ResultsThe cumulative incidence of severe UGIB did not decrease throughout the study period, regardless of the subgroup analysis. In the total population, it was 199 per 100 000 inhabitants (95% CI 197 to 201) in 2013–2014 and 260 (95% CI 258 to 263) in 2017–2018. The absolute risk of severe UGIB was 50% lower in the subgroup B than in the full cohort. It decreased further by 50% in the subgroup D when compared with subgroup B. The risk of severe UGIB was 1.5–1.9 fold higher in young women than in young men; an indication of over-the-counter NSAIDs use being more prevalent in women than men in this age group.ConclusionWe found no evidence to support a relationship between reduced prescribing of NSAIDs and the incidence of severe UGIB in the Netherlands since 2013. The relationship was also not observed when we removed the effect of risk factors.

Efficacy and Safety of Anticoagulation Treatment in COVID-19 Patient Subgroups Identified by Clinical-Based Stratification and Unsupervised Machine Learning: A Matched Cohort Study

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning.Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC.Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 μg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC.Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score

Background and Objectives:The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS) is a clinical model that predicts the risk of walking inability in GBS patients, and was developed with data from Dutch patients. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region-specificity.Methods:We used prospective data from the first 1500 patients included in IGOS, aged ≥ 6 years and unable to walk independently. We evaluated if the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using two measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC), and (2) calibration: observed versus predicted probability of being unable to walk independently. To improve the model predictions we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors.Results:For validation of mEGOS at entry 809 patients were eligible (Europe/North America n=677, Asia n=76, other=56), and 671 for validation of mEGOS at week 1 (Europe/North America n=563, Asia n=65, other=43). AUC-values were >0.7 in all regional subgroups. In the Europe/North America subgroup observed outcomes were worse than predicted, while in Asia observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort.Discussion:The mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in GBS patients, also in countries outside The Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America.Classification of Evidence:This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in GBS patients.ClinicalTrials.gov Identifier:NCT01582763

Issues Facing the Birth Parents and Their Implications for Open Adoption

The 210 children in the full cohort came from 142 families. Their birth parents’ circumstances provide a context for evaluating adoption outcomes. The chapter explores data collected from the children’s case files and records presented to the court at the time the order was made. Parents demonstrated a high incidence of factors known to be associated with recurrent child abuse: 31% of mothers had experienced abuse in their own childhoods; 45% were known to statutory child welfare services before their child’s birth, and 29% had already experienced the permanent removal of a child. Almost all parents struggled with complex factors including mental health problems, substance misuse, unstable relationships and domestic abuse that placed their children at risk of harm; for some parents, cognitive impairment was an exacerbating factor. About 10% of birth parents had died, and 23% of mothers and 60% of fathers had already lost contact with children before the adoption placement.

Effect modification of greenness on PM2.5 associated all-cause mortality in a multidrug-resistant tuberculosis cohort

RationaleEvidence for the association between fine particulate matter (PM2.5) and mortality among patients with tuberculosis (TB) is limited. Whether greenness protects air pollution-related mortality among patients with multidrug-resistant tuberculosis (MDR-TB) is completely unknown.Methods2305 patients reported in Zhejiang and Ningxia were followed up from MDR-TB diagnosis until death, loss to follow-up or end of the study (31 December 2019), with an average follow-up of 1724 days per patient. 16-day averages of contemporaneous Normalised Difference Vegetation Index (NDVI) in the 500 m buffer of patient’s residence, annual average PM2.5 and estimated oxidant capacity Ox were assigned to patients regarding their geocoded home addresses. Cox proportional hazards regression models were used to estimate HRs per 10 μg/m3 exposure to PM2.5 and all-cause mortality among the cohort and individuals across the three tertiles, adjusting for potential covariates.ResultsHRs of 1.702 (95% CI 1.680 to 1.725) and 1.169 (1.162 to 1.175) were observed for PM2.5 associated with mortality for the full cohort and individuals with the greatest tertile of NDVI. Exposures to PM2.5 were stronger in association with mortality for younger patients (HR 2.434 (2.432 to 2.435)), female (2.209 (1.874 to 2.845)), patients in rural (1.780 (1.731 to 1.829)) and from Ningxia (1.221 (1.078 to 1.385)). Cumulative exposures increased the HRs of PM2.5-related mortality, while greater greenness flattened the risk with HRs reduced in 0.188–0.194 on average.ConclusionsIndividuals with MDR-TB could benefit from greenness by having attenuated associations between PM2.5 and mortality. Improving greener space and air quality may contribute to lower the risk of mortality from TB/MDR-TB and other diseases.

Complementary and Integrative Health Approaches and Opioid Prescriptions Among Older Veterans With Chronic Pain

Complementary and integrative health (CIH) approaches are recommended in national guidelines as viable options for managing chronic pain and de-prescribing opioids. We followed 1,993,455 Veterans with musculoskeletal disorders for two years who were not using opioids at study entry. CIH exposure was ascertained from primary care visits for acupuncture, massage and chiropractic care via natural language processing and structured data. Opioid prescriptions during the 2-year follow-up were abstracted from Veterans Health Administration (VHA) electronic pharmacy records. Propensity score (PS) was used to match CIH recipients with non-recipients with most comparable baseline characteristics. Overall, 140,902 (7.1%) Veterans received CIH, with a prevalence of 2.7% for Veterans aged ≥ 65y, comparing to 6.3% and 10.5% for those aged 50-64y and ≤ 49y, respectively. Among the 1:1 PS-matched sub-cohort (136,148 pairs), Cox proportional hazard model revealed that time to fill first opioid prescriptions was significantly longer for CIH recipients (mean: 587 days) than non-recipients (mean: 491 days), with adjusted Hazard Ratio of 0.48 (95% Confidence Interval (CI): 0.45-0.51) for Veterans ≥ 65y, 0.44 (95% CI: (95% CI: 0.43-0.45) for 50-64y and 0.47 (95% CI: 0.46-0.48) for age ≤ 49y group (p value for interaction, 0.003). Sensitivity analyses among full cohort or modeling total supply of first opioid prescriptions derived consistent results. These findings suggest potential benefit of CIH use in delaying and reducing opioids prescriptions for patients with chronic pain and may have implication for older Veterans ≥ 65y who have been found less likely to seek CIH therapies than their younger counterparts.

Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation

Background Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR. Methods In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression. Results After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h. Conclusions Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.