Nevin Manimala

Neurology. 2021 Oct 11:10.1212/WNL.0000000000012919. doi: 10.1212/WNL.0000000000012919. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.

METHODS: We evaluated phenotypic associations between migraine and 19 lipoprotein subfractions measures in the Women’s Genome Health Study (WGHS, N=22,788). We then investigated genetic relationships between these traits using summary statistics from the International Headache Genetics Consortium (IHGC) for migraine (N_case=54,552, N_control=297,970) and combined summary data for lipoprotein subfractions (N up to 47,713).

RESULTS: There was a significant phenotypic association (odds ratio=1.27 [95% confidence interval:1.12-1.44]) and a significant genetic correlation at 0.18 (P=0.001) between migraine and triglyceride-rich lipoproteins (TRLP) concentration but not for LDL or HDL subfractions. Mendelian randomization (MR) estimates were largely null implying that pleiotropy rather than causality underlies the genetic correlation between migraine and lipoprotein subfractions. Pleiotropy was further supported in cross-trait meta-analysis revealing significant shared signals at four loci (chr2p21 harboring THADA, chr5q13.3 harboring HMGCR, chr6q22.31 harboring HEY2, and chr7q11.23 harboring MLXIPL) between migraine and lipoprotein subfractions. Three of these loci were replicated for migraine (P<0.05) in a smaller sample from the UK Biobank. The shared signal at chr5q13.3 colocalized with expression of HMGCR, ANKDD1B, and COL4A3BP in multiple tissues.

CONCLUSIONS: The current study supports the association between certain lipoprotein subfractions, especially for TRLP, and migraine in populations of European ancestry. The corresponding shared genetic components may be help identify potential targets for future migraine therapeutics.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.

PMID:34635557 | DOI:10.1212/WNL.0000000000012919

BMJ Open. 2021 Oct 11;11(10):e055575. doi: 10.1136/bmjopen-2021-055575.

ABSTRACT

OBJECTIVES: To compare the incidence and severity of invasive pneumococcal diseases (IPDs), pneumococcal pneumonia and all-cause pneumonia during the COVID-19 pandemic period with universal masking and social distancing with that of previous 5 years.

DESIGN: Retrospective observational study on incidence of IPDs, pneumococcal pneumonia and all-cause pneumonia between January 2015-December 2019 and March 2020-March 2021. January-February 2020 was excluded from analysis as it was treated as a transitional period between normal time and pandemic.

SETTING: Episode-based data by retrieval of hospitalisation records from the Hospital Authority’s territory-wide electronic medical record database in Hong Kong.

PARTICIPANTS: Hospitalised patients with IPD (n=742), pneumococcal pneumonia (n=2163) and all-cause pneumonia (including COVID-19 pneumonia, n=453 999) aged 18 years or above. Control diagnoses were included to assess confounding from health-seeking behaviours.

PRIMARY AND SECONDARY OUTCOMES: Primary outcome is the incidence of diseases between two periods. Secondary outcomes include disease severity surrogated by length of stay and mortality.

RESULTS: Monthly average number of IPD, pneumococcal pneumonia and all-cause pneumonia hospitalisation significantly decreased by 88.9% (95% CI 79.8% to 98.0%, p<0.0005), 72.5% (95% CI 65.9% to 79.1%, p<0.0005) and 17.5% (95% CI 16.8% to 18.2%, p<0.0005), respectively. Changes in trend from January 2015-December 2019 to March 2020-March 2021 were -70% (95% CI -87% to -35%, p=0.0025), -43% (95% CI -59% to -19%, p=0.0014) and -11% (95% CI -13% to -10%, p<0.0005), respectively. Length of stay for IPD and pneumococcal pneumonia episodes were insignificantly different in the two periods. No reductions in hospitalisations for control diagnoses were observed.

CONCLUSIONS: Incidence of IPD, pneumococcal pneumonia and all-cause pneumonia decreased during the COVID-19 pandemic. This was observed with universal masking and social distancing. We postulated this is related to reduced transmission of respiratory viruses and bacteria.

PMID:34635536 | DOI:10.1136/bmjopen-2021-055575

BMJ Open. 2021 Oct 11;11(10):e053179. doi: 10.1136/bmjopen-2021-053179.

ABSTRACT

OBJECTIVES: Previous studies have investigated the association between socioeconomic characteristics and fractures among children, producing different results. In a population-based study, we previously found an increased risk of fractures among children living in an urban municipality compared with rural municipalities. This study aimed to evaluate the importance of socioeconomic variables for the incidence of fractures among 0-17 year olds.

SETTING, DESIGN AND OUTCOME MEASURE: We present a longitudinal, observational study of a population 0-17 years of age. Data from an injury database were linked with additional socioeconomic data for the population at risk. These were 55 758 individuals residing within the primary catchment area of a regional hospital in northern Sweden. Using the number of fractures as the outcome, we fitted a generalised linear mixed model for a Poisson response with socioeconomic variables at the family level as independent variables while controlling for age, sex and place of residence.

RESULTS: We found a significant association between higher levels of family income and the risk of fracture, rate ratio 1.40 (1.28-1.52) p<0.001 when comparing the highest income quintile to the lowest as well as the number of siblings and the risk of fracture. Children with one or two siblings had a rate ratio of 1.28 (1.19-1.38) p<0.001 when compared with children with no siblings. Parents’ educational level and having a single parent showed no significant association with fractures. The previously observed association between municipalities and fracture risk was less pronounced when taking family-level socioeconomic variables into account.

CONCLUSION: Our results indicate that children from families with higher income and with siblings are at greater risk of sustaining fractures.

PMID:34635530 | DOI:10.1136/bmjopen-2021-053179

BMJ Open. 2021 Oct 11;11(10):e050827. doi: 10.1136/bmjopen-2021-050827.

ABSTRACT

OBJECTIVES: To analyse the empirical support of the functional ability concept in the healthy ageing framework developed by the WHO in a sample of the Philippine older population. According to this framework, environmental factors may enhance or hinder functional ability, which is the person’s ability to do what they value, broadly represented by subjective well-being. Moreover, this network of relationships may be moderated by personal characteristics such as gender.

DESIGN: Cross-sectional observational study.

SETTING: Philippines, general population.

PARTICIPANTS: Respondents of the 2016 National Disability Prevalence Survey/Model Functioning Survey aged 50+ (N=2825).

PRIMARY AND SECONDARY OUTCOME MEASURES: Latent (unobserved) measures of functional ability, environmental factors (physical environmental factors and social network and support) and subjective well-being (positive affect, negative affect and evaluative well-being) were obtained from different items from the survey questionnaire using a SEM framework.

RESULTS: We found that the relationship between environmental factors and the three components of subjective well-being considered in this study was partially explained by differences in functional ability. The portion of those effects accounted for by functional ability was comparatively larger for the physical than for the social environmental factors. We found no evidences of gender differences in this network of relationships.

CONCLUSIONS: These findings suggest the relevance of functional ability at explaining the relationship between environmental factors and subjective well-being in older adults. Future studies may replicate these findings longitudinally and including other relevant measures as the person’s objective level of intrinsic capacity.

PMID:34635522 | DOI:10.1136/bmjopen-2021-050827

BMJ Open. 2021 Oct 11;11(10):e047711. doi: 10.1136/bmjopen-2020-047711.

ABSTRACT

OBJECTIVES: To explore lay perceptions of bleeding during and after delivery, and measure the frequency of self-reported indicators of bleeding.

SETTING: Yola, North-East Nigeria.

PARTICIPANTS: Women aged 15-49 years who delivered in the preceding 2 years of data collection period (2015-2016), and their family members who played key roles.

METHODS: Data on perceptions of bleeding were collected through 7 focus group discussions, 21 in-depth interviews and 10 family interviews. Sampling was purposive and data were analysed thematically. A household survey was then conducted with 640 women using cluster sampling on postpartum bleeding indicators developed from the qualitative data; data were analysed descriptively.

RESULTS: Perceptions of excessive bleeding fell under four themes: quantity of blood lost; rate/duration of blood flow; symptoms related to blood loss and receiving birth interventions/hearing comments from birth attendants. Young and less educated rural women had difficulty quantifying blood loss objectively, including when shown quantities using bottles. Respondents felt that acceptable blood loss levels depended on the individual woman and whether the blood is ‘good’ or ‘diseased/bad.’ Respondents believed that ‘diseased’ blood was a normal result of delivery and universally took steps to help it ‘come out.’ In the quantitative survey, indicators representing less blood loss were reported more frequently than those representing greater loss, for example, more women reported staining their clothes (33.6%) than the bed (18.1%) and the floor (6.2%). Overall, indicators related to quantity and rate of blood flow had higher frequencies compared with symptom and intervention-related/comment-related indicators.

CONCLUSION: Women quantify bleeding during and after delivery in varied ways and some women do not see bleeding as problematic. This suggests the need for standard messaging to address subjectivity. The range of indicators and varied frequencies highlight the challenges of measuring excessive bleeding from self-reports. More work is needed in improving and testing validity of questions.

PMID:34635515 | DOI:10.1136/bmjopen-2020-047711

BMJ Open. 2021 Oct 11;11(10):e045086. doi: 10.1136/bmjopen-2020-045086.

ABSTRACT

OBJECTIVES: The influence of age on intensive care unit (ICU) decision-making is complex, and it is unclear if it is based on expected subjective or objective patient outcomes. To address recent concerns over age-based ICU decision-making, we explored patient-assessed quality of life (QoL) in ICU survivors before the COVID-19 pandemic.

DESIGN: A systematic review and meta-analysis of cohort studies published between January 2000 and April 2020, of elderly patients admitted to ICUs.

PRIMARY AND SECONDARY OUTCOME MEASURES: We extracted data on self-reported QoL (EQ-5D composite score), demographic and clinical variables. Using a random-effect meta-analysis, we then compared QoL scores at follow-up to scores either before admission, age-matched population controls or younger ICU survivors. We conducted sensitivity analyses to study heterogeneity and bias and a qualitative synthesis of subscores.

RESULTS: We identified 2536 studies and included 22 for qualitative synthesis and 18 for meta-analysis (n=2326 elderly survivors). Elderly survivors’ QoL was significantly worse than younger ICU survivors, with a small-to-medium effect size (d=0.35 (-0.53 and -0.16)). Elderly survivors’ QoL was also significantly greater when measured slightly before ICU, compared with follow-up, with a small effect size (d=0.26 (-0.44 and -0.08)). Finally, their QoL was also marginally significantly worse than age-matched community controls, also with a small effect size (d=0.21 (-0.43 and 0.00)). Mortality rates and length of follow-up partly explained heterogeneity. Reductions in QoL seemed primarily due to physical health, rather than mental health items.

CONCLUSIONS: The results suggest that the proportionality of age as a determinant of ICU resource allocation should be kept under close review and that subjective QoL outcomes should inform person-centred decision -aking in elderly ICU patients.

PROSPERO REGISTRATION NUMBER: CRD42020181181.

PMID:34635510 | DOI:10.1136/bmjopen-2020-045086

BMJ Evid Based Med. 2021 Oct 11:bmjebm-2020-111634. doi: 10.1136/bmjebm-2020-111634. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).

DESIGN: Systematic review and meta-analysis.

SETTING: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.

PARTICIPANTS: Patients with AF.

MAIN OUTCOME MEASURES: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I² statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist.

RESULTS: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I²=59.9%), $6353.24 ($4076.03 to $8630.45; I²=0%), $7664.58 ($2979.79 to $12 349.37; I²=0%) and $8573.07 ($1877.05 to $15 269.09; I²=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I²=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs.

CONCLUSIONS: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.

PROSPERO REGISTERATION NUMBER: CRD 42019146610.

PMID:34635480 | DOI:10.1136/bmjebm-2020-111634

J Med Imaging Radiat Sci. 2021 Oct 8:S1939-8654(21)00223-X. doi: 10.1016/j.jmir.2021.09.010. Online ahead of print.

ABSTRACT

BACKGROUND: As new treatments and technologies have been introduced in radiation oncology, the clinical roles of radiation therapists (RTs) have expanded. However, there are few formal learning opportunities for RTs. An online, anatomy, radiology and contouring bootcamp (ARC Bootcamp) originally designed for medical residents was identified as a prospective educational tool for RTs. The purpose of this study was to evaluate an RT edition of the ARC Bootcamp on knowledge, contouring, and confidence, as well as to identify areas for future modification.

METHODS: Fifty licensed RTs were enrolled in an eight-week, multidisciplinary, online RT ARC Bootcamp. Contouring practice was available throughout the course using an online contouring platform. Outcomes were evaluated using a pre-course and post-course multiple-choice quiz (MCQ), contouring evaluation and qualitative self-efficacy and satisfaction survey.

RESULTS: Of the fifty enrolled RTs, 30 completed the course, and 26 completed at least one of the post-tests. Nineteen contouring dice similarity coefficient (DSC) scores were available for paired pre- and post-course analysis. RTs demonstrated a statistically significant increase in mean DSC scoring pooled across all contouring structures (mean ± SD improvement: 0.09 ± 0.18 on a scale from 0 to 1, p=0.020). For individual contouring structures, 3/15 reached significance in contouring improvement. MCQ scores were available for 26 participants and increased after RT ARC Bootcamp participation with a mean ± SD pre-test score of 18.6 ± 4.2 (46.5%); on a 40-point scale vs. post-test score of 24.5 ± 4.3 (61.4%) (p < 0.001). RT confidence in contouring, anatomy knowledge and radiographic identification improved after course completion (p < 0.001). Feedback from RTs recommended more contouring instruction, less in-depth anatomy review and more time to complete the course.

CONCLUSIONS: The RT ARC Bootcamp was an effective tool for improving anatomy and radiographic knowledge among RTs. The course demonstrated improvements in contouring and overall confidence. However, only approximately half of the enrolled RTs completed the course, limiting statistical power. Future modifications will aim to increase relevance to RTs and improve completion rates.

PMID:34635471 | DOI:10.1016/j.jmir.2021.09.010

An Pediatr (Engl Ed). 2021 Oct 9:S2341-2879(21)00161-7. doi: 10.1016/j.anpede.2020.08.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management.

OBJECTIVES: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit.

METHODS: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed.

RESULTS: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)).

CONCLUSIONS: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

PMID:34635463 | DOI:10.1016/j.anpede.2020.08.013

Stat Med. 2021 Oct 11. doi: 10.1002/sim.9218. Online ahead of print.

ABSTRACT

This article discusses regression analysis of clustered interval-censored failure time data in the presence of a cured fraction or subgroup. Such data often occur in many areas, including epidemiological studies, medical studies, and social sciences. For the problem, a class of semiparametric transformation nonmixture cure models is presented and for estimation, the maximum likelihood estimation procedure is derived. For the implementation of the proposed method, we develop a novel EM algorithm based on a Poisson variable-based augmentation. An extensive simulation study is conducted and suggests that the proposed approach works well in practical situations. Finally the method is applied to an example that motivated this study.

PMID:34634837 | DOI:10.1002/sim.9218