Category: Nevin Manimala

PLoS One. 2023 Jan 30;18(1):e0280657. doi: 10.1371/journal.pone.0280657. eCollection 2023.

ABSTRACT

INTRODUCTION: Most strategies for prevention of venous thromboembolism focus on preventing recurrent events. Yet, primary prevention might be possible through approaches targeting the whole population or high-risk patients. To inform possible prevention strategies, population-based information on the ability of genetic risk scores to identify risk of incident venous thromboembolism is needed.

MATERIALS AND METHODS: We used proportional hazards regression to relate two published genetic risk scores (273-variants versus 5-variants) with venous thromboembolism incidence in the Atherosclerosis Risk in Communities Study (ARIC) cohort (n = 11,292), aged 45-64 at baseline, drawn from 4 US communities.

RESULTS: Over a median of 28 years, ARIC identified 788 incident venous thromboembolism events. Incidence rates rose more than two-fold across quartiles of the 273-variant genetic risk score: 1.7, 2.7, 3.4 and 4.0 per 1,000 person-years. For White participants, age, sex, and ancestry-adjusted hazard ratios (95% confidence intervals) across quartiles were strong [1 (reference), 1.30 (0.99,1.70), 1.85 (1.43,2.40), and 2.58 (2.04,3.28)] but weaker for Black participants [1, 1.05 (0.63,1.75), 1.37 (0.84,2.22), and 1.32 (0.80,2.20)]. The 5-variant genetic risk score showed a less steep gradient, with hazard ratios in Whites of 1, 1.17 (0.89,1.54), 1.48 (1.14,1.92), and 2.18 (1.71,2.79). Models including the 273-variant genetic risk score plus lifestyle and clinical factors had a c-statistic of 0.67.

CONCLUSIONS: In the general population, middle-aged adults in the highest quartile of either genetic risk score studied have approximately two-fold higher risk of an incident venous thromboembolism compared with the lowest quartile. The genetic risk scores show a weaker association with venous thromboembolism for Black people.

PMID:36716319 | DOI:10.1371/journal.pone.0280657

PLoS One. 2023 Jan 30;18(1):e0280744. doi: 10.1371/journal.pone.0280744. eCollection 2023.

ABSTRACT

This prospective quasi-experimental study from the NASAM (National Approach to Standardize and Improve Mechanical Ventilation) collaborative assessed the impact of evidence-based practices including subglottic suctioning, daily assessment for spontaneous awakening trial (SAT), spontaneous breathing trial (SBT), head of bed elevation, and avoidance of neuromuscular blockers unless otherwise indicated. The study outcomes included VAE (primary) and intensive care unit (ICU) mortality. Changes in daily care process measures and outcomes were evaluated using repeated measures mixed modeling. The results were reported as incident rate ratio (IRR) for each additional month with 95% confidence interval (CI). A comprehensive program that included education on evidence-based practices for optimal care of mechanically ventilated patients with real-time benchmarking of daily care process measures to drive improvement in forty-two ICUs from 26 hospitals in Saudi Arabia (>27,000 days of observation). Compliance with subglottic suctioning, SAT and SBT increased monthly during the project by 3.5%, 2.1% and 1.9%, respectively (IRR 1.035, 95%CI 1.007-1.064, p = 0.0148; 1.021, 95% CI 1.010-1.032, p = 0.0003; and 1.019, 95%CI 1.009-1.029, p = 0.0001, respectively). The use of neuromuscular blockers decreased monthly by 2.5% (IRR 0.975, 95%CI 0.953-0.998, p = 0.0341). The compliance with head of bed elevation was high at baseline and did not change over time. Based on data for 83153 ventilator days, VAE rate was 15.2/1000 ventilator day (95%CI 12.6-18.1) at baseline and did not change during the project (IRR 1.019, 95%CI 0.985-1.053, p = 0.2812). Based on data for 8523 patients; the mortality was 30.4% (95%CI 27.4-33.6) at baseline, and decreased monthly during the project by 1.6% (IRR 0.984, 95%CI 0.973-0.996, p = 0.0067). A national quality improvement collaborative was associated with improvements in daily care processes. These changes were associated with a reduction in mortality but not VAEs. Registration The study is registered in clinicaltrials.gov (NCT03790150).

PMID:36716310 | DOI:10.1371/journal.pone.0280744

J Cell Physiol. 2023 Jan 30. doi: 10.1002/jcp.30954. Online ahead of print.

ABSTRACT

Murburn concept constitutes the thesis that diffusible reactive species or DRS are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn posttranslational modifications (PTMs) result because murburn/murzyme functionalism is integral to cellular existence. Cells must incorporate the inherently stochastic nature of operations mediated by DRS. Due to the earlier/inertial stigmatic perception that DRS are mere agents of chaos, several such outcomes were either understood as deterministic modulations sponsored by house-keeping enzymes or deemed as unregulated nonenzymatic events resulting out of “oxidative stress”. In the current review, I dispel the myths around DRS-functions, and undertake systematic parsing and analyses of murburn modifications of proteins. Although it is impossible to demarcate all PTMs into the classical or murburn modalities, telltale signs of the latter are evident from the relative inaccessibility of the locus, non-specificities and mechanistic details. It is pointed out that while many murburn PTMs may be harmless, some others could have deleterious or beneficial physiological implications. Some details of reversible/irreversible modifications of amino acid residues and cofactors that may be subjected to phosphorylation, halogenation, glycosylation, alkylation/acetylation, hydroxylation/oxidation, etc. are listed, along with citations of select proteins where such modifications have been reported. The contexts of these modifications and their significance in (patho)physiology/aging and therapy are also presented. With more balanced explorations and statistically verified data, a definitive understanding of normal versus pathological contexts of murburn modifications would be obtainable in the future.

PMID:36716112 | DOI:10.1002/jcp.30954

Clin Orthop Relat Res. 2023 Jan 2. doi: 10.1097/CORR.0000000000002536. Online ahead of print.

ABSTRACT

BACKGROUND: Tibial turnup-plasty is a rarely performed surgical option for large bone defects of the distal or entire femur and can serve as an alternative to hip disarticulation or high above-knee amputation. It entails pedicled transport of the ipsilateral tibia with or without the proximal hindfoot for use as a vascularized autograft. It is rotated 180° in the coronal or sagittal plane to the remaining proximal femur or pelvis, augmenting the functional length of the thigh. Prior reports consist of small case series with heterogeneous surgical techniques. Patient-reported outcome measures after the procedure have not been reported, and ambulatory status after the procedure is also unknown.

QUESTIONS/PURPOSES: (1) What proportion of patients underwent reoperation after tibial turnup-plasty? (2) What is the ambulatory status and what proportion of patients used a prosthesis after tibial turnup-plasty? (3) What are the Patient-Reported Outcome Measurement Information System (PROMIS) Global-10 mental and physical function scores after tibial turnup-plasty?

METHODS: A retrospective analysis was performed of 11 patients who underwent tibial turnup-plasty between 2003 and 2021 by a single orthopaedic oncology division in collaboration with a reconstructive plastic surgery team. Nine patients were men, with a median age of 55 years (range 34 to 75 years). All had chronic infections after arthroplasty or oncologic reconstructions, with a median number of 13 surgeries before turnup-plasty. All were considered to have no other surgical options other than hip disarticulation or high transfemoral amputation. All patients who were offered this possibility accepted it. Data of interest included patient demographics and comorbidities, surgical history that led to limb compromise, medical and surgical perioperative complications, date of prosthesis fitting, and functional capacity at the most recent follow-up interval based on ambulatory status and PROMIS Global-10 mental and physical function scores. The statistical analysis was descriptive.

RESULTS: The median number of reoperations after turnup-plasty was one (range 0 to 11). Of the six patients who underwent at least one reoperation, indications for surgery included wound infection (four patients), nonunion of the osteosynthesis site (two), heterotopic ossification (one), tumor recurrence (one), and flap hypoperfusion treated with local tissue revision (one). One patient underwent conversion to external hemipelvectomy for tumor recurrence. Ten of the 11 patients were ambulatory at the final follow-up interval with standard above-knee amputation prostheses. Two ambulated unassisted, four used a single crutch or cane, and four used two crutches or a walker. Of the nine patients for whom scores were available, the median PROMIS Global-10 physical and mental health scores were 48 (range 30 to 68) and 53 (range 41 to 68), both within the standard deviation of the population mean of 50.

CONCLUSION: The tibial turnup-plasty is a complex surgical option for patients with large bone defects of the femur for whom there are no alternative surgeries capable of producing residual extremities with acceptable functional length. This should be viewed as a procedure of last resort to avoid a hip disarticulation or a high transfemoral amputation in patients who have typically undergone numerous prior operations. Although ambulation with a prosthesis within 1 year can be expected, almost all patients will require an assistive device to do so, and reoperations are frequent.

LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID:36716090 | DOI:10.1097/CORR.0000000000002536

JMIR Res Protoc. 2023 Jan 30;12:e38273. doi: 10.2196/38273.

ABSTRACT

BACKGROUND: Spinal metastases of lung cancer (SMLC) usually have a high degree of malignancy and require multimodality treatment. Patients with SMLC who experience clinical symptoms (eg, local pain, emerging or potential spinal instability, and progressive neurological dysfunction) require surgical treatment. However, there are discrepancies in the comparison of outcomes between surgical treatment and nonsurgical treatment.

OBJECTIVE: This paper presents the protocol for a study that aims to compare the clinical outcomes of surgical treatment and nonsurgical treatment for SMLC, explore the prognostic factors of SMLC, and establish a survival prediction model based on these prognostic factors.

METHODS: This is a prospective cohort study, with an anticipated sample size of 240 patients (120 patients in the surgical group and 120 patients in the nonsurgical group). We will collect baseline data, including demographic, clinical, and radiological information, as well as data from patient-reported questionnaires. Patients will be followed up at 3, 6, 12, and 24 months after treatment, and survival status will be assessed every 3 months. The primary outcome is the overall survival period. Prognostic factors associated with overall survival will be analyzed by univariate and multivariate Cox proportional hazards regression. Odds ratios with 95% CIs will be presented. Statistical significance is set at P<.05.

RESULTS: This study has been approved by our institute’s Medical Science Research Ethics Committee (IRB00006761-M2021085) after a careful audit of the design and content. Patient enrollment began in June 2022 at our hospital. Data collection is expected to be completed by early 2026, and the study results will be published by mid-2027.

CONCLUSIONS: In this study, we propose to set up a prospective cohort of patients with SMLC to investigate the outcomes between surgical treatment and nonsurgical treatment. We will explore the role of surgical treatment in SMLC and provide guidance to peer surgeons.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100048151; http://www.chictr.org.cn/showproj.aspx?proj=129450.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38273.

PMID:36716088 | DOI:10.2196/38273

Health Rep. 2023 Jan 18;34(1):16-31. doi: 10.25318/82-003-x202300100002-eng.

ABSTRACT

BACKGROUND: This study described the differences in the hospitalization rates of First Nations children and youth living on and off reserve, Inuit children and youth living in Inuit Nunangat (excluding Nunavik), and Métis children and youth, relative to non-Indigenous children and youth and examined rate changes across 2006 and 2011.

DATA AND METHODS: The 2006 and the 2011 Canadian Census Health and Environment Cohorts provided five years of hospital records that Statistics Canada linked to peoples’ self-reported Indigenous identity as recorded on the census. Causes of hospitalizations were based on the most responsible diagnosis coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada, aggregated by chapter code. Age-standardized hospitalization rates (ASHRs) were calculated per 100,000 population. Rate ratios (RRs) were reported for each Indigenous group relative to non-Indigenous children and youth.

RESULTS: For the 2006 and the 2011 cohorts, ASHRs were generally higher among Indigenous children and youth than among non-Indigenous children and youth. For some health conditions, hospitalization patterns also varied across the two time periods within the given Indigenous groups. Among children, leading elevated RRs occurred for diseases of the respiratory system, the digestive system and injuries. Elevated mental health-related RRs were observed among all Indigenous groups for both cohort years of youth. Significant increases in mental health-related ASHRs were observed in 2011 compared with 2006 among all youth groups, except for Inuit youth living in Inuit Nunangat, possibly due in part to data limitations. Among Indigenous youth, elevated RRs were observed for pregnancy, childbirth and the puerperium, and for injuries. For all youth (except Inuit), childbirth-related ASHRs decreased in 2011 compared with 2006.

INTERPRETATION: Findings align with previously observed hospitalization disparities between Indigenous and non-Indigenous children and youth. These data enabled the tracking of changes over time to partly address national information gaps about population health outcomes for children and youth, namely hospitalization.

PMID:36716076 | DOI:10.25318/82-003-x202300100002-eng

Health Rep. 2023 Jan 18;34(1):3-15. doi: 10.25318/82-003-x202300100001-eng.

ABSTRACT

BACKGROUND: Cancer survival estimates provide insights into the effectiveness of early detection and treatment. The stage of cancer at diagnosis is an important determinant of survival, reflecting the extent and spread at the time of disease detection. This work provides stage-specific, five-year survival results not previously available for Canada.

DATA AND METHODS: Data reflect the population-based Canadian Cancer Registry death-linked analytic file covering the period from 2010 to 2017. The stage at diagnosis was determined by the Collaborative Stage Data Collection System. Five-year net survival (NS) estimates for Canada excluding Quebec were derived using the Pohar Perme estimator for the five most commonly diagnosed cancers.

RESULTS: Except for prostate cancer, NS decreased monotonically with increased stage at diagnosis. For example, female breast cancer NS estimates were 100% (stage I), 92% (stage II), 74% (stage III) and 23% (stage IV). Apart from lung cancer, stage I NS exceeded 90% for all cancers studied. The largest sex-specific difference in NS was for lung cancer stage I (female 66%; male 56%). Stage-specific NS generally decreased with age, particularly for early-stage lung cancer. Between the 2010-to-2012 and 2015-to-2017 periods, NS improved among stage IV prostate, female breast and lung cancer cases, as well as for stage I and III lung cancer cases; however, it did not improve at any stage for colon or rectal cancer cases.

INTERPRETATION: The work highlights the importance of detecting cancer early, when treatment is most effective. It demonstrates some progress in stage-specific survival among top cancers in Canada and offers data to inform health policy, including screening, and clinical decisions regarding cancer treatment.

PMID:36716075 | DOI:10.25318/82-003-x202300100001-eng

JAMA Netw Open. 2023 Jan 3;6(1):e2253590. doi: 10.1001/jamanetworkopen.2022.53590.

ABSTRACT

IMPORTANCE: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death.

OBJECTIVE: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US.

DESIGN, SETTING, AND PARTICIPANTS: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021.

MAIN OUTCOMES AND MEASURES: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years).

RESULTS: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19’s role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP.

PMID:36716029 | DOI:10.1001/jamanetworkopen.2022.53590

JAMA Netw Open. 2023 Jan 3;6(1):e2253687. doi: 10.1001/jamanetworkopen.2022.53687.

ABSTRACT

IMPORTANCE: Limited prior research suggests that transgender and gender diverse (TGD) people may have higher mortality rates than cisgender people.

OBJECTIVE: To estimate overall and cause-specific mortality among TGD persons compared with cisgender persons.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from general practices in England contributing to the UK’s Clinical Practice Research Datalink GOLD and Aurum databases. Transfeminine (assigned male at birth) and transmasculine (assigned female at birth) individuals were identified using diagnosis codes for gender incongruence, between 1988 and 2019, and were matched to cisgender men and women according to birth year, practice, and practice registration date and linked to the Office of National Statistics death registration. Data analysis was performed from February to June 2022.

MAIN OUTCOMES AND MEASURES: Cause-specific mortality counts were calculated for categories of disease as defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision chapters. Overall and cause-specific mortality rate ratios (MRRs) were estimated using Poisson models, adjusted for index age, index year, race and ethnicity, Index of Multiple Deprivation, smoking status, alcohol use, and body mass index.

RESULTS: A total of 1951 transfeminine (mean [SE] age, 36.90 [0.34] years; 1801 White [92.3%]) and 1364 transmasculine (mean [SE] age, 29.20 [0.36] years; 1235 White [90.4%]) individuals were matched with 68 165 cisgender men (mean [SE] age, 33.60 [0.05] years; 59 136 White [86.8%]) and 68 004 cisgender women (mean [SE] age, 33.50 [0.05] years; 57 762 White [84.9%]). The mortality rate was 528.11 deaths per 100 000 person-years (102 deaths) for transfeminine persons, 325.86 deaths per 100 000 person-years (34 deaths) for transmasculine persons, 315.32 deaths per 100 000 person-years (1951 deaths) for cisgender men, and 260.61 deaths per 100 000 person-years (1608 deaths) for cisgender women. Transfeminine persons had a higher overall mortality risk compared with cisgender men (MRR, 1.34; 95% CI, 1.06-1.68) and cisgender women (MRR, 1.60; 95% CI, 1.27-2.01). For transmasculine persons, the overall MMR was 1.43 (95% CI, 0.87-2.33) compared with cisgender men and was 1.75 (95% CI, 1.08-2.83) compared with cisgender women. Transfeminine individuals had lower cancer mortality than cisgender women (MRR, 0.52; 95% CI, 0.32-0.83) but an increased risk of external causes of death (MRR, 1.92; 95% CI, 1.05-3.50). Transmasculine persons had higher mortality from external causes of death than cisgender women (MRR, 2.77; 95% CI, 1.15-6.65). Compared with cisgender men, neither transfeminine nor transmasculine adults had a significantly increased risk of deaths due to external causes.

CONCLUSIONS AND RELEVANCE: In this cohort study of primary care data, TGD persons had elevated mortality rates compared with cisgender persons, particularly for deaths due to external causes. Further research is needed to examine how minority stress may be contributing to deaths among TGD individuals to reduce mortality.

PMID:36716027 | DOI:10.1001/jamanetworkopen.2022.53687

JAMA Pediatr. 2023 Jan 30. doi: 10.1001/jamapediatrics.2022.5642. Online ahead of print.

ABSTRACT

IMPORTANCE: High-intensity drinking (HID) (≥10 drinks in a row) is associated with acute negative outcomes. Identifying factors associated with HID initiation in adolescence and how it is associated with young adulthood outcomes can inform screening and prevention.

OBJECTIVE: To identify when individuals initiate HID and speed of escalation from first drink and first binge to first HID; characteristics associated with initiation and escalation; and whether these characteristics are associated with weekly alcohol consumption, HID frequency, and symptoms of alcohol use disorder at age 20 years.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed web-based survey data from respondents in the US who reported alcohol use in the past 30 days recruited from the 2018 12th grade Monitoring the Future study and surveyed again from February 14 through April 17, 2020, at modal age 20 years in the Young Adult Daily Life Study. Only respondents who reported HID by modal age 20 years were included in the analyses.

EXPOSURES: Retrospective alcohol use initiation and self-reported alcohol use measures.

MAIN OUTCOMES AND MEASURES: Key retrospective measures included year of initiation for alcohol, first binge (≥5 drinks), and HID (≥10 drinks). Measures at age 20 years included weekly alcohol consumption, HID frequency, and Alcohol Use Disorders Identification Test (AUDIT) scores. Covariates included biologic sex, race and ethnicity, parental college education, family history of alcohol problems, and college status. Descriptive statistics and multivariable regression models were used, and all analyses were weighted.

RESULTS: Of the 451 participants with data eligible for analysis, 62.0% were male (38.0% female). On average, alcohol, binge, and HID were initiated during high school. Mean time of escalation from first drink to first HID was 1.9 (95% CI, 1.8-2.1) years and between first binge and first HID, 0.7 (95% CI, 0.6-0.8) years. Initiating HID by grade 11 (vs later) was associated with higher average weekly alcohol consumption (adjusted incidence rate ratio [aIRR], 1.40; 95% CI, 1.10-1.79]), HID frequency (aIRR, 2.01; 95% CI, 1.25-3.22]), and AUDIT score (adjusted odds ratio, 1.17; 95% CI, 1.02-1.34]) at age 20 years. Escalation from first binge to first HID in the same year (vs ≥1 year) was associated with higher HID frequency at age 20 years (aIRR, 1.66; 95% CI, 1.06-2.61).

CONCLUSIONS AND RELEVANCE: These findings suggest that understanding ages and patterns of HID initiation and escalation associated with particular risk may facilitate screening for adolescents and young adults.

PMID:36716022 | DOI:10.1001/jamapediatrics.2022.5642