117 research outputs found
Smoking and infertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study
Objective
To investigate the association between smoking and infertility.
Design
Prospective study.
Setting
Nationwide cohort.
Patients
28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study.
Intervention
Self-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization.
Main outcome measure
Infertility (time-to-pregnancy â„12 months).
Results
Having ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]crude, 1.19; 95% confidence interval [CI] 1.11â1.28; ORadjusted 1.12; 95% CI, 1.03â1.21), also after adjusting for the partnerâs tobacco use. Later smoking initiation (+1 SD [3.2 years]: ORcrude, 0.94; 95% CI, 0.88â0.99; ORadjusted 0.89; 95% CI, 0.84â0.95) and smoking cessation (vs. not quitting: ORcrude, 0.83; 95% CI, 0.75â0.91; ORadjusted, 0.83; 95% CI, 0.75â0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization.
Conclusions
We did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.publishedVersio
Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap) alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.
UNLABELLED: The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS) for the treatment of uncomplicated falciparum malaria. METHODS: Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population using mean time to reduce baseline parasitemia by 90% (PC90). A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT) population. RESULTS: In the Day 3 PP population for the adult group (N = 85), mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5]), 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2]) and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2]) groups. For children in the Day 3 PP population (N = 92), mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0]) and 12.8 h (-7.4 h [95%CI -12.9, -1.8]), respectively. An analysis of mean time to PC90 for the Day 14 PP and ITT populations was consistent with the primary analysis. Treatment emergent, drug-related adverse events were experienced in 35.3% (41/116) of adults and 70.1% (75/107) of children; mostly hematological and gastroenterological. The nature and incidence of adverse events was similar between the groups. No dose-related changes in laboratory parameters were observed. Nine serious adverse events due to any cause occurred in five subjects including two cases of hemolysis believed to be associated with drug treatment (one adult, one child). One adult died of anaphylactic shock, not associated with investigational therapy. CONCLUSIONS: CPG-DDS plus artesunate demonstrated advantages over CPG-DDS alone for the primary efficacy endpoint (mean time to PC90) except in children for the 1 mg/kg artesunate dose. Based on a pre-defined decision matrix, the primary endpoint in the child group supported an artesunate dose of 4 mg/kg. Secondary endpoints also supported a 4 mg/kg artesunate dose to take forward into the remainder of the development program. TRIAL REGISTRATION: ClinicalTrials.gov NCT00519467
Computed Tomography With Intravenous Contrast Alone: The Role of Intraâabdominal Fat on the Ability to Visualize the Normal Appendix in Children
Background Computed tomography ( CT ) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous ( IV ) contrast alone ( CT IV ) may be sufficient, however, particularly in patients with adequate intraâabdominal fat ( IAF ). Objectives The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. Methods This was a retrospective 16âcenter study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF . Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as âadequateâ if there was any amount of fat completely surrounding the cecum and âinadequateâ if otherwise. Results A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF . The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [ CI ] = 67.2% to 78.0%); the proportions were 89% (95% CI  = 81.5% to 94.5%) and 63% (95% CI  = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF . Conclusions Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight. Resumen TomografĂa Computarizada Ănicamente con Contraste Intravenoso: El Papel de la Grasa Intrabadominal en la Capacidad para Visualizar el ApĂ©ndice Normal en los Niños Introduction La tomografĂa computarizada ( TC ) con contraste entĂ©rico es usada frecuentemente para evaluar a los niños con sospecha de apendicitis. El uso de la TC Ășnicamente con contraste intravenoso ( TC IV ) puede ser suficiente, especialmente en pacientes con adecuada grasa intrabdominal ( GIA ). Objetivos 1) Determinar la capacidad de los radiĂłlogos para visualizar el apĂ©ndice normal (sin enfermedad) con TC IV en niños, y valorar si la cantidad de GIA afecta a esta capacidad; y 2) valorar la asociaciĂłn entre la idoneidad de la GIA y las caracterĂsticas del paciente. MetodologĂa Estudio retrospectivo de 16 hospitales que utilizĂł una base de datos prexistente de TC abdominales. Se incluyĂł a los niños entre 3 y 18 años que tenĂan una TC IV , una medida del peso e historia de apendectomĂa conocida por la revisiĂłn de la historia clĂnica. La muestra se eligiĂł en base a la edad con el fin de conseguir una muestra con y sin GIA adecuada. Los radiĂłlogos de cada centro releyeron las TC IV de sus centros para valorar la visualizaciĂłn del apĂ©ndice y la adecuaciĂłn de la GIA . La GIA se clasificĂł como âadecuadaâ si habĂa cualquier cantidad de grasa completamente alrededor del ciego e âinadecuadaâ si era de otra manera. Resultados Se incluyeron 280 pacientes, con una media de edad de 10,6 años (rango 3,1 a 17,9 años). Ninguno tenĂa historia previa de apendectomĂa; por lo tanto todos los pacientes tuvieron un apĂ©ndice presumiblemente normal. Ciento dos pacientes (36,4%) tuvieron GIA adecuada. El porcentaje de apĂ©ndices normales visualizados con TC IV fue de 72,9% ( IC 95% = 67,2% a 78,0%); la proporciĂłn fue 89% ( IC 95% = 81,5% a 94,5%), y 63% ( IC 95% = 56,0% a 70,6%) en aquĂ©llos con y sin GIA adecuada ( IC 95% para la diferencia de proporciones = 16% a 36%). El mayor peso y la mayor edad se asociaron fuertemente con la adecuaciĂłn de la GIA (p < 0,001), y el peso resultĂł ser el mayor factor predictivo, especialmente en mujeres. Aunque se asociĂł estadĂsticamente, se vio un solapamiento en los pesos y edades de aquĂ©llos con y sin GIA adecuada. Conclusiones Los protocolos que usan la TC IV para visualizar el apĂ©ndice pueden razonablemente incluir el peso, la edad, o ambas como consideraciones para determinar cuĂĄndo esta aproximaciĂłn es apropiada. Sin embargo, aunque la cantidad de GIA serĂĄ frecuentemente mĂĄs apropiada en los pacientes mĂĄs mayores y de mayor peso, la predicciĂłn certera de adecuaciĂłn de GIA es altamente desafiante si se basa sĂłlo en la edad y el peso.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99695/1/acem12185.pd
Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women
ChlorproguanilâDapsoneâArtesunate versus ArtemetherâLumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria
Chlorproguanilâdapsoneâartesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemetherâlumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients
Retrieval accuracy, statistical significance and compositional similarity in protein sequence database searches
Protein sequence database search programs may be evaluated both for their retrieval accuracyâthe ability to separate meaningful from chance similaritiesâand for the accuracy of their statistical assessments of reported alignments. However, methods for improving statistical accuracy can degrade retrieval accuracy by discarding compositional evidence of sequence relatedness. This evidence may be preserved by combining essentially independent measures of alignment and compositional similarity into a unified measure of sequence similarity. A version of the BLAST protein database search program, modified to employ this new measure, outperforms the baseline program in both retrieval and statistical accuracy on ASTRAL, a SCOP-based test set
Composition-based statistics and translated nucleotide searches: Improving the TBLASTN module of BLAST
BACKGROUND: TBLASTN is a mode of operation for BLAST that aligns protein sequences to a nucleotide database translated in all six frames. We present the first description of the modern implementation of TBLASTN, focusing on new techniques that were used to implement composition-based statistics for translated nucleotide searches. Composition-based statistics use the composition of the sequences being aligned to generate more accurate E-values, which allows for a more accurate distinction between true and false matches. Until recently, composition-based statistics were available only for protein-protein searches. They are now available as a command line option for recent versions of TBLASTN and as an option for TBLASTN on the NCBI BLAST web server. RESULTS: We evaluate the statistical and retrieval accuracy of the E-values reported by a baseline version of TBLASTN and by two variants that use different types of composition-based statistics. To test the statistical accuracy of TBLASTN, we ran 1000 searches using scrambled proteins from the mouse genome and a database of human chromosomes. To test retrieval accuracy, we modernize and adapt to translated searches a test set previously used to evaluate the retrieval accuracy of protein-protein searches. We show that composition-based statistics greatly improve the statistical accuracy of TBLASTN, at a small cost to the retrieval accuracy. CONCLUSION: TBLASTN is widely used, as it is common to wish to compare proteins to chromosomes or to libraries of mRNAs. Composition-based statistics improve the statistical accuracy, and therefore the reliability, of TBLASTN results. The algorithms used by TBLASTN are not widely known, and some of the most important are reported here. The data used to test TBLASTN are available for download and may be useful in other studies of translated search algorithms
Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission
Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11â1.70] ng/mL vs 0.24 [0.10â0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51â.60]).</jats:p
Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study
BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47â795 (75·2%) of 63â525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11â185 [86·6%] of 12â909 vs 36â415 [72·4%] of 50â278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70â0·89], p=0·0001, for 70â79 years; 0·52 [0·46â0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75â80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council
Evaluation of a COVID â19 fundamental nursing care guideline versus usual care: The COVIDâNURSE cluster randomized controlled trial
Aim: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVIDâ19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient healthârelated quality of life and costâeffectiveness. Design: Parallel twoâarm, clusterâlevel randomized controlled trial. Methods: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVIDâ19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patientâreported coâprimary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intentionâtoâtreat analyses. Results: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570â572 (98.1%â98.5%) patient participants in 14 clusters. We found no evidence of betweenâgroup differences on any patient, nurse or economic outcomes. We found betweenâgroup differences over time, in favour of the intervention, for three of our five coâprimary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the âotherâ ethnicity subgroup. Conclusion: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on nonâwhite British patients' experience of care. Implications for the Profession and/or Patient Care: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. Impact: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on nonâwhite British patients' experience of care. Reporting Method: CONSORT and CONSERVE. Patient or Public Contribution: Patients with experience of hospitalization with COVIDâ19 were involved in guideline development and writing, trial management and interpretation of findings
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