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Clinical Pharmacology and Therapeutics May 2022Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to...
Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically-based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1,000 simulated women who were 2 days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
Topics: Female; Humans; Infant; Breast Feeding; Lactation; Milk, Human; Ondansetron; Postpartum Period
PubMed: 35076931
DOI: 10.1002/cpt.2530 -
Frontiers in Psychiatry 2021The COVID-19 pandemic has posed notable challenges to post-secondary students, causing concern for their psychological well-being. In the face of school closures,...
The COVID-19 pandemic has posed notable challenges to post-secondary students, causing concern for their psychological well-being. In the face of school closures, academic disruptions, and constraints on social gatherings, it is crucial to understand the extent to which mental health among post-secondary students has been impacted in order to inform support implementation for this population. The present meta-analysis examines the global prevalence of clinically significant depression and anxiety among post-secondary students during the COVID-19 pandemic. Several moderator analyses were also performed to examine sources of variability in depression and anxiety prevalence rates. A systematic search was conducted across six databases on May 3, 2021, yielding a total of 176 studies (1,732,456 participants) which met inclusion criteria. Random-effects meta-analyses of 126 studies assessing depression symptoms and 144 studies assessing anxiety symptoms were conducted. The pooled prevalence estimates of clinically elevated depressive and anxiety symptoms for post-secondary students during the COVID-19 pandemic was 30.6% (95% CI: 0.274, 0.340) and 28.2% (CI: 0.246, 0.321), respectively. The month of data collection and geographical region were determined to be significant moderators. However, student age, sex, type (i.e., healthcare student vs. non-healthcare student), and level of training (i.e., undergraduate, university or college generally; graduate, medical, post-doctorate, fellow, trainee), were not sources of variability in pooled rates of depression and anxiety symptoms during the pandemic. The current study indicates a call for continued access to mental health services to ensure post-secondary students receive adequate support during and after the COVID-19 pandemic. PROSPERO website: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021253547.
PubMed: 34955924
DOI: 10.3389/fpsyt.2021.777251 -
JAMA Network Open Dec 2021With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for...
IMPORTANCE
With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking.
OBJECTIVES
To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps.
EVIDENCE REVIEW
A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic.
FINDINGS
Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations.
CONCLUSIONS AND RELEVANCE
This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.
Topics: Accidental Falls; Aged; Aged, 80 and over; Combined Modality Therapy; Consensus; Environment Design; Health Promotion; Health Services for the Aged; Humans; Medication Review; Middle Aged; Osteoporosis; Physical Therapy Modalities; Practice Guidelines as Topic; Wounds and Injuries
PubMed: 34910151
DOI: 10.1001/jamanetworkopen.2021.38911 -
Clinical Pharmacokinetics Feb 2022The use of continuous renal replacement therapy (CRRT) for renal support has increased substantially in critically ill children compared with intermittent modalities...
BACKGROUND AND OBJECTIVE
The use of continuous renal replacement therapy (CRRT) for renal support has increased substantially in critically ill children compared with intermittent modalities owing to its preferential effects on hemodynamic stability. With the expanding role of CRRT, the quantification of extracorporeal clearance and the effect on primary pharmacokinetic parameters is of the utmost importance. Within this review, we aimed to summarize the current state of the literature and compare published pharmacokinetic analyses of commonly used medications in children receiving CRRT to those who are not.
METHODS
A systematic search of the literature within electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science was conducted. Published studies that were included contained relevant information on the use of commonly administered medications to children, from neonates to adolescents, receiving CRRT. Pharmacokinetic parameters that were analyzed included volume of distribution, total clearance, extracorporeal clearance, area under the curve, and elimination half-life. Information regarding CRRT circuit, flow rates, and membrane components was analyzed to investigate differences in pharmacokinetics between each modality.
RESULTS
Forty-five studies met the final inclusion criteria within this systematic review, totaling 833 pediatric patients, with 586 receiving CRRT. Antimicrobials were the most common pharmacological class represented within the literature, representing 81% (35/43) of studies analyzed. Children receiving CRRT largely had similar volume of distribution and total clearance to critically ill children not receiving CRRT, suggesting reno-protective dose adjustments may lead to subtherapeutic dosing regimens in these patients. Overall, there was a tendency for hydrophilic agents, with a low protein binding to undergo elevated total clearance in these children. However, results should be interpreted with caution because of the large variability amongst patient populations and heterogeneity with CRRT modalities, flow rates, and use of extracorporeal membrane oxygenation within studies. This review was able to identify that variation in solute removal, or CRRT modalities, properties (i.e., flow rates), and membrane composition, may have differing effects on the pharmacokinetics of commonly administered medications.
CONCLUSIONS
The current state of the literature regarding medications administered to children receiving CRRT largely focuses on antimicrobials. Significant gaps remain with other commonly used medications such as sedatives and analgesics. Overall reporting of patient clinical characteristics, CRRT settings, and circuit composition was poor, with only 10% of articles including all relevant information to assess the impact of CRRT on total clearance. Changes in pharmacokinetics because of CRRT often required higher than labeled doses, suggesting renally adjusted or reno-protective doses may lead to subtherapeutic dosing regimens. A thorough understanding of the interplay between patient, drug, and CRRT-circuit factors are required to ensure adequate delivery of dosing regimens to this vulnerable population.
Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Child; Continuous Renal Replacement Therapy; Critical Illness; Extracorporeal Membrane Oxygenation; Humans; Infant, Newborn; Renal Replacement Therapy
PubMed: 34846703
DOI: 10.1007/s40262-021-01085-z -
Frontiers in Neurology 2021The global burden of dementia has increasingly shifted to low- and middle-income regions that lack essential data for monitoring epidemiological progression, and policy...
The global burden of dementia has increasingly shifted to low- and middle-income regions that lack essential data for monitoring epidemiological progression, and policy and planning support. Drawing upon data that have emerged since the last known estimates published in 2015, this study aims to update dementia estimates in the Latin America and Caribbean (LAC) region for the years 2020, 2030, and 2050 through the application of a recently validated Bayesian approach for disease estimates useful when data sources are scarce. A comprehensive parallel systematic review of PubMed, EMBASE, PsycINFO, Global Health, and LILACS was conducted to identify prospective population-based epidemiological studies on dementia published in English from 2013 to 2018 in LAC. English and non-English data cited by a recent review on dementia estimates in LAC were also examined for additional data. A Bayesian normal-normal hierarchical model (NNHM) was developed to estimate age-specific and age-adjusted dementia prevalence in people aged 60+. Using age-specific population projections from the UN, the total number of people affected by dementia for the years 2020, 2030, and 2050 were estimated. 1,414 studies were identified, of which only 7 met the inclusion criteria. The studies had 7,684 participants and 1,191 dementia cases. The age-standardized prevalence of all forms of dementia in LAC was 8% (95% CI: 5-11.5%) in people aged 60+. The estimated prevalence varied with age, increasing from 2.5% (95% CI: 0.08-4.0%) in the 60-69 age group, to 9.4% (95% CI: 5.4-13.2%) in the 70-79 age group and 28.9% (95% CI: 20.3-37.2%) in the ≥80 age group. The number of people age 60 and older living with dementia in LAC in 2020 was estimated at 6.86 (95% CI: 4.3-9.8) million, 9.94 (95% CI: 6.16-14.15) million in 2030, and 19.33 (95% CI: 12.3-13.6) million in 2050. We project an upward disease trajectory for dementia in LAC countries. The projection is likely an underestimation of the true dementia burden given the underrepresentation of rural and socio-economically deprived populations. More research is urgently needed to improve the accuracy of disease estimates, guide clinicians to improve evaluations for earlier recognition of dementia, and support the development of effective policies for improving dementia prevention, diagnosis and clinical management in LAC's diverse and aging communities.
PubMed: 34393965
DOI: 10.3389/fneur.2021.628520 -
Mayo Clinic Proceedings. Innovations,... Aug 2021To carry out a systematic review of the effect of cardiac rehabilitation (CR) and its components on cardiovascular outcomes in patients with stable angina.
OBJECTIVE
To carry out a systematic review of the effect of cardiac rehabilitation (CR) and its components on cardiovascular outcomes in patients with stable angina.
METHODS
We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from their inception up to November 1, 2017. The search was not restricted to time or publication status but was limited to the English language. Two independent investigators screened the identified studies and extracted the data in duplicate. We reviewed the included studies and, where possible, pooled their results and conducted meta-analyses. Risk of bias was assessed using Cochrane Collaboration tools.
RESULTS
The search identified 7508 studies. Ten randomized trials including 4005 participants with the mean (SD) age of 59.6 (5.7) years were considered eligible for inclusion in our analyses. The results of meta-analyses of exercise-based CR for patients with stable angina revealed that CR improved exercise capacity (the difference between baseline and follow-up was 0.76 watt [0.49 to 1.02] higher in the CR group vs the non-CR group) and decreased angina frequency (standard mean difference, -0.27 [CI, -0.43 to 0.11]). No significant differences were noted in other outcomes, including quality of life. Mortality could not be adequately assessed because it was analyzed in only 1 exercise-based CR study.
CONCLUSION
Our systematic review, involving a relatively small number of studies with low to moderate risk of bias and with considerable heterogeneity, found a significant decrease in angina frequency and increase in exercise capacity in patients with stable angina who participated in an exercise-based CR program. Studies involving the impact of components of CR are limited and generally report beneficial outcomes. Additional studies are needed to clarify the possible role of CR in the management of patients with stable angina.
PubMed: 34355130
DOI: 10.1016/j.mayocpiqo.2021.06.009 -
Annals of Work Exposures and Health Oct 2021This systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used...
OBJECTIVES
This systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used to identify actions necessary to improve the quality of the data.
METHODS
We searched Web of Science and Google Scholar until 24 December 2020 for relevant articles and extracted data on methodology and results.
RESULTS
The vast majority of data come from healthcare settings, with typically around 6% of samples having detectable concentrations of SARS-CoV-2 RNA and almost none of the samples collected had viable virus. There were a wide variety of methods used to measure airborne virus, although surface sampling was generally undertaken using nylon flocked swabs. Overall, the quality of the measurements was poor. Only a small number of studies reported the airborne concentration of SARS-CoV-2 virus RNA, mostly just reporting the detectable concentration values without reference to the detection limit. Imputing the geometric mean air concentration assuming the limit of detection was the lowest reported value, suggests typical concentrations in healthcare settings may be around 0.01 SARS-CoV-2 virus RNA copies m-3. Data on surface virus loading per unit area were mostly unavailable.
CONCLUSIONS
The reliability of the reported data is uncertain. The methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments should be standardized to facilitate more consistent interpretation of contamination and to help reliably estimate worker exposure.
Topics: COVID-19; Humans; Occupational Exposure; RNA, Viral; Reproducibility of Results; SARS-CoV-2; Workplace
PubMed: 34329379
DOI: 10.1093/annweh/wxab026 -
Ageing Research Reviews Nov 2021Intergenerational engagement could benefit health and wellbeing within an ageing population. This systematic review evaluated the impacts of intergenerational engagement... (Review)
Review
BACKGROUND
Intergenerational engagement could benefit health and wellbeing within an ageing population. This systematic review evaluated the impacts of intergenerational engagement on cognitive, social, and health outcomes in healthy older adults and older adults with mild cognitive impairment.
RESEARCH DESIGN AND METHODS
Comprehensive literature searches were undertaken, with records filtered according to pre-registered criteria. Study quality was formally assessed, and a narrative synthesis of the findings produced.
RESULTS
Forty-four studies were reviewed. Regarding quantitative evidence, 4 out of 8 studies found significant intergenerational engagement effects on cognitive outcomes, 15 of 24 on social outcomes, and 21 of 31 on health-related outcomes. Qualitative evidence was also important for understanding perceived impacts and experiences of intergenerational programmes. Only 11 studies fully met criteria for high quality research, of which the majority focused on social outcomes.
DISCUSSION AND IMPLICATIONS
There are a range of potential benefits of intergenerational engagement, most notably regarding anxiety, generativity, cross-age attitudes, and physical activity. However, heterogeneity in programme context, sample design, dosage, and duration indicate that more research is required to enable wider implementation and generalisability. Scientific rigour in both quantitative and qualitative research should also be employed as far as possible, to provide the highest quality evidence.
Topics: Aged; Cognition; Exercise; Health Status; Humans; Outcome Assessment, Health Care
PubMed: 34237435
DOI: 10.1016/j.arr.2021.101400 -
Healthcare (Basel, Switzerland) Jun 2021Eagle syndrome occurs when elongated styloid process or ossification of the stylohyoid ligament interfere with the surrounding anatomical structures giving rise to... (Review)
Review
BACKGROUND
Eagle syndrome occurs when elongated styloid process or ossification of the stylohyoid ligament interfere with the surrounding anatomical structures giving rise to various symptoms. Watt W. Eagle identified two types: stylo-hyoid classic syndrome and stylo-carotid artery syndrome. The aim of this systematic review of the literature is to evaluate correlations between Eagle syndrome and traumatic events or teeth extractions.
METHODS
out of 294 articles, the final study allowed the identification of 13 studies focusing on traumatic events. Out of 342 articles, the final study allowed the analysis of two studies regarding extractive dental events.
RESULTS
13 articles showed correlations between the onset of symptoms in Eagle syndrome and traumatic events and highlighted two possibilities: traumatic event could fracture the already elongated styloid process or calcified stylohyoid ligament; trauma itself triggers the pathophysiological mechanisms that lead to lengthening of styloid process or calcification of stylohyoid ligament and therefore the typical symptoms. The only two case reports concerning Eagle syndrome symptoms after extractive dental events describe the onset of classic type.
CONCLUSIONS
The analyzed articles confirm correlation between traumatic event and onset of typical symptoms of Eagle syndrome. There is not enough literature linking extractive dental events to Eagle syndrome.
TRIAL REGISTRATION
CRD42020185176.
PubMed: 34209816
DOI: 10.3390/healthcare9070825 -
Nicotine & Tobacco Research : Official... Oct 2021Smoking can cause mucociliary clearing dysfunction and poor pulmonary immunity, leading to more severe infection. We performed this study to explore the association... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Smoking can cause mucociliary clearing dysfunction and poor pulmonary immunity, leading to more severe infection. We performed this study to explore the association between smoking and mortality of coronavirus disease 2019 (COVID-19) patients utilizing a quantitative meta-analysis on the basis of adjusted effect estimates.
AIMS AND METHODS
We conducted a systematic search of the online databases including PubMed, Web of Science, Scopus, and Embase. Only articles reporting adjusted effect estimates on the association between smoking and the risk of mortality among COVID-19 patients in English were included. Newcastle-Ottawa scale was fitted to assess the risk of bias. A random-effects model was applied to calculate the pooled effect with the corresponding 95% confidence interval (CI).
RESULTS
A total of 73 articles with 863 313 COVID-19 patients were included in this meta-analysis. Our results indicated that smoking was significantly associated with an increased risk for death in patients with COVID-19 (pooled relative risk = 1.19, 95% CI = 1.12-1.27). Sensitivity analysis indicated that our results were stable and robust.
CONCLUSIONS
Smoking was independently associated with an increased risk for mortality in COVID-19 patients.
IMPLICATIONS
This present study may contribute to summarizing the association between smoking and the risk of COVID-19 mortality based on adjusted effect estimates. More detailed and complete data on smoking status should be collected to more accurately estimate the effect of smoking on COVID-19 mortality.
Topics: COVID-19; Humans; Risk; Tobacco Smoking
PubMed: 34049390
DOI: 10.1093/ntr/ntab112