10957 research outputs found
Sort by
A survey on the use of continuous positive airway pressure in newborn care in Kenya in 2017–2018
Get PDFBackground
Globally, complications of preterm birth are the leading cause of under-5-mortality. Respiratory distress syndrome (RDS) is a common and life-threatening complication among preterm infants. Continuous positive airway pressure (CPAP) is a relatively simple and effective intervention that is recommended for RDS treatment. However, appropriate infrastructure and processes are required to ensure that it is used safely, effectively and sustainably. This study describes how CPAP was used in newborn care in Kenya between 2017–2018. Our aim was to identify enablers, barriers and gaps in CPAP use.
Methods
A cross-sectional survey was carried out across all newborn baby units in Kenya between 2017–2018, as part of a evaluation of CPAP use in newborn care. Descriptive statistics were used to analyse the quantitative data.
Results
Twenty-three hospitals across 15 (32%) of the counties in Kenya were providing CPAP in newborn care. The survey was conducted in 19 hospitals, amounting to 83% of all hospitals providing CPAP in newborn care in the country. Sub-county (level 4) and county (level 5) referral had fewer resources (i.e., trained staff, infrastructure and equipment) than the national referral (level 6) and private hospitals. In addition, there was a wide variation in the CPAP devices used and the resources for supporting CPAP use across different hospitals.
Conclusion
We found access to CPAP for neonates with RDS was inequitable in Kenya. There were also disparities in the availability of resources, personnel, and guidelines to support its implementation. Lack of standardisation of CPAP use in newborn care was especially evident in the public sector. To optimise coverage and standardisation of CPAP use in newborn care in Kenya, our results support ongoing partnerships to strengthen public and private healthcare sectors involving the implementation of strategies to improve infrastructure for newborn care, train and retain staff, and provide additional equipment
Outcome measures for randomised clinical trials and multicentre observational studies of cardiovascular diseases published in major clinical journals: systematic review and evidence mapping
Get PDFBackground
Outcome measure choice and definition can determine the result of the study. We describe outcome measures and their definitions for cardiovascular studies in highly cited medical journals.
Methods
Cardiovascular phase III or IV randomised clinical trials (RCTs) or multicentre observational studies published in theNew England Journal of Medicine,LancetorJournal of the American Medical Associationbetween 1 January 2013 and 6 June 2024 from Embase and Ovid Medline were included. Two independent reviewers selected the studies and extracted the primary and secondary outcome measures from each publication.
Results
386 studies (83% RCTs; 17% observational) representing 10 699 147 participants were included. Studies investigated coronary heart disease (51%), cardiomyopathy/heart failure (22%), heart rhythm disease (15%), valvular heart disease (11%) and ‘other’ cardiovascular diseases (1%), with 45% investigating a device and 48% funded by industry. The most frequently reported primary outcome measure was a composite (63%), the most frequent component of which was myocardial infarction (58%). The use of a composite for the primary outcome measure increased from 49% of studies in 2013 to a peak of 85% in 2018. From 2013 to 2023, the median number of secondary outcome measures per study increased for RCTs (3–8) and observational studies (0–7). Definitions for cardiovascular mortality, myocardial infarction and stroke varied across the studies.
Conclusions
For cardiovascular studies published in highly cited journals, there has been an expansion in the use of primary composite outcome measures and secondary outcome measures, with heterogeneity in the definition of primary outcome measures. A standardised approach to the use of cardiovascular outcomes measures is required
Standard of care in advanced HIV disease: review of HIV treatment guidelines in sub-Saharan African countries-an extension study of eight countries
Get PDFIntroduction
The World Health Organization (WHO) has published guidelines for the management of patients with advanced HIV disease (AHD) but mortality remains high. Adoption of WHO recommendations by national guidelines is poorly documented. We aimed to extend our prior review of six national management guidelines by including additional countries from sub-Saharan Africa.
Methods
We identified guidelines of eight additional countries participating in a multicountry trial of azithromycin prophylaxis for AHD. Data was extracted in five domains including definition of AHD (1 item), screening (6 items), prophylaxis (6 items), supportive care (1 items), and HIV treatment (4 items) and scored agreement of each national guideline with the WHO guidelines.
Results
Six of the eight national guidelines had a designated section for AHD. Compared with the WHO guideline, the agreement score for national guidelines was between 7 and 17 out of 18, whereby disagreement is mainly driven by missing information. None of the national guidelines had more than three items not in agreement with the WHO guidelines, and the maximum number of items not addressed by any one guideline was eight. Main areas of disagreement were the targeted population for start of ART in presence of tuberculosis meningitis (1/8 in agreement) and urine lipoarabinomannan screening (2/8 in agreement). The targeted population group for cotrimoxazole prophylaxis and its discontinuation was in line with the WHO recommendations in 3/8 national guidelines. Except one guideline, all documents showed similar overall agreement, irrespectively of publication date.
Conclusion
National guidelines for the management of people with AHD are broadly in agreement with WHO guidelines. Main areas of disagreement are recommendations regarding urine lipoarabinomannan screening, cotrimoxazole prophylaxis and start of antiretroviral therapy in presence of tuberculosis
Genetic Determinants of the Familial Hypercholesterolaemia Phenotype
Get PDFIndividuals with familial hypercholesterolaemia (FH) have severely elevated plasma concentrations of low‐density lipoprotein cholesterol (LDL‐C) from birth and as a consequence have an elevated morbidity and mortality due to the development of coronary heart disease (CHD). Monogenic FH can be caused by carrying a single copy of a pathogenic variant in any of four genes (LDLR/APOB/PCSK9/APOE), which are all involved in the clearance of LDL‐C from the blood by the liver. FH is one of the most common inherited disorders, with an estimated prevalence of carriers of around 1/280 individuals in most populations and ancestry groups. However, such variants can be found usually only in 20%–30% of clinically FH subjects, and in the majority of the no‐variant individuals, the phenotype is most likely explained by the inheritance of a greater‐than‐average number of common variants of small effect, with such individuals better given the diagnosis of ‘polygenic hypercholesterolaemia’. Also, in a proportion of no‐variant subjects who meet the clinical criteria, the most likely explanation is due to overproduction of Lp(a) which is an LDL‐C particle with a bound copy of the ‘little‐a’ protein. Here, we review the research that has elucidated the genetic architecture of the FH phenotype and discuss recent studies and future prospects of finding additional genes where variants can cause FH
Identifying Maternal Conditions Leading to Gabapentinoid Prescriptions in Pregnancy Using Electronic Health Records from Six European Countries: A Contribution from the IMI ConcePTION Project
Get PDFIntroduction and Objective
Given the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety studies, we aimed to develop algorithms for identifying maternal conditions leading to gabapentinoid prescribing among pregnant women using data from six electronic healthcare data sources across Europe.
Methods
The study was conducted in Finland, France (Haute-Garonne), Italy (Emilia Romagna), Norway, Spain (Valencian region), and Wales (UK), covering three million pregnancies from 2006 to 2020. Algorithms were developed to detect epilepsy, neuropathic pain, and generalized anxiety disorder (GAD) (approved indications for gabapentinoids by the European Medicines Agency, with the exception of gabapentin for GAD) using data ± 1 year around the gabapentinoid prescription date. Data included prescriber specialty, primary and specialized health care diagnoses, and co-prescription/dispensation data. Additional analyses investigated potential unlicensed indications (such as fibromyalgia, restless legs syndrome, bipolar disorder) and potential for abuse (using codes for substance use disorders and alcohol withdrawal).
Results
Gabapentinoids were prescribed/dispensed in 1770 pregnancies (7.7 per 1000) in Spain, 2912 pregnancies (6.6 per 1000) in Wales, 3163 pregnancies (3.6 per 1000) in Norway, 2406 pregnancies (3.0 per 1000) in Finland, 908 pregnancies (2.2 per 1000) in Italy, and 269 pregnancies (1.9 per 1000) in France. A maternal condition related to gabapentinoid prescriptions was identified by the algorithm in 2797 (88.4%) in Norway, 2180 (74.9%) in Wales, 1269 (71.7%) in Spain, 1534 (63.8%) in Finland, 163 (60.6%) in France, and 396 (43.6%) pregnancies in Italy. Anxiety (licensed or unlicensed) was the most commonly captured condition in Wales (70.5%), Spain (51.5%), Finland (42.0%), and Italy (26.2%), whereas neuropathic pain prevailed in Norway (76.9%) and France (49.8%). Epilepsy was the least frequent maternal condition leading to gabapentinoid prescriptions across all data sources (below 15% of all pregnancies). The relative preponderance of these conditions differed between pregabalin and gabapentin. Additionally, unlicensed indications were captured in 0% to 13% of pregnancies, depending on the data source. The analyses of potential for abuse showed that records of alcohol withdrawal and/or substance use disorders (within 1 year before and after the gabapentinoids prescription/dispensation date) were present in 3% of pregnancies in Italy and up to 23% in Wales.
Conclusions
Our study provides valuable insights into gabapentinoid use during pregnancy, with anxiety being the most common condition among pregnant women with gabapentinoid prescriptions in Finland, Italy, Spain, and Wales, whereas neuropathic pain predominated in France and Norway. Moreover, we found that between 3 and 23% of these pregnancies were associated with substance abuse, underscoring the need for careful prescribing of commonly abused medicines. The proposed methods for detecting maternal conditions leading to prescribing will facilitate accurate assessment of medication use and safety during pregnancy, whilst addressing confounding by indication
From Inner Sense to Outer Action: Interoception and Impulsive Compulsive Behavior Disorders in Parkinson's Disease
Get PDFBackground
Impulsive‐compulsive behavior disorders (ICBDs) in Parkinson's disease (PD) include impulse control disorders (ICDs) and compulsive behaviors, often linked to dopaminergic treatment and altered reward processing. Interoception, the perception of internal bodily signals, plays a key role in emotional regulation and decision‐making. Neuroimaging studies suggest that alterations in interoceptive and reward‐related brain circuits may underlie ICDs in PD. However, the relationship between interoception and ICDs remains underexplored.
Objective
To investigate the relationship between impulse control disorders (ICD) severity and interoceptive abilities—specifically interoceptive accuracy, insight, and self‐reported interoception—in PD patients.
Methods
Fifty‐one participants were assessed using the Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP‐RS) alongside measures of interoceptive performance, anxiety, depression, and apathy.
Results
Higher ICD severity predicted increased interoceptive insight and sensibility. No significant link was found between ICD severity and interoceptive accuracy. Additionally, higher Levodopa Equivalent Daily Dose (LEDD) was related to lower interoceptive insight, suggesting a potential modulatory effect of dopaminergic therapy on meta‐cognitive interoception.
Conclusions
These findings highlight the complex interplay between ICDs and interoception, suggesting that heightened self‐reported interoception and interoceptive insight may reinforce impulsive behaviors in PD via enhanced bodily signal salience. This study contributes to understanding the characteristics of ICDs in PD, implicating reward‐related circuits such as the insula and anterior cingulate cortex
Epidemiology of intestinal parasite infections and multiparasitism and their impact on growth and hemoglobin levels during childhood in tropical Ecuador: A longitudinal study using molecular detection methods
Get PDFBackground
There are few longitudinal epidemiological studies of intestinal parasitic infections (IPI) and their health effects. We studied the epidemiology and determinants of IPI and multiparasitism during childhood using molecular methods for parasite detection and analysed their effects on growth and hemoglobin levels.
Methods
Random sample of 401 children from an Ecuadorian birth cohort followed up to 8 years of age. Data on environmental and sociodemographic characteristics were collected by questionnaires. Stool samples were collected, and weight, height, and hemoglobin levels were measured at 7 and 13 months, and 2, 3, 5, and 8 years. Stool samples were analysed using multi-parallel quantitative polymerase chain reaction for the presence of soil-transmitted helminth (STH) (Ascaris lumbricoides, Trichuris trichiura, Ancylostoma spp. Necator americanus, and Strongyloides stercoralis) and protozoal (Giardia lamblia, Entamoeba histolytica, and Cryptosporidium spp.) parasites. Associations between risk factors and infections, and between infections and nutritional outcomes were estimated using generalized estimated equations applied to longitudinal binary or continuous outcomes.
Results
IPI were observed in 91.3% of the cohort during follow-up with peak proportions between 3 and 8 years, while multiparasitism increased more gradually (32.5% at 8 years). Factors significantly associated with multiparasitism included lower birth order, day care, Afro-Ecuadorian ethnicity, urban residence, lower household income, and maternal STH infections. IPI during follow-up were associated with lower hemoglobin (difference = -0.102, 95% CI -0.192 - -0.013, P = 0.025), height-for-age (difference = -0.126, 95% CI -0.233 - -0.019, P = 0.021) and weight-for-age (difference, -0.129, 95% CI -0.257 - -0.022, P = 0.018) z scores. Multiparasitism had the strongest negative effects on growth (height-for-age, -0.289, 95% CI -0.441- -0.137, P < 0.001; weight-for-age, -0.228, 95% CI -0.379 - -0.077, P = 0.003), with some evidence of greater effects with greater number of parasite species.
Conclusion
IPI infections and multiparasitism were frequent during early childhood in this Ecuadorian cohort. IPI was associated with reduced weight, height, and hemoglobin trajectories while children with multiparasitism had the greatest growth deficits. Our data highlight the adverse health effects of multiparasitism during childhood in endemic settings and the need for integrated programmes of control and prevention to eliminate associated morbidity
Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets
Get PDFCeramides are bioactive lipid mediators involved in apoptosis, inflammation, and fibrosis. This narrative review provides a concise overview of the emerging role of ceramides in cardiovascular disease with an emphasis on atherosclerotic vascular disease and heart failure, suggesting the potential use of ceramides in risk stratification and as putative therapeutic targets. Recent developments based on observational evidence and genetic associations, including Mendelian randomization studies in humans, are summarized and put into context with experimental evidence for the role of ceramides in human and animal models of disease. Emerging scores composed of ceramides and phosphatidylcholines that are based on the length and desaturation of the N-acyl chains are discussed in the light of novel data demonstrating age- and sex-specific differences. Also reviewed is the structural heterogeneity of the sphingoid bases, including non-conventional sphingolipids that are increasingly recognized for their importance in health and disease. Lastly, novel targets and potential modalities for tissue-specific transfer of drugs are discussed
Cost‐Effectiveness of a Personalised Self‐Management Intervention for People Living With Long Covid: The LISTEN Randomised Controlled Trial
Get PDFBackground
In the United Kingdom, at least 1.9 million people are estimated to have experienced long Covid, of which 1.3 million have symptoms lasting for more than a year. The Long CovId Personalised Self‐managemenT support EvaluatioN (LISTEN) trial evaluated the effectiveness and cost‐effectiveness of a co‐designed personalised self‐management support intervention for non‐hospitalised people living with long Covid.
Methods
We conducted a pragmatic, multicentre, two‐arm, parallel group and superiority randomised controlled trial for people who had experienced at least one long Covid symptom for 12 weeks or longer. A cost–utility analysis was undertaken alongside the LISTEN trial from both a UK National Health Service (NHS) and personal social services (PSS) and a societal perspective. Implementation costs were determined from study records, and quality of life and health and care resource use were collected by questionnaire at 6‐week and 3‐month follow‐ups. Incremental net monetary benefit (INMB) analyses evaluated the cost‐effectiveness of the intervention at a range of willingness‐to‐pay thresholds.
Results
A total of 544 participants were included in the health economic analysis, of which 62.5% had complete data. The average cost of delivering the LISTEN intervention was £846 per participant. At 3‐month follow‐up, mean quality‐adjusted life years (QALYs) were 0.005 (95% CI −0.004 to 0.014) greater for participants receiving the LISTEN intervention compared to usual care. From the NHS and PSS perspective, total adjusted mean costs were £491 (95% CI, £128 to £854) lower in the usual care arm. From the societal perspective, participants in the usual care arm lost more hours of work and usual activities and received more informal care, with the LISTEN intervention dominating usual care.
Conclusions
At accepted UK thresholds, the LISTEN intervention was not cost‐effective from an NHS and PSS perspective, but it was found to be cost‐effective from a societal perspective due to the impact of long Covid on work, informal care and usual activities. Further research is required to understand the costs and benefits of self‐management support for longer‐term horizons.
Patient and Public Contribution
We are grateful for the contributions of the LISTEN Public and Patient Involvement and Engagement group comprising seven people (Anne Domeney, Ian Patel, Carol Rowe, Judith Parsons, Rebecca Beltran, Elizabeth Treadwell and Maria Ines de Sousa de Abreu) with long Covid who supported co‐design, communications, trial recruitment and dissemination activities.
Trial Registration
ISRCTN36407216, registered 27 January 2022
Clinical prediction models to diagnose neonatal sepsis in low-income and middle-income countries: a scoping review
Get PDFIntroduction
Neonatal sepsis causes significant morbidity and mortality worldwide but is difficult to diagnose clinically. Clinical prediction models (CPMs) could improve diagnostic accuracy, facilitating earlier treatment for cases and avoiding antibiotic overuse. Neonates in low-income and middle-income countries (LMICs) are disproportionately affected by sepsis, yet no review has comprehensively synthesised evidence for CPMs validated in this setting.
Methods
We performed a scoping review of CPMs to diagnose neonatal sepsis using Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Global Index Medicus and the Cochrane Library. The most recent searches were performed on 16 June 2024. We included studies published in English or Spanish that validated a new or existing CPM for neonatal sepsis in any healthcare setting in an LMIC. Studies were excluded if they validated a prognostic model or where data for neonates could not be separated from a larger paediatric population. Studies were selected by two independent reviewers and summarised by narrative synthesis.
Results
From 4598 unique records, we included 82 studies validating 44 distinct models in 24 252 neonates. Most studies were set in neonatal intensive or special care units (n=64, 78%) in middle-income countries (n=81, 99%) and included neonates already suspected of sepsis (n=58, 71%). Only four studies (5%) were set in the WHO African region, and only one study included data from a low-income country. Two-thirds of CPMs (n=30) required laboratory parameters, and three-quarters (n=34) were only validated in one study.
Conclusion
Our review highlights several literature gaps, particularly a paucity of studies validating models in the lowest-income countries where neonatal sepsis is most prevalent, and models for the undifferentiated neonatal population that do not rely on laboratory tests. Furthermore, heterogeneity in study populations, definitions of sepsis and reporting of models inhibits meaningful comparison between studies and may hinder progress towards useful diagnostic tools
Access Repository Dashboard
Do you manage St George's Online Research Archive? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!