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EBioMedicine Dec 2023Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a...
BACKGROUND
Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a role in hand osteoarthritis. We characterised gut microbiome-related metabolites in people with symptomatic hand osteoarthritis (SHOA) in two independent cohorts.
METHODS
Using data collected from a large-sample community-based observational study (discovery cohort), we assessed the relations of the microbial function and plasma key metabolites related to altered microbial function with SHOA. Finally, we verified the relations of plasma metabolites to SHOA in an independent observational study (validation cohort).
FINDINGS
In the discovery cohort (n = 1359), compared to those without SHOA, participants with SHOA had significantly altered microbial functions related to tryptophan metabolism (Q = 0.025). Therefore we measured the plasma tryptophan metabolites and found that participants with SHOA had higher levels of 5-hydroxyindoleacetic acid (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.09-1.42) and 5-hydroxytryptophol (OR = 1.13, 95% CI: 1.04-1.23), but lower levels of indole-3-lactic acid (ILA) (OR = 0.85, 95% CI: 0.72-1.00), skatole (OR = 0.93, 95% CI: 0.88-0.99) and 3-hydroxyanthranilic acid (OR = 0.90, 95% CI: 0.85-0.96). Findings from the validation cohort (n = 142) verified that lower levels of ILA were related to SHOA (OR = 0.70, 95% CI: 0.53-0.92).
INTERPRETATION
Alterations of the microbial function of tryptophan biosynthesis and tryptophan metabolites, especially lower levels of ILA, are associated with SHOA. These findings suggest the role of the microbiome and tryptophan metabolites in developing of SHOA and may contribute to future translational opportunities.
FUNDING
National Key Research and Development Plan and National Natural Science Foundation of China.
Topics: Humans; China; Gastrointestinal Microbiome; Microbiota; Osteoarthritis; Tryptophan; Observational Studies as Topic
PubMed: 38006743
DOI: 10.1016/j.ebiom.2023.104892 -
BMC Geriatrics Jul 2023Frailty is a clinical syndrome of accelerated aging associated with adverse outcomes. Frailty is prevalent among patients with chronic kidney disease but is infrequently... (Review)
Review
BACKGROUND
Frailty is a clinical syndrome of accelerated aging associated with adverse outcomes. Frailty is prevalent among patients with chronic kidney disease but is infrequently assessed in clinical settings, due to lack of consensus regarding frailty definitions and diagnostic tools. This study aimed to review the practice of frailty assessment in nephrology populations and evaluate the context and timing of frailty assessment.
METHODS
The search included published reports of frailty assessment in patients with chronic kidney disease, undergoing dialysis or in receipt of a kidney transplant, published between January 2000 and November 2021. Medline, CINAHL, Embase, PsychINFO, PubMed and Cochrane Library databases were examined. A total of 164 articles were included for review.
RESULTS
We found that studies were most frequently set within developed nations. Overall, 161 studies were frailty assessments conducted as part of an observational study design, and 3 within an interventional study. Studies favoured assessment of participants with chronic kidney disease (CKD) and transplant candidates. A total of 40 different frailty metrics were used. The most frequently utilised tool was the Fried frailty phenotype. Frailty prevalence varied across populations and research settings from 2.8% among participants with CKD to 82% among patients undergoing haemodialysis. Studies of frailty in conservatively managed populations were infrequent (N = 4). We verified that frailty predicts higher rates of adverse patient outcomes. There is sufficient literature to justify future meta-analyses.
CONCLUSIONS
There is increasing recognition of frailty in nephrology populations and the value of assessment in informing prognostication and decision-making during transitions in care. The Fried frailty phenotype is the most frequently utilised assessment, reflecting the feasibility of incorporating objective measures of frailty and vulnerability into nephrology clinical assessment. Further research examining frailty in low and middle income countries as well as first nations people is required. Future work should focus on interventional strategies exploring frailty rehabilitation.
Topics: Humans; Frailty; Nephrology; Aging; Consensus; Databases, Factual; Observational Studies as Topic
PubMed: 37479978
DOI: 10.1186/s12877-023-04101-y -
Nephrology (Carlton, Vic.) Oct 2020In evidence-based medicine, clinical research questions may be addressed by different study designs. This article describes when randomized controlled trials (RCT) are... (Review)
Review
In evidence-based medicine, clinical research questions may be addressed by different study designs. This article describes when randomized controlled trials (RCT) are needed and when observational studies are more suitable. According to the Centre for Evidence-Based Medicine, study designs can be divided into analytic and non-analytic (descriptive) study designs. Analytic studies aim to quantify the association of an intervention (eg, treatment) or a naturally occurring exposure with an outcome. They can be subdivided into experimental (ie, RCT) and observational studies. The RCT is the best study design to evaluate the intended effect of an intervention, because the randomization procedure breaks the link between the allocation of the intervention and patient prognosis. If the randomization of the intervention or exposure is not possible, one needs to depend on observational analytic studies, but these studies usually suffer from bias and confounding. If the study focuses on unintended effects of interventions (ie, effects of an intervention that are not intended or foreseen), observational analytic studies are the most suitable study designs, provided that there is no link between the allocation of the intervention and the unintended effect. Furthermore, non-analytic studies (ie, descriptive studies) also rely on observational study designs. In summary, RCTs and observational study designs are inherently different, and depending on the study aim, they each have their own strengths and weaknesses.
Topics: Confounding Factors, Epidemiologic; Evidence-Based Medicine; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Research Design
PubMed: 32542836
DOI: 10.1111/nep.13742 -
Canadian Journal of Psychiatry. Revue... Oct 2021Suicide rates are higher in rural compared to urban areas. Although this pattern appears to be driven by higher rates among men, there is limited evidence about the... (Review)
Review
Rural-Urban Differences in Suicide Mortality: An Observational Study in Newfoundland and Labrador, Canada: Différences de la Mortalité Par Suicide en Milieu Rural-Urbain: Une Étude Observationnelle à Terre-Neuve et Labrador, Canada.
BACKGROUND
Suicide rates are higher in rural compared to urban areas. Although this pattern appears to be driven by higher rates among men, there is limited evidence about the characteristics of rural people who die by suicide in Canada. The objective of this study was to examine the demographics, manner of death, and social and clinical antecedents of people who died by suicide in rural areas compared to urban areas.
METHODS
We conducted an observational study of all suicide deaths that occurred among Newfoundland and Labrador residents between 1997 and 2016 using a linked data set derived from a comprehensive review of provincial medical examiner records. We used tests and χ to assess associations between rural/urban status and variables related to demographics, circumstances, and manner of death, as well as social and medical history. Logistic regression was utilized to assess the independent contribution of any variable found to be significant in univariate analysis.
RESULTS
Rural people who died by suicide accounted for 54.8% of all deaths over a 20-year period. Overall, 81.6% of people who died were male. Compared to urban, rural people who died by suicide were younger, more likely to use firearms or hanging, and had a higher mean blood alcohol content at the time of death (27.69 vs. 22.95 mmol/L). Rural people were also less likely to have had a known history of a prior suicide attempt, psychiatric disorder, alcohol or substance abuse, or chronic pain.
DISCUSSION
The demographic and clinical differences between rural and urban people who died by suicide underscore the need for suicide prevention approaches that account for place-based differences. A key challenge for suicide prevention in rural communities is to ensure that interventions are developed and implemented in a manner that fits local contexts.
Topics: Canada; Firearms; Humans; Male; Newfoundland and Labrador; Observational Studies as Topic; Rural Population; Substance-Related Disorders; Urban Population
PubMed: 33576277
DOI: 10.1177/0706743721990315 -
Journal of Bone and Mineral Research :... May 2020The Women's Health Initiative (WHI) is a large longitudinal study designed to investigate strategies for the prevention and control of common chronic diseases in... (Review)
Review
The Women's Health Initiative (WHI) is a large longitudinal study designed to investigate strategies for the prevention and control of common chronic diseases in postmenopausal women, including cardiovascular disease, cancer, and osteoporotic fractures. The WHI consisted of three overlapping clinical trials of hormone therapy, diet modification to reduce total dietary fat, and calcium/vitamin D supplementation. Women who were ineligible for the hormone therapy or diet modification trials or not interested were invited to participate in the observational study. Women were recruited into WHI from 1993 to 1998 at 40 US clinical centers. WHI enrolled 26,046 underrepresented minority women and 135,762 white women. Women could participate in each trial if eligible. The final enrollment included 27,347 women in the hormone trial; 48,835 women in the diet modification trial; 36,282 women in the calcium/vitamin D trial, and 93,676 in the observational study. After the main study ended in 2005, women were invited to continue follow-up for exposures and outcomes through two extensions to 2020. Proposals were recently submitted to continue follow-up through 2027. Information was collected on an extensive number of risk factors for fractures at baseline and over the follow-up, including fall and fracture history, weight patterns, comorbidities, diet, reproductive history, medications, anthropometry, and biomarkers. Bone mineral density was measured at three WHI clinical centers (n = 11,020) chosen to maximize race/ethnic diversity. WHI encourages outside investigators to make use of the publicly available WHI data and to access the biobank of specimens (www.whi.org). © 2020 American Society for Bone and Mineral Research.
Topics: Dietary Supplements; Female; Humans; Longitudinal Studies; Observational Studies as Topic; Osteoporotic Fractures; United States; Vitamin D; Women's Health
PubMed: 32286708
DOI: 10.1002/jbmr.4026 -
Nature Reviews. Rheumatology Jul 2015Over the past decade, an increasing number of observational studies have examined the effectiveness or safety of treatments for rheumatoid arthritis. Unlike randomized... (Review)
Review
Over the past decade, an increasing number of observational studies have examined the effectiveness or safety of treatments for rheumatoid arthritis. Unlike randomized controlled trials (RCTs), however, observational studies of drug effects have methodological limitations such as confounding by indication. Active-comparator designs and new-user designs can help mitigate such biases in observational studies and improve the validity of their findings by making them more closely approximate RCTs. In an active-comparator study, the drug of interest is compared with another agent commonly used for the same indication, rather than with no treatment (a 'non-user' group). This principle helps to ensure that treatment groups have similar treatment indications, attenuating both measured and unmeasured differences in patient characteristics. The new-user study includes a cohort of patients from the time of treatment initiation, enabling assessment of patients' pretreatment characteristics and capture of all events occurring during follow-up. These two principles should be considered when designing or reviewing observational studies of drug effects.
Topics: Arthritis, Rheumatoid; Bias; Confounding Factors, Epidemiologic; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 25800216
DOI: 10.1038/nrrheum.2015.30 -
Randomized and non-randomized designs for causal inference with longitudinal data in rare disorders.Orphanet Journal of Rare Diseases Nov 2021In the United States, approximately 7000 rare diseases affect 30 million patients, and only 10% of these diseases have existing therapies. Sound study design and causal... (Review)
Review
In the United States, approximately 7000 rare diseases affect 30 million patients, and only 10% of these diseases have existing therapies. Sound study design and causal inference methods are essential to demonstrate the therapeutic efficacy, safety, and effectiveness of new therapies. In the rare diseases setting, several factors challenge the use of typical parallel control designs: the small patient population size, genotypic and phenotypic diversity, and the complexity and incomplete understanding of the disorder's progression. Repeated measures, when spaced appropriately relative to disease progression and exploited in design and analysis, can increase study power and reduce variability in treatment effect estimation. This paper reviews these longitudinal designs and draws the parallel between some new and existing randomized studies in rare diseases and their less well-known controlled observational study designs. We show that self-controlled randomized crossover and N-of-1 designs have similar considerations as the observational case series and case-crossover designs. Also, randomized sequential designs have similar considerations to longitudinal cohort studies using sequential matching or weighting to control confounding. We discuss design and analysis considerations for valid causal inference and illustrate them with examples of analyses in multiple rare disorders, including urea cycle disorder and cystic fibrosis.
Topics: Cohort Studies; Humans; Longitudinal Studies; Observational Studies as Topic; Randomized Controlled Trials as Topic; Rare Diseases; Research Design
PubMed: 34814939
DOI: 10.1186/s13023-021-02124-5 -
Nicotine & Tobacco Research : Official... Jan 2023Indigenous North Americans have the highest cigarette smoking prevalence among all racial and ethnic groups in the United States. We seek to identify effective... (Review)
Review
INTRODUCTION
Indigenous North Americans have the highest cigarette smoking prevalence among all racial and ethnic groups in the United States. We seek to identify effective components of smoking cessation interventions in Indigenous people in the United States associated with favorable cessation outcomes.
METHODS
A review of literature studying smoking cessation interventions in Indigenous North Americans (American Indians and Alaska Natives) from January 2010 through August 2021 was completed. The primary objective of this study was to identify components of interventions associated with positive smoking cessation outcomes in Indigenous people. The studies identified were synthesized in a meta-narrative approach.
RESULTS
Ten studies out of 608 titles were included (6 randomized trials, 2 single-arm studies, 1 cohort study, and 1 prospective observational study). Five categories of smoking cessation interventions were identified; phone or web-based tools, culturally-tailored interventions, the inclusion of Indigenous study personnel, pharmaceutical cessation aids, and behavioral health interventions. Phone and web tools, cultural tailoring, and inclusion of Indigenous personnel conditions inconsistently influenced smoking cessation. Pharmaceutical aids were viewed favorably among participants. Individualized behavioral counseling sessions were effective at promoting smoking cessation, as was input from local communities in the planning and implementation phases of study.
CONCLUSION
A successful smoking cessation intervention in Indigenous North Americans includes Tribal or community input in intervention design and implementation; should provide individualized counseling sessions for participants, and offer access to validated smoking cessation tools including pharmacotherapy.
IMPLICATIONS
This study identifies a paucity of smoking interventions utilizing standard of care interventions in Indigenous North Americans. Standard of care interventions including individualized cessation counseling and pharmacotherapy were effective at promoting cessation. The use of novel culturally tailored cessation interventions was not more effective than existing evidence-based care with the exception of including Tribal and local community input in intervention implementation. Future smoking cessation interventions in Indigenous North Americans should prioritize the use of standard of care cessation interventions.
Topics: Humans; United States; Smoking Cessation; Cohort Studies; Behavior Therapy; Counseling; Population Groups; Observational Studies as Topic
PubMed: 35869642
DOI: 10.1093/ntr/ntac181 -
BMJ Open Sep 2022Chemotherapy-induced peripheral neuropathy is a frequent side effect of some chemotherapies that can cause postural control disorders and has a serious impact on quality...
INTRODUCTION
Chemotherapy-induced peripheral neuropathy is a frequent side effect of some chemotherapies that can cause postural control disorders and has a serious impact on quality of life (QoL). An enhanced understanding of postural control dysfunction could help build a systematic and accurate assessment as well as specific exercises to limit the impact on QoL. This study aims to assess the influence of chemotherapy on postural control and the QoL for women with gynaecological cancer.
METHODS AND ANALYSIS
This prospective observational study will include 37 participants with cancer treated using neurotoxic chemotherapy. Their postural control in various conditions (rigid and foam surfaces, eyes open and closed, with and without tendon vibration, and dual tasks), limits of stability, QoL and modified Total Neuropathy Score will be assessed. A linear mixed model will compare postural control pre-chemotherapy and post-chemotherapy.
ETHICS AND DISSEMINATION
This study was approved by an ethical review board in Geneva (CCER-2020-01639). The study findings will be disseminated through conference presentations and publications in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT04692168.
Topics: Humans; Female; Quality of Life; Postural Balance; Peripheral Nervous System Diseases; Prospective Studies; Genital Neoplasms, Female; Observational Studies as Topic
PubMed: 36691184
DOI: 10.1136/bmjopen-2022-061664 -
BMJ Open Jun 2022Neurodegenerative and psychiatric disorders (NPDs) confer a huge health burden, which is set to increase as populations age. New, remotely delivered diagnostic...
Protocol for Rhapsody: a longitudinal observational study examining the feasibility of speech phenotyping for remote assessment of neurodegenerative and psychiatric disorders.
INTRODUCTION
Neurodegenerative and psychiatric disorders (NPDs) confer a huge health burden, which is set to increase as populations age. New, remotely delivered diagnostic assessments that can detect early stage NPDs by profiling speech could enable earlier intervention and fewer missed diagnoses. The feasibility of collecting speech data remotely in those with NPDs should be established.
METHODS AND ANALYSIS
The present study will assess the feasibility of obtaining speech data, collected remotely using a smartphone app, from individuals across three NPD cohorts: neurodegenerative cognitive diseases (n=50), other neurodegenerative diseases (n=50) and affective disorders (n=50), in addition to matched controls (n=75). Participants will complete audio-recorded speech tasks and both general and cohort-specific symptom scales. The battery of speech tasks will serve several purposes, such as measuring various elements of executive control (eg, attention and short-term memory), as well as measures of voice quality. Participants will then remotely self-administer speech tasks and follow-up symptom scales over a 4-week period. The primary objective is to assess the feasibility of remote collection of continuous narrative speech across a wide range of NPDs using self-administered speech tasks. Additionally, the study evaluates if acoustic and linguistic patterns can predict diagnostic group, as measured by the sensitivity, specificity, Cohen's kappa and area under the receiver operating characteristic curve of the binary classifiers distinguishing each diagnostic group from each other. Acoustic features analysed include mel-frequency cepstrum coefficients, formant frequencies, intensity and loudness, whereas text-based features such as number of words, noun and pronoun rate and idea density will also be used.
ETHICS AND DISSEMINATION
The study received ethical approval from the Health Research Authority and Health and Care Research Wales (REC reference: 21/PR/0070). Results will be disseminated through open access publication in academic journals, relevant conferences and other publicly accessible channels. Results will be made available to participants on request.
TRIAL REGISTRATION NUMBER
NCT04939818.
Topics: Feasibility Studies; Humans; Longitudinal Studies; Mental Disorders; Mobile Applications; Observational Studies as Topic; Speech
PubMed: 35667724
DOI: 10.1136/bmjopen-2022-061193