Tag: statistics

Trials. 2024 Jan 6;25(1):29. doi: 10.1186/s13063-023-07894-w.

ABSTRACT

This protocol paper presents an updated statistical analysis plan of the protocol of a randomised controlled trial. The randomised controlled trial investigates the effect of integrating smoking cessation interventions at outpatient opioid agonist therapy (OAT) clinics for persons with opioid dependency receiving OAT medication. The intervention group receives weekly follow-up including a short behavioural intervention and provision of nicotine replacement products. The control group receives standard treatment. The duration of the intervention is 16 weeks and the follow-up was completed by the end of October 2023. The primary outcome is defined as the proportion of participants reducing the number of cigarettes smoked by at least a 50% at week 16 of the intervention period. The primary outcome will be analysed according to intention-to-treat principles. Missing outcome data will be set equal to the baseline values. Development and reporting of the statistical analysis plan follow the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials.Trial registration ClinicalTrials.gov NCT05290025. Registered on 22 March 2022.

PMID:38184633 | DOI:10.1186/s13063-023-07894-w

Eur J Med Res. 2024 Jan 6;29(1):31. doi: 10.1186/s40001-023-01596-4.

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group.

METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test.

RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS.

CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.

PMID:38184629 | DOI:10.1186/s40001-023-01596-4

J Transl Med. 2024 Jan 6;22(1):29. doi: 10.1186/s12967-023-04776-2.

ABSTRACT

BACKGROUND: The current therapeutic algorithm for Advanced Stage Melanoma comprises of alternating lines of Targeted and Immuno-therapy, mostly via Immune-Checkpoint blockade. While Comprehensive Genomic Profiling of solid tumours has been approved as a companion diagnostic, still no approved predictive biomarkers are available for Melanoma aside from BRAF mutations and the controversial Tumor Mutational Burden. This study presents the results of a Multi-Centre Observational Clinical Trial of Comprehensive Genomic Profiling on Target and Immuno-therapy treated advanced Melanoma.

METHODS: 82 samples, collected from 7 Italian Cancer Centres of FFPE-archived Metastatic Melanoma and matched blood were sequenced via a custom-made 184-gene amplicon-based NGS panel. Sequencing and bioinformatics analysis was performed at a central hub. Primary analysis was carried out via the Ion Reporter framework. Secondary analysis and Machine Learning modelling comprising of uni and multivariate, COX/Lasso combination, and Random Forest, was implemented via custom R/Python scripting.

RESULTS: The genomics landscape of the ACC-mela cohort is comparable at the somatic level for Single Nucleotide Variants and INDELs aside a few gene targets. All the clinically relevant targets such as BRAF and NRAS have a comparable distribution thus suggesting the value of larger scale sequencing in melanoma. No comparability is reached at the CNV level due to biotechnological biases and cohort numerosity. Tumour Mutational Burden is slightly higher in median for Complete Responders but fails to achieve statistical significance in Kaplan-Meier survival analysis via several thresholding strategies. Mutations on PDGFRB, NOTCH3 and RET were shown to have a positive effect on Immune-checkpoint treatment Overall and Disease-Free Survival, while variants in NOTCH4 were found to be detrimental for both endpoints.

CONCLUSIONS: The results presented in this study show the value and the challenge of a genomics-driven network trial. The data can be also a valuable resource as a validation cohort for Immunotherapy and Target therapy genomic biomarker research.

PMID:38184610 | DOI:10.1186/s12967-023-04776-2

Cardiovasc Diabetol. 2024 Jan 6;23(1):15. doi: 10.1186/s12933-023-02110-0.

ABSTRACT

BACKGROUND: Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI.

METHODS: This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke.

RESULTS: During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13-1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96-1.45) or METS-IR (HR, 1.00; 95%CI 0.98-1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model.

CONCLUSIONS: The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

PMID:38184591 | DOI:10.1186/s12933-023-02110-0

Harm Reduct J. 2024 Jan 6;21(1):5. doi: 10.1186/s12954-024-00928-9.

ABSTRACT

BACKGROUND: With growing rates of unregulated drug toxicity death and concerns regarding COVID-19 transmission among people who use drugs, in March 2020, prescribed safer supply guidance was released in British Columbia. This study describes demographic and substance use characteristics associated with obtaining prescribed safer supply and examines the association between last 6-month harm reduction service access and obtaining prescribed safer supply.

METHODS: Data come from the 2021 Harm Reduction Client Survey administered at 17 harm reduction sites across British Columbia. The sample included all who self-reported use of opioids, stimulants, or benzodiazepines in the prior 3 days (N = 491), given active use of these drugs was a requirement for eligibility for prescribed safer supply. The dependent variable was obtaining a prescribed safer supply prescription (Yes vs. No). The primary independent variables were access to drug checking services and access to overdose prevention services in the last 6 months (Yes vs. No). Descriptive statistics (Chi-square tests) were used to compare the characteristics of people who did and did not obtain a prescribed safer supply prescription. Multivariable logistic regression models were run to examine the association of drug checking services and overdose prevention services access with obtaining prescribed safer supply.

RESULTS: A small proportion (n = 81(16.5%)) of the sample obtained prescribed safer supply. After adjusting for gender, age, and urbanicity, people who reported drug checking services access in the last 6 months had 1.67 (95% CI 1.00-2.79) times the odds of obtaining prescribed safer supply compared to people who had not contacted these services, and people who reported last 6 months of overdose prevention services access had more than twice the odds (OR 2.08 (95% CI 1.20-3.60)) of prescribed safer supply access, compared to people who did not access these services.

CONCLUSIONS: Overall, the proportion of respondents who received prescribed safer supply was low, suggesting that this intervention is not reaching all those in need. Harm reduction services may serve as a point of contact for referral to prescribed safer supply. Additional outreach strategies and service models are needed to improve the accessibility of harm reduction services and of prescribed safer supply in British Columbia.

PMID:38184576 | DOI:10.1186/s12954-024-00928-9

BMC Med Genomics. 2024 Jan 6;17(1):14. doi: 10.1186/s12920-023-01788-1.

ABSTRACT

BACKGROUND: Though persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD).

METHODS: We isolated genomic DNA from cryopreserved Peripheral Blood Mononuclear Cells of 79 volunteers. We amplified the protein-coding region of the NAT2 gene by polymerase chain reaction (PCR) and sequenced PCR products using the Sanger sequencing method. Sequencing reads were mapped and aligned to the NAT2 reference using the Geneious software (Auckland, New Zealand). Statistical analyses were performed using RStudio version 4.3.2 (2023.09.1 + 494).

RESULTS: The most frequent haplotype was the wild type NAT2^*4 (37%). Five genetic variants: 282C > T (NAT2^*13), 341 T > C (NAT2^*5), 803A > G (NAT2*12), 590G > A (NAT2*6) and 481C > T (NAT2*11) were observed with allele frequencies of 29%, 18%, 6%, 6%, and 4% respectively. According to the bimodal distribution of acetylation activity, the predicted phenotype was 76% rapid (mainly consisting of the wildtype NAT2^*4 and the NAT2*13A variant). A higher proportion of rapid acetylators were female, 72% vs 28% male (p = 0.022, odds ratio [OR] 3.48, 95% confidence interval [CI] 1.21 to 10.48). All variants were in HWE. NAT2 341 T > C was in strong complete LD with the 590G > A variant (D’ = 1.0, r² = – 0.39) but not complete LD with the 282C > T variant (D’ = 0.94, r² = – 0.54).

CONCLUSION: The rapid acetylation haplotypes predominated. Despite the LD observed, none of the SNPs could be termed tag SNP. This study adds to the genetic characterisation data of African populations at NAT2, which may be useful for developing relevant pharmacogenomic tools for TB therapy. To support optimised, pharmacogenomics-guided TB therapy, we recommend genotype-phenotype studies, including studies designed to explore gender-associated differences.

PMID:38184575 | DOI:10.1186/s12920-023-01788-1

BMC Public Health. 2024 Jan 6;24(1):111. doi: 10.1186/s12889-023-17532-4.

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) vaccine hesitancy is a global challenge. In low- and middle-income countries (LMICs), the problem has persisted despite vaccine availability and decreasing infections. In Uganda, there is still limited information on the extent and predictors of vaccine hesitancy. This study sought to assess the prevalence and predictors of COVID-19 vaccine hesitancy, and the effectiveness of an intervention that involved community pharmacy counseling in combating COVID-19 vaccine hesitancy.

METHODS: A total of 394 participants were enrolled in a 4-week prospective cohort interventional study. The study was conducted across eight community pharmacies in Mbarara City, between 9:00 AM and 5:00 PM daily. The study personnel ascertained the vaccination status of all clients seeking community pharmacy services. All unvaccinated clients were consecutively assessed for eligibility, and eligible clients were systematically enrolled after receiving the community pharmacy services for which they requested. The study intervention involved structured participant counseling (within the pharmacy premise), follow-up short message service (weekly), and telephone calls (bi-weekly). Only participants who did not accept to receive the COVID-19 vaccine despite counseling were followed up for four weeks, or until they accepted to receive a COVID-19 vaccine. The effectiveness of the community pharmacy counseling intervention was determined as an increase in COVID-19 vaccine acceptance, and desirable attitudinal change towards COVID-19 disease, vaccination exercise, and vaccines. Descriptive analysis was used to summarize data, and multivariate analysis was used to determine the predictors of COVID-19 vaccine hesitancy. A p-value < 0.05 was considered statistically significant.

RESULTS: Out of 394 participants, 221 (56%) were hesitant to receive a COVID-19 vaccine. Participants expressed several reasons (mean 2±1) for COVID-19 vaccine hesitancy, mostly concerning vaccine safety (N=160, 47.3%). The overall COVID-19 vaccine acceptance rate increased by 25.4 percent points (43.9 – 69.3 percent points) after the study intervention. Age, religion, level of education, distance from the nearest public health facility, having a friend/family diagnosed with COVID-19, and personal suspicion of contracting COVID-19 were significant predictors of COVID-19 vaccine hesitancy.

CONCLUSION: COVID-19 vaccine hesitancy is a big challenge in Uganda. A mix of sociodemographic and COVID-19 vaccine perceptions are the key predictors of COVID-19 vaccine hesitancy. Although COVID-19 vaccines were not available at the time of the study, this study found that structured counseling interventions can improve COVID-19 vaccine acceptance rates. Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other healthcare settings.

PMID:38184570 | DOI:10.1186/s12889-023-17532-4

Lipids Health Dis. 2024 Jan 6;23(1):3. doi: 10.1186/s12944-023-01997-8.

ABSTRACT

BACKGROUND: In Sub-Saharan Africa, the prevalence of dyslipidemia is on the rise, with studies showing dyslipidemia as a contributing factor to the progression of premalignant lesions to cervical cancer. In Uganda, cervical cancer and dyslipidemia are common health concerns, considering the increasing trends of dyslipidemia in the general population and inadequate information regarding dyslipidemia and cervical lesions. This study aimed to determine the prevalence of dyslipidemia and its association with precancerous and cancerous lesions of the cervix among women attending a cervical cancer clinic at the Uganda Cancer Institute.

METHODS: This cross-sectional study was conducted from February to April 2022 among women with premalignant and malignant lesions of the cervix. Data on social demographics and health-seeking behaviours were collected using a pretested structured questionnaire after written informed consent had been obtained. Pap smear collection preceded visual inspection with acetic acid; cervical biopsies were collected appropriately from eligible participants; and cervical lesions were classified using the Bethesda system 2014. Serum lipids, total cholesterol (T.C.), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc), and triglycerides (T.G.s) were analysed using the COBAS™ 6000 Clinical Chemistry Analyser. The associations were assessed using the chi-square test, and P ≤ 0.05 was considered statistically significant.

RESULTS: The overall prevalence of dyslipidemia among women with cervical lesions was 118/159 (74%), and low HDLc was the most prevalent at 64.6% (95% CI 39.0-54.3). High T.C. (P = 0.05), high T.G.s (P = 0.011), and low HDL-c (P = 0.05) showed a significant association with precancerous lesions. High LDL-c (P = 0.019), high T.G.s (P = 0.02), and high T.G.s (P < 0.001) showed a statistically significant association with cancerous lesions.

CONCLUSION: The prevalence of dyslipidemia was high, with high TC, T.G.s, and low HDL-c significantly associated with precancerous lesions. Also, elevated T.G.s and high LDLc were significantly associated with cancerous lesions. Women may benefit from dyslipidemia screening along with cervical cancer screening.

WHAT THIS STUDY ADDS: The present study builds upon previous findings suggesting a link between dyslipidemia and cervical lesions by investigating the relationship between these two factors, specifically in women of this geographical location, where we need adequate information on these associations.

PMID:38184564 | DOI:10.1186/s12944-023-01997-8

BMC Public Health. 2024 Jan 6;24(1):106. doi: 10.1186/s12889-023-17590-8.

ABSTRACT

BACKGROUND: The most cost-effective malaria prevention and control strategy is the use of a bed net. However, several factors affect the ownership and usage of bed nets among the adult population. Hence, this study aimed to examine socio-demographic factors affecting bed net ownership, usage and malaria transmission among adult patients seeking healthcare in two Ghanaian urban cities.

METHODS: This hospital-based cross-sectional study was conducted, between January and September 2021, at Bremang Seventh-Day Adventist Hospital, Suame Municipal, Ashanti Region and Sunyani Municipal Hospital, Sunyani, Bono Region, Ghana. Structured questionnaires were administered to a total of 550 participants to ascertain their ownership and usage of the bed nets. Afterwards, finger prick blood samples were collected for malaria microscopy. Crude and adjusted prevalence ratios (PR) and their respective 95% CIs were calculated, using Poisson regression with robust standard errors, to show associated variables in bivariate and multivariate analyses respectively. R software (version 4.1.1) was used to perform all statistical analyses.

RESULTS: About 53.3% (n = 293) of participants owned at least one-bed net but only 21.5% (n = 118) slept under it the previous night. Those married were 2.0 (95% CI: 1.6 – 2.5) and 2.4 (95% CI: 1.6 – 3.5) times more likely to own and use a bed net respectively than those who never married. Also, pregnant women were 1.3 (95% CI: 1.1 – 1.6) and 1.8 (95% CI: 1.3 – 2.5) times more likely to own and use a bed net respectively than non-pregnant. Even though income levels were not associated with bed net ownership and usage, students were 0.4 (95% CI: 0.2 – 0.6) and 0.2 (95% CI: 0.1 – 0.5) times less likely to own and use bed net respectively compared to formally employed persons. The overall malaria prevalence rate was 7.8%. Malaria-negative patients were 1.6 (95% CI: 1.2 – 2.0) and 2.4 (95% CI: 1.4 – 4.1) times more likely to own and use bed nets respectively than malaria positive. Patients with tertiary education recorded the lowest malaria prevalence (3.5%, n = 4). None of those with a monthly income > $300 recorded a case of malaria. On the contrary, majority 83%, n/N = 25/30) of the malaria-positive patients earned ≤ $150.

CONCLUSION: The National Malaria Control Program should conduct comprehensive mapping of all urban population segments before launching mass bed net distribution campaigns, taking into account demographic and socioeconomic factors to enhance bed net utilization and reduce malaria prevalence.

PMID:38184552 | DOI:10.1186/s12889-023-17590-8

BMC Infect Dis. 2024 Jan 6;24(1):54. doi: 10.1186/s12879-023-08884-8.

ABSTRACT

BACKGROUND: Misconceptions and myths are still the bottlenecks for the prevention of HIV/AIDS transmission in developing countries. This study aimed to assess the prevalence and associated factors of misconception about HIV transmission among reproductive age groups using the most recently available Ethiopian Demographic and Health Surveydata.

METHODS: A cross-sectional study design was done using the Ethiopian Demographic and Health Survey 2016 data set. The data analysis was conducted using Statistical Package for Social Sciences version 25. Multivariable logistic regression analysis was done to identify associated factors of misconception about HIV/AIDS transmission. A p-value of < 0.05 and an adjusted odds ratio with a 95% confidence interval were considered to confirm a statistically significant association.

RESULTS: From the sample of 11,425 reproductive-age women, the prevalence of misconception about HIV/AIDS transmission among reproductive-age women in Ethiopia was 27.47%. Women residing in rural area [AOR:1.24; 95% CI: 1.03-1.75] compared to urban resident participants, attended primary education [AOR:0.58;95%CI: 0.49-0.68], attended secondary education [AOR:0.36;95%CI:0.29-0.46], attended higher education [AOR:0.24;95%CI: 0.18-0.32] compared to those participants without education, had history of HIV test [AOR:0.77; 95%CI: 0.67-0.88] compared to their counterpart, respondents living in Amhara region [AOR:0.44:95% CI:0.35-0.54], Benishangul [AOR: 0.34; 95% CI: 0.25-0.46], SNNPR [AOR:0.50; 95% CI: 0.38-0.67], Gambela [AOR:0.57; 95% CI: 0.42-0.79], Harari [AOR:0.62; 95% CI: 0.46-0.82], Addis Ababa [AOR:0.63; 95% CI: 0.49-0.81] compared to those living in Tigray and having richest wealth status[AOR:0.57;95% CI: 1.457-4.078] compared to those whose wealth index was poorest were significantly associated with the misconception about HIV transmission.

CONCLUSION: Over all the prevalence of misconception about HIV/AIDS transmission among reproductive-age women in Ethiopia was high. Residence, educational level, wealth index, region, and respondents who ever tested for HIV were significantly associated with the misconception about HIV/AIDS transmission. This high misconception could affect HIV/AIDS transmission and its prevention strategies unless timely and appropriate intervention should be taken. Strengthening strategies aimed at maximizing HIV/AIDS testing, scaling up educational status, and emphasizing regional-wide interventions might have a substantial contribution.

PMID:38184543 | DOI:10.1186/s12879-023-08884-8