Category: Statistics

Genome Res. 2024 Aug 12. doi: 10.1101/gr.278485.123. Online ahead of print.

ABSTRACT

Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes. Our approach uses a compact colored de Bruijn graph to approximate the intragenome distances between pairs of loci for a collection of bacterial genomes to account for the impacts of linkage disequilibrium (LD). We demonstrate the versatility of our approach to efficiently identify associations between loci linked with drug resistance and adaptation to the hospital niche in the major human bacterial pathogens Streptococcus pneumoniae and Enterococcus faecalis.

PMID:39134411 | DOI:10.1101/gr.278485.123

Musculoskeletal Care. 2024 Sep;22(3):e1924. doi: 10.1002/msc.1924.

ABSTRACT

BACKGROUND: Musculoskeletal (MSK) conditions affect over 20.3 million people in the UK, presenting a substantial economic impact on health and social services. Physiotherapy can alleviate MSK conditions, especially if delivered in the acute or sub-acute period. However, patients often present after significant waiting times.

OBJECTIVES: Our analysis examined how waiting times and the number of treatments influenced physiotherapy outcomes for MSK conditions.

DESIGN: Retrospective analysis of the Data for Impact, Physio First dataset.

METHODS: Logistic regression models assessed the effects of symptom duration, treatment frequency, and other variables on pain, Patient-Specific Functional Scores (PSFSs), and Goal Achievement (GA).

RESULTS: Analysis of 15,624 patient records showed that patients treated within two weeks of symptom onset were more likely to have favourable outcomes in pain (odds ratio [OR] = 2.01, 95% Confidence Interval [95% CI] = 1.65-2.45), PSFS (OR = 1.80, 95% CI = 1.55-2.08), and GA (OR = 1.74, 95% CI = 1.51-2.01) compared to those treated after longer durations. Receiving four or more treatment sessions significantly improved outcomes compared with only one session (pain: OR = 4.64, PSFS: OR = 5.72, GA: OR = 1.94, all p’s < 0.001), with no additional benefits beyond four sessions. Younger age was associated with better outcomes (approximately OR = 0.99 per year age difference). Other findings included better outcomes in males and in those with fewer previous episodes of the condition.

CONCLUSIONS: Shorter waiting times, a greater number of treatments, and younger patient age are associated with better physiotherapy outcomes for MSK conditions.

PMID:39134408 | DOI:10.1002/msc.1924

Rural Remote Health. 2024 Aug;24(3):8627. doi: 10.22605/RRH8627. Epub 2024 Aug 2.

ABSTRACT

INTRODUCTION: Chronic household food insecurity (HFI) and lack of food availability and accessibility in isolated communities are longstanding public health crises. This review aims to paint a more fulsome picture of food security initiatives in remote and isolated communities by examining programs across circumpolar countries, Australia, and Aotearoa New Zealand. This synthesis of research will contribute to an understanding of what types of initiatives exist and aid in the identification of best practices.

METHODS: The authors conducted a scoping review identifying articles that include either (1) an evaluation of an initiative with a quantitative food security outcome in remote and isolated communities, or (2) quantitative associations between exposure factors with food security outcomes. Inclusion criteria included English and French articles focused on remote and isolated communities in Canada, the US, Australia, New Zealand, Sweden, Norway, Finland, Greenland, and Russia from January 1997 to July 2022.

RESULTS: The article search yielded 1882 results, of which 96 fulfilled the inclusion criteria, including 26 studies evaluating initiatives, 66 studies evaluating exposure factors, and four studies that included both initiatives and exposure factors. The majority of the studies included in this review were conducted in Canada and Australia. No initiative studies conducted in Russia, Greenland, Norway, Finland, or Sweden fulfilled the criteria for inclusion in this review. The most common types of initiatives evaluated included school-based programs, market subsidies, and education initiatives, though a small number (<5) of other programs were evaluated, including traditional food programs and greenhouses. Though multiple programs resulted in lower food costs or increases in healthy food consumption in remote regions, the cost of a healthy diet in these areas remained high, as do levels of HFI. Factors associated with improved food security outcomes included higher income level, access to adequate housing, higher education level, access to transportation for harvesting, and the level of remoteness of a community. The studies included in this review also stressed the importance of access to and affordability of harvesting traditional foods in these regions.

CONCLUSION: Those living in remote and isolated communities are particularly vulnerable to food insecurity and lack of access and availability of healthy foods, which are compounded by a variety of socioeconomic factors. This study highlights the lack of quantitative evaluations of food security initiatives in remote and isolated communities, as well as the wide variety in measured outcomes. Authors of several of the included articles note that community-led initiatives, with strong partnerships and local champions, were recommended in these populations, given the culturally and geographically diverse groups living in remote and isolated areas.

PMID:39134397 | DOI:10.22605/RRH8627

Gut. 2024 Aug 12:gutjnl-2024-332648. doi: 10.1136/gutjnl-2024-332648. Online ahead of print.

ABSTRACT

OBJECTIVE: In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy).

DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).

RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively).

CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.

TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.

PMID:39134391 | DOI:10.1136/gutjnl-2024-332648

AJNR Am J Neuroradiol. 2024 Aug 12:ajnr.A8436. doi: 10.3174/ajnr.A8436. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Lateral decubitus CT myelography (LDCTM) is one of the main studies for the detection of CSF-venous fistulas (CVF), but detection of CVFs is dependent on intrathecal contrast density. The purpose of this investigation was to assess tolerability and technical performance of increased intrathecal doses of myelographic contrast compared to standard doses.

MATERIALS AND METHODS: Retrospective series of 24 patients who underwent LDCTM following administration of either 10 or 20 ml of intrathecal iodinated contrast media (300 or 320mg/mL iodine content). Patients were scanned in the initial lateral decubitus position, then turned to the contralateral side and re-scanned in the same session. Safety and tolerability of the 20 ml dosage was assessed from clinical records. Technical performance of the studies was compared between groups by measuring attenuation values over the lateral thecal sac at standardized levels. Both the initial scan and the scan after turning to the contralateral side were assessed.

RESULTS: No moderate or severe adverse event was recorded in either group. The 20-ml group showed higher attenuation values, which were statistically greater on the second side examined compared to the standard-dose group.

CONCLUSIONS: Increased volume of intrathecal contrast was well-tolerated and improved technical performance of LDCTM in this limited series. Further assessment of safety and impact on diagnostic yield using larger patient cohorts is warranted.

ABBREVIATIONS: LDCTM = lateral decubitus CT myelography; CVF = CSF-venous fistula; IOCM = iodinated contrast media.

PMID:39134376 | DOI:10.3174/ajnr.A8436

AJNR Am J Neuroradiol. 2024 Aug 12:ajnr.A8435. doi: 10.3174/ajnr.A8435. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Early opacification of the renal collecting system during CT myelography (CTM) performed for the evaluation of Spontaneous Intracranial Hypotension (SIH) has been demonstrated in prior studies. However, these investigations often included CTMs scanned >30 minutes after intrathecal contrast injection, a longer delay than the myelographic techniques used in current practice. The purpose of this study was to determine whether renal contrast excretion (RCE) measured during this earlier time period (≤30 minutes) can discriminate patients with SIH from patients without SIH.

MATERIALS AND METHODS: Single-center, retrospective cohort of consecutive patients presenting for evaluation of possible SIH between July 2021-May 2022. RCE was measured in both renal hila using standardized (5-15mm³) ROIs. ROC curves were constructed comparing RCE between patients with SIH to patients without SIH in the overall cohort, and within the subgroup of patients with negative myelograms.

RESULTS: The study cohort included 190 subjects. Both unadjusted and adjusted models demonstrated a statistically significant increase in renal contrast density among patients with SIH compared to those without SIH (p-values ≤ 0.001). The ROC curve showed moderate discrimination between these groups (AUC 0.76). However, using clinically meaningful test criteria of sensitivity >90% or specificity >90%, the two corresponding threshold HU values resulted in low specificity of 31.3% and sensitivity of 50.8%. Subgroup analysis of patients with negative myelograms showed poorer performance in discriminating SIH+ from SIH- (AUC 0.62). In this subgroup, using similar test criteria of sensitivity >90% or specificity >90 resulted in low specificities and sensitivities, at 26.0% and 37.5% respectively.

CONCLUSIONS: We found a statistically significant positive association between RCE and SIH diagnosis during early-phase CTM, however clinically useful thresholds based on cutoff values for renal HU resulted in poor sensitivities or specificities, with substantial false positives or false negatives, respectively. Thus, while we confirmed statistically significant differences in RCE in the ≤30 min time period, in keeping with prior investigations of more delayed time periods, overlap in renal attenuation values prevented the development of clinically useful threshold value for discriminating SIH+ from SIH-patients.

ABBREVIATIONS: SIH = spontaneous intracranial hypotension; RCE = renal contrast excretion; CTM = CT myelography; CVF = CSF-venous fistula; ICHD-3 = international classification of headache disorders third edition; CKD = chronic kidney disease.

PMID:39134375 | DOI:10.3174/ajnr.A8435

AJNR Am J Neuroradiol. 2024 Aug 12:ajnr.A8441. doi: 10.3174/ajnr.A8441. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: In ischemic stroke, leptomeningeal collaterals can provide delayed and dispersed compensatory blood flow to tissue-at-risk despite an occlusion and can impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that inclusion of this delayed and dispersed flow with an appropriately calculated Local Arterial Input Function (Local-AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion.

MATERIALS AND METHODS: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Dynamic susceptibility contrast MRI was imaged and post-processed to yield quantitative cerebral blood flow (qCBF) maps with both a traditionally chosen single arterial input function applied globally to the whole brain (i.e. “Global-AIF”) and a delay and dispersion corrected AIF (i.e. “Local-AIF”) that is sensitive to retrograde flow. Leptomeningeal collateral arterial recruitment was quantified with a pial collateral score from x-ray angiograms, and infarct growth calculated from serially acquired diffusion weighted MRI scans.

RESULTS: The degree of collateralization at x-ray correlated more strongly with qCBF using the Local-AIF in the ischemic penumbra (R²=0.81) than traditionally chosen Global-AIF (R²=0.05). qCBF using a Local-AIF was negatively correlated (less infarct progression as perfusion increased) with infarct growth (R² = 0.79) more strongly than a Global-AIF (R²=0.02).

CONCLUSIONS: In acute stroke, qCBF calculated with a Local-AIF is more accurate for assessing tissue status and collateral supply than traditionally chosen Global-AIFs. These findings support use of a Local-AIF that corrects for delayed and dispersed retrograde flow in determining quantitative tissue perfusion with collateral supply in occlusive disease.

ABBREVIATIONS: MRI = magnetic resonance imaging; DSC = dynamic susceptibility contrast; PCS = pial collateral score; MCAO = middle cerebral artery occlusion; MCA = middle cerebral artery; AIF = arterial input function; rCBF = relative cerebral blood flow; qCBF = quantitative cerebral blood flow.

PMID:39134367 | DOI:10.3174/ajnr.A8441

BMJ Glob Health. 2024 Aug 12;9(8):e015236. doi: 10.1136/bmjgh-2024-015236.

ABSTRACT

BACKGROUND: HIV testing and starting antiretroviral therapy (ART) are pivotal in treating people living with HIV (PLHIV) but sustaining PLHIV on treatment remains challenging. We assessed retention and attrition in community client-led antiretroviral distribution groups (CCLADs) in Uganda and identified positive deviant practices that foster long-term retention.

METHODS: Using explanatory mixed methods, we collected longitudinal medical data from 65 health facilities across 12 districts in East Central Uganda. Quantitative phase, from 18 April 2021 to 30 May 2021, employed survival analysis and Cox regression to assess retention and identify attrition risk factors. Qualitative inquiry focused on four districts with high attrition from 11 August 2021 to 20 September 2021, where we identified nine health facilities exhibiting high retention in CCLADs. We purposively selected 50 clients for in-depth interviews (n=22) or focus group discussions (n=28). Using thematic analysis, we identified positive deviant practices. We integrated quantitative and qualitative findings into joint displays.

RESULTS: Involving 3055 PLHIV, the study showed retention rates of 97.5% at 6 months, declining to 89.7% at 96 months. Attrition risk factors were lower levels of care (health centre three (adjusted HR (aHR) 2.80, 95% CI 2.00 to 3.65) and health centre four (aHR 3.61, 95% CI 2.35 to 5.54)); being unemployed (aHR 2.21, 95% CI 1.00 to 4.84); enrolment year into CCLAD (aHR 23.93, 95% CI 4.66 to 123.05) and virological failure (aHR 3.41, 95% CI 2.51 to 4.63). Of 22 clients interviewed, 8 were positive deviants. Positive deviants were characterised by prolonged retention in CCLADs, improved clinical outcomes and practised uncommon behaviours that enabled them to find better solutions than their peers. Positive deviant practices included fostering family-like settings, offering financial or self-development advice, and promoting healthy lifestyles.

CONCLUSIONS: Findings underscore the importance of addressing factors contributing to attrition and leveraging positive deviant practices to optimise retention and long-term engagement in HIV care.

PMID:39134343 | DOI:10.1136/bmjgh-2024-015236

BMJ Open Ophthalmol. 2024 Aug 12;9(1):e001732. doi: 10.1136/bmjophth-2024-001732.

ABSTRACT

BACKGROUND/AIMS: Population surveys are required to measure the prevalence of cataract blindness in the community. We conducted simultaneous surveys in two regions in Malaysia in 2023 to estimate the prevalence of untreated cataract, measure the visual outcomes after cataract surgery and compare the results with the survey in 2014.

METHODS: The surveys were done in Eastern and Sarawak administrative regions using the rapid assessment of avoidable blindness technique. It involved a multistage cluster sampling method, each cluster comprising 50 residents aged 50 years and older. The prevalence of cataract was determined through a visual acuity (VA) check and eye examination. The VA of those who had undergone cataract surgery was measured, and the findings were compared with the previous survey.

RESULTS: A total of 9709 subjects, 50 years old and older, were examined (percentages of response were 94.5% and 96.2% for Eastern and Sarawak, respectively). Comparing the current to the previous survey in 2014, the prevalence of cataract at all levels of surgical thresholds (except unilateral VA <6/60 and <6/18 in the Eastern) was reduced. The percentages of cataract surgery visual outcomes with good VA (6/12) were improved, and those with poor VA (<6/60) were reduced in both regions.

CONCLUSION: There was a reduction in cataract prevalence and improved visual outcomes in both regions. These favourable results could be attributed to the surgical performance monitoring initiatives and the community cataract programme implemented soon after the survey in 2014.

PMID:39134324 | DOI:10.1136/bmjophth-2024-001732

Photodiagnosis Photodyn Ther. 2024 Aug 10:104302. doi: 10.1016/j.pdpdt.2024.104302. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the correlations and consistency among the central corneal thickness (CCT) of healthy myopic patients measured with three different anterior segment analysis systems.

DESIGN: This was a retrospective study. The study included myopia patients who had undergone preoperative examinations in the refractive surgery department of our hospital between January 2021 and December 2023. The CCT was measured separately using Pentacam, Sirius, and IOLMaster 700.

METHODS: Statistical analysis was conducted using SPSS software. Correlations among the three groups of measured values were assessed using the Pearson method, and a simple scatter plot and fitting line were drawn. Bland‒Altman scatter plots and 95% limits of agreement (LoAs) were used to evaluate consistency in the data among the systems.

RESULTS: A total of 269 patients participated in the study, including 134 males (49.8%) and 135 females (50.2%). The CCT measurements by Pentacam, Sirius, and IOLMaster 700 instruments were found to be 541.63±31.67μm, 541.74±33.36μm, and 548.90±34.19μm respectively; significant differences were observed among these measurements (p<0.05). Significant differences were also observed in CCT between Pentacam and IOLMaster 700 as well as between Sirius and IOLMaster 700 (p<0.05). The CCT measurements by all three devices showed high positive correlation with all p values less than 0.001: Pentacam and Sirius, r=0.972; Pentacam and IOLMaster 700, r=0.966; and Sirius and IOLMaster 700, r=0.962. The respective 95% LoAs were -0.18∼0.18; -1.51∼-1.11; and -1.52∼-1.

CONCLUSION: The results indicate that there is a high correlation in measuring CCT for healthy myopic eyes using three different anterior segment analysis systems. However, the differences in the values measured by the three devices were statistically significant. Therefore, in actual clinical practice, it is suggested that the same device should be used to measureand evaluate the CCT across visits.

PMID:39134252 | DOI:10.1016/j.pdpdt.2024.104302