Cohort Of Patients Research Articles

Treatment effect analysis of the Frailty Care Bundle (FCB) in a cohort of patients in acute care settings

PurposeThe aim of this study is to explore the feasibility of using machine learning approaches to objectively differentiate the mobilization patterns, measured via accelerometer sensors, of patients pre- and post-intervention.MethodsThe intervention tested the implementation of a Frailty Care Bundle to improve mobilization, nutrition and cognition in older orthopedic patients. The study recruited 120 participants, a sub-group analysis was undertaken on 113 patients with accelerometer data (57 pre-intervention and 56 post-intervention), the median age was 78 years and the majority were female. Physical activity data from an ankle-worn accelerometer (StepWatch 4) was collected for each patient during their hospital stay. These data contained daily aggregated gait variables. Data preprocessing included the standardization of step counts and feature computation. Subsequently, a binary classification model was trained. A systematic hyperparameter optimization approach was applied, and feature selection was performed. Two classifier models, logistic regression and Random Forest, were investigated and Shapley values were used to explain model predictions.ResultsThe Random Forest classifier demonstrated an average balanced accuracy of 82.3% (± 1.7%) during training and 74.7% (± 8.2%) for the test set. In comparison, the logistic regression classifier achieved a training accuracy of 79.7% (± 1.9%) and a test accuracy of 77.6% (± 5.5%). The logistic regression model demonstrated less overfitting compared to the Random Forest model and better performance on the hold-out test set. Stride length was consistently chosen as a key feature in all iterations for both models, along with features related to stride velocity, gait speed, and Lyapunov exponent, indicating their significance in the classification.ConclusionThe best performing classifier was able to distinguish between patients pre- and post-intervention with greater than 75% accuracy. The intervention showed a correlation with higher gait speed and reduced stride length. However, the question of whether these alterations are part of an adaptive process that leads to improved outcomes over time remains.

Utility of diffusion weighted Magnetic Resonance Imagining to detect non-palpable undescended testis

Objective: To assess the effectiveness of diffusion-weighted magnetic resonance imaging (DW-MRI) in the detection of non-palpable undescended testis (NPUT) and to compare DW-MRI results with surgical findings. Methods: This descriptive, cross-sectional study was carried out at Dow Institute of Radiology, Dow University of Health Sciences. Karachi on a cohort of patients who underwent DW-MRI for suspected NPUT between 15th September, 2022 to 16th March, 2023. The study included 175 boys below the age of 16 years with history of clinically non-palpable testes. MRI scans were acquired using additional DWI sequence. Two radiology faculty of more than five years of experience independently evaluated the DW-MRI images for the presence or absence of testes in its normal anatomical position, abnormal location, side and size of testes. Results: Out of the 175 patients, DW-MRI successfully detected 128 (73.1%) non-palpable undescended testes. Statistical analysis in clinically detected cases of showed sensitivity of NPTU 0.8%, specificity of 92.5%, diagnostic accuracy 94.29%, positive predictive value 97.7%, and negative predictive value 84.1% for localizing undescended testes with Diffusion Weighted DW-MRI taking surgical findings as gold standard. Conclusion: DWI sequences complement the conventional MRI, increasing its sensitivity and diagnostic accuracy. By facilitating early and accurate diagnosis, DW-MRI has the potential to streamline patient management, reduce unnecessary surgical exploration, and ultimately improve the long-term reproductive health and quality of life for individuals with undescended testes. doi: https://doi.org/10.12669/pjms.40.9.8905 How to cite this: Naz N, Walid A, Rahim A, Lajpat K. Utility of diffusion weighted Magnetic Resonance Imagining to detect non-palpable undescended testis. Pak J Med Sci. 2024;40(9):---------. doi: https://doi.org/10.12669/pjms.40.9.8905 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study

PurposeSurvival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.MethodsIn total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping.ResultsA positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality.ConclusionThe OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.

Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy

BackgroundX-linked adrenoleukodystrophy (ALD) is a neurometabolic disorder caused by pathogenic variants in ABCD1 resulting very long-chain fatty acids (VLCFA) accumulation in plasma and tissues. Males can present with various clinical manifestations, including adrenal insufficiency, spinal cord disease, and leukodystrophy. Female patients typically develop spinal cord disease and peripheral neuropathy. Predicting the clinical outcome of an individual patient remains impossible due to the lack of genotype-phenotype correlation and predictive biomarkers.MethodsThe availability of a large prospective cohort of well-characterized patients and associated biobank samples allowed us to investigate the relationship between lipidome and disease severity in ALD. We performed a lipidomic analysis of plasma samples from 24 healthy controls, 92 male and 65 female ALD patients.ResultsHere we show that VLCFA are incorporated into different lipid classes, including lysophosphatidylcholines, phosphatidylcholines, triglycerides, and sphingomyelins. Our results show a strong association between higher levels of VLCFA-containing lipids and the presence of leukodystrophy, adrenal insufficiency, and severe spinal cord disease in male ALD patients. In female ALD patients, VLCFA-lipid levels correlate with X-inactivation patterns in blood mononuclear cells, and higher levels are associated with more severe disease manifestations. Finally, hematopoietic stem cell transplantation significantly reduces, but does not normalize, plasma C26:0-lysophosphatidylcholine levels in male ALD patients. Our findings are supported by the concordance of C26:0-lysophosphatidylcholine and total VLCFA analysis with the lipidomics results.ConclusionsThis study reveals the profound impact of ALD on the lipidome and provides potential biomarkers for predicting clinical outcomes in ALD patients.

Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.

Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course. We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort. Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it. TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.

Evaluating the associations between dysautonomia, gastrointestinal transit, and clinical phenotype in patients with systemic sclerosis.

Our objective was to identify systemic sclerosis (SSc) patients with a high burden of autonomic symptoms and to determine whether they have a distinct clinical phenotype, gastrointestinal (GI) transit or extraintestinal features. In a prospective cohort of SSc patients with GI disease, clinical data were systematically obtained at routine visits. Dysautonomia was identified by the Composite Autonomic Symptom Score (COMPASS)-31questionnaire. GI transit was measured by whole-gut scintigraphy. Associations between total COMPASS-31 scores and clinical features, GI symptoms, and transit were evaluated. Comparisons between patients with global autonomic dysfunction [(GAD); ≥5 positive COMPASS-31 subdomains] and those with limited autonomic dysfunction [(LAD); <5 positive subdomains] were also studied. 91 patients with SSc and GI involvement were included [mean age 57, 90% female, 74% limited cutaneous disease, 83% significant GI disease (Medsger score ≥2)]. The mean COMPASS-31 score in SSc was higher than controls (38.8 vs. 7.2). 33% had GAD, 67% had LAD. Patients with GAD were more likely to have limited SSc (93% vs. 65%; p<0.01) and have sicca symptoms (100% vs. 77%; p=0.01). Gastric and colonic transit were faster in patients with GAD (p<0.05). Upper GI involvement (Medsger GI score of 1 or 2) was associated with higher total COMPASS-31 scores (p=0.02). Symptoms of global dysautonomia are seen in up to one-third of patients with SSc and GI involvement. Identifying specific clinical characteristics associated with GAD in SSc will help to identify a population that may benefit from therapies that modulate the autonomic nervous system.

Religiosity and Health Outcomes in a Cohort of Romanian Patients Hospitalized for COVID-19.

There is a growing body of evidence for the interrelation between health status and religious beliefs. Our aim was to evaluate the level of religiosity in patients hospitalized for COVID-19 and to assess the link between religiosity and measurable health outcomes.This was an observational, single-center study which included patients with moderate-to-severe forms of COVID-19.A total of 112 patients were enrolled in the study, of whom 77 were highly religious (CRS-15 score ≥ 4) and 35 non-highly religious (CRS-15 score < 4).There was no difference in demographics or prevalence of comorbidities between the two groups. Furthermore, we found no difference between groups in radiological extension of lung lesions, length of hospital stays, or ICU need; however, in-hospital mortality rate was significantly lower in highly religious group (1% vs. 14%, p = 0.005). Serum ferritin level at admission was significantly lower (p = 0.03) and prevalence of post-COVID-19 pulmonary sequelae significantly higher in highly religious group (p = 0.02).

Prehospital stroke detection scales: A head-to-head comparison of 7 scales in patients with suspected stroke.

Several prehospital scales have been designed to aid paramedics in identifying stroke patients in the ambulance setting. However, external validation and comparison of these scales are largely lacking. To compare all published prehospital stroke detection scales in a large cohort of unselected stroke code patients. We conducted a systematic literature search to identify all stroke detection scales. Scales were reconstructed with prehospital acquired data from two observational cohort studies: the Leiden Prehospital Stroke Study (LPSS) and PREhospital triage of patients with suspected STrOke (PRESTO) study. These included stroke code patients from four ambulance regions in the Netherlands, including 15 hospitals and serving four million people. For each scale, we calculated the accuracy, sensitivity and specificity for a diagnosis of stroke (ischemic, hemorrhagic or TIA). Moreover, we assessed the proportion of stroke patients who received reperfusion treatment with intravenous thrombolysis or endovascular thrombectomy that would have been missed by each scale. We identified 14 scales, of which seven (CPSS, FAST, LAPSS, MASS, MedPACS, OPSS, and sNIHSS-EMS) could be reconstructed. Of 3317 included stroke code patients, 2240 (67.5%) had a stroke (1528 ischemic, 242 hemorrhagic, 470 TIA) and 1077 (32.5%) a stroke mimic. Of ischemic stroke patients, 715 (46.8%) received reperfusion treatment. Accuracies ranged from 0.60 (LAPSS) to 0.66 (MedPACS, OPSS and sNIHSS-EMS), sensitivities from 66% (LAPSS) to 84% (MedPACS and sNIHSS-EMS), and specificities from 28% (sNIHSS-EMS) to 49% (LAPSS). MedPACS, OPSS and sNIHSS-EMS missed the fewest reperfusion-treated patients (10.3-11.2%), whereas LAPSS missed the most (25.5%). Prehospital stroke detection scales generally exhibited high sensitivity but low specificity. While LAPSS performed poorest, MedPACS, sNIHSS-EMS and OPSS demonstrated the highest accuracy and missed the fewest reperfusion-treated stroke patients. Use of the most accurate scale could reduce unnecessary stroke code activations for patients with a stroke mimic by almost a third, but at the cost of missing 16% of strokes and 10% of patients who received reperfusion treatment.

Racial and socioeconomic disparities in NSCLC molecular diagnostics uptake.

Precision therapies, such as targeted and immunotherapies, have substantially changed the landscape of late-stage non-small cell lung cancer (NSCLC). Yet utilization of these therapies is disproportionate across strata defined by race and socioeconomic status (SES), possibly due to disparities in molecular diagnostic testing (or "biomarker testing"), which is a prerequisite to treatment. We extracted a cohort of NSCLC patients from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. The primary outcome was receipt of a molecular diagnostic test, based on claims data. The primary predictors were race and SES. Likelihood of receiving a molecular diagnostic test, and overall survival (OS), were investigated using logistic and Cox proportional hazards regression, adjusted for sex, age, residence, histology, marital status, and comorbidity. Of the 28,511 NSCLC patients, 11,209 (39.3%) received molecular diagnostic testing. Compared to White patients, fewer Black patients received a molecular diagnostic test (40.4% vs 27.9%; p < .001). After adjustment, Black patients (ORadj [odds ratio]: 0.64; 95% CI [confidence interval]: 0.58-0.71) and those living in areas with greater poverty (ORadj: 0.85; 95% CI: 0.80-0.89) had statistically significant decreased likelihood of molecular diagnostic testing. Patients who did receive testing had a statistically significant decreased risk of death (HRadj [hazards ratio]: 0.74; 95% CI: 0.72-0.76). These results held in the stratified analysis of stage IV NSCLC patients. Disparities exist in comprehensive molecular diagnostics, which is critical for clinical decision making. Addressing barriers to molecular testing could help close gaps in cancer care and improve patient outcomes.

Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH. We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI. In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%). Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Temporal variation in the effectiveness of biologics in asthma: Effect modification by changing patient characteristics

BackgroundThe underlying population of patients selected for each respiratory monoclonal antibody might change as other biologics are approved. ObjectiveTo evaluate effect modification by calendar time of the effectiveness of each respiratory biologics in asthma. MethodsThe Effectiveness of Respiratory biologics in Asthma (ERA) is a retrospective cohort of severe asthma patients from the Mass General Brigham clinics between January 2013 and September 2023. Periods were pre-specified as the anti-IgE (2013–2015), anti-IL5 (2016–2018), anti-IL4/13 (2019–2021) or anti-alarmin (2022–2023) era. We evaluated each biologic's effect on asthma-related exacerbations comparing the one-year period before and after therapy initiation using Poisson regression and Cox regression for time-to-first exacerbation. ResultsOf 647 biologic-naïve patients, 165 initiated omalizumab, 235 anti-IL5, 227 dupilumab, and 20 tezepelumab. Omalizumab's effectiveness improved as more biologics were approved: incidence rate ratio (IRR) 1.16 [0.94–1.43] anti-IgE era vs. 0.54 [0.37–0.80] anti-IL4/13-alarmin era. Omalizumab patients in the anti-IL4/13-alarmin era had lower blood eosinophil counts and less chronic rhinosinusitis with nasal polyps (CRSwNP). For anti-IL5s, effectiveness peaked in the anti-IL4/13 era (IRR 0.52 [0.42–0.64]) when patients had higher BMI and less concomitant CRSwNP. Dupilumab was most effective in the anti-IL4/13 era (IRR 0.60 [0.50–0.72]). There were fewer current smokers in dupilumab patients in the anti-IL4/13 era. Results were similar in time-to-event analyses and in sensitivity analyses accounting for the COVID-19 pandemic. ConclusionThere are temporal variations in the effectiveness of biologics partly explained by the shift in the underlying population, particularly for omalizumab. Though having more choices was associated with better patient selection for omalizumab, this was inconsistent for other biologics.

The potential benefits of concomitant statins treatment in patients with non-muscle-invasive bladder cancer.

To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

Barriers and facilitators to bridging the healthcare digital divide for the older adults: A qualitative research from patients in China.

The aim of this study was to explore the barriers and facilitators underlying the healthcare digital divide by using qualitative methodologies, integrated with the Capabilities, Opportunities, Motivations, and Behaviors (COM-B) as well as the Behavior Change Wheel (BCW) theoretical frameworks. To conduct a thorough analysis, semi-structured，in-depth interviews were orchestrated among a cohort of older patients who had experiences with digital healthcare systems. Data were meticulously analyzed via Colaizzi's seven-step methodological procedure. Nine barriers were elucidated, including physical limitation, inadequate training and support, self-imposed denial, failure to rebuild the digital healthcare environment, equipment constraints, deficits in communication and feedback, skepticism regarding data accuracy and validity, sense of social deprivation, and network information boycott. Conversely, eleven facilitators were identified, encompassing peer modeling, availability of training and support, reconstructive efforts toward the digital healthcare environment, mandatory usage, familial influence, media impact, scientific publicity and education, enhancement of self-efficacy, sense of social participation, perceived convenience, and access to healthful information. Based on the COM-B and BCW models, healthcare organizations may be able to improve their digital healthcare support systems (capabilities), technical design, network speed, and equipment configuration (opportunities), as well as focus on "human-computer integration," the parallel existence of digital technology and humanistic care, and taking into account the issues of information security, accuracy, and human rights equality (motivation) while benefiting the patients, in order to bridge the healthcare digital divide for the older adults.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

CXCR7 genetic variant predicts treatment response of pegylated-interferon α in HBeAg-positive chronic hepatitis B patients

ObjectivesCXC chemokine receptor 7 (CXCR7) plays pivotal roles in different virus infections. However, no research focused on the role of CXCR7 in hepatitis B virus (HBV)-infected patients. The primary aim of this study is to elucidate the role of CXCR7 in predicting the treatment response of chronic hepatitis B (CHB) patients undergoing pegylated interferon-alpha (PegIFNα) therapy. MethodsTwo cohorts with a total of 945 Chinese CHB patients (Cohort 1, n = 238; Cohort 2, n = 707) were enrolled in this retrospective study, all the patients were positive for hepatitis B e antigen (HBeAg) and received PegIFNα treatment for 48 weeks and followed-up for 24 weeks post-treatment. Nineteen tag single-nucleotide polymorphisms (SNPs) were selected within and surrounding the CXCR7 gene region. The associations of CXCR7 SNPs and polygenic score (PGS) with PegIFNα treatment response were investigated in the two cohorts. ResultsAmong the 19 candidate SNPs of CXCR7, rs2952665 (A > G) was significantly associated with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <3.3log10IU/mL, P = 0.002) and hepatitis B surface antigen (HBsAg) decline (P = 0.015) in the two cohorts at week 72. Furthermore, a PGS comprising CXCR7_rs2952665 and five additional SNPs, which were previously recognized as biomarkers of PegIFNα treatment response, demonstrated a robust correlation with both CR (P = 1.38 × 10−12) and HBsAg decline (P = 0.003) in all the patients. ConclusionThis research illustrated that CXCR7_rs2952665 is a promising predictor of the PegIFNα therapy efficiency in Chinese HBeAg-positive CHB patients. A PGS consisting of CXCR7_rs2952665 and five previously reported SNPs predicts treatment response to PegIFNα better.

Do Botulinum Toxin Injections for Upper Face Rejuvenation and Lateral Canthal Rhytids Have Unintended Effects on Tear Production?

To report the influence of botulinum toxin A (BoNTA) injections on basal tear production, as measured by Schirmer's test with anesthesia in patients seeking eyelid surgery. A retrospective cohort of patients requesting esthetic eyelid surgery reviewed by a single clinician between January 2021 to April 2024, assessed with Schirmer's test with anesthesia. Demographic data, history of BoNTA treatment in the periocular region, ocular surface disease index dry eye symptom frequency, and requirement for ocular lubricants were recorded. Patients with no history of BoNTA were designated as group 1. Patients with a positive recent history of periocular BoNTA were designated as group 2. The proportions of eyes with Schirmer's test with anesthesia (basal tear production) test result <5 mm ("low"), 5 to 9 mm ("borderline"), and ≥10 mm ("normal") were compared between groups. Seven hundred twenty-two eyes (361 patients) were assessed, of which 670 eyes (335 patients) met the inclusion criteria. Mean age was 55.1 (range, 17-93) years, with 71.3% female. Schirmer's data in group 1 were "low" at 32.9%, "borderline" at 26.4%, and "normal" at 40.7%. In contrast, group 2 had significantly lower results (P ≤ 0.05), with readings "low" at 48.3%, "borderline" at 26.7%, and "normal" at 25.0%. However, there were no significant differences between groups in ocular surface disease index symptom frequency scores or ocular lubricant requirements. Patients who had received BoNTA injections had significantly lower basal tear production compared with patients who had never received BoNTA. Esthetic BoNTA treatment may be associated with an unintended effect of decreased basal tear production and subsequent risk of dry eye.

Slow Gait Speed Predicts Incident Dementia, Mortality, and Long-Term Functional Outcome in Cerebral Small-Vessel Disease.

Gait impairment is observed in patients with small vessel disease (SVD); however, the association between gait function and long-term outcome remains unclear. This study aimed to clarify the predictive value of gait function on incident dementia, survival and functional outcome. Data were derived from a Japanese cohort of patients with SVD. This study included 522 participants who underwent 3-m timed up and go test (TUG), and gait speed, TUG time, was divided into tertiles. Magnetic resonance imaging was used to evaluate severity of white matter hyperintensities, lacunes, and medial temporal atrophy. Primary outcome was dementia. All-cause death and functional outcome by modified Rankin scale at the last visit was also evaluated. The median age was 71 years, and median TUG time was 9.91 s. During follow-up period of 4.8 years, 32 cases of dementia occurred. Cox proportional hazard analysis revealed that slow gait speed (TUG time > 10.88 s) was associated with a significantly higher risk of incident dementia than fast (TUG time < 9.03) and middle (TUG time, 9.04-10.87 s) speeds after adjusting risk factors, Mini-Mental State Examination, SVD severity and brain atrophy (adjusted hazard ratio, 2.73; 95% confidence interval, 1.16-6.42, p = 0.022). Slow speed was also associated with mortality and poor functional outcome compared with other speeds (adjusted odds ratio, 4.19; 95% confidence interval 1.92-9.18, p < 0.001). Gait function was associated with incident dementia, mortality and poor functional outcome independently of cognitive function, brain atrophy, and SVD severity.

Hospitalization and Health Resource Utilization in Emergency Department Cases of Diabetic Foot Infections in the U.S. from 2012 to 2021: A Nationally Representative Analysis

Objectives: The objective of this paper was to assess hospitalizations and health resource utilization associated with diabetic foot infection (DFI)-related visits within emergency departments (EDs) in the U.S. Methods: This nationally representative, cross-sectional historical cohort utilized the Centers for Disease Control and Prevention’s (CDC’s) National Hospital Ambulatory Medical Care Survey across a ten-year period from 2012 to 2021. Inclusion criteria were as follows: adults ≥18 years of age; a diagnosis of Type 1 or Type 2 diabetes mellitus; presence of a DFI. Comparisons were drawn relative to a cohort of patients with diabetes without foot complications. Study outcomes included 72-hour (72 h) ED revisit, hospitalization, and length of stay (LOS). Top diagnoses and medications were also reported. Multivariable, generalized, linear regression analyses were employed, controlling for key demographics, health system factors, clinical characteristics, and year. Results: An estimated 150.6 million ED visits included a diabetes diagnosis, with 2.4 million involving a DFI (1.6%). Approximately half of DFI cases were hospitalized (43.7%). Anti-infective medications were prescribed in 83.1% of DFI cases, including vancomycin in 28.1%. Multivariable analyses observed that DFIs were associated with a 3.002 times higher odds of hospital admissions (CI: 2.145–4.203, p &lt; 0.001) and a 55.0% longer LOS (IR = 1.550, CI: 1.241–1.936, p &lt; 0.001). DFIs were not significantly associated with a 72 h ED revisit. Conclusions: This nationally representative study of 2.4 million DFI-related ED visits in the U.S. observed higher odds of hospital admissions and a longer LOS for DFIs versus diabetes without foot complications. Continued research should seek to assess prevention and coordinated treatment interventions prior to the emergence of DFIs requiring ED care.

Platform enabling population-level imaging and data linkage in Scotland

Scotland has more than five million people within a single health system, using a single central Picture Archiving and Commication System (PACS) for radiography data. This enabled the project team to build a research resource exceeding a petabyte of imaging from 2010 onwards, with open-source tooling to collate and de-identify images on demand. Image metadata, treatment and diagnostic records can be used to define large cohorts of patients then make the data available remotely to researchers in a Trusted Research Environment (TRE). Original identifiable images are stored in one of three isolated zones with controlled data transfer to protect patient privacy and prevent inadvertent disclosure. Linkage to other records is performed in the second zone on de-identified images using encrypted patient identifiers. Automated screening with optical character recognition and natural language processing was implemented to identify and redact personally identifiable information before release to researchers in the third zone. A recent extension to this system has provided an ongoing feed of routine imaging, which is securely shared with regional counterparts to ensure the minimal possible additional load is placed on clinical PACS resources and avoid duplicate requests. The project launched in April 2022 and since then a variety of research projects have already used this environment and data representing millions of pounds of funding, some using large cohorts with historical data up to 14 years old, re-assessing historical scans with the benefit of subsequent diagnosis to investigate possible early warning signs of conditions including dementia and pre-cancerous lung nodules.

Prevalence and factors associated to calcium pyrophosphate arthritis in patients with gout

Aim: To ascertain the prevalence of calcium pyrophosphate arthritis (CPPA) at diagnosis and during follow-up of patients with gout. Methods: Inception cohort of patients with gout prospectively recruited and followed-up from 1994–2023. Gout-case was defined as crystal-proved tophus or arthritis, or the presence of tophus plus double contour with ultrasonography. CPPA was defined as the presence of intra-leukocyte calcium pyrophosphate (CPP) crystals in synovial fluid (SF) and neat chondrocalcinosis in plain radiographs. Age, gender, time from onset of symptoms, number of flares, joint distribution, previous and prescribed treatments, colchicine prophylaxis, comorbidities, alcohol intake, use of diuretics, renal function, and previous vascular disease were available for analysis. Results: A total of 1,544 patients with gout, with an average of 4-year follow-up, were available for analysis. CPPA was observed in 127/1,544 cases (8.2%). In 37/1,544 patients (2.4%) CPP and monosodium urate (MSU) crystals were observed in the same SF sample at gout diagnosis, and 90/1,544 (5.8%) showed CPP crystals apart from the diagnosis of gout. CPPA-gout cases had more flares per year, but no more frequent polyarticular distribution at baseline compared to non-CPPA-gout. CPPA-gout cases were older at baseline and showed lower renal function. Women, patients using diuretics, patients with hypertension, and those with previous vascular events showed CPPA more frequently. Multivariate analysis showed that only age and use of diuretics were independently associated with CPPA, as other variables apparently associated were dependent on aging. Interestingly, an analysis of the prevalence in the three decades available showed an increased CPPA diagnosis through time, probably associated with increased awareness of the association. Conclusions: (1) CPPA is not infrequent in patients with gout; (2) it is associated with aging and diuretic use; (3) awareness of this association may increase the rate of diagnosis.