Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy

Multiple Long-Term Conditions and Disability are Independently Associated with Higher Risk of Fall Among Community Adults: a Cross-Sectional Study

Aqeel M Alenazi,1 Norah A Alhwoaimel,1 Bader A Alqahtani,1 Mohammed M Alshehri,2 Ahmed S Alhowimel,1 Kamlesh Khunti,3 Mohammed S Alghamdi4 1Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 2Department of Physical Therapy, Jazan University, Jazan, Saudi Arabia; 3Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, UK; 4Department of Medical Rehabilitation Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Aqeel M Alenazi, Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Alt-Kharj, 11942, Saudi Arabia, Tel +966115886354, Email [email protected]; [email protected]: Previous studies have suggested an association between falls and the presence of Multiple Long-Term Conditions (MLTC) or disabilities. However, there is limited understanding of how these factors independently or collectively contribute to the risk of falls and fear of falling among community-dwelling adults.Objective: This study examined the independent association between MLTC and the presence of disability with the risk of falls among community adults.Methods: A cross-sectional study included 324 adults (age ≥ 50). Demographic and clinical data included age, sex, body mass index (BMI), MLTC (≥ two chronic diseases) risk of fall (ie, history of fall in the previous 12-months, number of falls, and recurrent falls). The Barthel Index and Falls Efficacy Scale-International (FES-I) were used to assess disability and fear of fall, respectively.Results: MLTC (Odds Ratio (OR) 2.50, 95% Confidence Interval (CI) [1.26, 4.95], p=0.009), and disability (OR 1.71, 95% CI [1.04, 2.79], p = 0.034) were independently associated with history of falls. MLTC (Incidence Rate Ratio (IRR) 2.87, 95% CI [1.93, 4.29], p < 0.001) and disability (IRR 1.86 95% CI [1.46, 2.36], p < 0.001) were independently associated with an increased number of falls. MLTC (OR 4.50, 95% CI [1.78, 11.36], p = 0.001) and disability (OR 2.82, 95% CI [1.58, 5.05], p < 0.001) were independently associated with recurrent falls. MLTC (B = 6.45, p < 0.001) and disability (B = 3.05, p = 0.025) were independently associated with increased fear of falling.Conclusion: This study indicated that both MLTC and disability are independently associated with falls, number of falls and fear of falling in this population.Keywords: falling, disabilities, impairments, functional limitations, multiple chronic diseases, multimorbidity, Saud

Diagnostic Accuracy of Integrating Ultrasound and Shear Wave Elastography in Assessing Carpal Tunnel Syndrome Severity: a Prospective Observational Study

Ahmed Mohamed El-Maghraby,1 Yassir Edrees Almalki,2 Mohammad Abd Alkhalik Basha,1 Mohamad Gamal Nada,1 Fatma El Ahwany,1 Sharifa Khalid Alduraibi,3 Shaker Hassan S Alshehri,4 Asim S Aldhilan,3 Ziyad A Almushayti,3 Alaa K Alduraibi,3 Mervat Aboualkheir,5 Osama Attia,6 Mona M Amer,7 Ahmed M Abdelkhalik Basha,8 Ibrahim M Eladl1 1Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, 44519, Egypt; 2Division of Radiology, Department of Internal Medicine, Medical College, Najran University, Najran, 61441, Kingdom of Saudi Arabia; 3Department of Radiology, College of Medicine, Qassim University, Buraidah, 52571, Kingdom of Saudi Arabia; 4Department of Orthopedic Surgery, College of Medicine, King Khalid University, Abha, 61421, Kingdom of Saudi Arabia; 5Department of Internal Medicine, College of Medicine, Taibah University, Madinah, 42361 Kingdom of Saudi Arabia; 6Department of Internal Medicine, Faculty of Human Medicine, Zagazig University, Zagazig, 44519, Egypt; 7Department of Neurology, Faculty of Human Medicine, Zagazig University, Zagazig, 44519, Egypt; 8Faculty of General Medicine, Saint Petersburg State University, Egypt Branch, Cairo, 11646, EgyptCorrespondence: Yassir Edrees Almalki, Email [email protected]: Carpal tunnel syndrome (CTS) is a common condition characterized by compression of the median nerve (MN) within the carpal tunnel. Accurate diagnosis and assessment of CTS severity are crucial for appropriate management decisions. This study aimed to investigate the combined diagnostic utility of B-mode ultrasound (US) and shear wave elastography (SWE) for assessing the severity of CTS in comparison to electrodiagnostic tests (EDT).Materials and Methods: This prospective observational study was conducted over 9-month periods at a tertiary care hospital. A total of 48 patients (36 females, 12 males; mean age 44 ± 10.9 years; age range 28– 57 years) with clinically suspected CTS were enrolled. All patients underwent EDT, US, and SWE. Based on the EDT results, CTS cases were categorized into four groups: mild, moderate, severe, and negative. The cross-sectional area (CSA) and elasticity (E) of the MN were measured at the tunnel inlet (CSAu and Eu) and pronator quadratus region (CSAo and Eo). The differences (CSAu-CSAo and Eu-Eo) were calculated. The primary outcomes were the diagnostic performance of CSAu, CSAu-CSAo, Eu, and Eu-Eo in differentiating moderate/severe from mild/negative CTS compared to EDT findings. Secondary outcomes included a correlation of US/SWE parameters with EDT grades and between each other. ANOVA, correlation, regression, and receiver operating characteristic (ROC) curve analyses were performed.Results: CSAu and CSAu–CSAo increased progressively with worsening CTS severity. E measurements were significantly higher in moderate-to-severe CTS compared to mild or negative cases. The combined metric of CSAu-CSAo at a 5 mm threshold exhibited enhanced performance, with a higher sensitivity (83.3%), specificity (100%), and area under the curve (AUC) (0.98), surpassing the results of CSAu when used independently. Similarly, the SWE measurements indicated that Eu-Eo at a 56.1kPa cutoff achieved an AUC of 0.95, with a sensitivity of 93.3% and specificity of 94.4%, outperforming the metrics for Eu when used alone, which had an AUC of 0.93, with identical sensitivity and specificity values (93.3% and 94.4%, respectively).Conclusion: The integration of ultrasound, shear wave elastography, and electrodiagnostic tests provides a comprehensive approach to evaluate anatomical and neurological changes and guide management decisions for CTS.Keywords: carpal tunnel syndrome, median never, ultrasound, shear wave elastograph

Sleep quality is associated with vitamin B12 status in female Arab students

Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5; body mass index, 23.6 kg/m2 ± 5.2) at King Saud University, Riyadh, Saudi Arabia. Fasting blood samples were analyzed regarding the serum vitamin B12 and blood lipids. Anthropometric, socio-demographic, clinical history, stress, physical activity, and dietary data were collected. We assessed the sleep statuses of the participants using the PSQI. Around 72% of the participants were “poor” sleepers (PSQI > 5). Subgroup analysis within the tertiles showed that participants with higher vitamin B12 in the second and third tertiles reported better scores for sleep quality (B ± SE = −12.7 ± 5.6, p = 0.03; B ± SE = −32.7 ± 16.4, p = 0.05, respectively) and also reported a lower use of sleep medication (B ± SE = −21.2 ± 9.9, p = 0.03, in the second tertile only), after adjusting for the waist–hip ratio and stress. However, sleep was not found to be directly associated with either serum vitamin B12 or dietary vitamin B12. In conclusion, the serum vitamin B12 results show that the participants with higher vitamin B12 in the second and third tertiles reported better scores on the sleep quality scale and a lower use of sleep medication. However, no such associations were observed with the overall PSQI. More studies with larger sample sizes are needed to establish a direct relationship between sleep and vitamin B12

Comorbidities and Risk Factors for Severe Outcomes in COVID-19 Patients in Saudi Arabia: A Retrospective Cohort Study

Purpose: The first novel coronavirus disease-19 (COVID-19) case in the Kingdom of Saudi Arabia (KSA) was reported in Qatif in March 2020 with continual increase in infection and mortality rates since then. In this study, we aim to determine risk factors which effect severity and mortality rates in a cohort of hospitalized COVID-19 patients in KSA. Method: We reviewed medical records of hospitalized patients with confirmed COVID-19 positive results via reverse-transcriptase-polymerase-chain-reaction (RT-PCR) tests at Prince Mohammed Bin Abdulaziz Hospital, Riyadh between May and August 2020. Data were obtained for patient’s demography, body mass index (BMI), and comorbidities. Additional data on patients that required intensive care unit (ICU) admission and clinical outcomes were recorded and analyzed with Python Pandas. Results: A total of 565 COVID-19 positive patients were inducted in the study out of which, 63 (11.1%) patients died while 101 (17.9%) patients required ICU admission. Disease incidences were significantly higher in males and non-Saudi nationals. Patients with cardiovascular, respiratory, and renal diseases displayed significantly higher association with ICU admissions (p&lt; 0.001) while mortality rates were significantly higher in COVID-19 patients with cardiovascular, respiratory, renal and neurological diseases. Univariate cox proportional hazards regression model showed that COVID-19 positive patients requiring ICU admission [Hazard’s ratio, HR=4.2 95% confidence interval, CI 2.5– 7.2); p&lt; 0.001] with preexisting cardiovascular [HR=4.1 (CI 2.5– 6.7); p&lt; 0.001] or respiratory [HR=4.0 (CI 2.0– 8.1); p=0.010] diseases were at significantly higher risk for mortality among the positive patients. There were no significant differences in mortality rates or ICU admissions among males and females, and across different age groups, BMIs and nationalities. Hospitalized patients with cardiovascular comorbidity had the highest risk of death (HR=2.9, CI 1.7– 5.0; p=0.020). Conclusion: Independent risk factors for critical outcomes among COVID-19 in KSA include cardiovascular, respiratory and renal comorbidities

Monomeric C-reactive protein localized in the cerebral tissue of damaged vascular brain regions is associated with neuro-inflammation and neurodegeneration - an immunohistochemical study

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and β-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1β) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Global, regional, and national burden of low back pain, 1990–2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background: Low back pain is highly prevalent and the main cause of years lived with disability (YLDs). We present the most up-to-date global, regional, and national data on prevalence and YLDs for low back pain from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Methods: Population-based studies from 1980 to 2019 identified in a systematic review, international surveys, US medical claims data, and dataset contributions by collaborators were used to estimate the prevalence and YLDs for low back pain from 1990 to 2020, for 204 countries and territories. Low back pain was defined as pain between the 12th ribs and the gluteal folds that lasted a day or more; input data using alternative definitions were adjusted in a network meta-regression analysis. Nested Bayesian meta-regression models were used to estimate prevalence and YLDs by age, sex, year, and location. Prevalence was projected to 2050 by running a regression on prevalence rates using Socio-demographic Index as a predictor, then multiplying them by projected population estimates. Findings: In 2020, low back pain affected 619 million (95% uncertainty interval 554–694) people globally, with a projection of 843 million (759–933) prevalent cases by 2050. In 2020, the global age-standardised rate of YLDs was 832 per 100 000 (578–1070). Between 1990 and 2020, age-standardised rates of prevalence and YLDs decreased by 10·4% (10·9–10·0) and 10·5% (11·1–10·0), respectively. A total of 38·8% (28·7–47·0) of YLDs were attributed to occupational factors, smoking, and high BMI. Interpretation: Low back pain remains the leading cause of YLDs globally, and in 2020, there were more than half a billion prevalent cases of low back pain worldwide. While age-standardised rates have decreased modestly over the past three decades, it is projected that globally in 2050, more than 800 million people will have low back pain. Challenges persist in obtaining primary country-level data on low back pain, and there is an urgent need for more high-quality, primary, country-level data on both prevalence and severity distributions to improve accuracy and monitor change. Funding: Bill and Melinda Gates Foundation

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study

Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. Design Registry based observational study. Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021 Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients). Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease. Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07). Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions