Subgroup Analysis Research Articles

Maintaining ideal cardiovascular health is associated with higher serum anti-aging protein klotho in the middle-aged and older populations

ObjectivesMaintaining ideal cardiovascular health (CVH) is believed to have potential anti-aging benefits. The American Heart Association (AHA) recently updated the “Life's Essential 8 (LE8)” metrics to measure ideal CVH, but its connection with the anti-aging protein klotho is still unclear. We aimed to explore the relationship between ideal cardiovascular health and serum anti-aging protein klotho in a nationally representative US middle-aged and older population. DesignA cross-sectional study. SettingThe National Health and Nutrition Examination Survey (2007−2016). ParticipantsA total of 9457 middle-aged and older participants. MeasurementsIdeal CVH scores and their components were defined according to the guidelines set by the AHA. Serum klotho detected by enzyme-linked immunosorbent assay. Weighted multivariable linear regression and restricted cubic spline were employed to examine the association between CVH score and klotho. Subgroup analyses were conducted, stratified by age (40−59 and 60−79), sex (Male and Female), race (Mexican American, non-Hispanic White, non-Hispanic Black, and Others) and chronic kidney disease (Yes and No) in fully adjusted models. ResultsA total of 9457 middle-aged and older participants were included in this study, with a mean age of 55.27 ± 0.17 years. The mean serum klotho level in the population was 849.33 ± 5.39 pg/mL. After controlling for potential confounders, the LE8 score showed a positive correlation with serum klotho levels (β: 1.32; 95% CI 0.73, 1.91), and a non-linear dose-response relationship was observed. Furthermore, we also discovered a positive relationship between health behaviors score and health factors score and serum klotho levels (β: 0.48; 95% CI 0.07, 0.88 and β: 1.05; 95% CI 0.54, 1.56, respectively), particularly a stronger correlation between health factors and serum klotho. In the subgroup analysis, we observed a significant interaction between LE8 score and sex and race. (P for interaction <0.05). ConclusionsLE8 and its subscale scores were positively associated with serum klotho levels in the middle-aged and older populations. Promoting the maintenance of ideal CVH can contribute to delaying the aging process.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Meta-analysis of the Relationship between Type 2 Diabetes Mellitus and Renal Cancer Risk.

This study aimed to investigate the relationship between type 2 diabetes mellitus and the risk of renal cancer. A search was carried out on PubMed, Embase, Web of Science, China Biology Med-icine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and other data-bases. The search period was from 2000 to 2022. The two authors independently conducted literature screening, extracted literature data, and then conducted a literature quality evaluation. The type of study is a cohort study. Meta-analysis was carried out on the included literature through Stata12.0 software, and the combined value was calculated with RR value and 95% confidence interval. Subgroup analysis was carried out to explore the impact of different factors on the overall results. A total of 10 articles were included. Through cohort study, the meta-analysis on the risk of type 2 diabetes and renal cancer showed that the combined effect value Risk Ratio (RR) = 1.57 with 95% Confidence Intervals (CI) (1.36, 1.82) and P<0.05. The difference had a signif-icant impact, indicating that the risk of renal cancer in type 2 diabetes patients was 1.55 times higher than that in non-type 2 diabetes patients. The subgroup analysis showed that the combined effect value RR and 95% CI for men was 1.49 (1.26, 1.75), and the combined effect value RR and 95% CI for women was 1.60 (1.35, 1.88), which was basically consistent. Type 2 diabetes can significantly increase the risk of renal cell carcinoma, and the former is a risk factor for the latter. It is suggested that multi-center studies with larger sample sizes should be conducted in the future, and adjustments should be made according to the type of diabetes, the source of the study population, the pathological type of renal cell carcinoma, the use of hypoglycemic drugs, and other factors, to provide a reliable basis for the study of the relationship between diabetes and renal cell carcinoma. At present, the specific mechanism of diabetes increasing the risk of renal cell carcinoma and whether diabetes increases mortality due to renal cell carcinoma is still unclear and needs further research.

Association between gasping and survival among out-of-hospital cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation: The SOS-KANTO 2017 study

AimThis study aimed to assess the association between gasping and survival among out-of-hospital cardiac arrest (OHCA) patients requiring extracorporeal cardiopulmonary resuscitation (ECPR). MethodsThis prospective, multicenter, observational study was conducted between 2019 and 2021. We categorized adult patients requiring ECPR into those with or without gasping prior to hospital arrival. The primary outcome was the 30-day survival. We performed multivariable logistic regression analyses fitted with generalized estimating equations and subgroup analyses based on the initial rhythm and age. ResultsOf the 9,909 patients with OHCA requiring ECPR, 332 were enrolled in the present study, including 92 (27.7%) and 240 (72.3%) with and without gasping, respectively. The 30-day survival was higher in patients with gasping than in those without gasping (35.9% [33/92] vs. 16.2% [39/240]). In the logistic regression analysis, gasping was significantly associated with improved 30-day survival (adjusted odds ratio: 3.01; 95% confidence interval, 1.64–5.51). Subgroup analyses demonstrated similar trends in patients with an initial non-shockable rhythm and older age. ConclusionsGasping was associated with improved survival in OHCA patients requiring ECPR, even those with an initial non-shockable rhythm and older age. Clinicians may select the candidates for ECPR appropriately based on the presence of gasping.

Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: Secondary analysis of data from a randomised controlled trial

BackgroundThe aims were to assess whether a specific subgroup(s) of patients had a clinically significant benefit in their knee specific outcome or health-related quality of life (HRQoL) when undergoing robotic total knee arthroplasty (rTKA) when compared to manually performed TKA (mTKA). MethodsOne hundred patients were randomised to either rTKA or mTKA, 50 to each group, of which 46 and 41 were available for functional review at 6-months, respectively. Subgroup analysis was undertaken for sex, age (<67-years versus ≥ 67-years), preoperative WOMAC score (<40 versus ≥ 40) and EQ-5D utility (<0.604 versus ≥ 0.604). ResultsMale patients undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (mean difference (MD) 16.3, p = 0.011) at 2-months, function (MD 12.6, p = 0.032) and total score (MD 12.7, p = 0.030), and OKS (MD 6.0, p = 0.030) at 6-months. Patients < 67-years old undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 10.3, p = 0.039) at 2-months, and function (MD 12.9, p = 0.040) and total (MD 13.1, p = 0.038) scores at 6-months. Patients with a preoperative WOMAC total score of < 40 points undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 14.6, p = 0.044) at 6-months. Patients with a preoperative EQ-5D utility of <0.604 undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 15.5, p = 0.011) at 2-months. ConclusionPatients of male sex, younger age, worse preoperative knee specific function and HRQoL had a clinically significantly better early functional outcome with rTKA when compared to mTKA.

Factors associated with medical consumable availability in level 1 facilities in Malawi: a secondary analysis of a facility census.

Medical consumable stock-outs negatively affect health outcomes not only by impeding or delaying the effective delivery of services but also by discouraging patients from seeking care. Consequently, supply chain strengthening is being adopted as a key component of national health strategies. However, evidence on the factors associated with increased consumable availability is limited. In this study, we used the 2018-19 Harmonised Health Facility Assessment data from Malawi to identify the factors associated with the availability of consumables in level 1 facilities, ie, rural hospitals or health centres with a small number of beds and a sparsely equipped operating room for minor procedures. We estimate a multilevel logistic regression model with a binary outcome variable representing consumable availability (of 130 consumables across 940 facilities) and explanatory variables chosen based on current evidence. Further subgroup analyses are carried out to assess the presence of effect modification by level of care, facility ownership, and a categorisation of consumables by public health or disease programme, Malawi's Essential Medicine List classification, whether the consumable is a drug or not, and level of average national availability. Our results suggest that the following characteristics had a positive association with consumable availability-level 1b facilities or community hospitals had 64% (odds ratio [OR] 1·64, 95% CI 1·37-1·97) higher odds of consumable availability than level 1a facilities or health centres, Christian Health Association of Malawi and private-for-profit ownership had 63% (1·63, 1·40-1·89) and 49% (1·49, 1·24-1·80) higher odds respectively than government-owned facilities, the availability of a computer had 46% (1·46, 1·32-1·62) higher odds than in its absence, pharmacists managing drug orders had 85% (1·85, 1·40-2·44) higher odds than a drug store clerk, proximity to the corresponding regional administrative office (facilities greater than 75 km away had 21% lower odds [0·79, 0·63-0·98] than facilities within 10 km of the district health office), and having three drug order fulfilments in the 3 months before the survey had 14% (1·14, 1·02-1·27) higher odds than one fulfilment in 3 months. Further, consumables categorised as vital in Malawi's Essential Medicine List performed considerably better with 235% (OR 3·35, 95% CI 1·60-7·05) higher odds than other essential or non-essential consumables and drugs performed worse with 79% (0·21, 0·08-0·51) lower odds than other medical consumables in terms of availability across facilities. Our results provide evidence on the areas of intervention with potential to improve consumable availability. Further exploration of the health and resource consequences of the strategies discussed will be useful in guiding investments into supply chain strengthening. UK Research and Innovation as part of the Global Challenges Research Fund (Thanzi La Onse; reference MR/P028004/1), the Wellcome Trust (Thanzi La Mawa; reference 223120/Z/21/Z), the UK Medical Research Council, the UK Department for International Development, and the EU (reference MR/R015600/1).

Dental age estimation methods applied to Indian children and adolescents: A systematic review and meta-analysis

Country-specific systematic reviews and meta-analyses have been proposed to compile the available literature and rank methods based on their performance for a target population. India is a country with a vast scientific literature on dental age estimation. This systematic review aimed to provide evidence to help the decision of experts regarding the method of choice for dental age estimation in India. The research protocol was registered in Open Science Framework. Literature Search was performed in Embase, LILACS, MedLine (via PubMed), SciELO, Scopus and Web of Science. Grey Literature was searched in Google Scholar and ProQuest. Observational cross-sectional studies that compared chronological and estimated ages using Demirjian (original [DEM] and Chaillet's modification [modified-DEM]) and Acharya (ACH) methods were included. JBI tool was used to assess the risk of bias. The search detected 9799 studies, out of which 56 were eligible (n=13,107 panoramic radiographs of Indian individuals). Low risk of bias was registered for 48 studies, while 8 presented a moderate risk of bias. The meta-analysis showed a standardized mean difference between chronological and estimated ages of -0.11 (95%CI: -0.29; 0.07), 0.74 (95%CI: 0.39; 1.09), and -0.01 (95%CI: -0.23; 0.22) years for DEM, modified-DEM and ACH, respectively. High heterogeneity (I2=88-93%) was observed across studies for all the methods, including subgroup analyses based on sex. This study ranked ACH, DEM and modified-DEM (from the best to the worse) performances in the Indian population.

Friedreich Ataxia Caregiver-Reported Health Index: Development of a Novel, Disease-Specific Caregiver-Reported Outcome Measure.

The Friedreich ataxia (FRDA) scientific community needs access to patient-centered outcome measures that satisfy regulatory guidelines and are capable of tracking clinically meaningful changes in FRDA disease burden. The objective of this research was to develop a novel, disease-specific caregiver-reported outcome measure for use in FRDA research and clinical care. In prior work, we conducted qualitative interviews and a cross-sectional study of FRDA caregivers and patients to determine the symptoms of greatest importance to individuals with FRDA. We designed the Friedreich Ataxia Caregiver-Reported Health Index (FACR-HI) to serially measure the symptoms of greatest importance to patients and utilized factor analysis, beta testing, reliability testing, and cross-sectional subgroup analysis to further evaluate and optimize this disease-specific outcome measure. The FACR-HI was designed to measure total disease burden and disease burden in 18 symptomatic domains. The FACR-HI total score demonstrated high internal consistency (Cronbach's α = 0.98) and test-retest reliability (intraclass correlation coefficient = 0.96). Beta interview participants found the FACR-HI to be highly relevant, comprehensive, and easy to use. FACR-HI total and subscale scores were associated with functional staging for ataxia scores and speech impairment. Initial evaluation of the FACR-HI supports its content validity, test-retest reliability, and construct validity as a caregiver-reported outcome measure for assessing how pediatric individuals with FRDA feel and function. The FACR-HI provides a potential mechanism to quantify changes in multifactorial FRDA disease burden during future clinical trials.

The effect of early weight-bearing and later weight-bearing rehabilitation interventions on outcomes after ankle fracture surgery: A systematic review and meta-analysis of randomised controlled trials.

This systematic review aimed to analyse the effect of early weight bearing versus late weight bearing on rehabilitation outcomes after ankle fractures, which primarily include ankle function scores, time to return to work/daily life and complication rates. The China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Science and Technology Journal, Web of Science, PubMed, Embase and Cochrane Library databases were searched. The focus was on identifying randomised controlled trials centred on early weight-bearing interventions for post-operative ankle fracture rehabilitation. All databases were searched for eligible studies published within the period from database inception to 20 June 2023. The eligible studies were screened according to the inclusion criteria. Study quality was evaluated using the methodology recommended by the Cochrane Handbook for the Systematic Evaluation of Interventions. Two authors independently performed the literature search and data extraction. Eligible studies were subjected to meta-analyses using Review Manager 5.3. Based on the time points at which post-operative ankle function was reported in the studies included in this paper, we decided to perform a meta-analysis of ankle function scores at 6weeks post-operatively, 12weeks post-operatively, 24-26weeks post-operatively and 1year post-operatively. A total of 11 papers, comprising 862 patients, were included. Meta-analysis indicated that patients receiving early weight-bearing interventions, which referred to weight-bearing for 6weeks post-operatively, experienced enhancements in ankle function scores (Olerud-Molander score, AOFAS score or Baird-Jackson score) at various post-operative milestones: 6weeks (SMD=0.69, 95% CI: 0.49-0.88 and p<0.01), 12weeks (SMD=0.57, 95% CI: 0.22-0.92 and p<0.01) and the 24-26weeks range (SMD=0.52, 95% CI: 0.20-0.85 and p<0.01). The results of subgroup analyses revealed that the effects of early weight-bearing interventions were influenced by ankle range-of-motion exercises. Additionally, early weight bearing allows patients to return to daily life and work earlier, which was evaluated by time when they resumed their preinjury activities (MD=-2.74, 95% CI: -3.46 to -2.02 and p<0.01), with no distinct elevation in the incidence of complications (RR=1.49, 95% CI: 0.85-2.61 and p>0.05). The results showed that early weight bearing is effective in improving ankle function among post-operative ankle fracture patients and allows patients to return to daily life earlier. Significantly, the safety profile of early weight bearing remains favourable, with no higher risk of complications than late weight bearing.

Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrence.

The aim was to examine rifaximin plus lactulose efficacy in patients with cirrhosis at a risk of developing overt HE who were stratified by important baseline characteristics such as comorbid ascites or diabetes. Pooled post hoc subgroup analysis of adults receiving rifaximin 550mg twice daily plus lactulose or lactulose alone for 6 months in a phase 3 randomized, double-blind trial and a phase 4 open-label trial was conducted. Rifaximin plus lactulose was more efficacious than lactulose alone for reducing the risk of overt HE recurrence and HE-related hospitalization in adults grouped by select baseline disease characteristics.

Urinary catheterization during laparoscopic inguinal hernia repair: Really necessary or a habit?

BackgroundDuring laparoscopic inguinal hernia repair (LIH) repair, it is common practice to insert a urinary catheter (UC) to mitigate the risk of bladder injury or acute postoperative urinary retention. However, this procedure often leads to potential complications or infections. This study aims to evaluate the implications of the UC placement during LIH repair. MethodsThis retrospective, monocentric study included patients who underwent LIH repair between 01/01/2018 to 31/12/2022. Patients were divided into two groups: UC and no-UC. Results212 patients were included: 119 (56 %) in the no-UC group and 93 (44 %) in the UC group. The UC group presented a higher prevalence of bilateral hernias (38.7 % vs. 52.7 %), (p=0.01) and a greater frequency of intraperitoneal approach (TAPP) (83.9 % vs. 100 %), (p=0.01). No intraoperative complications were attributable to the absence of the UC. Four patients in the UC group had postoperative acute urinary retention necessitating intermittent catheterization, allowing discharge (p = 0.13). Rates of readmission and reoperation rates were comparable between groups. One month post-surgery, 7.5 % of UC group patients (vs. 0.8 %) developed urinary tract infection (p=0.01). Subgroup analysis confirmed a higher incidence of urinary tract infections in unilateral hernia and in TAPP procedure. ConclusionRoutine UC insertion during LIH repair seems unnecessary; rather, it increases the risk of postoperative urinary tract infections and should thus be avoided.

Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers

IntroductionRenin-angiotensin-aldosterone system inhibitors (RAAS-I) have been shown to prolong overall survival in patients with liver metastasized colorectal cancer in combination with antiangiogenic treatment. The effects of RAAS-I combined with neoadjuvant chemotherapy on colorectal cancer liver metastasis remain unexplored. We aimed to study the response of patients undergoing liver resection to RAAS-I in combination with neoadjuvant therapy to elucidate their potential benefits. MethodsBetween February 2005 and May 2012, 62 patients fulfilled the inclusion criteria for distant metastasis (cM1) and comparable computed tomography or magnetic resonance tomography scans in the Picture Archiving Communication System of our center before and after neoadjuvant chemotherapy. Follow-up data and clinicopathological characteristics were collected from a prospective database and retrospectively investigated. The chemotherapeutic response to liver metastasis was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria 1.1. ResultsComparing the average reduction of measured lesions, a significant response to chemotherapy was detected in the patients receiving RAAS-I (n = 24) compared to those who did not (n = 38) (P = 0.031). Interestingly, the effect was more distinctive when the size reduction was compared between high responses with more than 50% size reduction of all measured lesions (P = 0.011). In the subgroup analysis of patients receiving bevacizumab treatment, high responses to chemotherapy were observed only in the RAAS-I cohort (28.6% versus 0%, P = 0.022). ConclusionsFor neoadjuvantly treated patients, concomitant antihypertensive treatment with RAAS-I showed a higher total size reduction of liver metastasis as a sign of treatment response, especially in combination with antiangiogenic treatment with bevacizumab.

Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up.

The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction=0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

Appropriateness of recommended chest compression depths for cardiopulmonary resuscitation based on chest computed tomography parameters among Thai population: A multicenter retrospective study

AimWe evaluated the appropriateness of various chest compression (CC) depths among Thai population by comparing the calculated heart compression fraction (HCF) using mathematical methods based on chest computed tomography (CT) measurements. MethodsThis multicenter retrospective cross-sectional study was conducted from September 2014 to December 2020. Chest parameters included external anteroposterior diameter (EAPD), internal anteroposterior diameter (IAPD), heart anteroposterior diameter (HAPD), and non-cardiac soft tissue measured at the level of maximum left ventricular diameter (LVmax). We compared the HCFs as calculated from CT parameters using different CC depths at 5 cm, 6 cm, 1/4 of EAPD, and 1/3 of EAPD, with further subgroup analysis stratified by sex and BMI. ResultsA total of 2927 eligible adult patients with contrast-enhanced chest CT were included. The study group had mean age of 60.1 ± 14.7 years, mean BMI of 22 ± 4.4 kg/m2, and were 57% males. The mean HCFs were 41.5%, 53.5%, 42.4%, and 62.6%, for CC depths of 50 mm, 60 mm, 1/4 of EAPD, and 1/3 of EAPD respectively. HCF was significantly lower in male patients for all CC depths. Advanced age and higher BMI showed significant correlation with lower HCF for CC depths of 50 mm and 60 mm. ConclusionThe CC depth measure of 50–60 mm demonstrated efficacy in maintaining HCF and coronary perfusion in the general population except for geriatric and obese individuals. Adjusting CC depth to 1/4–1/3 of the EAPD yielded better outcomes. Future research should prioritize determining individualized CC depths based on EAPD proportion.

Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study

Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease (eGFR <30ml/min per 1.73m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30ml/min per 1.73m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days-0.09%, 95% CI:-0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI:-0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI:-0.03 to 0.09%), ischaemic stroke (ARR at 90 days-0.06%, 95% CI:-0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI:-0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Time-varying impacts of green credit on carbon productivity in China: New evidence from a non-parametric panel data model

In the context of global climate change threatening human survival, and in a post-pandemic era that advocates for a global green and low-carbon economic recovery, conducting an in-depth analysis to assess whether green finance can effectively support low-carbon economic development from a dynamic perspective is crucial. Unlike existing research, which focuses solely on the average effects of green credit (GC) on carbon productivity (CP), we introduce a non-parametric panel data model to investigate GC's impact on CP across 30 provinces in China from 2003 to 2021, verifying a significant time-varying effect. Specifically, during the first phase (2003–2008), GC negatively impacted CP. In the second phase (2009–2014), this negative influence gradually diminished and transformed into a positive effect. In the third phase (2015–2021), GC continued to positively influence CP, although this effect became insignificant during the pandemic. Further subgroup analysis reveals that in the regions with low environmental regulations, GC did not significantly boost CP throughout the sample period. In contrast, in the regions with high environmental regulations, GC's positive effect persisted in the mid to late stages of the sample period. Additionally, compared to the regions with low levels of marketization, the impact of GC on CP was more pronounced in highly marketized regions. This indicates that the promoting effect of GC on CP depends on strong support from environmental regulations and well-functioning market mechanisms. By adopting a non-parametric approach, this study reveals variations in the impact of GC on CP across different stages and under the influence of the pandemic shock, offering new insights into the relationship between GC and China's CP.

Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis.

The purpose of our meta-analysis was to look at the impact of modified nutrition risk in the critically ill (mNUTRIC) on mortality in patients with critical illness. Literature relevant to this meta-analysis was searched in PubMed, Web of Science, and Cochrane Library till 26 August 2023. Prospective or retrospective studies, patients >18 years of age, studies that reported on mortality and mNUTRIC (mNUTRIC cut-off score) were included. The QUIPS tool was used to evaluate the risk for bias in prognostic factors. A total of 31 studies on mNUTRIC score, involving 13,271 patients were included. The summary area under the curve (sAUC) of 0.80 (95% CI: 0.76-0.83) illustrates the mNUTRIC score's strong discrimination. The pooled sensitivity was 0.79 (95% CI: 0.74-0.84) and pooled specificity was 0.68 (95% CI: 0.63-0.73). We found no discernible variation in the mNUTRIC's prediction accuracy among cut-off values of <5 and >5 in our subgroup analysis and sAUC values were 0.82 (95% CI: 0.78-0.85) and 0.78 (95% CI: 0.74-0.81), respectively. We observed that mNUTRIC can discriminate between critically ill individuals and predict their mortality. CRD42023460292. Prakash J, Verma S, Shrivastava P, Saran K, Kumari A, Raj K, et al. Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(5):495-503.

Association of NOTCH3 Variant Risk Category With 2-Year Clinical and Radiologic Small Vessel Disease Progression in Patients With CADASIL.

Pathogenic variants in NOTCH3 are the main cause of hereditary cerebral small vessel disease (SVD). SVD-associated NOTCH3 variants have recently been categorized into high risk (HR), moderate risk (MR), or low risk (LR) for developing early-onset severe SVD. The most severe NOTCH3-associated SVD phenotype is also known as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to investigate whether NOTCH3 variant risk category is associated with 2-year progression rate of SVD clinical and neuroimaging outcomes in CADASIL. A single-center prospective 2-year follow-up study was performed of patients with CADASIL. Clinical outcomes were incident stroke, disability (modified Rankin Scale), and executive function (Trail Making Test B given A t-scores). Neuroimaging outcomes were mean skeletonized mean diffusivity (MSMD), normalized white matter hyperintensity volume (nWMHv), normalized lacune volume (nLV), and brain parenchymal fraction (BPF). Cox regression and mixed-effect models, adjusted for age, sex, and cardiovascular risk factors, were used to study 2-year changes in outcomes and differences in disease progression between patients with HR-NOTCH3 and MR-NOTCH3 variants. One hundred sixty-two patients with HR (n = 90), MR (n = 67), and LR (n = 5) NOTCH3 variants were included. For the entire cohort, there was 2-year mean progression for MSMD (β = 0.20, 95% CI 0.17-0.23, p = 7.0 × 10-24), nLV (β = 0.13, 95% CI 0.080-0.19, p = 2.1 × 10-6), nWMHv (β = 0.092, 95% CI 0.075-0.11, p = 8.8 × 10-20), and BPF (β = -0.22, 95% CI -0.26 to -0.19, p = 3.2 × 10-22), as well as an increase in disability (p = 0.002) and decline of executive function (β = -0.15, 95% CI -0.30 to -3.4 × 10-5, p = 0.05). The HR-NOTCH3 group had a higher probability of 2-year incident stroke (hazard ratio 4.3, 95% CI 1.4-13.5, p = 0.011), and a higher increase in MSMD (β = 0.074, 95% CI 0.013-0.14, p = 0.017) and nLV (β = 0.14, 95% CI 0.034-0.24, p = 0.0089) than the MR-NOTCH3 group. Subgroup analyses showed significant 2-year progression of MSMD in young (n = 17, β = 0.014, 95% CI 0.0093-0.019, p = 1.4 × 10-5) and premanifest (n = 24, β = 0.012, 95% CI 0.0082-0.016, p = 1.1 × 10-6) individuals. In a trial-sensitive time span of 2 years, we found that patients with HR-NOTCH3 variants have a significantly faster progression of major clinical and neuroimaging outcomes, compared with patients with MR-NOTCH3 variants. This has important implications for clinical trial design and disease prediction and monitoring in the clinic. Moreover, we show that MSMD is a promising outcome measure for trials enrolling premanifest individuals.

Incidence and prevalence of headache in influenza: A 2010-2021 surveillance-based study.

Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. All consecutive patients who met the definition criteria of influenza-like illness during the influenza seasons 2010-2011 through 2021-2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020-2021) and 21.69 cases per 1000 patients (season 2017-2018). The prevalence of headache was 66.1% (95% CI = 65.1%-67.1%), varying between 49.6% (season 2021-2022) and 80.1% (season 2010-2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study

BackgroundHyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin–angiotensin–aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting.MethodsA lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF.ResultsPatiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions.ConclusionPatiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.