Genetic susceptibility to neurodevelopmental conditions associates with neonatal DNA methylation patterns in the general population: an individual participant data meta-analysis.

Background: Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in foetal (neuro)development. While epigenetic processes are considered an important underlying pathway between genetic susceptibility and neurodevelopmental conditions, it is unclear (i) whether genetic susceptibility to these conditions is associated with epigenetic patterns, specifically DNA methylation (DNAm), already at birth; (ii) to what extent DNAm patterns are unique or shared across conditions, and (iii) whether these neonatal DNAm patterns can be leveraged to enhance genetic prediction of (neuro)developmental outcomes. Methods: We conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and schizophrenia, quantified using polygenic scores (PGSs) on cord blood DNAm, using four population-based cohorts (n pooled=5,802), all North European. Heterogeneity statistics were used to estimate overlap in DNAm patterns between PGSs. Subsequently, DNAm-based measures of PGSs were built in a target sample, and used as predictors to test incremental variance explained over PGS in 130 (neuro)developmental outcomes spanning birth to 14 years. Outcomes: In probe-level analyses, SCZ-PGS associated with neonatal DNAm at 246 loci (p<9×10-8), predominantly in the major histocompatibility complex. Functional characterization of these DNAm loci confirmed strong genetic effects, significant blood-brain concordance and enrichment for immune-related pathways. 8 loci were identified for ASD-PGS (mapping to FDFT1 and MFHAS1), and none for ADHD-PGS. Regional analyses indicated a large number of differentially methylated regions for all PGSs (SCZ-PGS: 157, ASD-PGS: 130, ADHD-PGS: 166). DNAm signals showed little overlap between PGSs. We found suggestive evidence that incorporating DNAm-based measures of genetic susceptibility at birth increases explained variance for several child cognitive and motor outcomes over and above PGS. Interpretation: Genetic susceptibility for neurodevelopmental conditions, particularly schizophrenia, is detectable in cord blood DNAm at birth in a population-based sample, with largely distinct DNAm patterns between PGSs. These findings support an early-origins perspective on schizophrenia. Funding: HorizonEurope; European Research Council.

Overview of clinical status, treatment, and long-term outcomes of pediatric autosomal-dominant polycystic kidney disease: a nationwide survey in Taiwan.

This retrospective study investigated the incidence, medication use, and outcomes in pediatric autosomal-dominant polycystic kidney disease (ADPKD) using Taiwan's National Health Insurance Research Database (NHIRD). A 1:4 matched control group of individuals included in the NHIRD during the same period was used for comparative analyses. A total of 621 pediatric patients were identified from 2009 to 2019 (mean age, 9.51 ± 6.43 years), and ADPKD incidence ranged from 2.32 to 4.45 per 100,000 individuals (cumulative incidence, 1.26-1.57%). The incidence of newly developed hypertension, anti-hypertensive agent use, nephrolithiasis, and proteinuria were significantly higher in the ADPKD group than the non-ADPKD group (0.7 vs. 0.04, 2.26 vs. 0.30, 0.4 vs. 0.02, and 0.73 vs. 0.05 per 100 person-years, respectively). The adjusted hazard ratios for developing hypertension, proteinuria, nephrolithiasis and anti-hypertensive agent use in cases of newly-diagnosed pediatric ADPKD were 12.36 (95% CI 4.92-31.0), 13.49 (95% CI 5.23-34.79), 13.17 (95% CI 2.48-69.98), and 6.38 (95% CI 4.12-9.89), respectively. The incidence of congenital cardiac defects, hematuria, urinary tract infections, gastrointestinal diverticulosis, dyslipidemia, and hyperuricemia were also higher in the ADPKD group. Our study offers valuable insights into the epidemiology of pediatric ADPKD in Taiwan and could help in formulating guidelines for its appropriate management.

Differences in End-of-Life Care Between Patients Who Died of Cancer Diseases and Those Who Died of Noncancer Diseases.

Background and Purpose: Patients with advanced noncancer diseases or advanced cancer diseases may experience similar symptom burdens during the end of their lives. This study aimed to evaluate the differences in receiving hospice care service and in receiving aggressive end-of-life care between patients who died of cancer diseases and those who died of noncancer diseases. Methods: This cross-sectional population-based study used data from the Taiwan National Health Insurance Research Database. Subjects who died of cancers or noncancer diseases from 2010 through 2019 were analyzed to identify the information on patient's characteristics, receipt of hospice care service, receipt of cardiopulmonary resuscitation (CPR) during the last hospitalization, and receipt of airway support interventions during the last hospitalization. The independent effects of various characteristics on the receipt of hospice care, CPR during the last hospitalization, and airway support interventions during the last hospitalization were evaluated using multivariate logistic regressions. Results: A total of 587,490 patients were included, of which 434,142 died of cancers and 153,348 died of noncancer diseases. There were significant trends of increase in receiving hospice care service and significant trends of decrease in receiving CPR or airway support interventions during the last hospitalization in both patients who died of cancers and those who died of noncancer diseases. Compared with patients who died of cancers, those who died of noncancer diseases were less likely to receive hospice care service (adjusted odds ratio [AOR]: 0.087; 95% confidence interval [CI]: 0.085-0.089) and had a higher risk of receiving CPR (AOR: 3.610; 95% CI: 3.521-3.704) or airway support interventions during the last hospitalization (AOR: 3.086; 95% CI: 3.021-3.165). Conclusions: Hospice care service should be promoted for all patients with end-stage diseases especially those with noncancer diseases.

Pain Medication Frequency and Fall Risk Among Community-Dwelling Older Adults With Arthritis.

Pain medication is commonly used among older adults with arthritis, elevating the risk of falling. We examined fall risks related to the frequency of taking pain medication among community-dwelling older adults with arthritis by analyzing a nationally representative sample of community-dwelling Medicare beneficiaries aged >65 with self-reported arthritis (n = 4,225) in the 2015 National Health and Aging Trends Study. The survey-weighted logistic regression revealed that after controlling for confounding factors, recent falls were associated with taking pain medication daily compared to never (OR = 1.45, 95% CI: 1.06, 1.96). The other categories of medication frequency, compared to never, were not associated with fall risk. Findings suggest that more prudent use of pain medication should be stressed by health care providers for older adults with arthritis to help reduce the risk of falls and fall injuries. Nonpharmacological pain management is encouraged to support active living among older adults with arthritis.

The challenges of recruiting never-smokers with chronic obstructive pulmonary disease from the large population-based Swedish CArdiopulmonary bioImage study (SCAPIS) cohort.

Background: A substantial proportion of individuals with COPD have never smoked, and it is implied to be more common than previously anticipated but poorly studied. Aim: To describe the process of recruitment of never-smokers with COPD from a population-based cohort (n = 30 154). Methods: We recruited never-smokers with COPD, aged 50-75 years, from six University Hospitals, based on: 1) post broncho-dilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70 and 2) FEV1 50-100% of predicted value and 3) being never-smokers (self-reported). In total 862 SCAPIS participants were identified, of which 652 were reachable and agreed to a first screening by telephone. Altogether 128 (20%) were excluded due to previous smoking or declined participation. We also applied a lower limit of normal (LLN) of FEV1/FVC (z-score<-1.64) according to the Global Lung Initiative to ensure a stricter definition of airflow obstruction. Results: Data on respiratory symptoms, health status, and medical history were collected from 492 individuals, since 32 were excluded at a second data review (declined or previous smoking), prior to the first visit. Due to not matching the required lung function criteria at a second spirometry, an additional 334 (68%) were excluded. These exclusions were by reason of: FEV1/FVC ≥0.7 (49%), FEV1 > 100% of predicted (26%) or z-score ≥ -1,64 (24%). Finally, 154 never-smokers with COPD were included: 56 (36%) women, (mean) age 60 years, FEV1 84% of predicted, FEV1/FVC: 0.6, z-score: -2.2, Oxygen saturation: 97% and BMI: 26.8 kg/m2. Conclusions: The challenges of a recruitment process of never-smokers with COPD were shown, including the importance of correct spirometry testing and strict inclusion criteria. Our findings highlight the importance of repeated spirometry assessments for improved accuracy in diagnosing COPD.

Temporal changes in the risk of six-month post-covid symptoms: a national population-based cohort study.

It is unclear how the risk of post-covid symptoms evolved during the pandemic, especially before the spread of Severe Acute Respiratory Syndrome Coronavirus 2 variants and the availability of vaccines. We used modified Poisson regressions to compare the risk of six-month post-covid symptoms and their associated risk factors according to the period of first acute covid: during the French first (March-May 2020) or second (September-November 2020) wave. Non-response weights and multiple imputation were used to handle missing data. Among participants aged 15 or more in a national population-based cohort, the risk of post-covid symptoms was 14.6% (95% CI: 13.9%, 15.3%) in March-May 2020, versus 7.0% (95% CI: 6.3%, 7.7%) in September-November 2020 (adjusted RR: 1.36, 95% CI: 1.20, 1.55). For both periods, the risk was higher in the presence of baseline physical condition(s), and it increased with the number of acute symptoms. During the first wave, the risk was also higher for women, in the presence of baseline mental condition(s), and it varied with educational level. In France in 2020, the risk of six-month post-covid symptoms was higher during the first than the second wave. This difference was observed before the spread of variants and the availability of vaccines.

Outcomes of Patients Living with HIV Hospitalized due to COVID-19: A 3-Year Nationwide Study (2020-2022).

Scientific reports on the association between human immunodeficiency virus (HIV) in patients with COVID-19 and mortality have not been in agreement. In this nationwide study, we described and analyzed the demographic and clinical characteristics of people living with HIV (PLWH) and established that HIV infection is a risk factor for mortality in patients hospitalized due to COVID-19. We collected data from the National Hospital Data Information System at Hospitalization between 2020 and 2022. We included patients admitted to the hospital with a diagnosis of COVID-19. We established a cohort of patients with PLWH and compared them to patients without HIV (non-PLWH). For multivariate analyses, we performed binary logistic regression, using mortality as the dependent variable. To improve the interpretability of the results we also applied penalized regression and random forest, two well-known machine-learning algorithms. A broad range of comorbidities, as well as sex and age data, were included in the final model as adjusted estimators. Our data of 1,188,160 patients included 6,973 PLWH. The estimated hospitalization rate in this set was between 1.43% and 1.70%, while the rate among the general population was 0.83%. Among patients with COVID-19, HIV infection was a risk factor for mortality with an odds ratio (OR) of 1.25 (95% CI, 1.14-1.37, p < 0.001). PLWH are more likely to be hospitalized due to COVID-19 than are non-PLWH. PLWH are 25% more likely to die due to COVID-19 than non-PLWH. Our results highlight that PLWH should be considered a population at risk for both hospitalization and mortality.

Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study.

BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

The Impact of Longer Biliopancreatic Limb Length on Weight Loss and Comorbidity Improvement at 5 Years After Primary Roux-en-Y Gastric Bypass Surgery: A Population-Based Matched Cohort Study.

INTRODUCTION: Different limb lengths are used in Roux-en-Y gastric bypass (RYGB) surgery, as there is no consensus which limb length strategy has the best outcomes. The biliopancreatic limb (BPL) is thought to play an important role in achieving weight loss and associated comorbidity resolution. The objective of this study was to assess the impact of a longer BPL on weight loss and comorbidity improvement at 5 years after primary RYGB. METHODS: All patients aged ≥ 18 years undergoing primary RYGB between 2014-2017 with registered follow-up 5 years after surgery were included. Long BPL was defined as BPL ≥ 100 cm and short BPL as BPL < 100 cm. The primary outcome was achieving at least 25% total weight loss (TWL) at 5 years. Secondary outcomes included absolute %TWL and improvement of comorbidities. A propensity score matched logistic and linear regression was used to estimate the difference in outcomes between patients with long and short BPL. RESULTS: At 5 years, long BPL had higher odds to achieve ≥ 25% TWL (odds ratio (OR) 1.19, 95% confidence interval (CI) [1.01 - 1.41]) and was associated with 1.26% higher absolute TWL (ß = 1.26, 95% CI [0.53 - 1.99]). Furthermore, long BPL was more likely to result in improved diabetes mellitus (OR = 2.17, 95% CI [1.31 - 3.60]) and hypertension (OR = 1.45, 95% CI [1.06 - 1.99]). CONCLUSION: Patients undergoing RYGB with longer BPL achieved higher weight loss and were more likely to achieve improvement of comorbidities at 5 years.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Use of Azithromycin Attributable to Acute SARS-CoV-2 Infection.

PURPOSE: In the early stages of the COVID-19 pandemic, preliminary results that later proved to be incorrect suggested the possible efficacy of anti-infective drugs such as azithromycin for the treatment of SARS-CoV-2 infection. These preliminary data may have influenced the prescription of azithromycin. However, no individual-level data linking the use of this antibiotic to acute SARS-CoV-2 infection are available. The present analysis aims to fill this gap. METHODS: A retrospective population-based cohort design was used including patients diagnosed with SARS-CoV-2 infection in the period ranging from February 2020 to February 2022. The data source for antibiotic consumption was the drug database of outpatient prescriptions of Emilia-Romagna Region (Italy). Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Consumption rates and percentages of azithromycin DDDs (defined daily doses) during the acute phase of the infection were compared with a previous control period and with the post-acute phase. Analyses were stratified by four groups according to the prevalent virus variant at time of diagnosis. RESULTS: Comparing the previous control period with the acute phase of infections, the rates of azithromycin consumption (DDD per 1000 individuals per day) increased from 1.17 to 23.11, from 0.80 to 33.03, from 0.81 to 21.01, and from 1.02 to 9.76, in the pre-Alpha, Alpha, Delta, and Omicron periods, respectively. Similarly, the percentages of individuals receiving azithromycin, and the azithromycin DDDs percentages over total systemic antibiotics DDDs increased in acute phases of infection compared with control periods. The consumption rates and percentages returned to preinfection levels in the post-acute phase. In the study period, 12.9% of the use of azithromycin in the entire adult population of Emilia-Romagna was attributable to acute SARS-CoV-2 infection. CONCLUSIONS: Considering the low likelihood of bacterial coinfections, the increased azithromycin consumption in the acute phase of SARS-CoV-2 infection suggests inappropriate prescribing of this antibiotic.

Patterns of Prescription Medication Use Before Diagnosis of Early Age-Onset Colorectal Cancer: Population-Based Descriptive Study.

BACKGROUND: Colorectal cancer (CRC) is estimated to be the fourth most common cancer diagnosis in Canada (except for nonmelanoma skin cancers) and the second and third leading cause of cancer-related death in male and female individuals, respectively. OBJECTIVE: The rising incidence of early age-onset colorectal cancer (EAO-CRC; diagnosis at less than 50 years) calls for a better understanding of patients' pathway to diagnosis. Therefore, we evaluated patterns of prescription medication use before EAO-CRC diagnosis. METHODS: We used linked administrative health databases in British Columbia (BC), Canada, to identify individuals diagnosed with EAO-CRC between January 1, 2010, and December 31, 2016 (hereinafter referred to as "cases"), along with cancer-free controls (1:10), matched by age and sex. We identified all prescriptions dispensed from community pharmacies during the year prior to diagnosis and used the Anatomical Therapeutic Chemical Classification system Level 3 to group prescriptions according to the drug class. A parallel assessment was conducted for individuals diagnosed with average age-onset CRC (diagnosis at age 50 years and older). RESULTS: We included 1001 EAO-CRC cases (n=450, 45% female participants; mean 41.0, SD 6.1 years), and 12,989 prescriptions were filled in the year before diagnosis by 797 (79.7%) individuals. Top-filled drugs were antidepressants (first; n=1698, 13.1%). Drugs for peptic ulcer disease and gastroesophageal reflux disease (third; n=795, 6.1%) were more likely filled by EAO-CRC cases than controls (odds ratio [OR] 1.4, 95% CI 1.2-1.7) and with more frequent fills (OR 1.8, 95% CI 1.7-1.9). We noted similar patterns for topical agents for hemorrhoids and anal fissures, which were more likely filled by EAO-CRC cases than controls (OR 7.4, 95% CI 5.8-9.4) and with more frequent fills (OR 15.6, 95% CI 13.1-18.6). CONCLUSIONS: We observed frequent prescription medication use in the year before diagnosis of EAO-CRC, including for drugs to treat commonly reported symptoms of EAO-CRC.

Care-seeking for difficulties conceiving in sub-Saharan Africa: findings from population-based surveys in eight geographies.

STUDY QUESTION: What is the nature of women's care-seeking for difficulties conceiving in sub-Saharan Africa (SSA), including the correlates of seeking biomedical infertility care at a health facility? SUMMARY ANSWER: Care-seeking for difficulties getting pregnant was low, much of which involved traditional or religious sources of care, with evidence of sociodemographic disparities in receipt of biomedical care. WHAT IS KNOWN ALREADY: Nearly all research on infertility care-seeking patterns in SSA is limited to clinic-based studies among the minority of people in these settings who obtain facility-based services. In the absence of population-based data on infertility care-seeking, we are unable to determine the demand for services and disparities in the use of more effective biomedical sources of care. STUDY DESIGN, SIZE, DURATION: We used cross-sectional, population-based data from the Performance Monitoring for Action (PMA) female survey in eight geographies in SSA, including nationally representative data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda and regionally representative data from two provinces in the Democratic Republic of the Congo (DRC) (Kinshasa and Kongo Central) and two states in Nigeria (Kano and Lagos). We employed a multi-stage cluster random sampling design with probability proportional to size selection of clusters within each geography to produce representative samples of women aged 15-49. Samples ranged from 1144 in Kano, Nigeria, to 9489 in Kenya. PMA collected these data between November 2021 and December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: We restricted the sample to women who had ever had sex, with analytic samples ranging from 854 in Kano to 8,059 in Kenya, then conducted descriptive and bivariable analyses to examine characteristics of those who sought care for difficulties getting pregnant. Among those who reported seeking care, we conducted bivariable and multivariable logistic regression analyses to determine factors associated with receipt of biomedical services from a health facility. All analyses were conducted separately by geography. MAIN RESULTS AND THE ROLE OF CHANCE: Our study found low levels of care-seeking for difficulties getting pregnant among sexually active women in eight geographies in SSA, ranging from 3.7% (Kenya) to 15.3% (Côte d'Ivoire). Of this, 51.8% (Burkina Faso) to 86.7% (Kinshasa) involved receipt of biomedical services in health facilities. While many factors were consistently associated with infertility care-seeking from any source across geographies, factors associated with receipt of biomedical care specifically were less pronounced. This may be a result of the highly limited sources of infertility services in SSA; thus, even privileged groups may struggle to obtain effective treatment for difficulties getting pregnant. However, we did observe disparities in biomedical care-seeking in our bivariable results in several geographies, with the wealthiest women, those with more education, and those residing in urban areas generally more likely to have sought biomedical care for difficulties getting pregnant. LIMITATIONS, REASONS FOR CAUTION: Our data lacked details on the nature of the services received and outcomes, and we do not have information on reasons why women chose the sources they did. Small samples of women who sought care limited our power to detect significant differences in care-seeking by women's characteristics in several geographies. WIDER IMPLICATIONS OF THE FINDINGS: Infertility and access to appropriate treatment are issues of reproductive health and human rights. While our results do not indicate to what extent use of non-biomedical sources of care is driven by preferences, cost, or lack of accessible services, it is clear from our results and existing literature that more needs to be done to ensure access to affordable, quality, cost-effective infertility services in SSA. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Bill & Melinda Gates Foundation (INV009639) and the National Institute of Child Health and Human Development (K01HD107172). The funders were not involved in the study design, analyses, manuscript writing, or the decision to publish. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme.

BACKGROUND: The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England. METHOD: We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme. RESULTS: In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average. CONCLUSION: Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers.

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

Lung function in relation to brain aging and cognitive transitions in older adults: A population-based cohort study.

BACKGROUND: We investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms. METHODS: A population-based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n = 462) had 6-year follow-up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease. RESULTS: In fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR] = 1.89; 95% confidence interval [CI] = 1.23-2.92) and CIND (HR = 1.55; 95% CI = 1.01-2.38) and CIND progression to dementia, although not statistically significantly (HR = 2.44; 95% CI = 0.78-6.88). People with poor PEF also experienced the fastest ventricular enlargement (ß coefficient = 0.67 mL/year; 95% CI = 0.13-1.21) and had the highest likelihood of developing lacunes (odds ratio = 5.05; 95% CI = 1.01-25.23). DISCUSSION: Poor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage. HIGHLIGHTS: Poor lung function increased the risk of dementia and mild cognitive impairment (MCI). Poor lung function accelerated the progression from MCI to dementia. Poor lung function was linked to brain microvascular damage and global brain atrophy.

Differential interplay between multimorbidity patterns and frailty and their mutual mediation effect on mortality in old age.

BACKGROUND: Multimorbidity and frailty often concurrently occur among older adults. OBJECTIVES: To assess the reciprocal association between multimorbidity (condition count and patterns) and frailty and examine the mutual mediation effect of multimorbidity and frailty in their associations with mortality among Chinese older adults. METHODS: This nationwide population-based longitudinal study included 16,563 participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey who were surveyed in 2008 and followed up in 2011, 2014, and 2018. Frailty phenotype was assessed by the modified Fried criteria and vital status was ascertained from family members. Cross-lagged panel model (CLPM) was used to test bidirectional associations between multimorbidity and frailty. The direct and indirect effects of multimorbidity and frailty on mortality were evaluated using the combined CLPM with survival analysis. RESULTS: Three multimorbidity patterns were identified: cardiometabolic diseases, cognitive-sensory disorder, and arthritis-digestive-respiratory diseases. The number of chronic conditions and cognitive-sensory disease pattern showed bidirectional associations with frailty across waves (range for ß: 0.046-0.109; all P < 0.001), while cardiometabolic and arthritis-digestive-respiratory patterns unidirectionally predicted frailty change. Furthermore, frailty mediated 23%-27% of the association between multimorbidity and mortality. Only the number of conditions and cognitive-sensory disease pattern were significant mediators in the association between frailty and mortality, with the proportion of mediation ranging 4%-12%. CONCLUSIONS: Multimorbidity measures including condition count and cognitive-sensory disease pattern are bi-directionally associated with frailty in older adults. These multimorbidity measures and frailty partially mediated each other's association with mortality, with frailty acting as a more prominent pathway in the association between multimorbidity and mortality.

Comparison of associations between alcohol consumption and metabolic syndrome according to three definitions: The Swedish INTERGENE study.

Background: While prevalence estimates differ by definition of metabolic syndrome (MetS), it is less clear how different definitions affect associations with alcohol consumption. Methods: We included 3051 adults aged 25-77 from the baseline examination of the Swedish INTERGENE cohort (2001-2004). Using multiple logistic regression, we investigated cross-sectional associations between ethanol intake and MetS defined according to the Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). Alcohol exposure categories comprised abstinence, and low, medium, and high consumption defined via sex-specific tertiles of ethanol intake among current consumers. Covariates included sociodemographics, health, and lifestyle factors. Results: MetS prevalence estimates varied between 13.9 % (ATP III) and 25.3 % (JIS), with higher prevalence in men than women. Adjusted for age and sex, medium-high alcohol consumption was associated with lower odds of MetS compared to low consumption, while no difference was observed for abstainers. Only the most specific (and thus severe) definition of MetS (ATP III) showed decreasing odds for ethanol intake when adjusted for all covariates. Conclusion: Our study shows that alcohol-related associations differ by definition of MetS. The finding that individuals with the most stringently defined MetS may benefit from alcohol consumption calls for further well-controlled studies.

Bidirectional relationship between C-reactive protein and depressive symptoms considering cumulative effect among Chinese middle-aged and older adults.

Introduction: Research examining the bidirectional relationship between C-reactive protein (CRP) and depressive symptoms, while accounting for cumulative effect of repeated episodes of CRP or depressive symptoms, is currently deficient in non-Western populations. Methods: A nationally representative population-based cohort data from the Chinese Health and Retirement Longitudinal Study (CHARLS) was utilized. In bi-directional analysis, we considered both single determinations and two successive determinations of CRP or depressive symptoms. Multivariate logistic regression assessed the association between elevated CRP levels at baseline or repeated episodes of CRP elevations over two successive determinations and subsequent elevated depressive symptoms, and vice versa. Results: Although single determinations of CRP or depressive symptoms yielded non-significant results in both directions, full multivariate models, adjusting for baseline depressive symptoms, socio-demographic characteristics, health-related behaviors, metabolic measures, and health status, revealed a significantly positive association based on two successive determinations of CRP or depressive symptoms. This significant association was observed between cumulative effects of sustained CRP elevations over two successive determinations (2 vs. 0) and subsequent elevated depressive symptoms (OR=1.58; 95% CI: 1.15 to 2.17) and between cumulative effect of repeated episodes of depression (2 vs. 0) and later elevated CRP (OR=1.26; 95% CI: 1.02 to 1.56). Furthermore, sex-stratified analyses confirmed the robustness of these relationships. Conclusion: There are bidirectional associations between depressive symptoms and CRP, driven by the cumulative effect of repeated episodes of CRP or depressive symptoms among middle-aged and older Chinese adults. These findings hold significant clinical implications, highlighting the potential of both anti-inflammatory and anti-depression approaches.

Acquisition of peak bone mass in a Norwegian youth cohort: longitudinal findings from the Fit Futures study 2010-2022.

In a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass. PURPOSE: To examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood. METHOD: In a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16-19 years into adulthood (age of 26-29) on three occasions: 2010-2011 (Fit Futures 1 (FF1)), 2012-2013 (FF2), and 2021-2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3. RESULTS: From the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059-1.082) to 1.076 (1.065-1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029-1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091-1.116); 27 years, 1.063 (1.050-1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133-1.148); 27 years, 1.204 (1.196-1.212), p < 0.001; males: 16 years, 1.179 (1.170-1.188); 27 years, 1.310 (1.296-1.315), p < 0.001). CONCLUSION: BMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.