A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country.

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

Method for accurate removal of trabecular bone samples from a curved articulating surface of the distal femur.

BACKGROUND: Knowing the mechanical properties of trabecular bone is critical for many branches of orthopaedic research. Trabecular bone is anisotropic and the principal trabecular direction is usually aligned with the load it transmits. It is therefore critical that the mechanical properties are measured as close as possible to this direction, which is often perpendicular to a curved articulating surface. METHODS: This study presents a method to extract trabecular bone cores perpendicular to a curved articulating surface of the distal femur. Cutting guides were generated from computed tomography scans of 12 human distal femora and a series of cutting tools were used to release cylindrical bone cores from the femora. The bone cores were then measured to identify the angle between the bone core axis and the principal trabecular axis. FINDINGS: The method yielded an 83% success rate in core extraction over 10 core locations per distal femur specimen. In the condyles, 97% of extracted cores were aligned with the principal trabecular direction. INTERPRETATION: This method is a reliable way of extracting trabecular bone specimens perpendicular to a curved articular surface and could be useful across the field of orthopaedic research.

The Contribution of Soft Tissue and Bony Stabilizers to the Hip Suction Seal: A Systematic Review of Biomechanical Studies.

BACKGROUND: Previous biomechanical studies have identified capsular closure, labral repair or reconstruction, and osteochondroplasty as important surgical interventions to improve hip stability. PURPOSE: To investigate the outcome metrics used to quantify hip stability and assess and measure the relative contributions of the labrum, capsule, and bone to hip stability through a quantitative analysis. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: PubMed and Embase databases were searched using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included studies evaluated cadaveric hip biomechanics related to capsular, labral, and bony management during hip arthroscopy. Studies were assessed for distraction force and distance, fluid measures, and contact forces used to quantify the suction seal. Exclusion criteria included open surgery, arthroplasty, reorientation osteotomy, or traumatic dislocation. RESULTS: A total of 33 biomechanical studies comprising 322 hips that evaluated 1 or more of the following were included: distraction force or distance (24 studies), fluid measures (10 studies), and contact forces (6 studies). Compared with a capsulotomy or capsulectomy, capsular repair or reconstruction demonstrated greater resistance to distraction (standardized mean difference [SMD], 1.13; 95% CI, 0.46-1.80; P = .0009). Compared with a labral tear, a labral repair or reconstruction demonstrated less resistance to distraction (SMD, -0.67; 95% CI, -1.25 to -0.09; P = .02). Compared with a labral debridement, repair or reconstruction demonstrated greater resistance to distraction (SMD, 1.74; 95% CI, 1.23 to 2.26; P < .00001). No quantitative analysis was feasible from studies evaluating the effect of osseous resection due to the heterogeneity in methodology and outcome metrics assessed. CONCLUSION: Most biomechanical evidence supports capsulotomy repair or reconstruction to improve hip distractive stability at the end of hip arthroscopic surgery. While the repair of a torn labrum does not improve distractive resistance, it is superior to labral debridement in most biomechanical studies.

Early Postoperative Activities of Daily Living Do Not Adversely Affect Joint Torques or Translation Regardless of Capsular Condition: A Cadaveric Study.

PURPOSE: To evaluate the impact of capsular management on joint constraint and femoral head translations during simulated activities of daily living (ADL). METHODS: Using 6 (n = 6) cadaveric hip specimens, the effect of capsulotomies and repair was then evaluated during simulated ADL. Joint forces and rotational kinematics associated with gait and sitting, adopted from telemeterized implant studies, were applied to the hip using a 6-degrees of freedom (DOF) joint motion simulator. Testing occurred after creation of portals, interportal capsulotomy (IPC), IPC repair, T-capsulotomy (T-Cap), partial T-Cap repair, and full T-Cap repair. The anterior-posterior (AP), medial-lateral (ML), and axial compression DOFs were operated in force control, whereas flexion-extension, adduction-abduction, and internal-external rotation were manipulated in displacement control. Resulting femoral head translations and joint reaction torques were recorded and evaluated. Subsequently, the mean-centered range of femoral head displacements and peak signed joint restraint torques were calculated and compared. RESULTS: During simulated gait and sitting, the mean range of AP femoral head displacements with respect to intact exceeded 1% of the femoral head diameter after creating portals, T-Caps, and partial T-Cap repair (Wilcoxon signed rank P < .05); the mean ranges of ML displacements did not. Deviations in femoral head kinematics varied by capsule stage but were never very large. No consistent trends with respect to alterations in peak joint restrain torques were observed. CONCLUSIONS: In this cadaveric biomechanical study, capsulotomy and repair minimally affected resultant femoral head translation and joint torques during simulated ADLs. CLINICAL RELEVANCE: The tested ADLs appear safe to perform after surgery, regardless of capsular status, because adverse kinematics were not observed. However, further study is required to determine the importance of capsular repair beyond time-zero biomechanics and the resultant effect on patient-reported outcomes.

Major low anterior resection syndrome has equivalent health-related quality of life implications as having a permanent colostomy.

BACKGROUND: The literature is inconclusive when comparing health-related quality of life following restorative anterior resection (AR) compared with abdominoperineal resection (APR). Consideration of functional outcomes may explain this inconsistency. The aim of this study was to compare health-related quality of life in patients post-anterior resection, stratified by low anterior resection syndrome score, and post-abdominoperineal resection patients. METHODS: A cross-sectional study of consecutive patients post APR and AR for rectal or sigmoid adenocarcinoma at a tertiary centre in Sydney, Australia (Jan 2012- Dec 2021) was performed. HRQoL outcomes (SF36v2 physical [PCS] and mental component summary [MCS] scores) were compared between APR and AR patients, with subgroup analyses stratifying AR patients according to LARS score (no/minor/major). Age- and gender-adjusted comparisons were performed by linear regression. RESULTS: Overall, 248 post-AR patients (57.3% male, mean age 70.8 years, SD 11.6) and 64 post-APR patients (62.5% male, mean age 68.1 years, SD 13.1) participated. When stratified by LARS, 'major LARS' had a similar negative effect on age-and sex-adjusted PCS scores as APR. 'No LARS' (p < 0.001) and 'minor LARS' (p < 0.001) patients had higher PCS scores compared to post-APR patients. 'Major LARS' had a similarly negative effect on MCS scores compared with post-APR patients. MCS scores were higher in 'no LARS' (p = 0.006) compared with APR patients. CONCLUSIONS: Postoperative bowel dysfunction significantly impacts health-related quality of life. Patients with 'major LARS' have health-related quality of life as poor as those following APR. This requires consideration when counselling patients on postoperative health-related quality of life, especially where poor postoperative bowel function is anticipated following restorative surgery.

A mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H replicated retrospective histopathological examination findings in differentiating benign goitre from malignant papillary thyroid cancer in a cohort of Malaysian patients.

Thyroid malignancy status is usually confirmed through histopathological examination (HPE) following thyroidectomy. In Malaysia, the application of molecular markers in pre-operative diagnosis of thyroid cancer remains unexplored. In this study, BRAF and NRAS gene mutation panel was assessed, and the results were compared with retrospective HPE findings. Malaysian patients with benign goitre (BTG: n=33) and papillary thyroid cancer (PTC: n=25; PTCa: n=20, PTCb: n=5) were recruited at Universiti Malaya Medical Centre from September 2019 to December 2022. PCR-direct DNA sequencing of BRAFV600, NRASG12, NRASG13, and NRASQ61 was conducted on DNA extracted from the patients' thyroid tissue specimens following thyroidectomy and HPE. BRAFV600E and NRASQ61R mutations showed absolute PTC-specificity with PTC-sensitivity of 32% and 28%, respectively. NRASQ61H demonstrated lower PTC-specificity (94%) but higher PTC-sensitivity (72%) compared to the BRAFV600E and NRASQ61R mutations. Although the NRASG12 and NRASG13 variants were absent in this study, a novel NRASV14D mutation was detected in a PTCa patient. Unlike PTCb, coexistence of BRAFV600E and NRASQ61 variants was commonly observed among the PTCa patients. Notably, all PTCb patients had NRASQ61H mutation with one patient carried both the NRASQ61H and BRAFV600E mutations. Association analysis revealed potential link between gender, BRAFV600E mutation and lymph node metastasis. In conclusion, mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H did not discriminate the two PTC subtypes but replicated the retrospective HPE findings in differentiating BTG from PTC. The application of this mutation panel in pre-operative diagnosis of thyroid nodules requires further validation in a larger sample size, preferably incorporating fineneedle aspirate biopsies.

Cross-sectional study to assess the psychological morbidity of women facing possible miscarriage.

INTRODUCTION: Threatened miscarriage is a common complication of pregnancy. This study aimed to assess psychological morbidity in women with threatened miscarriage, with the goal of identifying early interventions for women at risk of anxiety or depression. METHODS: Women in their first trimester attending an Early Pregnancy Assessment Clinic were recruited between July 2013 and June 2015. They were asked to complete the 12-item General Health Questionnaire (GHQ-12), the Beck Depression Inventory (BDI), Spielberger's State Anxiety Inventory State form (STAI-S), the Fatigue Scale-14 (FS-14), and the Profile of Mood States (POMS) before consultation. They were also asked to rate anxiety levels before and after consultation using a visual analogue scale (VAS). RESULTS: In total, 1390 women completed the study. The mean ± standard deviation of GHQ-12 (bi-modal) and GHQ-12 (Likert) scores were 4.04 ± 3.17 and 15.19 ± 5.30, respectively. Among these women, 48.4% had a GHQ-12 (bi-modal) score ≥4 and 76.7% had a GHQ-12 (Likert) score >12, indicating distress. The mean ± standard deviation of BDI, STAI-S, and FS-14 scores were 9.35 ± 7.19, 53.81 ± 10.95, and 2.40 ± 0.51, respectively. The VAS score significantly decreased after consultation (P<0.001). Compared with women without a history of miscarriage, women with a previous miscarriage had higher GHQ-12, BDI, and POMS scores (except for fatigue-inertia and vigour-activity subscales). A higher bleeding score was strongly positively correlated with GHQ-12 (Likert) score. There were weak correlations between pain score and the GHQ-12 (bi-modal) ≥4, BDI >12, and POMS scores (except for confusion-bewilderment subscale which showed a strong positive correlation). CONCLUSION: Women with threatened miscarriage experience a considerable psychological burden, emphasising the importance of early recognition for timely management.

Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery: a systematic review, meta-analysis and trial sequential analysis.

Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I2 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p < 0.0001). It was encouraging to see the evidence that the administration of intravenous tranexamic in patients undergoing non-cardiac surgery was not associated with an increased risk of thromboembolic outcomes. However, our trial sequential analysis demonstrated that currently available evidence is not yet sufficient to reach a firm conclusion.

Viewpoint: Clinicians' Perspectives on How Disease Modifying Drugs for Alzheimer's Disease Impact Specialty Care.

Clinicians specialized in the diagnosis and management of persons living with early-stage Alzheimer's disease need to enable access, for those meeting criteria, to the new class of disease modifying drugs (DMDs). These drugs act on amyloid ß42 and delay progression of symptoms. Thus, there will be interest from patients and families. Over the short term, the use of antibodies administered intravenously with serial MRIs to detect amyloid-related imaging abnormalities (ARIA) may require participation in structured phase 4 studies or in registries with third party funding for support staff and MRI scans. In the mid term, the availability of oral anti-amyloid therapy, likely with lower risk of ARIA, may transform clinical practice to a model of screening suitable patients using plasma biomarkers, with a subsequent rapid referral to a specialized memory clinic. Eventually, the biological profile of patients for amyloid, tau, and inflammation will determine which type of DMD to use. We are optimistic that clinicians will gain confidence with the use DMDs and answer the increasing needs of our aging population.

White Matter Hyperintensity as a Vascular Contribution to the AT(N) Framework.

The AT(N) framework enables the classification of an individual within the biological Alzheimer's disease (AD) continuum by pairing the cognitive stage with the biomarker status of amyloid-beta (Aß, A), tau (T) and neurodegeneration (N). AD is a multifactorial disease that may involve different pathogenic mechanisms such as cerebrovascular disease (CVD). Therefore, biomarkers of these mechanisms can be added to the AT(N) framework to enhance the biomarker characterization of individuals within the AD continuum. In AD, white matter hyperintensities (WMH) which are postulated to develop as a result of chronic ischemia from small vessel CVD are shown to play a role in the aetiology. However, the interplay of WMH with Aß and tau pathophysiology in AD remains unclear. In this review, we summarized the studies that evaluated the associations between WMH and AD pathophysiology (Aß and tau). We found that the evidence supporting the association of WMH with Aß was mixed, and this may be explained by the relative contributions of WMH due to its differential load and anatomical distribution. More studies are also needed to determine the association of WMH with tau pathology. Future longitudinal studies with harmonized methodologies to quantify WMH and account for the anatomical differences of WMH are required to validate the relationship between WMH and AT(N) biomarkers. This will allow a clearer understanding of the utility of WMH as a vascular biomarker in the AT(N) framework. Novel CVD biomarkers will also have the potential to further elucidate the contributions of CVD to the AD pathophysiology.

Five-year retrospective review of ultrasound-guided manual vacuum aspiration for first-trimester miscarriage.

INTRODUCTION: Manual vacuum aspiration is increasingly accepted as an alternative to medical or surgical evacuation of the uterus after first-trimester miscarriage. This study aimed to assess the efficacy of ultrasound-guided manual vacuum aspiration (USG-MVA) in the management of first-trimester miscarriage. METHODS: This retrospective analysis included adult women with first-trimester miscarriage who underwent USG-MVA in Hong Kong between July 2015 and February 2021. The primary outcome was the efficacy of USG-MVA in terms of complete evacuation of the uterus, without the need for further medical or surgical intervention. Secondary outcomes included tolerance of the entire procedure, the success rate of karyotyping using chorionic villi, and procedural safety (ie, any clinically significant complications). RESULTS: In total, 331 patients were scheduled to undergo USG-MVA for first-trimester miscarriage or incomplete miscarriage. The procedure was completed in 314 patients and well-tolerated in all of those patients. The complete evacuation rate was 94.6% (297/314), which is similar to the rate (98.1%) achieved by conventional surgical evacuation in a previous randomised controlled trial in our unit. There were no major complications. Samples from 95.2% of patients were suitable for karyotyping, which is considerably higher than the rate of suitable samples (82.9%) obtained via conventional surgical evacuation in our previous randomised controlled trial. CONCLUSION: Ultrasound-guided manual vacuum aspiration is a safe and effective method to manage first-trimester miscarriage. Although it currently is not extensively used in Hong Kong, its broader clinical application could avoid general anaesthesia and shorten hospital stay.

Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

AIMS: Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. MATERIALS AND METHODS: Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. RESULTS: In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). CONCLUSIONS: GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

Results From Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities.

Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities includes a summary of results and grades for 10 physical activity indicators and highlights how these grades are interpreted by stakeholders. The disability classification was based on the UNICEF/Washington Group on Disability Statistics measure, Generalized Anxiety Disorder (GAD7) measure, or education status. Data between 2017 and 2021 were reviewed by 24 physical activity specialists using benchmarks adapted for data on disabilities from the Active Healthy Kids Global Alliance. The grades were assigned as follows: Overall Physical Activity, C+; Organized Sport, C; Active Play, D; Active Transportation, B; Family and Peers, C+; School, B; Community and Environment, C-; Government, A-; sedentary behavior and physical fitness were graded as incomplete. Stakeholder focus-group discussions highlighted the need for multidisciplinary cooperation and increasing competence of specialists working with children to promote a physically active lifestyle for all children.

The age-dependent association of risk factors with pancreatic cancer.

BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.