Meat consumption and the risk of hip fracture in women and men: two prospective Swedish cohort studies.

PURPOSE: To study the association between meat intake (predominantly red and processed meats) and the risk of hip fracture, as well as the association between meat intake and biomarkers of inflammation, oxidative stress, bone turnover, body composition, and bone mineral density (BMD). METHODS: Data from the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men) with repeated investigations and their respective clinical sub-cohorts was utilised. Incident hip fractures were ascertained through individual linkage to registers. Associations were investigated using multivariable Cox and linear regression analyses. RESULTS: During up to 23 years of follow-up (mean 18.2 years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. Each daily serving of meat intake conferred a hazard ratio (HR) of 1.03 (95% confidence interval [CI] 1.00; 1.06) for hip fracture. In quintile 5, compared to quintile 2, the HR was 1.11 (95% CI 1.01; 1.21) among all participants. In the sub-cohorts, meat intake was directly associated with circulating levels of interleukin-6, C-reactive protein, leptin, ferritin, parathyroid hormone, and calcium. CONCLUSION: A modest linear association was found between a higher meat intake and the risk of hip fractures. Our results from the sub-cohorts further suggest that possible mechanisms linking meat intake and hip fracture risk may be related to the regulation of bone turnover, subclinical inflammation, and oxidative stress. Although estimates are modest, limiting red and processed meat intake in a healthy diet is advisable to prevent hip fractures.

Dietary fatty acids and incident hip fractures in cohorts of women and men. A relative validation and follow-up study.

OBJECTIVES: Hip fractures are associated with a high burden of morbidity and mortality. Diet is essential for preventing fragility fractures, but the role of dietary fatty acids on the risk of hip fracture is uncertain. The aim was to investigate how intake of different dietary fatty acids relates to the risk of hip fracture. A relative validation of the long-term intake of dietary fatty acids estimated from food frequency questionnaires (FFQs) was also performed. DESIGN, SETTINGS AND PARTICIPANTS: We used data collected in two population-based cohorts, the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men, aged 45-82 years). Data from the repeated investigations in the cohorts and cross-sectional data from their clinical sub-cohorts were used. MEASUREMENTS: Diet data was collected in FFQs. Incident hip fractures were gathered by individual linkage to national registers. We performed Cox regression analysis to investigate associations between dietary fatty acids and hip fracture. Follow-up time was between January 1st, 1998 and December 31st, 2020. The validation was performed using correlation analyses, comparing fatty acids measured in adipose tissue with estimated fatty acid intakes from FFQs. RESULTS: During up to 23 years of follow-up (mean 18 years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. A low linoleic acid (LA) and high intakes of long-chain n-3 fatty acids were associated with higher hip fracture risk in a non-linear way. In quartile 4 compared to quartile 1 of LA, the multivariable-adjusted hazard ratio of hip fracture was 0.89 (95% Confidence Interval: 0.81, 0.97). The study confirmed the validity of FFQs to capture the intake of the specific dietary long-chain n-3 fatty acids. The estimated intake of LA, α-linolenic acid, and myristic acid were also adequately captured by the FFQs. Validity was confirmed in both women and men. CONCLUSION: A low to moderate intake of linoleic acid and a higher intake of long-chain n-3 fatty acids were associated with a higher risk of hip fractures. The results indicate that attention should be paid to dietary fatty acid composition for the optimal prevention of fragility fractures.

Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

BACKGROUND: Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk. METHODS: Genetic variants associated with plasma ghrelin were identified in a GWAS comprising 10,742 Swedish adults in the discovery (N = 6,259) and replication (N = 4,483) cohorts. The association between ghrelin and gastrointestinal cancer was examined through a two-sample MR analysis using the identified genetic variants as instruments and GWAS data from the UK Biobank, FinnGen, and a colorectal cancer consortium. RESULTS: GWAS found associations between multiple genetic variants within ±200 kb of the GHRL gene and plasma ghrelin. A two-sample MR analysis revealed that genetically predicted higher plasma ghrelin levels were associated with a lower risk of gastrointestinal cancer in UK Biobank and in a meta-analysis of the UK Biobank and FinnGen studies. The combined OR per approximate doubling of genetically predicted plasma ghrelin was 0.91 (95% confidence interval, 0.85-0.99; P = 0.02). Colocalization analysis revealed limited evidence of shared causal variants for plasma ghrelin and gastrointestinal cancer at the GHRL locus (posterior probability H4 = 24.5%); however, this analysis was likely underpowered. CONCLUSIONS: Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer. IMPACT: Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer.

Genome-wide association and Mendelian randomization study of fibroblast growth factor 21 reveals causal associations with hyperlipidemia and possibly NASH.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a hepatokine that produces metabolic benefits, such as improvements of lipid profile. We performed a genome-wide association study (GWAS) to identify genetic variants associated with circulating FGF21 and investigated the causal effects of FGF21 on pertinent outcomes using Mendelian randomization (MR). METHODS: We conducted a GWAS testing ∼7.8 million DNA sequence variants with circulating FGF21 in a discovery cohort of 6259 Swedish adults with replication in 4483 Swedish women. We then performed two-sample MR analyses of genetically predicted circulating FGF21 in relation to alcohol and nutrient intake, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available GWAS summary statistics data. RESULTS: Our GWAS identified multiple single-nucleotide polymorphisms with genome-wide significant associations (P < 5 × 10-8) with circulating FGF21 on chromosomes 2 and 19 in or near the GCKR and FGF21 genes, respectively. The strongest signal at the FGF21 locus (rs2548957, ß = 0.181, P < 2.18 × 10-42) displayed in two-sample MR analyses robust associations with lower alcohol intake, lower circulating low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, gamma-glutamyl transferase, and galectin-3 concentrations, and higher circulating insulin-like growth factor-I and alkaline phosphatase concentrations after correcting for multiple testing (P < 0.0018) whereas associations with fat mass, type 2 diabetes, and cardiovascular disease were largely null. CONCLUSIONS: We identified robust associations of certain genetic variants in or near the GCKR and FGF21 genes with circulating FGF21 concentrations. Furthermore, our results support a strong causal effect of FGF21 on improved lipid profile, reduced alcohol consumption and C-reactive protein concentrations, and liver function biomarkers including fibrosis. We found largely null or weak positive associations with fat mass, diabetes, and cardiovascular disease as well as higher insulin-like growth factor-I concentrations, which could indicate a compensatory increase to regulate the above FGF21 resistant states in humans.

Milk and Fermented Milk Consumption and Risk of Stroke: Longitudinal Study.

The role of milk and fermented milk consumption in stroke risk is unclear. We investigated associations of time-updated information on milk and fermented milk consumption (1997 and 2009) with total stroke, cerebral infarction, and hemorrhagic stroke risk among 79,618 Swedish women and men (mean age 61.3 years). During a mean follow-up of 17.7 years, we identified 9735 incident cases of total stroke, of which 7573 were cerebral infarctions, 1470 hemorrhagic strokes, and 692 unspecified strokes. Compared with an intake of 100 g/day of milk, the multivariable-adjusted hazard ratios (95% confidence interval) of cerebral infarction were 1.05 (1.02-1.08) for 0 g/day, 0.97 (0.95-0.99) for 200 g/day, 0.96 (0.92-1.00) for 400 g/day, 0.98 (0.94-1.03) for 600 g/day, and 1.01 (0.94-1.07) for 800 g/day. Corresponding estimates for hemorrhagic stroke were 0.98 (0.91-1.05) for 0 g/day, 1.02 (0.97-1.07) for 200 g/day, 1.07 (0.98-1.17) for 400 g/day, 1.13 (1.02-1.25) for 600 g/day, and 1.19 (1.03-1.36) for 800 g/day. No associations were observed between milk consumption and total stroke or for fermented milk consumption and any of the stroke outcomes. Higher long-term milk consumption based on repeated measures of intake was weakly and non-linearly associated with cerebral infarction, and was directly associated with hemorrhagic stroke.

Fracture risk across a wide range of physical activity levels, from sedentary individuals to elite athletes.

OBJECTIVE: To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity. METHODS: By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged from sedentary through elite athlete levels. Associations between physical activity and fracture outcomes were assessed with proportional hazards regression using restricted cubic splines with the mean physical activity (corresponding to 20-40 min walking or bicycling/day or 2-3 h exercise/week) as reference. RESULTS: Among 63,980 men and women (49-68 years) and during 13 years of follow-up, 8506 fractures occurred, including 2164 distal forearm, 779 proximal humerus, 346 clinical spine, and 908 hip fractures. Both lower and higher physical activity was associated with higher risk of any fracture compared to the mean. Physical activity at 1 standard deviation (SD) below the mean, corresponding to walking/bicycling <20 min/day or exercising <1-1 h/week, was associated with a lower risk of distal forearm fracture (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.85-0.99) and higher risk of hip fracture (HR: 1.24, 95% CI: 1.13-1.37), but no associations were seen above the mean physical activity level for these fractures. Physical activity was not associated with proximal humerus fracture but had a possible U-shaped association with clinical spine fracture. CONCLUSION: Physical activity was non-linearly associated with fracture risk and the association differed across fracture sites. Up to 2-3 h weekly exercise is beneficial for the prevention of hip fracture but may increase the risk of distal forearm fracture.

Prior loss of body mass index, low body mass index, and central obesity independently contribute to higher rates of fractures in elderly women and men.

We aimed to comprehensively evaluate the association of body composition with fracture risk using longitudinal data from a Swedish cohort of 44,366 women and men (mean age of 70 years) and a subcohort of 5022 women. We estimated hazard ratios (HRs) of fracture for baseline body mass index (BMI), BMI change during the prior 12 and 18 years, baseline waist-to-height ratio, total and regional distribution of fat and lean mass, with and without areal bone mineral density (BMD) adjustment. During follow-up (median 8.7 years), 7290 individuals sustained a fracture, including 4279 fragility fractures, of which 1813 were hip fractures. Higher baseline BMI and prior gain in BMI were inversely associated with all types of fracture. Lower fracture rate with higher baseline BMI was seen within every category of prior BMI change, whereas higher prior BMI gain conferred a lower rate of fracture within those with normal baseline BMI. Each standard deviation (SD) higher baseline waist-to-height ratio, after adjustment for BMI, was associated with higher rates of hip fracture in both women and men (HR 1.12; 95% CI, 1.05-1.19). In the subcohort (median follow-up 10 years), higher baseline fat mass index (FMI) and appendicular lean mass index (LMI) showed fracture-protective effects. After BMD adjustment, higher baseline BMI, total LMI, FMI, and higher prior BMI gain were associated with higher fracture rate. Baseline fat distribution also was associated with fracture rate; a 1-SD higher android to gynoid fat mass ratio in prior BMI gainers was associated with BMD-adjusted HRs of 1.16 (95% CI, 1.05-1.28) for any fracture and 1.48 (95% CI, 1.16-1.89) for hip fracture. This pattern was not observed among prior BMI losers. These findings indicate that for optimal fracture prevention, low baseline BMI, prior BMI loss and high baseline central obesity should be avoided in both women and men. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Urinary continence recovery and oncological outcomes after surgery for prostate cancer analysed by risk category: results from the LAParoscopic prostatectomy robot and open trial.

PURPOSE: To evaluate urinary continence (UC) recovery and oncological outcomes in different risk-groups after robot-assisted radical prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: We analysed 2650 men with prostate cancer from seven open (n = 805) and seven robotic (n = 1845) Swedish centres between 2008 and 2011 in a prospective non-randomised trial, LAPPRO. UC recovery was defined as change of pads less than once in 24 h. Information was collected through validated questionnaires. Rate of positive surgical margins (PSM) and biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) > 0.25 mg/ml, were recorded. We stratified patients into two risk groups (low-intermediate and high risk) based on the D'Amico risk classification system. RESULT: Among men with high-risk prostate cancer, we found significantly higher rates of UC recovery up to 24 months after RRP compared to RALP (66.1% vs 60.5%) RR 0.85 (CI 95% 0.73-0.99) while PSM was more frequent after RRP compared to RALP (46.8% vs 23.5%) RR 1.56 (CI 95% 1.10-2.21). In the same group no significant difference was seen in BCR. Overall, however, BCR was significantly more common after RRP compared to RALP at 24 months (9.8% vs 6.6%) RR 1.43 (Cl 95% 1.08-1.89). The limitations of this study are its non-randomized design and the relatively short time of follow-up. CONCLUSIONS: Our study indicates that men with high-risk tumour operated with open surgery had better urinary continence recovery but with a higher risk of PSM than after robotic-assisted laparoscopic surgery. No significant difference was seen in biochemical recurrence.  TRIAL REGISTRATION: ISRCTN06393679.

Pregnancy outcomes in women with immunoglobulin A nephropathy: a nationwide population-based cohort study.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) incidence peaks in childbearing age. Data on pregnancy outcomes in women with IgAN are limited. METHODS: We performed a register-based cohort study in a nationwide cohort of women with biopsy-verified IgAN in Sweden, comparing 327 pregnancies in 208 women with biopsy-verified IgAN and 1060 pregnancies in a matched reference population of 622 women without IgAN, with secondary comparisons with sisters to IgAN women. Adverse pregnancy outcomes, identified by way of the Swedish Medical Birth Register, were compared through multivariable logistic regression and presented as adjusted odds ratios (aORs). Main outcome was preterm birth (< 37 weeks). Secondary outcomes were preeclampsia, small for gestational age (SGA), low 5-min Apgar score (< 7), fetal or infant loss, cesarean section, and gestational diabetes. RESULTS: We found that IgAN was associated with an increased risk of preterm birth (13.1% vs 5.6%; aOR = 2.69; 95% confidence interval [CI] = 1.52-4.77), preeclampsia (13.8% vs 4.2%; aOR = 4.29; 95%CI = 2.42-7.62), SGA birth (16.0% vs 11.1%; aOR = 1.84; 95%CI = 1.17-2.88), and cesarean section (23.9% vs 16.2%; aOR = 1.74, 95%CI = 1.14-2.65). Absolute risks were low for intrauterine (0.6%) or neonatal (0%) death and for low 5-min Apgar score (1.5%), and did not differ from the reference population. Sibling comparisons suggested increased risks of preterm birth, preeclampsia, and SGA in IgAN, but not of cesarean section. CONCLUSION: We conclude that although most women with IgAN will have a favorable pregnancy outcome, they are at higher risk of preterm birth, preeclampsia and SGA. Intensified supervision during pregnancy is warranted.

Combinations of dietary calcium intake and mediterranean-style diet on risk of hip fracture: A longitudinal cohort study of 82,000 women and men.

BACKGROUND AND AIMS: Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedish adults. METHODS: The study included 82,092 men and women at baseline. Diet and covariate data were collected twice, 12 years apart, using questionnaires. Information on incident hip fractures was collected from a national registry. Dietary calcium intake and mMED were each categorized into low, medium and high categories, and in nine combined strata of the two exposures. Multivariable adjusted hazard ratios (HR) of hip fracture with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression analysis, with time-updated information on exposures and covariates. Non-linear trends were assessed using restricted cubic splines. RESULTS: During 20 years of follow-up including 1,367,260 person-years at risk, 5938 individuals experienced a hip fracture. Dietary calcium intake and hip fracture were non-linearly associated, whereas adherence to mMED decreased hip fracture rates in a dose-response pattern. The lowest hip fracture rates were observed among women and men who reported a calcium intake of 800 mg or more, combined with a high adherence to mMED. In each stratum of calcium intake, the HRs of hip fracture were increasingly higher with lower adherence to mMED, compared with the reference level (high calcium and high mMED). Individuals with low calcium intake (<800 mg/day) or high calcium intake (>1200 mg/day) combined with low adherence to mMED had a HR of 1.54 (95% CI 1.28-1.85) and 1.50 (95% CI 1.26-1.77), respectively. No major differences in the hip fracture risk patterns were discerned between women and men. CONCLUSION: A moderate to high dietary calcium intake in the context of an overall healthy diet were associated with lower hip fracture rates.

Long-Term Prognostication for 20 114 Women With Small and Node-Negative Breast Cancer (T1abN0).

Background: Although small, node-negative breast cancer (ie, T1abN0) constitutes 20% of all newly diagnosed breast cancers, data on prognosis and prognostic factors are limited. Methods: We conducted a population-based cohort study including 20 114 Swedish women treated for T1abN0 breast cancer from 1977 onward. Patient and tumor data were collected from Swedish breast cancer registries. Cohort subjects were followed through linkage to the Cause of Death Register. We calculated the cumulative incidence of breast cancer-specific and overall death and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 9.1 years (range = 0-38), 915 women died of breast cancer and 5416 of any cause. The 10-, 20-, and 30-year cumulative incidences of breast cancer death were 3.4% (95% CI = 3.1% to 3.7%), 7.6% (95% CI = 7.1% to 8.2%), and 10.5% (95% CI = 9.6% to 11.4%), respectively. The multivariable hazard ratios and 95% confidence intervals of breast cancer death were 0.92 (95% CI = 0.88 to 0.97) for each additional calendar year of diagnosis, 4.38 (95% CI = 2.79 to 6.87) for grade 3 vs grade 1 tumors, 0.43 (95% CI = 0.31 to 0.62) for progesterone receptor-positive vs progesterone receptor-negative disease, and 2.01 (95% CI = 0.99 to 4.07) for HER2-positive vs HER2-negative disease. Women with grade 3 vs grade 1 tumors had a 56% increased risk of death from any cause (HR = 1.56, 95% CI = 1.30 to 1.88). Conclusions: The risk of breast cancer death in T1abN0 disease continues to increase steadily beyond 10 years after diagnosis, has improved over time, and varies substantially by tumor characteristics.

Discontinued dental care attendance among people with dementia: A register-based longitudinal study.

OBJECTIVE: To investigate the factors that increase the risk of discontinuing dental care utilisation after dementia is diagnosed in a population in Stockholm County, Sweden. BACKGROUND: As the progression of dementia results in a deteriorating ability to maintain good oral health, it is important to identify people at risk of discontinued dental care after being diagnosed with dementia. MATERIALS AND METHODS: This study is a register-based longitudinal study. Data were extracted from the Swedish Dementia Registry (SveDem), the Swedish National Patient Register, the Dental Health Register and the Municipal Dental Care Register (Stockholm County Council). The data included people using both general public dental services and care-dependent individuals. Dental visits three years before and after dementia had been diagnosed were analysed. RESULTS: In total, 10 444 people were included in the analysis, of which 19% did not have dental visits recorded after they were diagnosed with dementia. A logistic regression model, adjusted for relevant factors, showed that the factors associated with a greater risk for discontinued dental attendance were fewer remaining teeth (OR = 0.96, 95% CI = 0.95, 0.97) and living alone compared to living with another adult (OR = 1.23, 95% CI = 1.05, 1.43). People with Parkinson's disease dementia had a lower risk (OR = 0.40, 95% CI = 0.19, 0.84) than people with Alzheimer's disease. CONCLUSION: Patients, dental and healthcare personnel, and family members should all be aware of these risk factors so that appropriate support and oral care for people with dementia can be delivered.

Development and validation of non-guided bladder-neck and neurovascular-bundle dissection modules of the RobotiX-Mentor® full-procedure robotic-assisted radical prostatectomy virtual reality simulation.

BACKGROUND: Full-procedure virtual reality (VR) simulator training in robotic-assisted radical prostatectomy (RARP) is a new tool in surgical education. METHODS: Description of the development of a VR RARP simulation model, (RobotiX-Mentor®) including non-guided bladder neck (ngBND) and neurovascular bundle dissection (ngNVBD) modules, and assessment of face, content, and construct validation of the ngBND and ngNVBD modules by robotic surgeons with different experience levels. RESULTS: Simulator and ngBND/ngNVBD modules were rated highly by all surgeons for realism and usability as training tool. In the ngBND-task construct, validation was not achieved in task-specific performance metrics. In the ngNVBD, task-specific performance of the expert/intermediately experienced surgeons was significantly better than that of novices. CONCLUSIONS: We proved face and content validity of simulator and both modules, and construct validity for generic metrics of the ngBND module and for generic and task-specific metrics of the ngNVBD module.

Effusion cytology of malignant mesothelioma enables earlier diagnosis and recognizes patients with better prognosis.

A conclusive diagnosis of malignant mesothelioma (MM) can be based on effusion cytology using the guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM. Briefly, the diagnosis is obtained when the mesothelial phenotype of malignant cells is established by ancillary techniques. This study is based on the comparison of the overall survival rates of patients with MM when diagnosed by effusion cytology, histopathology, or a combination of both. A total of 144 patients were diagnosed with epithelioid and mixed-type pleural MM at Karolinska University Hospital between 2004 and 2013. The diagnosis was obtained by histopathology in 74 cases and by cytological examination of pleural effusion in 70 cases. In 29 of the latter cases, a diagnostic biopsy was obtained simultaneously. A total of 104 patients received chemotherapy. All diagnoses were supported by clinical findings, including computer tomography scans. The median time between first symptoms and diagnosis was similar for cytology and histopathology. However, a delay of more than 6 months after first symptoms was seen in many patients in the histopathology group, resulting in late onset of treatment. The overall survival and proportion of long-term survival were significantly better for cases diagnosed by cytology. Similarly, a better survival, following a cytological diagnosis, was also seen in patients who were only provided the best supportive care. Accurate cytological diagnosis enables conclusive diagnosis of MM. Our finding enables the initiation of treatment as soon as the cytological diagnosis is established, avoiding further delay and deterioration of patient survival and possibilities for treatment.

Milk and Fermented Milk Intake and Parkinson's Disease: Cohort Study.

Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson's disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40-159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160-200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201-400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose-response relationship. Fermented milk intake was not associated with increased risk of PD.

Combined associations of body mass index and adherence to a Mediterranean-like diet with all-cause and cardiovascular mortality: A cohort study.

BACKGROUND: It is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality. METHODS AND FINDINGS: Our longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997-2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6-8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson's weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96-1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48-1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16-1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone. CONCLUSIONS: These findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.

Nonsyndromic Craniosynostosis Is Associated with Increased Risk for Psychiatric Disorders.

BACKGROUND: Craniosynostosis is one of the most common craniofacial malformations demanding surgical treatment in infancy. Data on overall psychiatric morbidity among children with nonsyndromic craniosynostosis remain limited. This study investigated the risk of psychiatric disorders in nonsyndromic craniosynostosis. METHODS: The authors reviewed a register-based cohort of all individuals born with nonsyndromic craniosynostosis in Sweden between 1973 to 1986 and 1997 to 2012 (n = 1238). The nonsyndromic craniosynostosis cohort was compared with a matched community cohort (n = 12,380) and with unaffected full siblings (n = 1485). The authors investigated the risk of psychiatric disorders, suicide attempts, and suicides by using Cox regression adjusted for perinatal and somatic factors, season and birth year, sex, parental socioeconomic factors, and parental psychiatric disorders. RESULTS: Children with nonsyndromic craniosynostosis had a higher risk of any psychiatric disorder (adjusted Cox-derived hazard ratio, 1.70; 95 percent CI, 1.43 to 2.02), including intellectual disability (adjusted Cox-derived hazard ratio, 4.96; 95 percent CI, 3.20 to 7.70), language disorders (adjusted Cox-derived hazard ratio, 2.36; 95 percent CI, 1.57 to 3.54), neurodevelopmental disorders (adjusted Cox-derived hazard ratio, 1.30; 95 percent CI, 1.01 to 1.69), and other psychiatric disorders (adjusted Cox-derived hazard ratio, 1.43; 95 percent CI, 1.11 to 1.85). Full siblings with nonsyndromic craniosynostosis were more likely, in the crude analyses, to be diagnosed with any psychiatric disorder, including intellectual disability, language disorders, and neurodevelopmental disorders compared with nonaffected siblings. The higher risk for any psychiatric disorder and intellectual disability remained after adjusting for confounders. CONCLUSIONS: Children with nonsyndromic craniosynostosis demonstrated higher risks of any psychiatric disorder compared with children without nonsyndromic craniosynostosis. This risk cannot fully be explained by familial influences (i.e., genetic or environmental factors). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Reduced Risk of Reoperation Using Intramedullary Nailing with Femoral Neck Protection in Low-Energy Femoral Shaft Fractures.

BACKGROUND: In Sweden, approximately 1 in 4 women who are ≥50 years of age will sustain a hip fracture. Patients treated for a femoral shaft fracture are likely to have an even higher risk. We hypothesized that intramedullary nails protecting the femoral neck reduce the risk of subsequent hip fracture and allow the patient to avoid a challenging reoperation. METHODS: Between 2008 and 2010, 5,475 fractures of the femoral shaft, in patients who were ≥55 years of age, were registered in a national registry in Sweden. Of these patients, 897 fulfilled the inclusion criteria. We used radiographs and register data to identify the reasons for and the types of reoperation that occurred between the index surgical procedure and December 31, 2014. The categories of implants were determined through a review of radiographs as intramedullary nails with and without femoral neck protection. Reoperations related to peri-implant fractures (including hip fractures) were analyzed as a subgroup of all major reoperations. Multivariable-adjusted, cause-specific hazard ratios (HRs) were calculated to compare the risk of reoperation between cases with nails with and without femoral neck protection. RESULTS: Among the 897 patients, a total of 82 reoperations were performed. In 640 patients who were treated with intramedullary nails with femoral neck protection, there were 7 peri-implant fractures (no hip fractures) and 27 major reoperations. Among the 257 patients who were treated with intramedullary nails without femoral neck protection, 14 peri-implant hip fractures and 24 major reoperations were identified. Patients who received nails with femoral neck protection had a lower hazard for any peri-implant fracture (multivariable-adjusted cause-specific HR, 0.19 [95% confidence interval (CI), 0.07 to 0.5]) and major reoperation (multivariable-adjusted cause-specific HR, 0.51 [95% CI, 0.28 to 0.92]). CONCLUSIONS: Intramedullary nails with femoral neck protection in the treatment of low-energy femoral shaft fractures prevent secondary hip fractures and decrease the overall risk of reoperation for 4 to 6 years postoperatively. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study.

OBJECTIVE: Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environmental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organ-specific autoimmune diseases. DESIGN: Prospective twin cohort study. METHODS: We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data. RESULTS: Co-aggregation was more pronounced in monozygotic twins (median HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0.71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease. CONCLUSIONS: Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.