Effectiveness of a Smartphone App to Promote Physical Activity Among Persons With Type 2 Diabetes: Randomized Controlled Trial.

BACKGROUND: Physical activity is well known to have beneficial effects on glycemic control and to reduce risk factors for cardiovascular disease in persons with type 2 diabetes. Yet, successful implementation of lifestyle interventions targeting physical activity in primary care has shown to be difficult. Smartphone apps may provide useful tools to support physical activity. The DiaCert app was specifically designed for integration into primary care and is an automated mobile health (mHealth) solution promoting daily walking. OBJECTIVE: This study aimed to investigate the effect of a 3-month-long intervention promoting physical activity through the use of the DiaCert app among persons with type 2 diabetes in Sweden. Our primary objective was to assess the effect on moderate to vigorous physical activity (MVPA) at 3 months of follow-up. Our secondary objective was to assess the effect on MVPA at 6 months of follow-up and on BMI, waist circumference, hemoglobin A1c, blood lipids, and blood pressure at 3 and 6 months of follow-up. METHODS: We recruited men and women with type 2 diabetes from 5 primary health care centers and 1 specialized center. Participants were randomized 1:1 to the intervention or control group. The intervention group was administered standard care and access to the DiaCert app at baseline and 3 months onward. The control group received standard care only. Outcomes of objectively measured physical activity using accelerometers, BMI, waist circumference, biomarkers, and blood pressure were assessed at baseline and follow-ups. Linear mixed models were used to assess differences in outcomes between the groups. RESULTS: A total of 181 study participants, 65.7% (119/181) men and 34.3% (62/181) women, were recruited into the study and randomized to the intervention (n=93) or control group (n=88). The participants' mean age and BMI were 60.0 (SD 11.4) years and 30.4 (SD 5.3) kg/m2, respectively. We found no significant effect of the intervention (group by time interaction) on MVPA at either the 3-month (ß=1.51, 95% CI -5.53 to 8.55) or the 6-month (ß=-3.53, 95% CI -10.97 to 3.92) follow-up. We found no effect on any of the secondary outcomes at follow-ups, except for a significant effect on BMI at 6 months (ß=0.52, 95% CI 0.20 to 0.84). However, mean BMI did not differ between the groups at the 6-month follow-up. CONCLUSIONS: We found no evidence that persons with type 2 diabetes being randomized to use an app promoting daily walking increased their levels of MVPA at 3 or 6 months' follow-up compared with controls receiving standard care. The effect of the app on BMI was unclear, and we found nothing to support an effect on secondary outcomes. Further research is needed to determine what type of mHealth intervention could be effective to increase physical activity among persons with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03053336; https://clinicaltrials.gov/study/NCT03053336.

Ideal cardiovascular health and risk of death in a large Swedish cohort.

BACKGROUND: Ideal cardiovascular health (CVH) can be assessed by 7 metrics: smoking, body mass index, physical activity, diet, hypertension, dyslipidemia and diabetes, proposed by the American Heart Association. We examined the association of ideal CVH metrics with risk of all-cause, CVD and non-CVD death in a large cohort. METHODS: A total of 29,557 participants in the Swedish National March Cohort were included in this study. We ascertained 3,799 deaths during a median follow-up of 19 years. Cox regression models were used to estimate hazard ratios with 95% confidence intervals (95% CIs) of the association between CVH metrics with risk of death. Laplace regression was used to estimate 25th, 50th and 75th percentiles of age at death. RESULTS: Compared with those having 6-7 ideal CVH metrics, participants with 0-2 ideal metrics had 107% (95% CI = 46-192%) excess risk of all-cause, 224% (95% CI = 72-509%) excess risk of CVD and 108% (31-231%) excess risk of non-CVD death. The median age at death among those with 6-7 vs. 0-2 ideal metrics was extended by 4.2 years for all-causes, 5.8 years for CVD and 2.9 years for non-CVD, respectively. The observed associations were stronger among females than males. CONCLUSIONS: The strong inverse association between number of ideal CVH metrics and risk of death supports the application of the proposed seven metrics for individual risk assessment and general health promotion.

Nordic Nutrition Recommendations and risk of myocardial infarction and stroke: a prospective cohort study.

PURPOSE: The Nordic Nutrition Recommendations (NNR) are developed to prevent diet-related diseases. This study aimed to examine adherence to the NNR and risk of myocardial infarction (MI) and stroke among women and men in Sweden. METHODS: We followed 34,898 adults from 1997 to 2016. Dietary intake was assessed once at baseline using a food frequency questionnaire. Adherence scores corresponding to NNR-editions from 2023, 2012, 2004 and 1996 were calculated. Scores were categorized into low (reference category), moderate and high adherence. Cox proportional hazards regression models adjusted for potential confounders were used to estimate hazards ratios (HR) with 95% confidence intervals (CI). RESULTS: We identified 1649 incident cases of MI and 2071 incident cases of stroke during follow-up (mean 17.9 years). For each 1-point increase in the NNR2023-score (range 0-9), the rate of MI decreased by 14% (HR: 0.86; 95% CI 0.78-0.95). High adherence was associated with a lower rate of MI (HR: 0.72; 95% CI 0.59-0.87) (p-trend = 0.01). Moderate adherence was associated with a lower rate of stroke (HR: 0.88; 95% CI 0.78-0.99) (p-trend = 0.31). Among women, a 23% lower rate of MI (HR: 0.77; 95% CI 0.67-0.89) was observed for each 1-point increase, and high adherence was associated with a lower rate of MI (HR: 0.59; 95% CI 0.45-0.78). No associations were found in men. The results were similar, though attenuated, for earlier NNR-editions. CONCLUSION: Adherence to the NNR was associated with a reduced risk of MI. This association was more pronounced among women than among men and in more recent NNR-editions. The findings for stroke need further investigation.

The association of short and long sleep with mortality in men and women.

Both short (< 6 hr) and long (> 8 hr) sleep are associated with increased mortality. We here investigated whether the association between sleep duration and all-cause, cardiovascular disease and cancer mortality differs between men and women. A cohort of 34,311 participants (mean age and standard deviation = 50.5 ± 15.5 years, 65% women), with detailed assessment of sleep at baseline and up to 20.5 years of follow-up (18 years for cause-specific mortality), was analysed using Cox proportional hazards model to estimate HRs with 95% confidence intervals. After adjustment for covariates, all-cause, cardiovascular disease and cancer mortalities were increased for both < 5 hr and ≥ 9 hr sleep durations (with 6 hr as reference). For all-cause mortality, women who slept < 5 hr had a hazard ratio = 1.54 (95% confidence interval = 1.32-1.80), while the corresponding hazard ratio was 1.05 (95% confidence interval = 0.88-1.27) for men, the interaction being significant (p < 0.05). For cardiovascular disease mortality, exclusion of the first 2 years of exposure, as well as competing risk analysis eliminated the originally significant interaction. Cancer mortality did not show any significant interaction. Survival analysis of the difference between the reference duration (6 hr) and the short duration (< 5 hr) during follow-up showed a gradually steeper reduction of survival time for women than for men for all-cause mortality. We also observed that the lowest cancer mortality appeared for the 5-hr sleep duration. In conclusion, the pattern of association between short sleep duration and all-cause mortality differed between women and men, and the difference between men and women increased with follow-up time.

Interactive association between insomnia symptoms and sleep duration for the risk of dementia-a prospective study in the Swedish National March Cohort.

OBJECTIVE: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. METHODS: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11-1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00-1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00-1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. CONCLUSION: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.

Results of the first nationwide cohort study of outcomes in dialysis and kidney transplant patients before and after vaccination for COVID-19.

BACKGROUND: Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign. METHODS: Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started. RESULTS: On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7-2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4-0.7)] compared with KTRs. CONCLUSIONS: The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives.

Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden.

Importance: Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy. Objective: To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes. Design, Setting, and Participants: This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden. Exposures: New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels. Main Outcomes and Measures: Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users. Results: The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76). Conclusions and Relevance: In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.

Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci.

Response to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We examined item nonresponse behaviour across 109 questionnaire items in the UK Biobank (N = 360,628). Phenotypic factor scores for two participant-selected nonresponse answers, 'Prefer not to answer' (PNA) and 'I don't know' (IDK), each predicted participant nonresponse in follow-up surveys (incremental pseudo-R2 = 0.056), even when controlling for education and self-reported health (incremental pseudo-R2 = 0.046). After performing genome-wide association studies of our factors, PNA and IDK were highly genetically correlated with one another (rg = 0.73 (s.e. = 0.03)) and with education (rg,PNA = -0.51 (s.e. = 0.03); rg,IDK = -0.38 (s.e. = 0.02)), health (rg,PNA = 0.51 (s.e. = 0.03); rg,IDK = 0.49 (s.e. = 0.02)) and income (rg,PNA = -0.57 (s.e. = 0.04); rg,IDK = -0.46 (s.e. = 0.02)), with additional unique genetic associations observed for both PNA and IDK (P < 5 × 10-8). We discuss how these associations may bias studies of traits correlated with item nonresponse and demonstrate how this bias may substantially affect genome-wide association studies. While the UK Biobank data are deidentified, we further protected participant privacy by avoiding exploring non-response behaviour to single questions, assuring that no information can be used to associate results with any particular respondents.

Prospective study of weight loss and all-cause-, cardiovascular-, and cancer mortality.

Effects of repeated weight changes on mortality are not well established. In this prospective cohort study, we followed 34,346 individuals from 1997 to 2018 for all-cause mortality, and 2016 for cause-specific mortality. At baseline, participants self-reported amount and frequency of prior weight loss. During 20.6 (median) years of follow-up, we identified 5627 deaths; 1783 due to cancer and 1596 due to cardiovascular disease (CVD). We used Cox Proportional Hazards models to estimate multivariable-adjusted Hazard Ratios (HRs) and 95% confidence intervals (CI). Participants with a weight loss > 10 kg had higher rates of all-cause (HR 1.22; 95%CI 1.09-1.36) and CVD mortality (HR 1.27; 95%CI 1.01-1.59) compared to individuals with no weight loss. Men who had lost > 10 kg had higher all-cause (HR 1.55; 95%CI 1.31-1.84) and CVD mortality (HR 1.55; 95%CI 1.11-2.15) compared to men with no weight loss. Participants who had lost ≥ 5 kg three times or more prior to baseline had increased rates of all-cause (HR 1.16; 95%CI 1.03-1.30) and CVD mortality (HR 1.49; 95%CI 1.20-1.85) compared to participants with no weight loss. We found no association between weight loss and cancer mortality. We conclude that previous and repeated weight loss may increase all-cause and CVD mortality, especially in men.

Quality of laboratory biomarker monitoring during treatment with lithium in patients with bipolar disorder.

BACKGROUND: Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden. METHODS: This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007-2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid-stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out-migration, or to the end of 2018. RESULTS: We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9-7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium. CONCLUSIONS: In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels.

Cardiorenal Outcomes Among Patients With Atrial Fibrillation Treated With Oral Anticoagulants.

RATIONALE & OBJECTIVE: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). DOACs cause fewer bleeding complications, but their other advantages, particularly related to kidney outcomes, remain inconclusive. We studied the risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) after DOAC and VKA administration for nonvalvular AF. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Cohort study of Swedish patients enrolled in the Stockholm Creatinine Measurements (SCREAM) project with a diagnosis of nonvalvular AF during 2011-2018. EXPOSURE: Initiation of DOAC or VKA treatment. OUTCOME: Primary outcomes were CKD progression (composite of >30% estimated glomerular filtration rate [eGFR] decline and kidney failure) and AKI (by diagnosis or KDIGO-defined transient creatinine elevations). Secondary outcomes were death, major bleeding, and the composite of stroke and systemic embolism. ANALYTICAL APPROACH: Propensity score weighted Cox regression was used to balance 50 baseline confounders. Sensitivity analyses included falsification end points, subgroups, and estimation of per-protocol effects. RESULTS: We included 32,699 patients (56% initiated DOAC) who were observed for a median of 3.8 years. Their median age was 75 years, 45% were women, and 27% had an eGFR <60mL/min/1.73m2. The adjusted HRs for DOAC versus VKA were 0.87 (95% CI, 0.78-0.98) for the risk of CKD progression and 0.88 (95% CI, 0.80-0.97) for AKI. HRs were 0.77 (95% CI, 0.67-0.89) for major bleeding, 0.93 (95% CI, 0.78-1.11) for the composite of stroke and systemic embolism, and 1.04 (95% CI, 0.95-1.14) for death. The results were similar across subgroups of age, sex, and baseline eGFR when restricting to patients at high risk for thromboembolic events and when censoring follow up at treatment discontinuation or change in type of anticoagulation. LIMITATIONS: Missing information on time in therapeutic range and treatment dosages. CONCLUSIONS: Among patients with nonvalvular AF treated in routine clinical practice compared with VKA use, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding but a similar risk of the composite of stroke, systemic embolism, or death.

Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients.

BACKGROUND: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors' interplay remains unknown. METHODS: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo.  Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). RESULTS: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids' biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). CONCLUSIONS: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

Maternal Left Ventricular Function in Uncomplicated Twin Pregnancies: A Speckle-Tracking Imaging Longitudinal Study.

OBJECTIVE: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. METHODS: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10-15 week's gestation (w) (T1), 19-26 w (T2) and 30-38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters (at transmitral pulsed wave Doppler and mitral annular plane tissue Doppler), were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. RESULTS: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure (i.e., E/E') at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase (i.e., worsen) GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. CONCLUSION: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons.

Maternal Right Ventricular and Left Atrial Function in Uncomplicated Twin Pregnancies: A Longitudinal Study.

Objective: The knowledge regarding maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We performed a longitudinal investigation of maternal right ventricular (RV) and left atrial (LA) function in a cohort of uncomplicated twin pregnancies compared to singleton pregnancies. Study design: Healthy women with uncomplicated twin pregnancies were prospectively enrolled and assessed by transthoracic echocardiography at 10−15 weeks' (w) gestation (T1), 19-26 w gestation (T2), and 30−38 w gestation (T3). Subjects with uneventful singleton pregnancies were selected as controls at the same gestational ages. Cardiac findings were compared to those of women with uneventful singleton gestations. RV systolic and diastolic functions were assessed by conventional echocardiography (FAC, TAPSE, sPAP, E, A, DT) and tissue Doppler imaging (TDI) (E', A', S', IVA, IVCT, IVRT, ET, MPI), and LA dimensions were calculated. Speckle-tracking imaging was also applied to evaluate RV global longitudinal strain and LA 2D strains (at LV end-systole (LAS) and at atrial contraction (LAA)). Results: Overall, 30 uncomplicated twin and 30 uncomplicated singleton pregnancies were included. Regarding maternal RV function in twins, all the parameters (FAC, TAPSE, sPAP, E, A, E/A, DT, E/E', IVA, IVCT, MPI and 2D longitudinal strain) were almost stable throughout gestation, with the exception of the TDI findings (E' decreased from T1 to T3 (p = 0.03), while E'/A' increased from T1 to T2 and then decreased (p = 0.01); A' and basal S' increased (p = 0.04 and p = 0.03, respectively), while IVRT and ET significantly decreased (p = 0.009 and p = 0.007, respectively)). These findings were similar to those found for singleton pregnancies. LA dimensions significantly increased throughout gestation in both twins and singletons (p < 0.001), without intergroup difference. LA strains did not vary during either twin or singleton pregnancies, except for LAA in T1, which was higher among twins than among singletons. Conclusion: Maternal RV and LA function in uncomplicated twin pregnancies does not seem to undergo more significant changes than in singletons, being characterized by similar findings in RV systolic and diastolic functions, as well as LA dimensions and strains.

Atrophic gastritis is inversely associated with gastroesophageal reflux disease in a twin register based study.

BACKGROUND: The association between atrophic gastritis (AG) and symptomatic gastroesophageal reflux disease (GERD) needs to be better assessed. OBJECTIVE: We aimed to study this association in a twin setting, controlling for genetic and familial factors, in addition to a range of known covariates. METHODS: We performed a co-twin control study based on the Swedish Twin Registry, including confirmed monozygotic (MZ) and dizygotic (DZ) twins. AG was determined by the measurement of serum pepsinogen I (PGI) and pepsinogen II (PGII), with different cut-off values. GERD was defined using a structured questionnaire, by questions on symptoms of heartburn, acid regurgitation, pain behind the breastbone, and drug history. Patients were grouped into total GERD, less frequent (<1/week), and frequent GERD (≥1/week). RESULTS: A total of 12,533 twins were included in the study, among whom 37.7% showed less frequent GERD, and 18.7% had frequent GERD. There was an inverse association between AG and GERD, especially for frequent GERD. When PGI<30 was used as cut-off value for AG, the odds ratio (OR) and corresponding 95% confidence interval (CI) was 0.52 (0.44, 0.62). When PGI<70 and PGI/PGII<3 was used as cut-off value for AG, the OR (95% CI) was 0.53 (0.46, 0.63). A risk reduction for GERD was also observed in AG patients when the analysis was restricted in MZ or DZ twins. CONCLUSION: In this co-twin control study from the Swedish Twin Register, AG is persistently associated with a reduced risk for GERD, after controlling for genetic and shared familial factors.

Effect of sex on survival after resection of oesophageal cancer: nationwide cohort study.

BACKGROUND: Accumulating evidence suggests a survival benefit after curative oesophageal cancer surgery in women compared with men. The aim of this study was to explore sex disparities in survival after surgery with curative intent in patients with oesophageal cancer. METHODS: This was a population-based cohort study, including all patients with oesophageal or gastric cancer who underwent surgery with a curative intent between 2006 and 2017 in Sweden. Female versus male mortality rate ratio (MRR) and excess mortality rate ratio (EMRR) were used as measures of survival. Two different parametric models were designed to account for potential confounders. Patients with gastric cancer were used as a comparison group as no differences in survival between sexes were expected among these patients. RESULTS: A total of 1301 patients underwent resection for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. Women had a lower EMRR (0.76, 95 per cent c.i. 0.58 to 1.01, P = 0.056; 0.52, 95 per cent c.i. 0.32 to 0.84, P = 0.007 respectively) in both histological subtypes. The effect was more profound in early clinical stages, in patients receiving neoadjuvant treatment, and without postoperative complications. No sex-related difference was observed in survival of patients with gastric cancer. CONCLUSIONS: Women undergoing resection for oesophageal carcinoma have better survival compared with men.

Poor Oral Health and Esophageal Cancer Risk: A Nationwide Cohort Study.

BACKGROUND: Previous research indicates that poor dental health increases risks for certain types of cancers, including esophageal cancer. This study aimed to investigate the association with esophageal cancer using Swedish Dental Health Register. METHODS: This is a prospective cohort study. The exposures were dental diagnoses classified into healthy, caries, root canal infection, mild inflammation, and periodontitis, as well as number of remaining teeth, at baseline and during multiple visits. The outcome was the incidence of esophageal cancer, which was further divided into esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Cox proportional hazards models were used to estimate hazard ratios (HR) and its corresponding confidence intervals (CI). RESULTS: A total of 5,042,303 individuals were included in the study and 1,259 EAC and 758 ESCC cases were identified. Root canal infection at baseline was associated with 41% higher risk for EAC (HR, 1.41; 95% CI, 1.10-1.82), whereas periodontitis at baseline was linked to 32% and 45% higher risks for respective histopathological subtypes (HR for EAC, 1.32; 95% CI, 1.13-1.53; HR for ESCC, 1.45; 95% CI, 1.20-1.75). Fewer remaining teeth at baseline also increased the risks for both histopathological types of esophageal cancer, with a dose-response effect (Ptrend < 0.01). Cox regression analyses with time-varying exposures corroborated the above-mentioned results. CONCLUSIONS: Impaired dental health before cancer diagnosis is associated with excess risks for both histopathological subtypes of esophageal cancer. IMPACT: Our study provided corroborating evidence for the association between poor oral health and esophageal cancer risk.

Dietary fat intake and risk of Parkinson disease: results from the Swedish National March Cohort.

BACKGROUND: Following progressive aging of the population worldwide, the prevalence of Parkinson disease is expected to increase in the next decades. Primary prevention of the disease is hampered by limited knowledge of preventable causes. Recent evidence regarding diet and Parkinson disease is inconsistent and suggests that dietary habits such as fat intake may have a role in the etiology. OBJECTIVE: To investigate the association between intake of total and specific types of fat with the incidence of Parkinson disease. METHODS: Participants from the Swedish National March Cohort were prospectively followed-up from 1997 to 2016. Dietary intake was assessed at baseline using a validated food frequency questionnaire. Food items intake was used to estimate fat intake, i.e. the exposure variable, using the Swedish Food Composition Database. Total, saturated, monounsaturated and polyunsaturated fat intake were categorized into quartiles. Parkinson disease incidence was ascertained through linkages to Swedish population-based registers. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of the association between fat intake from total or specific types of fats and the incidence of Parkinson disease. The lowest intake category was used as reference. Isocaloric substitution models were also fitted to investigate substitution effects by replacing energy from fat intake with other macronutrients or specific types of fat. RESULTS: 41,597 participants were followed up for an average of 17.6 years. Among them, 465 developed Parkinson disease. After adjusting for potential confounders, the highest quartile of saturated fat intake was associated with a 41% increased risk of Parkinson disease compared to the lowest quartile (HR Q4 vs. Q1: 1.41; 95% CI: 1.04-1.90; p for trend: 0.03). Total, monounsaturated or polyunsaturated fat intake were not significantly associated with Parkinson disease. The isocaloric substitution models did not show any effect. CONCLUSIONS: We found that a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson disease. A diet low in saturated fat might be beneficial for disease prevention.

Metadata Correction: Clinical Outcomes Among Working Adults Using the Health Integrator Smartphone App: Analyses of Prespecified Secondary Outcomes in a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/24725.].

Association between total and leisure time physical activity and risk of myocardial infarction and stroke - a Swedish cohort study.

BACKGROUND: Physical inactivity is a known risk factor for cardiovascular disease, but it is unclear if total and leisure time activity have different impact on the risk of myocardial infarction and stroke. In this cohort, we aimed to investigate the associations between both total and leisure time physical activity in detail, and the risks of myocardial infarction and stroke, both overall and for men and women separately. METHODS: We assessed the association between total and leisure time physical activity on the risk of myocardial infarction and stroke in a cohort of 31,580 men and women through record linkages from 1997-2016. We used Cox proportional hazards regression models to estimate hazard ratios (HR) with 95% confidence intervals (CI) based on detailed self-reported physical activity. In the adjusted analyses, we included age, sex, body mass index, level of education, cigarette smoking, alcohol consumption, diabetes, lipid disturbance and hypertension as potential confounders. RESULTS: We identified 1,621 incident cases of myocardial infarction and 1,879 of stroke. Among men, there was an inverse association between leisure time activity and myocardial infarction in the third tertile compared to the first (HR: 0.78; 95% CI: 0.62-0.98; p for trend = 0.03). We also found an inverse association between leisure time activity and stroke in the third tertile compared to the first (HR: 0.78; 95% CI: 0.61-0.99; p for trend = 0.04), while the corresponding HR for stroke among women was 0.91; 95% CI: 0.74-1.13. We found no significant association between total physical activity and MI (HR: 1.12; 95% CI: 0.93-1.34) or stroke (HR: 1.14 95% CI: 0.94-1.39) comparing the highest to the lowest tertile in men. Women in the highest tertile of total physical activity had a 22% lower risk of myocardial infarction compared to the lowest tertile (HR: 0.78; 95% CI: 0.63-0.97; p for trend = 0.02) and an 8% (95% CI: 0.87-0.98) reduced risk of myocardial infarction with each 1 METh/day increase of leisure time physical activity. CONCLUSION: Total physical activity was inversely associated with the risk of myocardial infarction in women, while leisure time physical activity was inversely associated with the risk of myocardial infarction and stroke in men.