Self-rated health in old age, related factors and survival: A 20-Year longitudinal study within the Silver-MONICA cohort.

INTRODUCTION: Self-rated health (SRH) offers insights into the evolving health demographics of an ageing population. AIM: To assess change in SRH from old age to very old age and their associations with health and well-being factors, and to investigate the association between SRH and survival. METHODS: All participants in the MONICA 1999 re-examination born before 1940 (n = 1595) were included in the Silver-MONICA baseline cohort. The Silver-MONICA follow-up started in 2016 included participants in the Silver-MONICA baseline cohort aged 80 years or older. Data on SRH was available for 1561 participants at baseline with 446 of them also participating in the follow-up. The follow-up examination included a wide variety of measurements and tests. FINDINGS: Most participants rated their health as "Quite good" (54.5 %) at baseline. Over the study period, 42.6 % had stable SRH, 40.6 % had declined, and 16.8 % had improved. Changes in SRH were at follow-up significantly associated with age, pain, nutrition, cognition, walking aid use, self-paced gait speed, lower extremity strength, independence in activities of daily living, weekly physical exercise, outdoor activity, participation in organized activities, visiting others, morale, and depressive symptoms. SRH at baseline was significantly associated with survival (p < 0.05). CONCLUSION: This study demonstrates associations between changes in SRH and a multitude of health- and wellbeing-related factors, as well as a relation between survival and SRH, accentuating their relevance within the ageing population.

Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents.

Importance: Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. Objective: To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. Design, Setting, and Participants: This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Exposures: Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. Main Outcomes and Measures: The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. Results: A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%. Conclusions and Relevance: In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.

Blood Pressure Level in Late Adolescence and Risk for Cardiovascular Events : A Cohort Study.

BACKGROUND: Not enough is known about the association between blood pressure (BP) in adolescence and future cardiovascular events. OBJECTIVE: To measure this association using the 2017 American College of Cardiology/American Heart Association guidelines for classifying BP elevation. DESIGN: Cohort study. SETTING: Sweden. PARTICIPANTS: Males in late adolescence who were conscripted into the military from 1969 to 1997. MEASUREMENTS: Baseline BP was measured at conscription. The primary outcome was a composite of cardiovascular death or first hospitalization for myocardial infarction, heart failure, ischemic stroke, or intracerebral hemorrhage. RESULTS: The study included 1 366 519 males with a mean age of 18.3 years. The baseline BP was classified as elevated (120 to 129/<80 mm Hg) for 28.8% of participants and hypertensive (≥130/80 mm Hg) for 53.7%. During a median follow-up of 35.9 years, 79 644 had a primary outcome. The adjusted hazard ratio was 1.10 for elevated BP (95% CI, 1.07 to 1.13), 1.15 for stage 1 isolated systolic hypertension (ISH) (CI, 1.11 to 1.18), 1.23 for stage 1 isolated diastolic hypertension (IDH) (CI, 1.18 to 1.28), 1.32 for stage 1 systolic-diastolic hypertension (SDH) (CI, 1.27 to 1.37), 1.31 for stage 2 ISH (CI, 1.28 to 1.35), 1.55 for stage 2 IDH (CI, 1.42 to 1.69), and 1.71 for stage 2 SDH (CI, 1.58 to 1.84). The cumulative risk for cardiovascular events also increased gradually across BP stages, ranging from 14.7% for normal BP to 24.3% for stage 2 SDH at age 68 years. LIMITATION: This was an observational study of Swedish men. CONCLUSION: Increasing BP levels in late adolescence are associated with gradually increasing risks for major cardiovascular events, beginning at a BP level of 120/80 mm Hg. PRIMARY FUNDING SOURCE: Västerbotten County Council, Swedish Society for Medical Research, and Heart Foundation of Northern Sweden.

Safety and effectiveness of monovalent COVID-19 mRNA vaccination and risk factors for hospitalisation caused by the omicron variant in 0.8 million adolescents: A nationwide cohort study in Sweden.

BACKGROUND: Real-world evidence on the safety and effectiveness of Coronavirus Disease 2019 (COVID-19) vaccination against severe disease caused by the omicron variant among adolescents is sparse. In addition, evidence on risk factors for severe COVID-19 disease, and whether vaccination is similarly effective in such risk groups, is unclear. The aim of the present study was therefore to examine the safety and effectiveness of monovalent COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation in adolescents. METHODS AND FINDINGS: A cohort study was conducted using Swedish nationwide registers. The safety analysis included all individuals in Sweden born between 2003 and 2009 (aged 11.3 to 19.2 years) given at least 1 dose of monovalent mRNA vaccine (N = 645,355), and never vaccinated controls (N = 186,918). The outcomes included all-cause hospitalisation and 30 selected diagnoses until 5 June 2022. The vaccine effectiveness (VE) against COVID-19 hospitalisation, and risk factors for hospitalisation, were evaluated in adolescents given 2 doses of monovalent mRNA vaccine (N = 501,945), as compared to never vaccinated controls (N = 157,979), for up to 5 months follow-up during an omicron predominant period (1 January 2022 to 5 June 2022). Analyses were adjusted for age, sex, baseline date, and whether the individual was born in Sweden. The safety analysis showed that vaccination was associated with 16% lower (95% confidence interval (CI) [12, 19], p < 0.001) risk of all-cause hospitalisation, and with marginal differences between the groups regarding the 30 selected diagnoses. In the VE analysis, there were 21 cases (0.004%) of COVID-19 hospitalisation among 2-dose recipients and 26 cases (0.016%) among controls, resulting in a VE of 76% (95% CI [57, 87], p < 0.001). Predominant risk factors for COVID-19 hospitalisation included previous infections (bacterial infection, tonsillitis, and pneumonia) (odds ratio [OR]: 14.3, 95% CI [7.7, 26.6], p < 0.001), and cerebral palsy/development disorders (OR: 12.7, 95% CI [6.8, 23.8], p < 0.001), with similar estimates of VE in these subgroups as in the total cohort. The number needed to vaccinate with 2 doses to prevent 1 case of COVID-19 hospitalisation was 8,147 in the total cohort and 1,007 in those with previous infections or developmental disorders. None of the individuals hospitalised due to COVID-19 died within 30 days. Limitations of this study include the observational design and the possibility of unmeasured confounding. CONCLUSIONS: In this nationwide study of Swedish adolescents, monovalent COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse events resulting in hospitalisation. Vaccination with 2 doses was associated with a lower risk of COVID-19 hospitalisation during an omicron predominant period, also among those with certain predisposing conditions who should be prioritised for vaccination. However, COVID-19 hospitalisation in the general population of adolescents was extremely rare, and additional doses in this population may not be warranted at this stage.

Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.

Time-varying risk of death after SARS-CoV-2 infection in Swedish long-term care facility residents: a matched cohort study.

OBJECTIVES: To evaluate whether SARS-CoV-2 infection in residents of long-term care (LTC) facilities is associated with higher mortality after the acute phase of infection, and to estimate survival in uninfected residents. DESIGN: Extended follow-up of a previous, propensity score-matched, retrospective cohort study based on the Swedish Senior Alert register. SETTING: LTC facilities in Sweden. PARTICIPANTS: n=3604 LTC residents with documented SARS-CoV-2 until 15 September 2020 matched to 3604 uninfected controls using time-dependent propensity scores on age, sex, health status, comorbidities, prescription medications, geographical region and Senior Alert registration time. In a secondary analysis (n=3731 in each group), geographical region and Senior Alert registration time were not matched for in order to increase the follow-up time in controls and allow for an estimation of median survival. PRIMARY OUTCOME MEASURES: All-cause mortality until 24 October 2020, tracked using the National Cause of Death Register. RESULTS: Median age was 87 years and 65% were women. Excess mortality peaked at 5 days after documented SARS-CoV-2-infection (HR 21.5, 95% CI 15.9 to 29.2), after which excess mortality decreased. From the second month onwards, mortality rate became lower in infected residents than controls. The HR for death during days 61-210 of follow-up was 0.76 (95% CI 0.62 to 0.93). The median survival of uninfected controls was 1.6 years, which was much lower than the national life expectancy in Sweden at age 87 (5.05 years in men, 6.07 years in women). CONCLUSIONS: The risk of death after SARS-CoV-2 infection in LTC residents peaked after 5 days and decreased after 2 months, probably because the frailest residents died during the acute phase, leaving healthier residents remaining. The limited life expectancy in this population suggests that LTC resident status should be accounted for when estimating years of life lost due to COVID-19.

Obesity may increase survival, regardless of nutritional status: a Swedish cohort study in nursing homes.

BACKGROUND: To investigate the associations between the body mass index (BMI), Mini Nutritional Assessment-Short Form (MNA-SF) scores, and 2-year mortality. METHODS: A nationwide cohort study using data from a national quality register of older (age ≥ 65 years) nursing home residents (N = 47,686). Individuals were categorized according to BMI as underweight (< 18.5 kg/m2), normal-weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (class I, 30.0-34.9 kg/m2; class II, 35.0-39.9 kg/m2; class III, ≥ 40.0 kg/m2). Participants' nutritional status were categorized as good (MNA-SF score 12-14), at risk of malnutrition (MNA-SF score 8-11), or malnutrition (MNA-SF score 0-7). Associations with mortality were analysed using Cox proportional-hazards models. RESULTS: At baseline, 16.0% had obesity, and 14.6% were malnourished. During 2 years of follow-up, 23,335 (48.9%) individuals died. Compared with normal-weight individuals, mortality was greater among underweight individuals [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.55-1.69] and lesser among individuals with class I (HR 0.63, 95% CI 0.60-0.66), class II (HR 0.62, 95% CI 0.56-0.68), and class III (HR 0.80, 95% CI 0.69-0.94) obesity. Compared with individuals with good nutritional status, mortality was increased for those with malnutrition (HR 2.98,95% CI 2.87-3.10). Lower mortality among obese individuals was also seen in subgroups defined according to MNA-SF scores. CONCLUSIONS: Among older nursing home residents, obesity, including severe obesity, was associated with lower 2-year mortality. Higher BMIs were associated with better survival, regardless of nutritional status according to MNA-SF.

Effectiveness of a fourth dose of mRNA COVID-19 vaccine against all-cause mortality in long-term care facility residents and in the oldest old: A nationwide, retrospective cohort study in Sweden.

Background: The effect of a fourth dose of COVID-19 vaccine on the risk of death in the oldest and frailest individuals is unknown. Methods: Two matched cohorts were formed using Swedish nationwide registers. In the first, residents of long-term care facilities (LTCFs) given a fourth dose of an mRNA vaccine from 1 January 2022 onwards were matched 1:1 on birth year and county of residence to residents given at least a third dose (N = 24,524). In the second, all individuals aged ≥80 years given a fourth dose were matched 1:1 to individuals given at least a third dose (N = 394,104). Cox regression models were used to estimate hazard ratios for all-cause mortality in fourth-dose recipients as compared with in third-dose recipients, with relative vaccine effectiveness (VE) estimated as 1 minus the hazard ratio. Findings: From 7 days after baseline and onwards, there were 1119 deaths in the LTCF cohort during a median follow-up of 77 days and a maximum follow-up of 126 days. During days 7 to 60, the VE of the fourth dose was 39% (95% CI, 29-48), which declined to 27% (95% CI, -2-48) during days 61 to 126. In the cohort of all individuals aged ≥80 years, there were 5753 deaths during a median follow-up of 73 days and a maximum follow-up of 143 days. During days 7 to 60, the VE of the fourth dose was 71% (95% CI, 69-72), which declined to 54% (95% CI, 48-60) during days 61 to 143. The VE of the fourth dose seemed stronger when it was compared to third-dose recipients where at least four months had passed since vaccination (P < 0·001 for interaction). Interpretation: As compared with a third dose, a fourth dose of an mRNA COVID-19 vaccine, administered during the Omicron era, was associated with reduced risk of death from all causes in residents of LTCFs and in the oldest old during the first two months, after which the protection became slightly lower. These findings suggest that a fourth dose may prevent premature mortality in the oldest and frailest even after the emergence of the Omicron variant, although the timing of vaccination seems to be important with respect to the slight waning observed after two months. Funding: There was no funding source for this study.

Feasibility of an Online Delivered, Home-Based Resistance Training Program for Older Adults - A Mixed Methods Approach.

Background: Physical inactivity and low muscle mass are risk factors for falls, fractures and overall poor health. However, physical activity is reduced with increased age and only a fraction of older adults engages in resistance training (RT). Thus, strategies that facilitate RT among older adults are needed. The aim of the present study was to evaluate the effectiveness and user experience, and explore barriers and motivators toward an online delivered, home-based RT program in older adults with low muscle mass. Methods: Thirty men and women, 70-71 years of age with low muscle mass were assigned home-based RT with online exercise videos (3 times/week, 45 min/session for 10 weeks) accompanied with an initial supervised try-out session. Quantitative outcome measures included changes in lean body mass and physical function. Semi structured one-to-one interviews with a subset of the participants (n = 8) were also conducted to generate a greater understanding of the participants experience of the digitally supported RT. The material was transcribed and analyzed with qualitative content analysis. Results: Twenty-seven participants (90%) completed the trial. Lean body mass increased by 0.39 kg (95% CI: 0.06-0.72, p < 0.05) and chair stand time improved by 1.6 s (95% CI: 0.8-2.3, p < 0.001). No significant improvements were seen for balance or gait speed. The theme "Engaging in Digital Resistance Training with Personal Adaptation Leads to a Sense of Strength and Vitality" captured the participants experience of the intervention, where a sense of how the body was changing toward a more active lifestyle was described. Instructions, feedback, and intrinsic motivation were identified as key elements for compliance. Conclusion: The online delivered RT program for older adults with low muscle mass was feasible based on high compliance, user satisfaction, increased lean mass and improved chair-stand time. The participant experiences may explain the high compliance to the intervention and effects on outcomes. Based on these results, online delivered RT could be an accessible exercise routine for older adults with low muscle mass. More research is needed to verify the present findings and assess changes in a long-term perspective.

Prevalence, time-trends and clinical characteristics of hypertension in young adults: nationwide cross-sectional study of 1.7 million Swedish 18-year-olds, 1969-2010.

OBJECTIVE: The prevalence of hypertension in young adulthood, as well as the clinical characteristics associated with different hypertension subtypes, have been inconsistently described. Our aim was to assess the prevalence, time-trends and characteristics associated with isolated systolic hypertension (ISH), isolated diastolic hypertension and combined systodiastolic hypertension. METHODS: Serial cross-sectional analysis, using data from the Swedish conscription registry, including 1701 314 (99.2% male) individuals from 1969 to 2010. Risk factor associations were assessed through multivariable logistic regression. RESULTS: The prevalence of hypertension increased progressively during the study period, from 20.4% in 1969 to 29.3% in 2010, with ISH being the most common subtype (94.3%). ISH was associated with elevated resting heart rate (odds ratio 1.85, 95% confidence interval 1.84-1.86, per SD), increased exercise capacity (1.37, 1.36-1.39) and increased BMI (1.30, 1.29-1.31). Isolated diastolic hypertension and combined hypertension were also associated with elevated resting heart rate (1.37, 1.32-1.41 and 2.05, 1.99-2.11, respectively) and more strongly associated with increased BMI (1.36, 1.33-1.40 and 1.54, 1.51 - 1.58), but inversely associated with exercise capacity (0.79, 0.75-0.83 and 0.90, 0.86-0.95). CONCLUSION: The prevalence of hypertension in young adulthood has increased substantially over time, predominantly due to an increase in ISH. Risk factor patterns differed between ISH and other forms of hypertension, suggesting potentially different underlying mechanisms.

Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden.

BACKGROUND: Real-world evidence supporting vaccination against COVID-19 in individuals who have recovered from a previous SARS-CoV-2 infection is sparse. We aimed to investigate the long-term protection from a previous infection (natural immunity) and whether natural immunity plus vaccination (hybrid immunity) was associated with additional protection. METHODS: In this retrospective cohort study, we formed three cohorts using Swedish nationwide registers managed by the Public Health Agency of Sweden, the National Board of Health and Welfare, and Statistics Sweden. Cohort 1 included unvaccinated individuals with natural immunity matched pairwise on birth year and sex to unvaccinated individuals without natural immunity at baseline. Cohort 2 and cohort 3 included individuals vaccinated with one dose (one-dose hybrid immunity) or two doses (two-dose hybrid immunity) of a COVID-19 vaccine, respectively, after a previous infection, matched pairwise on birth year and sex to individuals with natural immunity at baseline. Outcomes of this study were documented SARS-CoV-2 infection from March 20, 2020, until Oct 4, 2021, and inpatient hospitalisation with COVID-19 as main diagnosis from March 30, 2020, until Sept 5, 2021. FINDINGS: Cohort 1 was comprised of 2 039 106 individuals, cohort 2 of 962 318 individuals, and cohort 3 of 567 810 individuals. During a mean follow-up of 164 days (SD 100), 34 090 individuals with natural immunity in cohort 1 were registered as having had a SARS-CoV-2 reinfection compared with 99 168 infections in non-immune individuals; the numbers of hospitalisations were 3195 and 1976, respectively. After the first 3 months, natural immunity was associated with a 95% lower risk of SARS-CoV-2 infection (adjusted hazard ratio [aHR] 0·05 [95% CI 0·05-0·05] p<0·001) and an 87% (0·13 [0·11-0·16]; p<0·001) lower risk of COVID-19 hospitalisation for up to 20 months of follow-up. During a mean follow-up of 52 days (SD 38) in cohort 2, 639 individuals with one-dose hybrid immunity were registered with a SARS-CoV-2 reinfection, compared with 1662 individuals with natural immunity (numbers of hospitalisations were eight and 113, respectively). One-dose hybrid immunity was associated with a 58% lower risk of SARS-CoV-2 reinfection (aHR 0·42 [95% CI 0·38-0·47]; p<0·001) than natural immunity up to the first 2 months, with evidence of attenuation thereafter up to 9 months (p<0·001) of follow-up. During a mean follow-up of 66 days (SD 53) in cohort 3, 438 individuals with two-dose hybrid immunity were registered as having had a SARS-CoV-2 reinfection, compared with 808 individuals with natural immunity (numbers of hospitalisations were six and 40, respectively). Two-dose hybrid immunity was associated with a 66% lower risk of SARS-CoV-2 reinfection (aHR 0·34 [95% CI 0·31-0·39]; p<0·001) than natural immunity, with no significant attenuation up to 9 months (p=0·07). To prevent one reinfection in the natural immunity cohort during follow-up, 767 individuals needed to be vaccinated with two doses. Both one-dose (HR adjusted for age and baseline date 0·06 [95% CI 0·03-0·12]; p<0·001) and two-dose (HR adjusted for age and baseline date 0·10 [0·04-0·22]; p<0·001) hybrid immunity were associated with a lower risk of COVID-19 hospitalisation than natural immunity. INTERPRETATION: The risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals who have survived and recovered from a previous infection remained low for up to 20 months. Vaccination seemed to further decrease the risk of both outcomes for up to 9 months, although the differences in absolute numbers, especially in hospitalisations, were small. These findings suggest that if passports are used for societal restrictions, they should acknowledge either a previous infection or vaccination as proof of immunity, as opposed to vaccination only. FUNDING: None.

Physical Activity in Late Middle- to Older-Aged People and Dementia, Cognitive, and Physical Function Two Decades Later.

INTRODUCTION: Low physical activity (PA) is a potential risk factor for dementia and cognitive impairment. However, few studies have focused on very old people (aged ≥80 years), the age group with highest prevalence of dementia. The aim was to investigate if PA associated with subsequent dementia, cognitive function, and gait speed (GS), in very old people. METHODS: A population-based survey was conducted in 1999 and followed-up between 2016 and 2019 in participants ≥80 years. Altogether 541 individuals (56.2% women), 64.9 ± 4.2 years of age at baseline participated. Self-rated baseline PA was categorized into low, medium, or high. Cognitive function was assessed with the Mini-Mental State Examination (MMSE), executive function with the Frontal Assessment Battery (FAB), and GS (in meters/second) was measured over 2.4 m at follow-up. RESULTS: During a mean of 19.0 ± 1.1 years, 175 (32.3%) developed dementia. Low or medium PA compared to high PA did not associate with subsequent dementia, and PA did not associate with future cognitive function (MMSE). PA associated with executive function (FAB) (unstandardized beta [95% confidence interval]) (0.67 [0.07-1.27]), but not after adjustments. PA associated with subsequent GS in the unadjusted model and after adjustment for age, sex, smoking, and education (0.06 [0.02-0.09], and 0.04 [0.01-0.08], respectively), but not after adding adjustment for hypertension, obesity, and glucose intolerance. CONCLUSION: No support was found for the hypothesis that low PA is a potential risk factor for dementia in very high age. However, PA and executive function were associated in unadjusted analyses which indicate that PA may be important for at least one aspect of cognitive function. The association between PA and GS around 2 decades later seems attenuated by cardiometabolic risk factors. Future investigations regarding PA, dementia, and cognitive decline may consider cardiometabolic risk factors such as hypertension, obesity, and glucose intolerance, and include repeated measures of PA over the life course.

Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts.

BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention.

Trends in Hip Fracture Incidence, Length of Hospital Stay, and 30-Day Mortality in Sweden from 1998-2017: A Nationwide Cohort Study.

In this nationwide cohort study, we investigated trends in hip fracture incidence, hospital length of stay (LOS), and 30-day mortality after admission in Sweden. The cohort included all individuals in Sweden aged ≥ 50 years with a first hip fracture diagnosis during 1998-2017 (N = 313,761). The outcomes were hip fracture incidence and 30-day mortality. The results showed that the incidence of hip fracture decreased from 79.2 to 46.7/10,000 population in women and from 35.7 to 26.5/10,000 population in men. In contrast, 30-day mortality increased from 4.3% to 6.2% in women (P < 0.001) and from 8.4% to 11.1% in men (P < 0.001). Strong risk factors (P < 1 × 10-25 for all) for 30-day mortality were older age, male sex, and shorter LOS. From 1998 to 2017, LOS decreased by on average 4 days and was shorter in both male and female aged ≥ 90 years compared to those aged 80-89 (P < 0.001 for comparisons). In conclusion, despite population aging, hip fracture incidence in Sweden has decreased over the last 20 years. However, short-term mortality has increased, which to some extent may partly be explained by the fact that LOS has decreased without being adapted to important risk factors.

Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden.

BACKGROUND: Vaccine effectiveness against COVID-19 beyond 6 months remains incompletely understood. We aimed to investigate the effectiveness of COVID-19 vaccination against the risk of infection, hospitalisation, and death during the first 9 months after vaccination for the total population of Sweden. METHODS: This retrospective, total population cohort study was done using data from Swedish nationwide registers. The cohort comprised all individuals vaccinated with two doses of ChAdOx1 nCoV-19, mRNA-1273, or BNT162b2, and matched unvaccinated individuals, with data on vaccinations and infections updated until Oct 4, 2021. Two outcomes were evaluated. The first was SARS-CoV-2 infection of any severity from Jan 12 to Oct 4, 2021. The second was severe COVID-19, defined as hospitalisation for COVID-19 or all-cause 30-day mortality after confirmed infection, from March 15 to Sept 28, 2021. FINDINGS: Between Dec 28, 2020, and Oct 4, 2021, 842 974 individuals were fully vaccinated (two doses), and were matched (1:1) to an equal number of unvaccinated individuals (total study cohort n=1 685 948). For the outcome SARS-CoV-2 infection of any severity, the vaccine effectiveness of BNT162b2 waned progressively over time, from 92% (95% CI 92 to 93; p<0·001) at 15-30 days, to 47% (39 to 55; p<0·001) at 121-180 days, and to 23% (-2 to 41; p=0·07) from day 211 onwards. Waning was slightly slower for mRNA-1273, with a vaccine effectiveness of 96% (94 to 97; p<0·001) at 15-30 days and 59% (18 to 79; p=0·012) from day 181 onwards. Waning was also slightly slower for heterologous ChAdOx1 nCoV-19 plus an mRNA vaccine, for which vaccine effectiveness was 89% (79 to 94; p<0·001) at 15-30 days and 66% (41 to 80; p<0·001) from day 121 onwards. By contrast, vaccine effectiveness for homologous ChAdOx1 nCoV-19 vaccine was 68% (52 to 79; p<0·001) at 15-30 days, with no detectable effectiveness from day 121 onwards (-19% [-98 to 28]; p=0·49). For the outcome of severe COVID-19, vaccine effectiveness waned from 89% (82 to 93; p<0·001) at 15-30 days to 64% (44 to 77; p<0·001) from day 121 onwards. Overall, there was some evidence for lower vaccine effectiveness in men than in women and in older individuals than in younger individuals. INTERPRETATION: We found progressively waning vaccine effectiveness against SARS-CoV-2 infection of any severity across all subgroups, but the rate of waning differed according to vaccine type. With respect to severe COVID-19, vaccine effectiveness seemed to be better maintained, although some waning became evident after 4 months. The results strengthen the evidence-based rationale for administration of a third vaccine dose as a booster. FUNDING: None.

A 15-year follow-up study of hip bone mineral density and associations with leisure time physical activity. The Tromsø Study 2001-2016.

AIMS: The aim was to investigate the long-term association between leisure time physical activity and hip areal bone mineral density (aBMD), in addition to change in hip aBMD over time, in 32-86 years old women and men. METHODS: Data were retrieved from the 2001, 2007-2008, and 2015-2016 surveys of the Tromsø Study, a longitudinal population study in Norway. Leisure time physical activity was assessed by the four-level Saltin-Grimby Physical Activity Level Scale which refers to physical exertion in the past twelve months. Hip aBMD was assessed by Dual-Energy X-ray Absorptiometry. Linear Mixed Model analysis was used to examine long-term associations between physical activity and hip aBMD (n = 6324). In addition, the annual change in hip aBMD was analyzed in a subsample of 3199 participants. RESULTS: Physical activity was significantly and positively associated with total hip aBMD in the overall cohort (p<0.005). Participants who reported vigorous activity had 28.20 mg/cm2 higher aBMD than those who were inactive (95% CI 14.71; 41.69, controlled for confounders), and even light physical activity was associated with higher aBMD than inactivity (8.32 mg/cm2, 95% CI 4.89; 11.76). Associations between physical activity and femoral neck aBMD yielded similar results. Hip aBMD decreased with age in both sexes, although more prominently in women. From 2001 to 2007-2008, aBMD changed by -5.76 mg/cm2 per year (95% CI -6.08; -5.44) in women, and -2.31 mg/cm2 (95% CI -2.69; -1.93), in men. From 2007-2008 to 2015-2016, the change was -4.45 mg/cm2 per year (95% CI -4.84; -4.06) in women, and -1.45 mg/cm2 (95% CI -1.92; -0.98) in men. CONCLUSIONS: In this cohort of adult men and women, physical activity levels were positively associated with hip aBMD in a dose-response relationship. Hip aBMD decreased with age, although more pronounced in women than men.

Association of dog ownership with accelerometer-measured physical activity and daily steps in 70-year-old individuals: a population-based cross-sectional study.

BACKGROUND: Dog ownership (DO) has been associated with higher levels of self-reported walking and physical activity. However, compared to device-based measures, self-reported measures of physical activity may suffer from bias due to recall and social desirability. They are also incapable of quantifying light-intensity physical activity (LPA) and step volume, both of which may have important health benefits, especially for older adults. In this study, we investigated the association of DO with accelerometer-measured physical activity of different intensities and daily steps in 70-year-old individuals. METHODS: This was a population-based cross-sectional study including 1406 participants aged 70 years [54.1% female] who participated in a health survey in Umeå, Sweden between February 2017-November 2019. All participants self-reported DO [yes/no]. Daily averages of LPA, moderate-to-vigorous-intensity physical activity (MVPA), and steps per day [steps/d] were measured for 1 week using hip-mounted Actigraph GT3X+ accelerometers. Associations were investigated using linear- and logistic regression models, adjusted for sociodemographic and health-related factors, date of examination, and accelerometer wear time. RESULTS: The prevalence of DO was 14.1% [N = 199]. After adjustment for all covariates, DO was associated with 19.2 more minutes/d of LPA [95% CI, 8.8-29.6], 11.4 more minutes/d of MVPA [95% CI, 8.0-14.9] and 1738 more steps/d [95% CI, 1326-2149]. DO was also associated with twice the odds of meeting the physical activity recommendations [OR, 2.07, 95% CI, 1.48-2.90]. Exploratory interaction analyses showed that the association between DO and steps/d was stronger [Pinteraction = 0.030] in female [ß = 2165, 95% CI, 1585-2744] than in male [ß =1255, 95% CI, 664-1845], with a similar trend for MVPA [Pinteraction = 0.082]. CONCLUSIONS: In this study of community-dwelling 70-year-old individuals, DO was associated with higher levels of daily LPA, MVPA, and steps. With the limitation of the observational design of the study, these findings add knowledge regarding the beneficial role that DO may play for promoting physical activity in the older population. In turn, these findings could support the development and evaluation of targeted interventions seeking to promote dog-friendly environments and facilitate dog walking in the community.

Effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden: A nationwide cohort study.

BACKGROUND: The effectiveness of heterologous prime-boost Coronavirus disease 2019 (Covid-19) vaccination is currently unknown. METHODS: From individuals vaccinated with two doses against Covid-19 in Sweden until July 5, 2021 (N=3,445,061), we formed a study cohort including 94,569 individuals that had received heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, 16,402 individuals that received heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination, and 430,100 individuals that received homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 prime-boost vaccination. In addition, 180,716 individuals were selected who were unvaccinated at the date of vaccination in the corresponding case. Unvaccinated individuals were censored at first dose of any vaccine. Baseline was the date of the second dose of any vaccine, with the same date in the corresponding unvaccinated individual. The outcome included incident symptomatic Covid-19 infection occurring >14 days after baseline. FINDINGS: During a mean follow-up time of 76 (range 1-183) days, symptomatic Covid-19 infection was confirmed in 187 individuals with heterologous vaccine schedules (incidence rate: 2.0/100,000 person-days) and in 306 individuals from the unvaccinated control group (incidence rate: 7.1/100,000 person-days). The adjusted vaccine effectiveness was 67% (95% CI, 59-73, P<0.001) for heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, and 79% (95% CI, 62-88, P<0.001) for heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination. When combined and analysed together, the two heterologous vaccine schedules had an effectiveness of 68% (95% CI, 61-74, P<0.001) which was significantly greater (Pinteraction<0.001) than the 50% effectiveness for homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 (95% CI, 41-58, P<0.001). INTERPRETATION: The findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period. These findings could have important implications for vaccination strategies and logistics, and consequently in the battle against the Covid-19 pandemic.

Association Between Risk of COVID-19 Infection in Nonimmune Individuals and COVID-19 Immunity in Their Family Members.

Importance: The association between COVID-19 immunity within families and the risk of infection in nonimmune family members is unknown. Objective: To investigate the association between risk of COVID-19 in nonimmune individuals and the number of their family members with known immunity acquired from a previous COVID-19 infection or full vaccination (2 vaccine doses). Design, Setting, and Participants: In this cohort study of data from nationwide registries in Sweden, all individuals who acquired immunity from either previous COVID-19 infection or full vaccination until May 26, 2021, were considered for inclusion. Each person with immunity was matched 1:1 to an individual without immunity from an identified cohort of individuals with families comprising 2 to 5 members. Exposures: Number of immune family members in each family on April 14, 2021 (index date), who acquired immunity from a previous COVID-19 infection or full vaccination (2 doses of the mRNA-1273, BNT162b2 mRNA, or ChAdOx1 nCoV-19 vaccine). Main Outcomes and Measures: Incident COVID-19 infection in nonimmune family members from April 15 to May 26, 2021. Results: A total of 1 789 728 individuals from 814 806 families were included in the analysis. Each family comprised 2 to 5 family members, with a mean (SD) age at baseline of 51.3 (19.5) years. During a mean (range) follow-up time of 26.3 (1-40) days, 88 797 of 1 549 989 (5.7%) nonimmune family members (mean [SD] age, 51.6 [17.7] years; 790 276 men [51.0%]) were diagnosed with COVID-19. There was an inverse dose-response association between the number of immune members in each family and the risk of incident COVID-19 infection in nonimmune family members. Nonimmune families with 1 immune family member had a 45% to 61% lower risk of contracting COVID-19 (hazard ratio [HR], 0.39-0.55; 95% CI, 0.37-0.61, P < .001). The risk reduction increased to 75% to 86% in families with 2 immune family members (HR, 0.14-0.25; 95% CI, 0.11-0.27; P < .001), 91% to 94% with 3 immune family members (HR, 0.06-0.09; 95% CI, 0.04-0.10; P < .001), and 97% with 4 immune family members (HR, 0.03; 95% CI, 0.02-0.05; P < .001). The results were similar for the outcome of COVID-19 infection that was severe enough to warrant a hospital stay. Conclusions and Relevance: In this cohort study, family members without immunity had a 45% to 97% lower risk of contracting COVID-19 as the number of immune family members increased. Vaccination is a key strategy for decreasing the transmission of the virus within families.

Does exercise prevent major non-communicable diseases and premature mortality? A critical review based on results from randomized controlled trials.

Observational studies show that physical activity is strongly associated with a reduced risk of premature mortality and major non-communicable diseases. We reviewed to which extent these associations have been confirmed in randomized controlled trials (RCTs) for the outcomes of mortality, cardiovascular disease (CVD), type 2 diabetes (T2D), and fracture. The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants. The results also indicate a lack of effect on cardiovascular mortality in people with chronic conditions, based on RCTs comprising ∼11,000 participants. Furthermore, there is inconsistent evidence regarding the effect of exercise on fractures in older adults, based on RCTs comprising ∼40,000 participants. Finally, based on RCTs comprising ∼17,000 participants, exercise reduces T2D incidence in people with prediabetes when combined with dietary modification, although evidence for the individual effect of exercise is lacking. Identified shortcomings of the current evidence include risks of publication bias, lack of high-quality studies in certain high-risk populations, and inconstant evidence with respect to some outcomes. Thus, additional large trials would be of value, especially with fracture as the primary outcome. In conclusion, according to current RCT evidence, exercise can prevent T2D assuming it is combined with dietary intervention. However, the current evidence shows that exercise does not prevent premature mortality or CVD, with inconsistent evidence for fractures.