Residence-matched Controls Research Articles

The influence of the multifactorial falls prevention programme on mortality.

Multifactorial falls prevention programmes (MFFPs) can prevent falls and fall-related injuries. We aimed to study MFFP patients' mortality compared with their sex-, age- and residence-matched population-based controls. This study is a Finnish single-centre retrospective register-based controlled cohort study of a total of 527 home-dwelling MFFP patients and their 3:1 age-, sex- and residence-matched population-based controls (n = 1581), who had not attended the MFFP. During the follow-up, the cumulative mortality of all patients was 40.4, and of controls 39.1 %. Hazard ratio was 0.82 (95% confidence interval 0.68 to 0.99), p= 0.041. Case patients had a 2.7 times greater risk to die due to accidents, but they had a lower risk to die due to dementia, compared with the control group. The 72-years-old or older participants had a lower mortality rate than the controls during follow-up. The MFFP seems to relate to a lower all-cause mortality when comparing MFFP patients with their age-, sex- and residence-matched controls. However, the MFFP did not seem to relate to a lower injury-related mortality. The relationship between the MFFP and lower all-cause mortality seemed to be strongest in the patients aged 72 years or older. Due to the study setting and population-based control group, it is difficult to draw solid conclusions and further studies are needed. A randomized controlled trial comparing the MFFP with standard care would give better insight on the effectiveness of a MFFP on mortality.

Risks of developing major psychiatric disorders among child and adolescent intensive care unit survivors

BackgroundThe mental health of child and adolescent intensive care unit (ICU) survivors is increasingly being researched. However, the literature on how various types of critical illness influence specific psychiatric disorders remains limited. MethodsThis study analyzed the data of 8704 child and adolescent ICU survivors and 87,040 age-, sex-, family income–, and residence-matched controls who were followed from enrollment to the end of 2013; the data covered the period from 1996 to 2013 and were extracted from a nationwide data set. The primary outcomes were the risks of five major psychiatric disorders (MPDs), namely schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). ResultsRelative to the controls, the child and adolescent ICU survivors (mean age = 10.33 years) exhibited higher risks of developing five MPDs. The associated hazard ratios (HRs) and confidence intervals (CIs) are as follows: PTSD, HR = 4.67, 95 % CI = 2.42–9.01; schizophrenia, HR = 3.19, 95 % CI = 2.27–4.47; BD, HR = 2.02, 95 % CI = 1.33–3.05; OCD, HR = 1.96, 95 % CI = 1.21–3.16; and MDD, HR = 1.68, 95 % CI = 1.44–1.95. The risks of developing MPDs varied across multiple types of critical illness related to ICU admission. ConclusionsThe risks of MPDs were significantly higher among the child and adolescent ICU survivors than among the controls. The development of appropriate MPD prevention strategies should be emphasized for this vulnerable population.

Predicting Alzheimer’s disease from cognitive footprints in mid and late life: How much can register data and machine learning help?

BackgroundReal-world data with decades-long medical records are increasingly available alongside the growing adoption of machine learning in healthcare research. We evaluated the performance of machine learning models in predicting the risk of Alzheimer’s disease (AD) using data from the Finnish national registers. MethodsWe conducted a case-control study using data from the Finnish MEDALZ (Medication use and Alzheimer’s disease) study. Altogether 56,741 individuals with incident AD diagnosis (age ≥ 65 years at diagnosis and born after 1922) and their 1:1 age-, sex-, and region of residence-matched controls were included. The association of risk factors, evaluated at different age periods (45–54, 55–64, 65+), and AD were assessed with logistic regression. Predictive accuracies of logistic regressions were compared with seven machine learning models (L1-regularized logistic regression, Naive bayes, Decision tree, Random Forest, Multilayer perceptron, XGBoost, and LightGBM). Findings63.5 % of cases and controls were females and the mean age was 79.1 (SD = 5.1). The strongest associations with AD were observed for head injuries at age 55–64 (OR, 95 % CI 1.33, 1.19–1.48) and 65+ (1.31, 1.23–1.40), followed by antidepressant use (1.30, 1.22–1.38) at 55–64 and antipsychotic use (1.27, 1.19–1.35) at 65+. The predictive accuracies of all models were low, with the best performance (AUC 0.603) observed in Random Forest for predicting AD onset at age 65–69. InterpretationAlthough significant associations were identified between many risk factors and AD, the low predictive accuracies suggest that specialised healthcare diagnosis data is not sufficient for predicting AD and linkage with other data sources is needed.

Sexually transmitted infection and teenage pregnancy in adolescents having parents with schizophrenia: a retrospective cohort study of 64,350 participants

BackgroundThe risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown.MethodsFrom the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified.ResultsCox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02–1.44), especially daughters (HR: 1.30, 95% CI: 1.06–1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29–1.67) compared with those having no parents with severe mental disorders.DiscussionThe positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group.

Arthroplasty Rates and Risk in Familial Mediterranean Fever Patients: A large Population-Based Study.

Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation in various organs, including the joints. Traditionally, the arthritis of FMF has been considered relatively harmless. However, anecdotal evidence has suggested that it may contribute to long-term joint damage, which may necessitate surgical joint replacement. This study aimed to investigate the rates of arthroplasty among FMF patients and compare it to the general population. The study used the electronic database of the largest healthcare organization in Israel to identify 9,769 FMF patients diagnosed between 2000 and 2016. A similar number of age-, gender-, and residency-matched controls were also identified. The rates of arthroplasty were compared between the two groups. A logistic regression model predicting the need for arthroplasty within the FMF group was formed to identify potential risk factors. Of the 9,769 FMF patients, 114 (1.2%) underwent arthroplasty, compared with 64 (0.7%) of the control group [unadjusted odds ratio (OR)=1.79, 95% confidence interval (CI) 1.32-2.43; partially adjusted OR = 1.97, 95% CI 1.40-2.77; fully adjusted OR = 1.92, 95% CI 1.35-2.72]. Within the FMF cohort, those of North African origin had a significantly higher risk of arthroplasty (OR = 6.89, 95% CI 5.09-9.33; p< 0.001). FMF patients can experience long-term joint damage that may require arthroplasty. Although this complication is relatively uncommon in FMF patients, it occurs almost twice as frequently as compared with the general population. FMF patients of North African origin are at an even higher risk.

Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension.

This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers. This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group-matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke. The mean level of serum L-carnitine in the stroke population was 4.7 μg/mL, which was significantly lower than that of the control group (5.7 μg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 μg/mL), the odds of stroke were 0.62 (95% CI, 0.39-1.00) in quintile 2, 0.66 (95% CI, 0.40-1.10) in quintile 3, 0.47 (95% CI, 0.28-0.81) in quintile 4, and 0.50 (95% CI, 0.30-0.84) in quintile 5. The trend test was significant (P=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38-0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine-stroke association was only observed in the normal folate group (P interaction, 0.039) and in the MTHFR CC genotype group (P interaction, 0.047). In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the MTHFR C677T variant were significant effect modifiers of the association.

Dietary acid load and risk of head and neck and oral cavity cancers: An epidemiologic study

AbstractAimMetabolic acidosis subsequent to a high dietary acid load (DAL) leads to inflammation and cell transformation, which are common features of cancer development. Because the epidemiologic evidence associating DAL and cancer risk is still limited, we sought to explore the potential role of DAL as a risk factor for head and neck and oral cavity tumors.MethodsA case–control study was performed on 1126 men (563 cases and 563 age frequency and residence matched controls), drawn from the major public hospitals in Montevideo, Uruguay. Participants were interviewed through a multi‐topic questionnaire, including a food frequency questionnaire. Food‐derived nutrients were calculated from available databases. DAL was calculated based on validated measures including potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Odds ratios (OR) were estimated by logistic regression, adjusting for potential confounders.ResultsWe found significant and direct associations between dietary acid load and risk of head and neck and oral cavity cancers (OR = 2.10 and OR = 1.95 for highest PRAL and NEAP, respectively). In addition, stratified analyses by subsites displayed the highest estimates for pharyngeal cancer (OR = 2.40 and OR = 2.28 for highest PRAL and NEAP, respectively). No association was found for oral cavity cancers.ConclusionsAn acidogenic diet may increase the risk of head and neck cancers. Our findings align well with our previous studies focused on other anatomic sites. Studies conducted on food groups and nutritional patterns align with our results. Further studies are needed to confirm these findings.

Systemic hormonal contraception and risk of venous thromboembolism

The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019. All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018-2019 and their 4:1 age-matched controls were further analyzed in a prospective nested case-control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism. Altogether, 1334 venous thromboembolism cases occurred during the follow-up period (incidence rate 1.14 per 1000 person-years, 95% confidence interval [CI] 1.08-1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27-1.58). Compared with non-use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62-5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98-2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99-3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12-23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61-4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02-2.37), cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06-2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95-5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol-containing preparations (aOR 2.20; 95% CI 1.82-2.65), followed by estradiol-containing preparations (aOR 1.39; 95% CI 1.04-1.87) with no risk for progestin-only hormonal contraception. Current use of estradiol-containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66-1.66). An increased risk of venous thromboembolism is associated with ethinylestradiol-containing combined preparations. The use of estradiol-containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone-containing combined oral contraceptives, whereas the use of progestin-only contraception is not associated with venous thromboembolism.

Association between AMPKα1 gene polymorphisms and gestational diabetes in the Chinese population: A case‐control study

AbstractAimThe aim is to examine the association between seven candidate single nucleotide polymorphisms in AMPKα1 and gestational diabetes in Chinese people.MethodWe used a matched nested case‐control study design, individuals including 334 participants with gestational diabetes and 334 healthy pregnant women. Confirmed 334 gestational diabetes cases and maternal age and district of residence matched controls (1:1) were enrolled. We examined seven candidate single nucleotide polymorphisms in AMPKα1 gene and the risk of gestational diabetes. The associations were estimated in Co‐dominant, Dominant, Recessive, and Alleles models. The odds ratios (ORs) and their 95% confidence intervals (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and gestational diabetes adjusting for maternal age, prepregnancy body mass index (BMI), fetal sex and parity.ResultAt the gene level, we found that AMPKα1 was associated with gestational diabetes (p = 0.008). After adjusting the covariates and multiple comparison correction, AMPKα1 (rsc1002424, rs10053664, rs13361707) polymorphisms were associated with the risk of gestational diabetes. In addition, gestational diabetes was related to the AAGGA haplotype comprising rs1002424, rs2570091, rs10053664, rs13361707 and rs3805486 in the haplotype models (p = 0.011).ConclusionsThis study provides evidence that the AMPKα1 genotypes (rs1002424 G/A, rs10053664 A/G, rs13361707 A/G) and the haplotype (AAGGA) are relevant genetic factors in a Chinese population with gestational diabetes.

Risk Factors of the First-Time Stroke in the Southwest of Saudi Arabia: A Case-Control Study.

Worldwide, stroke is the second leading cause of death and a frequent cause of permanent disability. The objective was to identify the first-time stroke modifiable risk factors in the Aseer region, southwest Saudi Arabia. In a multicenter hospital-based case-control study design, all first stroke patients admitted to hospitals in the Aseer region were included consecutively over one year. Age, sex, and geographical residence-matched controls were selected and included in a ratio of 1:1. Data collected included altitude (low or high), nationality, marital status, educational level, family history of stroke, history of diabetes mellitus, history of systemic hypertension, high cholesterol level, current smoking, obesity, and regular exercise practice. The study included 1249 first-time stroke patients and 1249 age, sex, and residence-matched controls. Hypertension, diabetes mellitus, obesity, and high cholesterol were significantly highly prevalent among cases (57.7%, 49.4%, 42.0%, 29.4%, respectively) compared to controls (31.8%, 25.9%, 30.8%, 12.1%, respectively). Practicing regular exercise was significantly highly prevalent among controls (29.9%) compared to cases (13.1%). Multivariable logistic regression analysis revealed that systemic hypertension (adjusted odds ratio (aOR) = 2.12, 95%CI: 1.74–2.57), diabetes mellitus (aOR = 1.73, 95%CI: 1.41–2.21), obesity (aOR = 1.95, 95%CI: 1.61–2.28) and high cholesterol (aOR = 1.64, 95%CI: 1.28–2.10) were significant risk factors, while regular exercise practice was a significant protective factor (aOR = 0.12, 95%CI: 0.05–0.26) for stroke. Hypertension, diabetes mellitus, obesity, and high cholesterol are major risk factors for stroke in the Aseer region of southwest Saudi Arabia. The protective role of regular physical activity in reducing the risk of stroke is evident. The observed higher prevalence of potentially modifiable risk factors among stroke cases encourages an urgent need to develop and implement a national program to control these factors.

Regional Comparisons of Associations Between Physical Activity Levels and Cardiovascular Disease: The Story of Atlantic Canada

BackgroundPhysical inactivity is an important risk factor for cardiovascular disease (CVD). Atlantic Canada is a region with lower physical activity (PA) levels and poorer CVD outcomes than the rest of Canada. Yet, within-region variation is expected. This study aimed to assess the association between PA and CVD and how this relationship varied on a regional level. MethodsThis cross-sectional study used data from the Atlantic Partnership for Tomorrow’s Health (PATH) Study. The cohort included 823 CVD cases and 2469 age-, sex-, and province of residence-matched controls between the ages 35 and 69. Data collected included self-reported CVD and PA levels as well as information on sociodemographic characteristics, health status, and lifestyle behaviours. Simple and multiple logistic regression were used to assess the association between PA and CVD. ResultsHigh PA levels were associated with a 26% reduction in the mean probability of CVD compared with low PA levels across the total population. Compared with high PA levels, moderate and low PA levels were associated with increased odds of CVD across all 4 provinces. However, regional variation was observed, with higher odds of CVD for low-to-moderate PA levels in Newfoundland and Labrador and New Brunswick compared with Nova Scotia and Prince Edward Island. ConclusionsAtlantic Canadians experience regional inequalities in the association between PA and CVD. Future work needs to explore underlying pathways driving these regional differences, which may be the impetus for interventions that mitigate risk and CVD burden in populations of greatest need.

Indoor volatile organic compounds exposures and risk of childhood acute leukemia: a case-control study in shanghai

A case-control study was conducted to investigate the relationship between indoor air pollution and childhood acute leukemia (AL) in Shanghai. 97 cases and 148 gender-, age-, and residence-matched controls were included. Indoor air pollution was evaluated by questionnaires and quantitative measurement including 14 volatile organic compounds (VOCs) and nitrogen dioxide (NO2) in the homes of the two groups. The levels of individual VOCs, VOC families, TVOC (sum of the concentrations of the individual VOCs) and NO2 were compared between the two groups. Exposure to styrene and butyl alcohol were associated with an increased risk of childhood AL (styrene: odds ratio (OR)=2.33, 95% confidence interval (CI): 1.07-5.07; butyl alcohol: OR = 2.51, 95%CI: 1.19-5.28); 4th quartile of chlorinated hydrocarbons (OR = 2.52, 95%CI: 1.02-6.26) and 3rd quartile of TVOC (OR = 4.03, 95%CI: 1.06-6.81) had significant higher ORs for childhood AL compared with that in the lowest quartiles. Elevated levels of individual VOCs, VOC families and TVOC were also associated with self-reported risk factors. Our findings suggest that VOCs exposure was associated with an elevated risk of childhood AL, underscore that more attention should be paid to indoor air pollution as a risk factor of childhood AL.

Sudden Sensorineural Hearing Loss Associated with Nutritional Anemia: A Nested Case-Control Study Using a National Health Screening Cohort.

Previous studies have suggested an association of anemia with hearing loss. The aim of this study was to investigate the association of nutritional anemia with sudden sensorineural hearing loss (SSNHL), as previous studies in this aspect are lacking. We analyzed data from the Korean National Health Insurance Service-Health Screening Cohort 2002–2015. Patients with SSNHL (n = 9393) were paired with 37,572 age-, sex-, income-, and region of residence-matched controls. Both groups were assessed for a history of nutritional anemia. Conditional logistic regression analyses were performed to calculate the odds ratios (ORs) (95% confidence interval, CI) for a previous diagnosis of nutritional anemia and for the hemoglobin level in patients with SSNHL. Subgroup analyses were conducted for age and sex. Age, sex, income, and region of residence were stratified. Obesity, smoking, drinking alcohol, systolic/diastolic blood pressure, fasting blood glucose, total cholesterol, and the Charlson Comorbidity Index were considered in the regression models. Nutritional anemia was present in 4.8% (449/9393) of patients with SSNHL and 4.0% (1494/37,572) of controls (p < 0.001). The SSNHL group demonstrated 1.20-fold higher odds for nutritional anemia (95% CI = 1.08–1.34, p = 0.001). Hemoglobin levels were not associated with SSNHL. In subgroups <60 years old, there was a consistent positive association of nutritional anemia with SSNHL (adjusted OR = 1.55, 95% CI = 1.11–2.15, p = 0.010 for men <60 years old, and adjusted OR = 1.22, 95% CI = 1.02–1.45, p = 0.028 for women <60 years old). Nutritional anemia, but not hemoglobin level, was associated with an increased risk of SSNHL.

Lower risk of primary Sjogren\u2019s syndrome in patients with dengue virus infection: a nationwide cohort study in Taiwan

The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based cohort study assessed the risk of ADs among patients with DV infection. We analyzed Taiwanese medical data from the Registry of the National Notifiable Disease Reporting System of Taiwan’s Centers for Disease Control between 1998 and 2015 and identified patients with DV infection. From the entire general population data in the National Health Insurance Research Database, we randomly selected a comparison cohort that was individual matching by age, sex, residence, and index date. We analyzed the risk of ADs using a Cox proportional hazards regression model stratified by sex, age, and residence. We enrolled 29,365 patients with DV infection (50.68% men; mean age, 44.13 years) and 117,460 age-, sex-, and residence-matched controls in the present study. The incidence rates of organ-specific ADs were nonsignificantly higher in the DV cohort than in the non-DV control cohort. An approximately 70% lower risk of primary Sjogren syndrome (pSS) was evident in the DV cohort than in the non-DV control cohort with an adjusted hazard ratio of 0.30 (95% confidence interval 0.13–0.67) after adjusting for comorbidities in matched design. By contrast, the other systemic ADs were nonsignificantly lower in the DV cohort than in the non-DV control cohort. This nationwide long-term cohort study demonstrated that patients with DV infection had a lower risk of primary Sjogren syndrome than those without DV infection.Key Points• This retrospective, longitudinal cohort observational study shows that patients with DV infection had a lower risk of pSS than those without DV infection.• The DV cohort had an approximately 70% lower risk of pSS than the control group, with a multivariate-adjusted HR of 0.30.• On the basis of this result, we contended that DV infection has a protective effect that reduces the risk of pSS.

Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

Rate and appropriateness of polypharmacy in older patients with hemophilia compared with age-matched controls.

In older people, multiple chronic ailments lead to the intake of multiple medications (polypharmacy) that carry a number of negative consequences (adverse events, prescription and intake errors, poor adherence, higher mortality). Because ageing patients with haemophilia (PWHs) may be particularly at risk due to their pre-existing multiple comorbidities (arthropathy, liver disease), we chose to analyse the pattern of chronic drug intake in a cohort of PWHs aged 60years or more. S+PHERA is a multicentre observational study, with the broad goal to evaluate prospectively the health status and medication intake in 102 older patients with severe haemophilia A or B compared with 204 age- and residence-matched controls chosen randomly from the same general practices of PWHs. The rate of potential drug-drug interactions (PDDI) was evaluated as a proxy of prescription appropriateness. After excluding replacement therapies and antiviral drugs, PWHs took in average less daily drugs than controls (2.4±2.5 vs 3.0±2.4) and had a lower rate of polypharmacy. Moreover, their prevalence of PDDI was lower (16.7% vs 27%). The rate of polypharmacy and the appropriateness of medications other than those for haemophilia and related comorbidities are acceptable in Italian PWHs, and better than those in their age peers without haemophilia, perhaps owing to drug tailoring and deprescribing by the specialized haemophilia centres at the time of regular visits. However, the PWHs investigated herewith were relatively young and the rate of polypharmacy and related PDDIs may become more prominent and crucial when older ages are reached, suggesting the need of continuous surveillance on prescribed drugs and the risk of drug-drug interactions.

Compulsory military service as a measure of later physical and cognitive performance in male survivors of childhood cancer

Background: Compromised physical fitness and cognitive difficulties have been reported as late effects of cancer treatment during childhood. To assess this issue, the military rankings of cancer survivors in medical checkups at call-up, and conscripts’ physical and cognitive performance during the first weeks of compulsory military education were compared to those of matched population controls without a history of cancer.Material and methods: A total of 1680 male patients born between 1960 and 1992 with a malignancy diagnosed before the age of 16 who were alive at the call-up age (18 years) were identified using the Finnish Cancer Registry, and five age, sex and place of residence matched controls for each patient using the Population Register Centre. Data on military service were gathered from Finnish Defense Forces. A conditional logistic regression analysis, the GEE-method with the cumulative logit link function, the chi-square test, the chi-square test for trend and a one-way analysis of variance were used in different analyses.Results: Cancer survivors were exempted from military service more often than the controls (p < .001). The fit-for-service frequency was highest for survivors of kidney tumors (68%) and lowest after irradiated brain tumors (19%). In service, the results of the 12-min running test were poorer than those of controls for leukemia/non-Hodgkin lymphoma (p = .03) and brain tumor (p = .01) survivors. Interestingly, the standing long-jump test was the only muscle test for which survivor groups performed worse than controls. Performance on cognitive tests only differed from controls in brain tumor survivors.Conclusions: Exemption from service is still common under the current guidelines, but fit-for-service survivors do well in military education. These results can be used for reassuring survivors that completion of military service is possible for those fulfilling the national general guidelines for military fitness.

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

BackgroundStudies investigating psychiatric disorders as Alzheimer's disease (AD) risk factors have yielded heterogeneous findings. Differences in time windows between the exposure and outcome could be one explanation. We examined whether (1) mental and behavioral disorders in general or (2) specific mental and behavioral disorder categories increase the risk of AD and (3) how the width of the time window between the exposure and outcome affects the results. MethodsA nationwide nested case-control study of all Finnish clinically verified AD cases, alive in 2005 and their age, sex and region of residence matched controls (n of case-control pairs 27,948). History of hospital-treated mental and behavioral disorders was available since 1972. ResultsAltogether 6.9% (n=1932) of the AD cases and 6.4% (n=1784) of controls had a history of any mental and behavioral disorder. Having any mental and behavioral disorder (adjusted OR=1.07, 95% CI=1.00–1.16) or depression/other mood disorder (adjusted OR=1.17, 95% CI=1.05–1.30) were associated with higher risk of AD with 5-year time window but not with 10-year time window (adjusted OR, 95% CI 0.99, 0.91–1.08 for any disorder and 1.08, 0.96–1.23 for depression). ConclusionsThe associations between mental and behavioral disorders and AD were modest and dependent on the time window. Therefore, some of the disorders may represent misdiagnosed prodromal symptoms of AD, which underlines the importance of proper differential diagnostics among older persons. These findings also highlight the importance of appropriate time window in psychiatric and neuroepidemiology research.

Systemic inflammation in acute intermittent porphyria: a case-control study.

This study aimed to examine whether acute intermittent porphyria (AIP) is associated with systemic inflammation and whether the inflammation correlates with disease activity. A case-control study with 50 AIP cases and age-, sex- and place of residence-matched controls was performed. Plasma cytokines, insulin and C-peptide were analysed after an overnight fast using multiplex assay. Long pentraxin-3 (PTX3) and complement activation products (C3bc and TCC) were analysed using enzyme-linked immunosorbent assay (ELISA). Urine porphobilinogen ratio (U-PBG, µmol/mmol creatinine), haematological and biochemical tests were performed using routine methods. Questionnaires were used to register AIP symptoms, medication and other diseases. All 27 cytokines, chemokines and growth factors investigated were increased significantly in symptomatic AIP cases compared with controls (P < 0·0004). Hierarchical cluster analyses revealed a cluster with high visfatin levels and several highly expressed cytokines including interleukin (IL)-17, suggesting a T helper type 17 (Th17) inflammatory response in a group of AIP cases. C3bc (P = 0·002) and serum immunoglobulin (Ig)G levels (P = 0·03) were increased significantly in cases with AIP. The U-PBG ratio correlated positively with PTX3 (r = 0·38, P = 0·006), and with terminal complement complex (TCC) levels (r = 0·33, P = 0·02). PTX3 was a significant predictor of the biochemical disease activity marker U-PBG in AIP cases after adjustment for potential confounders in multiple linear regression analyses (P = 0·032). Prealbumin, C-peptide, insulin and kidney function were all decreased in the symptomatic AIP cases, but not in the asymptomatic cases. These results indicate that AIP is associated with systemic inflammation. Decreased C-peptide levels in symptomatic AIP cases indicate that reduced insulin release is associated with enhanced disease activity and reduced kidney function.

No Increased Prevalence of Malignancies Among First-Degree Relatives of Patients with Chronic Myeloid Leukemia - Data from Population-Based Swedish Registries

Background:The etiology of chronic myeloid leukemia (CML) is essentially unknown with high doses of ionizing radiation being the only well established risk factor. We have recently published two large population-based studies showing an increased prevalence of other malignancies prior, as well as subsequent to a diagnosis of CML (Gunnarsson et al, Br J Haematol. 2015 Jun; 169(5): 683-8 and Gunnarsson et al, Leukemia. 2016 Jul; 30(7): 1562-7). One may therefore speculate that CML patients may have an increased congenital or acquired susceptibility to develop cancer. In the former case, one would expect an increased prevalence of malignancies among first-degree relatives (FDR) to CML patients.In a previous report based on the Swedish Cancer Registry, no increased aggregation of malignancies was detected among family members to CML patients diagnosed between 1958 and 2004 (Bjorkholm et al, Blood. 2013 Jul 18; 122(3): 460-1). However, a more strict definition of CML (requiring e.g. thepresence of a Philadelphia chromosome or the BCR/ABL fusion gene) was introduced with the updated WHO classification in 2002, making subsequently diagnosed CML cohorts more homogenous.Materials and methods:Aiming to establish the prevalence of malignancies among FDR of a large and well-defined contemporary CML cohort in Sweden compared to carefully matched controls, we have used four large Swedish population based registers.To identify Swedish patients with CML diagnosed between 2002 and 2013, we used the Swedish CML Register to which all CML patients diagnosed January 1st 2002 and later are reported. FDR were identified by use of the Swedish Multi-Generation Register, which comprises information about parent-sibling-offspring relationships of persons that has been registered in Sweden at some time since 1961 and born later than 1932.By linking this cohort to the Swedish Cancer Register, we retrieved information about malignancies for each FDR.Each CML patient was matched with five, age-, gender- and county of residence-matched controls, selected from the Swedish Total Population Register. All controls had to be alive and free of CML at the time of CML diagnosis for the matching CML patient.To calculate odds ratio (OR) and 95% confidence intervals (CI), conditional logistic regression were used.Results:In the Swedish CML register, 984 patients were identified. Among them 184 patients were excluded due to a birth year prior to 1932. Among the 800 remaining CML patients, 4 287 FDR were identified and included in the analysis (parents: 1 346, siblings: 1 497 and children: 1 444). Correspondingly, 20 930 matched controls were included in the analysis.In total, 611 malignancies were identified among the FDR of CML patients compared to 2844 in the control group yielding an OR of 1.057 (95% CI 0.962 - 1.162).Neither hematological malignancies nor solid tumors were increased in the CML-FDR group (Table 1). Notably, none of the FDRs in the CML-FDR group had a CML diagnosis.Conclusions:Using data from four large Swedish population based registers and based on the fate of more than 4 000 FDR of 800 CML patients diagnosed in the modern era of cytogenetics, as well as closely matched CML-free controls, we show that there is no familial aggregation of malignancies in FDRs of patients with CML. These results suggest that a hereditary predisposition to develop cancer is unlikely to be a part of the pathogenesis of CML. [Display omitted] DisclosuresHöglund:Akinion Pharmaceuticals: Consultancy; Janssen-Cilag: Honoraria. Lambe:AstraZeneca: Other: Stock Ownership ; Pfizer: Other: Stock Ownership . Richter:Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ariad: Honoraria, Research Funding. Själander:ARIAD: Consultancy.