Venous thromboembolism in cancer patients: a population-based cohort study.

The incidence of venous thromboembolism (VTE) in cancer patients may have changed in the past decade, possibly due to novel cancer therapies, improved survival, and high-resolution imaging. Danish medical registries were used to identify 499 092 patients with a first-time cancer diagnosis between 1997 and 2017, who were matched to 1 497 276 comparison individuals without cancer from the general population. We computed cumulative incidences of VTE 6 and 12 months after the diagnosis/index date. Hazard ratios (HRs) were calculated using Cox regression. Risk factors were examined by computing subdistribution hazard ratios (SHRs) in a competing-risk analysis. Cumulative incidence of VTE 12 months after the cancer diagnosis/index date was 2.3% (95% confidence interval [CI], 2.2% to 2.3%) in the cancer cohort and 0.35% (95% CI, 0.34% to 0.36%) in the comparison cohort (HR, 8.5; 95% CI, 8.2-8.8). Important risk factors for cancer patients were prior VTE (SHR, 7.6; 95% CI, 7.2-8.0), distant metastasis (SHR, 3.2; 95% CI, 2.9-3.4), and use of chemotherapy (SHR, 3.4; 95% CI, 3.1-3.7), protein kinase inhibitors (SHR, 4.1; 95% CI, 3.4-4.9), antiangiogenic therapy (SHR, 4.4; 95% CI, 3.8-5.2), and immunotherapy (SHR, 3.6; 2.8-4.6). Twelve-month incidence in the cancer cohort increased from 1.0% (95% CI, 0.9% to 1.2%) in 1997 to 3.4% (95% CI, 2.9% to 4.0%) in 2017, which was paralleled by improved 12-month survival and increased use of computed tomography scans, chemotherapy, and targeted therapies. In conclusion, the risk of VTE in cancer patients is increasing steadily and is ninefold higher than in the general population.

Comorbidity and risk of infection among patients with hip fracture: a Danish population-based cohort study.

Impact of comorbidity on infection risk among hip fracture patients is unclear. We found high incidence of infection. Comorbidity was an important risk factor for infection up to 1 year after surgery. Results indicates a need for additional investment in pre- and postoperative programs that assist patients with high comorbidity. PURPOSE: Comorbidity level and incidence of infection have increased among older patients with hip fracture. The impact of comorbidity on infection risk is unclear. We conducted a cohort study examining the absolute and relative risks of infection in relation to comorbidity level among hip fracture patients. METHODS: Utilizing Danish population-based medical registries, we identified 92,600 patients aged ≥ 65 years undergoing hip fracture surgery between 2004 and 2018. Comorbidity was categorized by Charlson comorbidity index scores (CCI): none (CCI = 0), moderate (CCI = 1-2), or severe (CCI ≥ 3). Primary outcome was any hospital-treated infection. Secondary outcomes were hospital-treated pneumonia, urinary tract infection, sepsis, reoperation due to surgical-site infection (SSI), and a composite of any hospital- or community-treated infection. We calculated cumulative incidence and hazard ratios (aHRs) adjusted for age, sex, and surgery year, including 95% confidence intervals (CIs). RESULTS: Prevalence of moderate and severe comorbidity was 40% and 19%, respectively. Incidence of any hospital-treated infection increased with comorbidity level within 0-30 days (none 13% vs. severe 20%) and 0-365 days (none 22% vs. 37% severe). Patients with moderate and severe comorbidity, compared to no comorbidity, had aHRs of 1.3 (CI: 1.3-1.4) and 1.6 (CI: 1.5-1.7) within 0-30 days, and 1.4 (CI: 1.4-1.5) and 1.9 (CI: 1.9-2.0) within 0-365, respectively. Highest incidence was observed for any hospital- or community-treated infection (severe 72%) within 0-365 days. Highest aHR was observed for sepsis within 0-365 days (severe vs. none: 2.7 (CI: 2.4-2.9)). CONCLUSION: Comorbidity is an important risk factor for infection up to 1 year after hip fracture surgery.

Time trends in use of non-steroidal anti-inflammatory drugs and opioids one year after total hip arthroplasty due to osteoarthritis during 1996-2018: a population-based cohort study of 103,209 patients.

OBJECTIVE: To examine time trends in the use of NSAIDs and opioids for patients with osteoarthritis undergoing total hip arthroplasty (THA) during 1996-2018. METHOD: Using Danish population-based medical databases, we identified 103,209 THA patients. Prevalence rates of NSAID and opioid use among preoperative users and non-users were calculated in four quarters (Q1-Q4) after THA by calendar periods (1996-2000, 2001-2006, 2007-2012 and 2013-2018). Prevalence rate ratios (PRR) were adjusted for age and gender. RESULTS: Among preoperative NSAID users and non-users, NSAID use in Q1 increased from 32.6% in 1996-2000 to 48.0% in 2013-2018 (PRR = 1.49, 95% CI: 1.42-1.55) and from 12.9% to 32.0% (PRR = 2.49 (2.32-2.67)), respectively. Among preoperative opioid users and non-users, opioid use in Q1 increased from 42.7% in 1996-2000 to 76.9% in 2013-2018 (PRR = 1.81 (1.73-1.89)) and from 15.2% to 58.2% (PRR = 3.85 (3.65-4.05)), respectively. NSAID use in Q4 decreased from 24.5% in 1996-2000 to 21.4% in 2013-2018 (PRR = 0.88 (0.83-0.93)) and from 6.9% to 5.6% (PRR = 0.81 (0.73-0.91)) in preoperative NSAIDs users and non-users, respectively. Opioid use in Q4 increased from 26.6% in 1996-2000 to 28.6% (PRR = 1.08 (1.02-1.15)) in 2013-2018 and from 4.1% to 5.0% (PRR = 1.25 (1.11-1.40)) in preoperative opioid users and non-users, respectively. CONCLUSION: We observed up to a 4-fold increase in NSAID and opioid use in Q1 during 1996-2018, while usage in Q4 did not change substantially. However, 5-6% of the preoperative non-users of NSAIDs and opioids were users in Q4, which might relate to inaccurate indication for or timing of THA and the post-surgical phasing out of analgesics use.

Male cellular telephone exposure, fecundability, and semen quality: results from two preconception cohort studies.

STUDY QUESTION: To what extent is exposure to cellular telephones associated with male fertility? SUMMARY ANSWER: Overall, we found little association between carrying a cell phone in the front pants pocket and male fertility, although among leaner men (BMI <25 kg/m2), carrying a cell phone in the front pants pocket was associated with lower fecundability. WHAT IS KNOWN ALREADY: Some studies have indicated that cell phone use is associated with poor semen quality, but the results are conflicting. STUDY DESIGN, SIZE, DURATION: Two prospective preconception cohort studies were conducted with men in Denmark (n = 751) and in North America (n = 2349), enrolled and followed via the internet from 2012 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: On the baseline questionnaire, males reported their hours/day of carrying a cell phone in different body locations. We ascertained time to pregnancy via bi-monthly follow-up questionnaires completed by the female partner for up to 12 months or until reported conception. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for the association between male cell phone habits and fecundability, focusing on front pants pocket exposure, within each cohort separately and pooling across the cohorts using a fixed-effect meta-analysis. In a subset of participants, we examined selected semen parameters (semen volume, sperm concentration and sperm motility) using a home-based semen testing kit. MAIN RESULTS AND THE ROLE OF CHANCE: There was little overall association between carrying a cell phone in a front pants pocket and fecundability: the FR for any front pants pocket exposure versus none was 0.94 (95% CI: 0.0.83-1.05). We observed an inverse association between any front pants pocket exposure and fecundability among men whose BMI was <25 kg/m2 (FR = 0.72, 95% CI: 0.59-0.88) but little association among men whose BMI was ≥25 kg/m2 (FR = 1.05, 95% CI: 0.90-1.22). There were few consistent associations between cell phone exposure and semen volume, sperm concentration, or sperm motility. LIMITATIONS, REASONS FOR CAUTION: Exposure to radiofrequency radiation from cell phones is subject to considerable non-differential misclassification, which would tend to attenuate the estimates for dichotomous comparisons and extreme exposure categories (e.g. exposure 8 vs. 0 h/day). Residual confounding by occupation or other unknown or poorly measured factors may also have affected the results. WIDER IMPLICATIONS OF THE FINDINGS: Overall, there was little association between carrying one's phone in the front pants pocket and fecundability. There was a moderate inverse association between front pants pocket cell phone exposure and fecundability among men with BMI <25 kg/m2, but not among men with BMI ≥25 kg/m2. Although several previous studies have indicated associations between cell phone exposure and lower sperm motility, we found few consistent associations with any semen quality parameters. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Institutes of Health, grant number R03HD090315. In the last 3 years, PRESTO has received in-kind donations from Sandstone Diagnostics (for semen kits), Swiss Precision Diagnostics (home pregnancy tests), Kindara.com (fertility app), and FertilityFriend.com (fertility app). Dr. L.A.W. is a fibroid consultant for AbbVie, Inc. Dr. H.T.S. reports that the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. Dr. M.L.E. is an advisor to Sandstone Diagnostics, Ro, Dadi, Hannah, and Underdog. Dr. G.J.S. holds ownership in Sandstone Diagnostics Inc., developers of the Trak Male Fertility Testing System. In addition, Dr. G.J.S. has a patent pending related to Trak Male Fertility Testing System issued. TRIAL REGISTRATION NUMBER: N/A.

Perceived psychological stress and risk of herpes zoster: a nationwide population-based cohort study.

BACKGROUND: Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. OBJECTIVES: To examine the association between perceived psychological stress and risk of HZ. METHODS: In a linked registry-based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen's Perceived Stress Scale (PSS) score (range 0-40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. RESULTS: The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person-years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86-1·16], 1·08 (95% CI 0·92-1·26), 1·05 (95% CI 0·90-1·23) and 1·14 (95% CI 0·97-1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores < 20 were not associated with increased HR of HZ, but thereafter the HR increased linearly from 1·10 (95% CI 0·85-1·41) to 2·22 (95% CI 1·32-3·75). CONCLUSIONS: Our study indicated that high levels of psychological stress are associated with increased risk of HZ.

Hospital-diagnosed overweight and obesity related to cancer risk: a 40-year Danish cohort study.

BACKGROUND: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. OBJECTIVES: To examine the overall cancer incidence and specific site-related cancer incidences among patients with overweight and obesity, compared to the general Danish population. METHODS: For this 40-year (1977-2016), nationwide, Danish cohort study, we reviewed medical databases to identify individuals with hospital-based overweight and obesity diagnoses. We computed age- and gender-standardized incidence ratios (SIRs) for subsequent cancer compared to the general population. RESULTS: We observed 20 706 cancers among 313 321 patients diagnosed with overweight and obesity (median age 43 years; median follow-up 6.7 years, range 1-40 years) compared to the 18 480 cancers expected; thus, the SIR was 1.12 [95% confidence interval (95% CI): 1.11-1.14]. The SIR associated with overweight and obesity was increased with concomitant comorbidities, like type 2 diabetes (SIR: 1.18; 95% CI: 1.13-1.23) and alcoholism-related diseases (SIR: 1.62; 95% CI: 1.45-1.82). The SIR was 1.31 (95% CI: 1.28-1.34) for cancers previously identified as obesity-related, including pancreatic (SIR: 1.38; 95% CI; 1.27-1.49) and postmenopausal breast cancer (SIR: 1.14; 95% CI: 1.09-1.19). Obesity/overweight status also elevated the SIRs for haematological (SIR: 1.24; 95% CI: 1.18-1.29) and neurological cancers (SIR: 1.19; 95% CI: 1.11-1.27]. In contrast, SIRs were 1.01 (95% CI: 0.97-1.05) for immune-related cancers, 0.88 (95% CI: 0.82-0.95) for malignant melanoma, and 0.88 (95% CI: 0.85-0.92) for hormone-related cancers, other than postmenopausal breast cancer. CONCLUSION: In this large cohort study, overweight and obesity was associated with increased risk of several common cancers.

Male alcohol consumption and fecundability.

STUDY QUESTION: Does male alcohol consumption affect fecundability? SUMMARY ANSWER: In data pooled across Danish and North American preconception cohort studies, we found little evidence of an association between male alcohol consumption and reduced fecundability. WHAT IS KNOWN ALREADY: Experimental and clinical studies have shown that alcohol affects male reproductive physiology, mainly by altering male reproductive hormones and spermatogenesis. However, few epidemiologic studies have examined the association between alcohol consumption and male fertility. STUDY DESIGN, SIZE, DURATION: Data were collected from two ongoing prospective preconception cohort studies: the Danish 'SnartForaeldre' (SF) study (662 couples) and the North American 'Pregnancy Study Online' (PRESTO) (2017 couples). Participants included in the current analysis were enrolled from August 2011 through June 2019 (SF) and from June 2013 through June 2019 (PRESTO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible men were aged ≥18 years in SF and ≥21 years in PRESTO, in a stable relationship with a female partner and not using contraception or receiving fertility treatment. In both cohorts, alcohol consumption/serving size was self-reported as number of beers (330 mL/12 oz.), glasses of white or red wine (120 mL/4 oz. each), dessert wine (50 mL/2 oz.) and spirits (20 mL/1.5 oz.). Overall alcohol consumption was categorized as none, 1-5, 6-13 and ≥14 standard servings per week. Total menstrual cycles at risk were calculated using data from female partners' follow-up questionnaires, which were completed every 8 weeks until self-reported pregnancy or 12 menstrual cycles, whichever came first. Analyses were restricted to couples that had been trying to conceive for ≤6 cycles at study entry. Proportional probability regression models were used to compute fecundability ratios (FRs) and 95% confidence interval (CIs). We adjusted for male and female age, female partner's alcohol consumption, intercourse frequency, previous history of fathering a child, race/ethnicity, education, BMI, smoking and consumption of sugar-sweetened beverages and caffeine. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative proportion of couples who conceived during 12 cycles of follow-up were 1727 (64.5%). The median (interquartile range) of total male alcohol consumption was 4.5 (2.0-7.8) and 4.1 (1.0-8.6) standard servings per week in the SF and PRESTO cohorts, respectively. In pooled analyses, adjusted FRs for male alcohol consumption of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 1.02 (95% CI: 0.90-1.17), 1.10 (95% CI: 0.96-1.27) and 0.98 (95% CI: 0.81-1.18), respectively. For SF, adjusted FRs of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 0.97 (95% CI: 0.73-1.28), 0.81 (95% CI: 0.60-1.10) and 0.82 (95% CI: 0.51-1.30), respectively. For PRESTO, adjusted FRs of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 1.02 (95% CI: 0.88-1.18), 1.20 (95% CI: 1.03-1.40) and 1.03 (95% CI: 0.84-1.26), respectively. LIMITATIONS, REASONS FOR CAUTION: Male alcohol consumption was ascertained at baseline only, and we did not distinguish between regular and binge drinking. In addition, we had insufficient numbers to study the effects of specific types of alcoholic beverages. As always, residual confounding by unmeasured factors, such as dietary factors and mental health, cannot be ruled out. Comorbidities thought to play a role in the reproductive setting (i.e. cancer, metabolic syndrome) were not considered in this study; however, the prevalence of cancer and diabetes was low in this age group. Findings for the highest categories of alcohol consumption (6-13 and ≥14 servings/week) were not consistent across the two cohorts. WIDER IMPLICATIONS OF THE FINDINGS: Despite little evidence of an association between male alcohol consumption and reduced fecundability in the pooled analysis, data from the Danish cohort might indicate a weak association between reduced fecundability and consumption of six or more servings per week. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Institutes of Health (R01-HD060680, R01-HD086742, R21-HD050264, R21-HD072326, R03-HD090315), the Novo Nordisk Foundation, Oticon Fonden, Politimester J.P.N. Colind og hustru Asmine Colinds mindelegat and Erna og Peter Houtveds studielegat. PRESTO receives in-kind donations from FertilityFriend.com, Kindara.com, Swiss Precision Diagnostics and Sandstone Diagnostics for the collection of data pertaining to fertility. Dr Wise serves as a consultant on uterine leiomyomata for AbbVie.com. All other authors declare no conflict of interest.

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

Increased maternal new-onset psychiatric disorders after delivering a child with a major anomaly: a cohort study.

BACKGROUND: The birth of a child with a major congenital anomaly may create chronic caregiving stress for mothers, yet little is known about their psychiatric outcomes. AIMS: To evaluate the association of the birth of a child with a major congenital anomaly with subsequent maternal psychiatric risk. METHODS: This Danish nationwide cohort study included mothers who gave birth to an infant with a major congenital anomaly (n = 19 220) between 1997 and 2015. Comparators were randomly selected mothers, matched on maternal age, year of delivery and parity (n = 195 399). The primary outcome was any new-onset psychiatric diagnosis. Secondary outcomes included specific psychiatric diagnoses, psychiatric in-patient admissions and redeemed psychoactive medicines. Cox models were used to estimate hazard ratios (HRs), adjusted for socioeconomic and medical variables. RESULTS: Mothers of affected infants had an elevated risk for a new-onset psychiatric disorder vs. the comparison group (adjusted HR, 1.16, 95% CI 1.11-1.22). The adjusted HR was particularly elevated during the first postpartum year (1.65, 95% CI 1.42-1.90), but remained high for years, especially among mothers of children with multiorgan anomalies (1.37, 95% CI 1.18-1.57). The risk was also elevated for most specific psychiatric diagnoses, admissions and medicines. CONCLUSIONS: Mothers who give birth to a child with a major congenital anomaly are at increased risk of new-onset psychiatric disorders, especially shortly after birth and for mothers of children with more severe anomalies. Our study highlights the need to screen for mental illness in this high-risk population, as well as to integrate adult mental health services and paediatric care.

The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence.

An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy-related exposures influence foetal growth cell division and organ functioning and may have a long-lasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.

Post-traumatic stress disorder and incident fractures in the Danish population.

Psychological stress may be associated with increased risk of fractures. It is unknown whether post-traumatic stress disorder (PTSD), a marker of chronic severe psychological stress occurring in response to a traumatic event, influences fracture risk. In this nationwide cohort study, persons with PTSD had an increased risk of fractures compared to the general population. INTRODUCTION: We conducted a population-based national cohort study in Denmark to examine the association between PTSD and incident fractures. METHODS: We examined the incidence rate of overall and specific fractures among patients with clinician-diagnosed PTSD (n = 4114), compared with the incidence rate in the general population from 1995 to 2013, using Danish medical registry data. We further examined differences in associations by gender, age, psychiatric and somatic comorbidity, and follow-up time. We calculated absolute risks, standardized incidence ratios (SIRs), and 95% confidence intervals (95% CIs). RESULTS: Risk of any fracture among persons with PTSD was 24% (95% CI 20%, 28%) over the study period. The SIR for any fracture was 1.7 (95% CI 1.6, 1.9). We found little evidence of effect measure modification of the association between PTSD and fractures in our stratified analyses. CONCLUSIONS: Our findings suggest that PTSD is associated with increased fracture risk.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Hyperkalaemia in people with diabetes: occurrence, risk factors and outcomes in a Danish population-based cohort study.

AIMS: To examine the incidence, risk factors and clinical outcomes of hyperkalaemia in people with diabetes in a real-world setting. METHODS: Using Danish health registries, we identified a population-based cohort of people with first-time drug-treated diabetes, in the period 2000-2012. First, the cumulative incidence of hyperkalaemia, defined as first blood test with potassium level >5.0 mmol/l after diabetes treatment initiation, was ascertained. Second, in a case-control analysis, risk factors were compared in people with vs without hyperkalaemia. Third, clinical outcomes were assessed among individuals with hyperkalaemia in a before-after analysis, and among people with and without hyperkalaemia in a matched cohort analysis. RESULTS: Of 68 601 individuals with diabetes (median age 62 years, 47% women), 16% experienced hyperkalaemia (incidence rate 40 per 1000 person-years) during a mean follow-up of 4.1 years. People who developed hyperkalaemia had a higher prevalence of chronic kidney disease [prevalence ratio 1.74 (95% CI 1.68-1.81)], heart failure [prevalence ratio 2.35 (95% CI 2.18-2.54)], use of angiotensin-converting enzyme inhibitors [prevalence ratio 1.24 (95% CI 1.20-1.28)], use of spironolactone [prevalence ratio 2.68 (95% CI 2.48-2.88)] and potassium supplements [prevalence ratio 1.59 (95% CI 1.52-1.67)]. In people with diabetes who developed hyperkalaemia, 31% were acutely hospitalized within 6 months before hyperkalaemia, increasing to 50% 6 months after hyperkalaemia [before-after risk ratio 1.67 (95% CI 1.61-1.72)]. The 6-month mortality rate after hyperkalaemia was 20%. Compared with matched individuals without hyperkalaemia, the hazard ratio for death was 6.47 (95% CI 5.81-7.21). CONCLUSIONS: One in six newly diagnosed people with diabetes experienced a hyperkalaemic event, which was associated with severe clinical outcomes and death.

Lubricant use during intercourse and time to pregnancy: a prospective cohort study.

OBJECTIVE: To assess the extent to which lubricant use during intercourse is associated with time to pregnancy (TTP). DESIGN: Prospective cohort study. SETTING: Denmark and North America. POPULATION: A total of 6467 women aged 18-49 years who were not using contraception or fertility treatment. METHODS: We pooled data from two continuing prospective cohort studies of pregnancy planners in Denmark (2011-2017) and North America (2013-2017). Female participants completed bimonthly questionnaires for 12 months or until they reported pregnancy. After restricting the study to women without a history of infertility who had been trying to conceive for six or fewer cycles at enrollment, 6467 women were retained for analysis. Self-reported lubricant use was categorised as water-based/not pH balanced, water-based/pH balanced 'fertility friendly', silicone-based, oil-based, or a combination of these. We used proportional probability models to calculate fecundability ratios (FRs) and 95% confidence intervals (95% CIs) for the association between lubricant use and fecundability, after adjusting for cohort and sociodemographic and lifestyle factors. MAIN OUTCOME MEASURE: Fecundability. RESULTS: At baseline, 17.5% of participants reported the use of lubricants, most commonly water-based/not pH balanced (11.4%). Compared with non-use of lubricants, FRs were 1.02 (95% CI 0.93-1.11) for water-based/not pH-balanced lubricant use, 1.01 (95% CI 0.86-1.18) for water-based/pH balanced 'fertility friendly' lubricant use, 1.23 (95% CI 0.94-1.61) for oil-based lubricant use, and 1.27 (95% CI 0.93-1.73) for silicone-based lubricant use. Associations between oil-based lubricant use and fecundability were inconsistent across subgroups of study cohort, age, parity, and intercourse frequency. CONCLUSIONS: Lubricant use was not associated with reduced fecundability in the preconception cohorts of pregnancy planners studied. TWEETABLE ABSTRACT: Lubricant use during intercourse was not associated with time to pregnancy in a study of pregnancy planners.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Excess risk of venous thromboembolism in hip fracture patients and the prognostic impact of comorbidity.

Hip fracture patients were at increased excess risk of venous thromboembolism (VTE) up to 1 year following hip fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity. INTRODUCTION: We compared the risk of VTE in hip fracture patients with that in the general population. We also examined whether and to what extent the association between hip fracture and VTE varied by comorbidity level. METHODS: Nationwide cohort study based on Danish health registries, 1995-2015. We identified hip fracture patients (n = 110,563) and sampled a comparison cohort without hip fracture from the general population (n = 552,774). Comorbidity was assessed using the Charlson comorbidity index. We calculated attributable fraction, as the proportion of the VTE rate, among persons exposed to both hip fracture and comorbidity, attributed to exposure interaction. RESULTS: The cumulative incidences of VTE were 0.73% within 30 days and 0.83% within 31-365 days among hip fracture patients, and 0.05 and 0.43% in the general population. Adjusted hazard ratios (HRs) of VTE among hip fracture patients were 17.29 [95% confidence interval (CI) 14.74-20.28] during the first 30 days and 2.13 (95% CI 1.95-2.32) during 31-365 days following hip fracture. The relative risks of VTE were 1.03 (95% CI 0.96-1.11) and 1.11 (95% CI 1.00-1.23) after 1-5 years and 6-10 years. During the first 30 days and 31-365 days, 14%/28% of VTE rates and 5%/4% of VTE rates were attributable to the interaction between hip fracture and severe/very severe comorbidity, respectively. Mortality risks within 30 days of VTE were 29.4% in hip fracture and 11.0% in general population cohorts. CONCLUSIONS: Hip fracture patients were at increased excess risk of VTE up to 1 year following their fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity.

Impact of body mass index on risk of acute kidney injury and mortality in elderly patients undergoing hip fracture surgery.

The literature is limited regarding risk factors for acute kidney injury (AKI) and mortality in hip fracture patients, although AKI is common in these patients. While obese patients were at increased risk of AKI, underweight patients with and without AKI had elevated mortality for up to 1 year after hip fracture surgery, compared with normal-weight patients. INTRODUCTION: This study aimed to examine risk of postoperative AKI and subsequent mortality, by body mass index (BMI) level, in hip fracture surgery patients aged 65 and over. METHODS: A regional cohort study using medical databases was used. We included all patients who underwent surgery to repair a hip fracture during the years 2005-2011 (n = 13,529) at hospitals in Northern Denmark. We calculated cumulative risk of AKI by BMI level during 5 days postsurgery and subsequent short-term (6-30 days postsurgery) and long-term (31-365 days post-surgery) mortality. We calculated crude and adjusted hazard ratios (aHRs) for AKI and death with 95% confidence intervals (CIs), comparing underweight, overweight, and obese patients with normal-weight patients. RESULTS: Risks of AKI within five postoperative days were 11.9, 10.1, 12.5, and 17.9% for normal-weight, underweight, overweight, and obese patients, respectively. Among those who developed AKI, short-term mortality was 14.1% for normal-weight patients compared to 23.1% for underweight (aHR 1.7 (95% CI 1.2-2.4)), 10.7% for overweight (aHR 0.9 (95% CI 0.6-1.1)), and 15.2% for obese (aHR 0.9 (95% CI 0.6-1.4)) patients. Long-term mortality was 24.5% for normal-weight, 43.8% for underweight (aHR 1.6 (95% CI 1.0-2.6)), 20.5% for overweight (aHR 0.8 (95% CI 0.6-1.2)), and 21.4% for obese (aHR 1.1 (95% CI 0.7-1.8) AKI patients. Similar associations between BMI and mortality were observed among patients without postoperative AKI, although the absolute mortality risk estimates by BMI were considerably lower in patients without than in those with AKI. CONCLUSIONS: Obese patients were at increased risk of AKI compared with normal-weight patients. Among patients with and without postoperative AKI, overweight and obesity were not associated with mortality. Compared to normal-weight patients, underweight patients had elevated mortality for up to 1 year after hip fracture surgery irrespective of the presence of AKI. The absolute mortality risks were higher in all BMI groups with the presence of AKI.

Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK.

AIMS: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function. METHODS: Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels. RESULTS: In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis. CONCLUSIONS: Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.

Preadmission use of selective serotonin reuptake inhibitors and short-term mortality in diabetic patients hospitalized due to stroke.

BACKGROUND: Patients with diabetes have an increased risk of stroke with a poor prognosis. Moreover, diabetic patients are at increased risk of depression and therefore likely to use selective serotonin reuptake inhibitors (SSRIs). We examined whether preadmission SSRI use was associated with increased mortality in diabetic patients hospitalized due to stroke. METHODS: Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetic patients in Denmark between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors. RESULTS: Amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischaemic stroke, 41.8% for intracerebral haemorrhage and 27.3% for subarachnoid haemorrhage). Amongst current SSRI users, 30-day stroke mortality was 23.3% (17.1% for ischaemic stroke, 50.7% for intracerebral haemorrhage and 28.6% for subarachnoid haemorrhage). Current SSRI use was associated with increased 30-day stroke mortality compared with nonuse [adjusted MRR 1.3, 95% confidence interval (CI) 1.1-1.5], with the highest risk observed amongst new users (MRR 1.5, 95% CI 1.2-1.8). Overall stroke mortality was driven by increased mortality due to ischaemic stroke, with adjusted MRRs of 1.3 (95% CI 1.1-1.7) for current users and 1.7 (95% CI 1.2-2.4) for new users. Propensity score-matched results were similar and robust across subgroups. CONCLUSION: In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischaemic stroke, compared with nonuse.