Male infertility and risk of cardiometabolic conditions: a population-based cohort study

Association between male infertility and male-specific malignancies: systematic review and meta-analysis of population-based retrospective cohort studies

After a new look at the history of the Marchioness del Valles conspiracy as part of the tensions that queen Margaret and her ladies caused at the Court of Philip III, the essay stresses the doubts, questions poned and interest that these circumstances aroused in the Spanish political and popular media in the early 17th century. Special attention is given to the information media which prepared and passed on these facts: rumours and oral narrations, announcements, historical and literary texts, relations of ambassadors, all in the framework of a budding public opinion structure.

Existing research suggests the impact of infertility on the risk of neurodevelopmental disorders in children, however, studies to date have failed to separate the impact of male and female infertility, often blurring the lines with proxies that encompass all forms of infertility. Moreover, while both health conditions co-occurring with infertility and genetic factors operating upstream have been suggested to influence the association between infertility and child outcomes, their roles and potential impact on observed associations remain unclear. The objectives of this study are to investigate the relationship between female infertility and autism in the child, differentiating it from the effects of male and the couple infertility; consider the role of various maternal and birth factors in the association; and examine the effects of shared familial confounders on the association. Danish population-based cohort study, including all singleton live births in Denmark 1998-2015, their parents and parents' siblings. The cohort was followed up until December 31, 2016. The exposure was a history of female infertility in the mother and the mother's sister. We examined four definitions of female infertility based on the ICD-10 codes derived from the Danish National Patient Register - any female infertility; specified female infertility; female exclusive infertility; and female or male infertility. The outcome was diagnosis of autism spectrum disorder (ASD) in the Danish Psychiatric Central Research Register or the national patient register. A multivariable Cox regression model was used to estimate the associations between female infertility and autism, accounting for child's sex, year of birth, maternal age, education level, chronic comorbidities, and pregnancy and birth complications. The effects of shared familial factors on the association were analyzed using exposure information from the child's maternal aunt. The cohort included 1,131,899 mother-child pairs, among which 18,374 children with ASD diagnosis. History of female infertility in the mother (all definitions) was significantly associated with autism in the child, with the association remaining robust after adjustment for covariates (HRadj=1.14 (95% CI, 1.03-1.26) for specified infertility). The diagnosis of infertility in a child's maternal aunt was also significantly linked to the child's autism risk, even after adjustment for maternal infertility (HRadj=1.10 (95% CI, 1.00-1.20). in This population-based birth cohort study, we found a slightly higher risk of autism in children born to mothers with a history of infertility, with the association remaining consistent across various definitions of female infertility and robust to adjustments for demographic, child, and maternal factors. The study suggests for the first time that shared familial factors, possibly both genetic and non-genetic, could be influencing both female infertility and the risk of autism in children, indicating a need for further investigation into these familial effects.

Study question Is male infertility independently associated with an increased risk of incident ischemic and non-ischemic heart disease, diabetes, and cerebrovascular disease? Summary answer Infertile men have a slightly increased risk of incident heart disease, diabetes and hypertension after controlling for measured confounders, however important confounders remain inadequately measured. What is known already Cohort studies suggest infertile men have an increased risk of incident cardiometabolic diseases, including diabetes, hypertension, heart disease and cerebrovascular disease, though findings are mixed. The reasons for this association are unclear, but cardiometabolic conditions and male infertility share a wide range of common etiological factors including age, chronic conditions such as obesity and obstructive sleep apnoea, cancers and their treatments, environmental exposures such as pollution and pesticides, lifestyle factors such as smoking and diet, autoimmune conditions such as lupus and Hashimoto’s thyroiditis, as well as congenital conditions such as cystic fibrosis and muscular dystrophy. Study design, size, duration A population-based cohort study included 446,100 men who conceived a child between January 2009 and September 2016 in New South Wales (NSW), Australia. Exclusion criteria included diagnosis of infertility before 2009, being under the age of 14 at the time of conception or a diagnosis of the outcome of interest in the 6.5 years before their index date. Participants were followed up for five years up until the latest date of September 2021. Participants/materials, setting, methods The study was conducted in NSW, Australia. Infertility status was determined by a diagnosis of male infertility in the Australian and New Zealand Assisted Reproduction Database, record of fertility-related procedures or dispensation of gonadotrophin medications. Outcomes assessed were incident ischemic heart disease, non-ischemic heart disease, all heart disease, diabetes, and cerebrovascular disease. Confounders were controlled for using inverse probability of treatment weighting and g-computation. Adjusted marginal risk ratios (aRR) were estimated using robust Poisson regression. Main results and the role of chance The number of events and 5-year crude incidence rates (CIR) for the outcomes were: hypertension (events: 17,445, fertile: 39.47 per 1,000 population, infertile: 64.42 per 1,000 population), all heart disease (events: 15,582, fertile: 35.21 per 1,000 population, infertile: 56.12 per 1,000 population), ischemic heart disease (events: 12,653 fertile: 28.45 per 1,000 population, infertile: 44.69 per 1,000 population), non-ischemic heart disease (events: 5,190, fertile: 11.57 per 1,000 population, infertile: 19.26 per 1,000 population) and cerebrovascular disease (events: 420, fertile: 1.15 per 1,000 population, infertile: 1.66 per 1,000 population). Compared with fertile men, infertile men demonstrated increased risk of incident disease for: hypertension aRR = 1.22 (95% CI 1.12–1.33, P < 0.01); all heart disease aRR = 1.21 (95% CI 1.11–1.32, P < 0.01); non-ischemic heart disease aRR = 1.24 (95% CI 1.06–1.44, P = 0.01) ischemic heart disease aRR = 1.16 (95% CI 1.05–1.28, P < 0.01) and diabetes aRR = 1.26 (95% CI 1.10, 1.44). There was no significant difference in incidence of cerebrovascular disease aRR = 1.01 (95% CI 0.55–1.84, P = 0.71). These results remained consistent in sensitivity analyses of men with a ten year follow up period. Limitations, reasons for caution The cohort includes men who fathered a child, so men who did not seek to or were unable to have a child and men with poor access to the reproductive healthcare may not be included. This may generate selection bias. We were unable to adequately control for several identified confounders. Wider implications of the findings Our study is the largest on this topic, with extensive control for confounders. Our findings align with published research, indicating infertile men have a slightly higher risk of incident diabetes, hypertension and heart disease. Understanding these associations may support earlier detection and proactive management of cardiometabolic conditions in infertile men. Trial registration number No

Frailty Screening in Critical Care at Scale

Recent research indicates long-term survival benefits of minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) for patients with esophageal and gastroesophageal junction (GEJ) cancers, but there is a need for more population-based studies. We conducted a prospective population-based nationwide cohort study including all patients in Sweden diagnosed with esophageal or junctional cancer who underwent a transthoracic esophagectomy with intrathoracic anastomosis. Data were collected from the Swedish National Register for Esophageal and Gastric Cancer in 2006-2019. Patients were grouped into OE and MIE including hybrid MIE (HMIE) and totally MIE (TMIE). Overall survival and short-term postoperative outcomes were compared using Cox regression and logistic regression models, respectively. All models were adjusted for age, sex, American Society of Anesthesiologists (ASA) score, clinical T and N stage, neoadjuvant therapy, year of surgery, and hospital volume. Among 1404 patients, 998 (71.1%) underwent OE and 406 (28.9%) underwent MIE. Compared with OE, overall survival was better following MIE (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.55-0.94), TMIE (HR 0.67, 95% CI 0.47-0.94), and possibly also after HMIE (HR 0.76, 95% CI 0.56-1.02). MIE was associated with shorter operation time, less intraoperative bleeding, higher number of resected lymph nodes, and shorter hospital stay compared with OE. MIE was also associated with fewer overall complications (odds ratio [OR] 0.70, 95% CI 0.47-1.03) as well as non-surgical complications (OR 0.64, 95% CI 0.40-1.00). MIE seems to offer better survival and similar or improved short-term postoperative outcomes in esophageal and GEJ cancers compared with OE in this unselected population-based cohort.

BackgroundHeadache is the most frequent symptom following head injury, but long-term follow-up of headache after head injury entails methodological challenges. In a population-based cohort study, we explored whether subjects hospitalized due to a head injury more often developed a new headache or experienced exacerbation of previously reported headache compared to the surrounding population.MethodsThis population-based historical cohort study included headache data from two large epidemiological surveys performed with an 11-year interval. This was linked with data from hospital records on exposure to head injury occurring between the health surveys. Participants in the surveys who had not been hospitalized because of a head injury comprised the control group. The head injuries were classified according to the Head Injury Severity Scale (HISS). Multinomial logistic regression was performed to investigate the association between head injury and new headache or exacerbation of pre-existing headache in a population with known pre-injury headache status, controlling for potential confounders.ResultsThe exposed group consisted of 294 individuals and the control group of 25,662 individuals. In multivariate analyses, adjusting for age, sex, anxiety, depression, education level, smoking and alcohol use, mild head injury increased the risk of new onset headache suffering (OR 1.74, 95% CI 1.05–2.87), stable headache suffering (OR 1.70, 95% CI 1.15–2.50) and exacerbation of previously reported headache (OR 1.93, 95% CI 1.24–3.02). The reference category was participants without headache in both surveys.ConclusionIndividuals hospitalized due to a head injury were more likely to have new onset and worsening of pre-existing headache and persistent headache, compared to the surrounding general population. The results support the entity of the ICHD-3 beta diagnosis “persistent headache attributed to traumatic injury to the head”.

Most women diagnosed with breast cancer are younger than 65 years of age. Population-based studies on cancer therapy-related cardiotoxicity have focused on older women. We sought to determine the risk of cardiotoxicity with breast cancer therapy in women with an age distribution representative of routine clinical practice. This was a population-based retrospective cohort study including 14 regional cancer centers in Ontario, Canada. Adult women receiving chemotherapy for stage I to III breast cancer between 2007 and 2012 were included. Cancer treatment was categorized as follows: anthracycline-based chemotherapy without trastuzumab, trastuzumab with nonanthracycline chemotherapy, anthracyclines followed by trastuzumab (sequential therapy), and chemotherapy without anthracycline/trastuzumab (other chemotherapy). The primary outcome was a composite of hospitalization or emergency room visit for congestive heart failure (CHF), outpatient diagnosis of CHF, or cardiovascular death. A sensitivity analysis limited the outcomes to hospital-based CHF events. Cause-specific hazard models were used accounting for the competing risk of noncardiovascular death. Of 18,540 women included (median age, 54 years; interquartile range, 47 to 63 years), 79% were younger than age 65 years. The cumulative incidence of the primary outcome was 3.08% (95% CI, 2.81% to 3.36%) by 3 years of follow-up, whereas in an age-matched sample of Ontario women (n = 92,700) without breast cancer, it was 0.96% (95% CI, 0.89% to 1.04%). Compared with those receiving other chemotherapy, patients receiving trastuzumab with nonanthracycline chemotherapy and sequential therapy were at a higher risk of cardiotoxicity (hazard ratio, 1.76 [95% CI, 1.19 to 2.60] and 3.96 [95% CI, 3.01 to 5.22], respectively). Hospital-based CHF events were only increased with sequential therapy (hazard ratio, 1.86; 95% CI, 1.07 to 3.22). In women with breast cancer and an age distribution representative of routine clinical practice, trastuzumab-based regimens, including those without anthracyclines, were associated with an increased risk of cardiotoxicity. Sequential therapy increased the risk of hospital-based CHF events.

BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization.MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes.ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care.ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.

Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association. In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.

We aimed to compare the oncological outcomes between Japanese women with uterine-confined and node-negative cervical cancer who underwent open surgery and those who underwent minimally invasive surgery (MIS). A population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry that ranged from 2011 to 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (group one, 2011–2014; group two, 2015–2018). The oncologic outcomes were compared between the MIS and open groups. When the MIS group (n = 225) was compared with open group (n = 2054), overall, there was no significant between-group difference in terms of overall survival. Based on Kaplan–Meier estimates, the probability of overall survival at four years was 99.5% in the MIS group and 97.2% in the open group (p = 0.1110). When examined according to the year of diagnosis, there were no significant between-group differences in the overall survival in both groups one and two. In this population-based cohort study, MIS did not compromise survival outcomes when compared with conventional open surgery in Japanese patients with uterine-confined and node-negative (FIGO 2018 stage I) cervical cancer.

BackgroundOnly a few population-based cohort studies have investigated the impact of atrial fibrillation (AF) on stroke in Japan.MethodsA total of 10 929 participants (4147 men and 6782 women) were included in this population-based prospective cohort study. Baseline data, including electrocardiograms (ECGs) to ascertain AF status, were obtained from April 1992 through July 1995 in 12 areas in Japan. Cox proportional hazards models were used to analyze the association of AF with stroke.ResultsA total of 54 participants had AF (0.49%). The mean follow-up period was 10.7 years, during which 405 strokes were identified; 12 of these occurred in participants with AF. The crude incidence of stroke in participants with and without AF was 14.9 and 4.5 per 1000 person-years in men, respectively, and 39.3 and 2.7 per 1000 person-years in women. After adjusting for geographical area, sex, age, smoking status, drinking status, obesity, hypertension, dyslipidemia, and diabetes mellitus, the hazard ratios (95% confidence interval) of AF in all participants and in male and female participants were 4.11 (2.28–7.41), 2.12 (0.77–5.84), and 10.6 (5.01–22.4), respectively. The population attributable fraction (PAF) of stroke caused by AF was 2.2%; the PAFs were 1.0% and 3.6% in men and women, respectively.ConclusionsThe present Japanese population-based prospective cohort study showed that AF is a major risk factor for stroke, especially in women.

We investigated the association between body mass index (BMI) and obesity-related cancer risk among individuals with/without incident hypertension (HTN), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) and the joint associations of overweight/obesity (BMI ≥25 kg/m2 ) and each cardiometabolic condition with obesity-related cancer risk METHODS: We conducted a population-based cohort (n = 1,774,904 individuals aged ≥40 years and free of cancer and cardiometabolic conditions at baseline) study between 2010 and 2018 with electronic health records from Spain. Our main outcome measures were hazard ratios (HRs) for incident obesity-related cancers and relative excess risk due to interaction (RERI). A total of 38,082 individuals developed obesity-related cancers after a median of 8 years of follow-up. The positive association between BMI and obesity-related cancer risk was similar among individuals free of cardiometabolic conditions (hazard ratio, HR per 5 kg/m2 : 1.08, 95% confidence interval, CI: 1.06-1.10) and with incident HTN (1.05, 1.01-1.08). The association among those with incident T2DM was null (0.98, 0.93-1.03). There was a positive additive interaction between overweight/obesity and CVD (relative excess risk due to interaction [RERI]: 0.19 [0.09, 0.30]), meaning that the combined association was 0.19 more than the sum of the individual associations. In contrast, a RERI of -0.24 (-0.28, -0.20) was observed for the combined association between overweight/obesity and T2DM. Public health strategies to reduce overweight can help prevent cancer cases among the general population and individuals with incident HTN/CVD. Further, weight-loss interventions seem to lead to a greater cancer risk reduction among individuals with CVD.

PurposeAlthough several previous studies have investigated the relationship between tamsulosin use and surgical complications of cataract surgery, no population-based cohort study has been conducted for the Asian population. We aimed to investigate the relationship between tamsulosin use and surgical complications of cataract surgery in the Korean elderly population.MethodsThis nationwide population-based retrospective cohort study included elderly patients (≥60 years) who had undergone cataract surgery in the period from 2003 to 2015. Baseline characteristics were age, sex, income, residence, and systemic, and ocular comorbidities (glaucoma, myopia, eye trauma, diabetes mellitus with ophthalmic manifestations, severe cataract, age-related macular degeneration). The exposure of interest was tamsulosin use within 1 year before cataract surgery. Logistic regression model was used to evaluate the relationship of tamsulosin use with surgical complications of cataract surgery.ResultsThe rate of surgical complications of cataract surgery was 0.88% (375/42,539) in the non-tamsulosin group and 0.83% (71/8,510) in the tamsulosin group. The groups showed no significant difference in the risk of surgical complications of cataract surgery in the unadjusted model [odds ratio (OR) = 0.946; 95% confidence interval (CI):0.733–1.220; P = 0.669]. Additionally, tamsulosin use was not significantly associated with surgical complications of cataract surgery in the fully adjusted model accounting for age, income, residence, and systemic and ocular comorbidities (OR = 0.997; 95% CI: 0.749–1.325; P = 0.981).ConclusionsThe rate or risk of surgical complications of cataract surgery does not change with tamsulosin use. We suggest that better surgical techniques and surgeons' cognizance of the patient's tamsulosin use could improve surgical outcomes, without increasing surgical complications.

Background:Early hospital readmissions (EHRs) occur commonly in kidney transplant recipients. Conflicting evidence exists regarding risk factors and outcomes of EHRs.Objective:To determine risk factors and outcomes associated with EHRs (ie, hospitalization within 30 days of discharge from transplant hospitalization) in kidney transplant recipients.Design:Population-based cohort study using linked, administrative health care databases.Setting:Ontario, Canada.Patients:We included 5437 kidney transplant recipients from 2002 to 2015.Measurements:Risk factors and outcomes associated with EHRs. We assessed donor, recipient, and transplant risk factors. We also assessed the following outcomes: total graft failure, death-censored graft failure, death with a functioning graft, mortality, and late hospital readmission.Methods:We used multivariable logistic regression to examine the association of each risk factor and the odds of EHR. To examine the relationship between EHR status (yes vs no [reference]) and the outcomes associated with EHR (eg, total graft failure), we used a multivariable Cox proportional hazards model.Results:In all, 1128 kidney transplant recipients (20.7%) experienced an EHR. We found the following risk factors were associated with an increased risk of EHR: older recipient age, lower income quintile, several comorbidities, longer hospitalization for initial kidney transplant, and older donor age. After adjusting for clinical characteristics, compared to recipients without an EHR, recipients with an EHR had an increased risk of total graft failure (adjusted hazard ratio [aHR]: 1.46, 95% CI: 1.29, 1.65), death-censored graft failure (aHR: 1.62, 95% CI: 1.36, 1.94), death with graft function (aHR: 1.34, 95% CI: 1.13, 1.59), mortality (aHR: 1.41, 95% CI: 1.22, 1.63), and late hospital readmission in the first 0.5 years of follow-up (eg, 0 to <0.25 years: aHR: 2.11, 95% CI: 1.85, 2.40).Limitations:We were not able to identify which readmissions could have been preventable and there is a potential for residual confounding.Conclusions:Results can be used to identify kidney transplant recipients at risk of EHR and emphasize the need for interventions to reduce the risk of EHRs.Trial registration:This is not applicable as this is a population-based cohort study and not a clinical trial.