Sex Differences In Patterns Research Articles

Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.

Sex differences in patterns of white matter neuroplasticity after balance training in young adults.

In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task. 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training. Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance). The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial.

Older women experience more adverse drug reactions (ADRs) than older men. However, the underlying basis for this sex difference is unclear. Sex (biological status) and/or gender (sociocultural constructs) influences on patterns of inappropriate prescribing in multimorbid older adults may be one reason for this ADR sex difference. In this secondary analysis, we examined whether incident ADR sex differences could be related to concurrent sex differences in potentially inappropriate prescribing. A retrospective secondary analysis of sex differences in the prevalence of potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs), and ADRs among the 1537 participants (47.2% female, median [IQR] age 78 [72-84] years) was undertaken in the SENATOR clinical trial database, conducted in six large European medical centers. We looked specifically for male/female differences relating to PIMs and PPOs (defined by STOPP/START version 2 criteria) identified within 48 h of acute hospitalization. We also assessed sex differences for ADRs identified at 14 days from admission or discharge, whichever came first. ADRs were assessed by blinded endpoint adjudication panel consensus. During hospitalization, significantly more females experienced ≥1 ADR compared to males (28% and 21%, respectively; odds ratio 1.40, 95% CI 1.10-1.78, p < 0.005). Nine of the 11 STOPP-criteria PIMs showing a significant sex difference occurred more often in females. Of the four START-criteria PPOs showing a significant sex difference, all occurred more often in females. Some sex-associated PIMs reflect higher prevalence of related conditions in older women. We conclude that specific STOPP-criteria PIMs and START-criteria PPOs were identified more frequently in older women than older men during acute hospitalization, possibly contributing to higher ADR incidence in older women. Prescribers should appreciate sex differences in exposure to potentially inappropriate prescribing and ADR risk, given the preponderance of older women over older men in most clinical settings.

Grey matter networks in women and men with dementia with Lewy bodies

Sex differences permeate many aspects of dementia with Lewy bodies (DLB), yet sex differences in patterns of neurodegeneration in DLB remain largely unexplored. Here, we test whether grey matter networks differ between sexes in DLB and compare these findings to sex differences in healthy controls. In this cross-sectional study, we analysed clinical and neuroimaging data of patients with DLB and cognitively healthy controls matched for age and sex. Grey matter networks were constructed by pairwise correlations between 58 regional volumes after correction for age, intracranial volume, and centre. Network properties were compared between sexes and diagnostic groups. Additional analyses were conducted on w-scored data to identify DLB-specific sex differences. Data from 119 (68.7 ± 8.4 years) men and 45 women (69.9 ± 9.1 years) with DLB, and 164 healthy controls were included in this study. Networks of men had a lower nodal strength compared to women. In comparison to healthy women, the grey matter networks of healthy men showed a higher global efficiency, modularity, and fewer modules. None of the network measures showed significant sex differences in DLB. Comparing DLB patients with healthy controls revealed global differences in women and more local differences in men. Modular analyses showed a more distinct demarcation between cortical and subcortical regions in men compared with women. While topologies of grey matter networks differed between sexes in healthy controls, those sex differences were diluted in DLB patients. These findings suggest a disease-driven convergence of neurodegenerative patterns in women and men with DLB, which may inform precision medicine in DLB.

Alcohol consumption and dependence risk among male and female Veterans: Trajectories and predictors

BackgroundWith few exceptions, previously conducted research on hazardous drinking among Veterans has employed samples in which the majority of participants identify as male. In addition, past studies have solely focused on alcohol consumption, rather than associated risk for dependence. In this study, we expanded upon the extant literature by investigating sex differences in trajectories and predictors of change in alcohol consumption and dependence risk among post-9/11 Veterans. MethodsA national sample of 1649 Veterans (50.0% female) were recruited in a five-wave longitudinal study that followed Veterans for up to 16 years after deployment. We used growth curve modeling to investigate trajectories of change in alcohol consumption and dependence risk among men and women Veterans. We examined predictors of growth, including demographics, support and resources, psychiatric symptoms, and trauma exposure. ResultsAmong male Veterans, alcohol consumption and dependence risk remained stagnant, which is in contrast to past work using non-Veteran samples. For female Veterans, consumption exhibited initial reductions that decelerated, and dependence risk reduced at a continuous rate. PTSD diagnosis was a significant predictor of individual differences in growth for men. Psychiatric symptoms (i.e., PTSD diagnosis, probable depression diagnosis, suicidal ideation) and psychosocial functioning were significant predictors of decreasing alcohol use for women. ConclusionsResults highlight important sex differences in patterns and predictors of change in alcohol consumption and dependence risk among post-9/11 Veterans. Findings are discussed in relation to screening for hazardous alcohol use and intervention strategies in this at-risk population.

Sex Differences in Psychopathology Following Potentially Traumatic Experiences

Various psychopathology may follow trauma; however, sex differences in these ranging manifestations of posttraumatic psychopathology remain understudied. To investigate sex-specific incidence of posttraumatic psychopathology. This population-based cohort study of Danish national health registries included a cohort of individuals who experienced a potentially traumatic event (PTE) from 1994 to 2016. Individuals were further categorized by presence of any pretrauma psychopathology. A comparison group of individuals who experienced a nontraumatic stressor (nonsuicide death of a first-degree relative) was examined as a reference cohort. At least 1 of 8 PTEs (eg, physical assault, transportation accident) derived through health registry International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, with additional qualifiers to improve classification accuracy. Incidence of 9 categories of ICD-10 psychiatric disorders recorded in registries within 5 years of PTEs. The standardized morbidity ratios (SMRs) for psychopathology outcomes were also calculated to compare individuals experiencing PTEs with those experiencing a nontraumatic stressor. This study included 1 398 026 individuals who had been exposed to trauma (475 280 males [34.0%]; 922 750 females [66.0%]). The group of males who had been exposed to trauma were evenly distributed across age, while most females in the trauma-exposed group were aged 16 to 39 years (592 385 [64.2%]). Males and females were equally distributed across income quartiles and predominantly single. Following PTEs, the most common diagnosis was substance use disorders for males (35 160 [7.4%]) and depressive disorders for females (29 255 [3.2%]); incidence proportions for these and other disorders were higher among males and females with any pretrauma psychopathology. Certain PTEs had elevated onset of various psychiatric disorders and some sex differences emerged. Following physical assault, associations were found with schizophrenia or psychotic disorders for males (SMR, 17.5; 95% CI, 15.9-19.3) and adult personality disorders for females (SMR, 16.3; 95% CI, 14.6-18.3). For noninterpersonal PTEs, males had larger SMRs for substance use, schizophrenia or psychotic disorders, and adult personality disorders (SMR, 43.4; 95% CI, 41.9-45.0), and females had larger SMRs for depressive disorders (SMR, 19.0; 95% CI, 18.6-19.4). Sex differences were also observed, particularly when considering pretrauma psychopathology. For example, among interpersonal PTEs, males were most likely to develop substance use disorders after physical assault, whereas females were more likely to develop various disorders, with stronger associations seen for females without pretrauma psychiatric diagnoses. Among noninterpersonal PTEs, exposure to toxic substance showed robust associations with psychopathology, particularly in those without pretrauma psychopathology, with sex-specific differences across psychiatric categories. Mental disorders after trauma were wide-ranging for males and females, and sex differences in patterns of posttraumatic psychopathology were more pronounced when accounting for pretrauma psychopathology. Findings provide new insights for sex-relevant PTEs and their mental health consequences. It also outlines future directions for advancing understanding of a constellation of posttraumatic psychopathology in males and females.

Differences in hidradenitis suppurativa patterns of cutaneous involvement between sexes: Insights from a cross-sectional study

Hidradenitis suppurativa is a chronic, inflammatory condition of the pilosebaceous unit in which patients manifest multiple, painful cutaneous nodules, abscesses and tunnels. These lesions are described to affect the intertriginous zones, however, the condition exhibits significant phenotypic variability. Such variability is influenced by the patients lifestyle, genetic predisposition and sex. In this cross-sectional study, we investigate sex differences in patterns of hidradenitis suppurativa skin involvement, specifically at site of first involvement and most bothersome cutaneous site of involvement.

Few sex-specific effects of fatigue on muscle synergies in a repetitive pointing task

Previous studies have identified some sex differences in how individual muscles change their activation during repetitive multi-joint arm motion-induced fatigue. However, little is known about how indicators of multi-muscle coordination change with fatigue in males and females. Fifty-six (29 females) asymptomatic young adults performed a repetitive, forward-backward pointing task until scoring 8/10 on a Borg CR10 scale while surface electromyographic activity of upper trapezius, anterior deltoid, biceps brachii, and triceps brachii was recorded. Activation coefficient, synergy structure, and relative weight of each muscle within synergies were calculated using the non-negative matrix factorization method. Two muscle synergies were extracted from the fatiguing task. The synergy structures were mostly preserved after fatigue, while the activation coefficients were altered. A significant Sex × Fatigue interaction effect showed more use of the anterior deltoid in males especially before fatigue in synergy 1 during shoulder stabilization (p = 0.04). As for synergy 2, it was characterized by variations in the relative weight of biceps, which was higher by 16 % in females compared to males (p = 0.04), and increased with fatigue (p = 0.03) during the elbow flexion acceleration phase and the deceleration phase of the backward pointing movement. Findings suggest that both sexes adapted to fatigue similarly, using fixed synergy structures, with alterations in synergy activation patterns and relative weights of individual muscles. Results support previous findings of an important role for the biceps and anterior deltoid in explaining sex differences in patterns of repetitive motion-induced upper limb fatigue.

Connectivity and molecular profiles of Foxp2- and Dbx1-lineage neurons in the accessory olfactory bulb and medial amygdala.

In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA. We show that a majority of AOB neurons that project directly to the MeA are of the Foxp2 lineage. Using single-neuron patch-clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the frequency of excitatory input to MeA Dbx1- and Foxp2-lineage neurons differs between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons, and lineage and sex differences in patterns of connectivity.

Sex differences in patterns of referral and resource utilization in the cardiology clinic: an outpatient analysis.

Women may have different management patterns than men in specialised care. Our aim was to assess potential sex differences in referral, management and outcomes of patients attending outpatient cardiac consultations. Retrospective observational analysis of patients ≥18 years referred for the first time from primary care to a tertiary hospital cardiology clinic in 2017-2018, comparing reasons for referral, decisions and post-visit outcomes by sex.A total of 5,974 patients, 2,452 (41.0%) men aged 59.2 ± 18.6 years and 3,522 (59.0%) women aged 64.5 ± 17.9 years (P < 0.001) were referred for a first cardiology consultation. The age-related referral rates were higher in women. The most common reasons for consultation were palpitations in women (n = 676; 19.2%) and ECG abnormalities in men (n = 570; 23.2%). Delays to cardiology visits and additional tests were similar. During 24 months of follow-up, women had fewer cardiology hospitalisations (204; 5.8% vs. 229; 9.3%; P = 0.003) and lower mortality (65; 1.8% vs. 66; 2.7%; P = 0.028), but those aged <65 years had more emergency department visits (756; 48.5% vs. 560; 39.9%, P < 0.001) than men. There are substantial sex differences in primary care cardiology referral patterns, including causes, rates, decisions and outcomes, which are only partially explained by age differences. Further research is needed to understand the reasons for these differences.

Sex Differences in Coronary Atherosclerotic Phenotype and Healing Pattern on Optical Coherence Tomography Imaging.

Layered plaque, a signature of previous plaque disruption, is a known predictor of rapid plaque progression. Layered plaque can be identified in vivo by optical coherence tomography. Studies have reported differences in plaque burden between women and men, but sex differences in the pattern of layered plaque are unknown. Preintervention optical coherence tomography images of 533 patients with chronic coronary syndromes were analyzed. Detailed plaque characteristics of layered and nonlayered plaques of the target lesion were compared between men and women. The prevalence of layered plaque was similar between men (N=418) and women (N=115; 55% versus 54%; P=0.832). In men, more features of plaque vulnerability were identified in layered plaque than in nonlayered plaque: lipid plaque (87% versus 69%; P<0.001), macrophages (69% versus 56%; P=0.007), microvessels (72% versus 39%; P<0.001), and cholesterol crystals (49% versus 30%; P<0.001). No difference in plaque vulnerability between layered and nonlayered plaques was observed in women. Layered plaque in men had more features consistent with previous plaque rupture than in women: interrupted pattern (74% versus 52%; P<0.001) and a greater layer index (1198 [781-1835] versus 943 [624-1477]; P<0.001). In men, layered plaques exhibit more features of vascular inflammation and vulnerability as well as evidence of previous plaque rupture, compared with nonlayered plaques, whereas in women, no difference was observed between layered and nonlayered plaques. Vascular inflammation (plaque rupture) may be the predominant mechanism of layered plaque in men, whereas a less inflammatory mechanism may play a key role in women. URL: http://www. gov; Unique Identifier: NCT01110538, NCT04523194.

Sex Differences in Patterns of Childhood Traumatic Experiences in Chinese Rural-To-Urban Migrant Children.

Children and adolescents are likely to be exposed to various types of childhood traumatic experiences (CTEs) with gender-specific patterns. Rural-to-urban migrant children have been demonstrated a greater risk of CTE exposure than local children. However, no study has investigated sex differences in the patterns of CTEs and predictive factors among Chinese children. A large-scale questionnaire survey of rural-to-urban migrant children (N = 16,140) was conducted among primary and junior high schools in Beijing. Childhood trauma history, including interpersonal violence, vicarious trauma, accidents and injuries was measured. Demographic variables and social support were also examined. Latent class analysis (LCA) was utilized to examine patterns of childhood trauma, and logistic regression was used to examine predictors. Four classes of CTEs were found among both boys and girls, labeled low trauma exposure, vicarious trauma exposure, domestic violence exposure, and multiple trauma exposure. The possibility of various CTEs in the four CTE patterns was higher among boys than girls. Sex differences also manifested in predictors of childhood trauma patterns. Our findings shed light on sex differences in CTE patterns and predictive factors in Chinese rural-to-urban migrant children, suggesting that trauma history should be considered along with sex, and sex-specific prevention and treatment programs should be developed.

Sex differences in patterns of associative memory-related activation in individuals at risk of Alzheimer's disease

The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how relationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in understanding the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.

Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.

Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.

The Ketogenic Diet Impairs Mitochondrial Function in Hearts of Male and Female Mice

Ketone bodies have been identified as an important fuel source during physiological and pathological stress. During exercise, augmenting ketone body metabolism in the skeletal muscle may enhance exercise performance while targeting ketone body metabolism in cardiac disease may improve cardiac function. These provocative, yet still debated, findings may promote the consumption of the ketogenic diet (KD) as a method to increase ketone body availability. Since the KD is a high‐fat, low carbohydrate diet, this dietary strategy has the potential to have untoward effects on the heart. Therefore, the purpose of this study was to evaluate the effects of short‐term consumption of the KD on cardiac mitochondrial function. A secondary objective was to evaluate potential sex differences in response to the KD. Male (n=9) and female (n=11) mice at four‐months of age were randomly assigned to a standard chow or KD (90% fat, 9% protein, 1% carbohydrates) group for 6 weeks. Body weight (BW) was obtained weekly. Glucose and ketone bodies were measured at the end of the dietary intervention via hand‐held meters. After 6 weeks, mitochondria were isolated from all hearts and respiration was assessed with an oxygen electrode system. During the first week, Male‐KD lost 2.5±1.5% of initial BW compared to an increase of 0.3±1.5% of initial BW for Male‐Chow. By the third week, both Male‐KD and Male‐Chow gained BW at a similar rate until the end of the study. In contrast, Female‐KD mice gained BW throughout the 6 weeks and the relative increased compared to baseline was approximately 1.7‐2.0‐fold greater than Female‐chow. Serum ketone bodies were significantly increased in both Male‐KD and Female‐KD mice compared to chow fed groups (Male‐chow, 0.33±0.05 vs. Male‐KD, 0.66±0.10 mM, P&lt;0.05; Female‐chow, 0.33±0.02 vs. Female‐KD, 0.66±0.11 mM, P&lt;0.05). There were no significant sex differences in serum ketone bodies or glucose. State 3 respiration with succinate + ADP was ~35% lower in both male and female KD groups (Male‐chow, 236±14 vs. Male‐KD, 148±11 nmol/min/mg, P&lt;0.05; Female‐chow, 186±22 vs. Female‐KD, 133±10 nmol/min/mg, P=0.08). State 3 respiration with pyruvate/malate + ADP were ~30% lower in both Male and female KD groups (Male‐chow, 157±18 vs. Male‐KD, 105±10 nmol/min/mg, P=NS; Female‐chow, 138±22 vs. Female‐KD, 81±8 nmol/min/mg, P=0.06). No statistically significant sex differences in mitochondria function were noted. In summary, 6‐weeks of KD results in sex differences in patterns of weight gain as male mice experience a transient weight loss and females gain weight throughout the study period. Despite the difference in weight gain, hearts from both males and females fed the KD have similar decrements in mitochondrial function. In conclusion, these findings suggest that the KD may negatively affect cardiac mitochondria and caution against the short‐term use of KD.

Sex Differences in the Patterns of Systemic Agent use Among Patients With Psoriasis: A Retrospective Cohort Study in Quebec, Canada.

Background: Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined. Objectives: To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation. Methods: We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002–2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients. Results: We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20–10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28–7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56–4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46–0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57–0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30–2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51–0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59–0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57–0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011. Conclusion: Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients’ characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.

Sex Differences in Patterns of Sleep Disorders Among Hospitalizations With Parkinson's Disease: 2004-2014 Nationwide Inpatient Sample.

This study aimed to examine patterns of sleep disorders among hospitalized adults 65 years and older as related to Parkinson's disease (PD) status and to evaluate sex differences in the associations between PD with sleep disorders. A cross-sectional study was conducted using 19,075,169 hospital discharge records (8,169,503 men and 10,905,666 women) from the 2004-2014 Nationwide Inpatient Sample databases. PD and sleep disorder diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification coding. Logistic regression models were constructed for each sleep disorder as a correlate of PD status; adjusted odds ratios (aOR) with their 95% confidence intervals (CIs) were calculated taking into account patient and hospital characteristics. Period prevalences of PD and sleep disorder were estimated to be 2.1% and 8.1%, respectively. Most sleep disorder types, with the exception of sleep-related breathing disorders, were positively associated with PD diagnosis. Statistically significant interactions by sex were noted for associations of insomnia (men: aOR = 1.29, 95% CI = 1.24-1.36; women: aOR = 1.17, 95% CI = 1.12-1.22), parasomnia (men: aOR = 3.74, 95% CI = 3.44-4.07; women: aOR = 2.69, 95% CI = 2.44-2.96), sleep-related movement disorder (men: aOR = 1.09, 95% CI = 1.07-1.11; women: aOR = 1.22, 95% CI = 1.20-1.25), and any sleep disorder (men: aOR = 1.06, 95% CI = 1.05-1.08; women: aOR = 1.15, 95% CI = 1.13-1.17) with PD status. Overall, hospitalized men are more likely to experience PD with insomnia or parasomnia, whereas hospitalized women are more likely to experience PD with sleep-related movement disorder or any sleep disorder. Prospective cohort studies are needed to replicate these cross-sectional findings.

Sex Differences in Antipsychotic and Benzodiazepine Prescribing Patterns: A Cohort Study of Newly Admitted Nursing Home Residents with Dementia in Ontario, Canada.

In nursing homes, residents with dementia frequently receive potentially inappropriate medications that are associated with an increased risk of adverse events. Despite known sex differences in clinical presentation and sociodemographic characteristics among persons with dementia, few studies have examined sex differences in patterns and predictors of potentially inappropriate medicationuse. The objectives of this study were to examine sex differences in the patterns of antipsychotic and benzodiazepine use in the 180days following admission to a nursing home, estimate clinical and sociodemographic predictors of antipsychotic and benzodiazepine use in male and female residents, and explore the effects of modification by sex on the predictors of using these drug therapies. We conducted a retrospective cohort study of 35,169 adults aged 66years and older with dementia who were newly admitted to nursing homes in Ontario, Canada between 2011 and 2014. Health administrative databases were linked to detailed clinical assessment data collected using the Resident Assessment Instrument (RAI-MDS 2.0). Cox proportional hazards models were adjusted for clinical and sociodemographic covariates to estimate the rate of antipsychotic and benzodiazepine initiation and discontinuation in the 180days following nursing home admission in the total sample and stratified by sex. Sex-covariate interaction terms were used to assess whether sex modified the association between covariates and the rate of drug therapy initiation or discontinuation following nursing home entry. Across 638 nursing homes, our analytical sample included 22,847 females and 12,322 males. At admission, male residents were more likely to be prevalent antipsychotic users than female residents (33.8% vs 28.3%; p < 0.001), and female residents were more likely to be prevalent benzodiazepine users than male residents (17.2% vs 15.3%, p < 0.001). In adjusted models, female residents were less likely to initiate an antipsychotic after admission (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.73-0.86); however, no sex difference was observed in the rate of benzodiazepine initiation (HR 1.04, 95% CI 0.96-1.12). Female residents were less likely than males to discontinue antipsychotics (HR 0.89, 95% CI 0.81-0.98) and benzodiazepines (HR 0.82, 95% CI 0.75-0.89). Sex modified the association between some covariates and the rate of changes in drug use (e.g., widowed males exhibited an increased rate of antipsychotic discontinuation (p-interaction = 0.03) compared with married males), but these associations were not statistically significant among females. Sex did not modify the effect of frailty on the rates of initiation and discontinuation. Males and females with dementia differed in their exposure to antipsychotics and benzodiazepines at nursing home admission and their patterns of use following admission. A greater understanding of factors driving sex differences in potentially inappropriate medication use may help tailor interventions to reduce exposure in this vulnerable population.

Associations between age and brain microstructure in older community-dwelling men and women: the Rancho Bernardo Study

Cytoarchitectural brain changes during normal aging remain poorly characterized, and it is unclear whether patterns of brain aging differ by sex. This study used restriction spectrum imaging to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99 years). Widespread associations with age in multiple diffusion compartments, including increased free water, decreased restricted and hindered diffusion, and reduced neurite complexity, were observed in the cortical gray matter, the white matter tracts, and the hippocampus. Age differences in cortical microstructure were largely independent of atrophy. Associations were mostly global, although foci of stronger effects emerged in the fornix, anterior thalamic radiation and commissural fibers, and the medial temporal, orbitofrontal, and occipital cortices. Age differences were stronger and more widespread for women than men, even after adjustment for education, hypertension, and body mass index. Restriction spectrum imaging may be a convenient, noninvasive tool for monitoring changes in diffusion properties that are thought to reflect reduced cellular fractions and neurite density or complexity, which occur with typical aging, and for detecting sex differences in patterns of brain aging.

Sex Differences in Patterns of Adverse Events to Opioid Analgesics

BackgroundOpioid analgesics are among the most commonly prescribed medications in the United States. Opioids are useful in the management of pain, but their use can also adversely affect patients. However, studies reporting patterns of adverse events due to use of opioid analgesics in men and women are still scarce. Understanding the individual characteristics affecting response to opioids may allow clinicians to better individualize treatments. In this study, we investigated sex differences in the patterns of adverse events as a result of opioid use.MethodsWe used data from 8,457 patients participating in the Mayo Clinic Biobank “Right Drug, Right Dose, Right Time (RIGHT protocol)” study of pre‐emptive genotyping who were prescribed at least one of four opioid medications (codeine, tramadol, hydrocodone, or oxycodone) between 01/01/2004 and 12/31/2017. Adverse events due to use of these medications were collected from the allergy section in each patient’s electronical medical record, and were organized into four Medical Dictionary for Regulatory Activities (MedDRA) categories: gastrointestinal (e.g. nausea, vomiting), skin and subcutaneous tissue (e.g. rash, itching), psychiatric (e.g. anxiety, hallucinations), and nervous system (e.g. headache, dizziness). We modeled sex differences in the risk of adverse events by each opioid, and sex differences in the risk of each adverse event due to any opioid using logistic regression adjusted for age, race, ethnicity, and body mass index (BMI).ResultsParticipants with at least one opioid prescription were 60.8% female, mostly white (94.2%) and non‐Hispanic (98.9%). Women (relative to men) were younger (median = 61.6 vs. 69.1, respectively), had lower BMI (median = 27.4 vs. 28.9), and were prescribed more codeine (18.8% vs. 15.5%). Overall, 456 (5.4%) persons had a note in the allergy section of their medical record indicating a problem with an opioid medication. Women were more likely than men to have a note in the allergy section referring to at least one opioid (6.6% and 3.5%, respectively; p &lt; 0.001). In addition, among participants who had at least one note related to opioid use in their allergy section, women were more likely to have notes regarding gastrointestinal complications (OR [95% CI] = 2.07 [1.3 – 3.2], p = 0.002), but less likely to have notes regarding psychiatric issues (OR [95% CI] = 0.30 [0.2 – 0.5], p &lt; 0.001).ConclusionWomen were more likely than men to experience adverse events due to use of codeine, tramadol, hydrocodone, and oxycodone. In addition, the types of adverse reactions differed between men and women. These data suggest that further studies are needed to ensure that both men and women have optimal responses to opioid medications.Support or Funding InformationThis work was supported by the Mayo Clinic Specialized Center of Research Excellent on Sex Differences, the Mayo Clinic Center for Individualized Medicine, the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, and the National Institutes of Health grants [U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project)], and [U01 HG06379 and U01 HG06379 Supplement (The Electronic Medical Record and Genomics (eMERGE) Network)].