GENLIB: new function to simulate haplotype transmission in large complex genealogies.

SUMMARY: Founder populations with deep genealogical data are well suited for investigating genetic variants contributing to diseases. Here, we present a major update of the genealogical analysis R package GENLIB, centered around a new function which can simulate the transmission of haplotypes from founders to probands along very large and complex user-specified genealogies. AVAILABILITY AND IMPLEMENTATION: The latest update of the GENLIB package (v1.1.9) contains the new gen.simuHaplo() function and is available on the CRAN repository and from https://github.com/R-GENLIB/GENLIB. Examples can be accessed at https://github.com/R-GENLIB/simuhaplo_functions.

Age-Related Eye Disease and Cognitive Function: The Search for Mediators.

PURPOSE: Age-related eye disease may be associated with cognitive decline, but the scientific literature has not been consistent. Furthermore, no studies have been able to explain the relationship. Our objective was to assess whether older adults with age-related macular degeneration (AMD) or glaucoma performed worse on 6 cognitive tests compared with older adults with normal vision and, if so, to understand why. DESIGN: Cross-sectional analysis of hospital-based study (Maisonneuve-Rosemont Hospital Ophthalmology Clinics, Montréal, Canada). PARTICIPANTS: Three hundred thirty-six adults 65 years of age or older with either AMD, glaucoma, or normal vision. METHODS: Cognition was measured with 6 cognitive tests administered orally. Activity levels were measured using the Victoria Longitudinal Study Activity Lifestyle Questionnaire. Visual acuity and visual field were measured. Multiple linear regression was used. Mediation was assessed using structural equation modeling. MAIN OUTCOME MEASURES: Results of the verbal fluency test (animal and letter versions), the digit span test (forward and backward versions), and the logical memory test (immediate and delayed recall). RESULTS: People with glaucoma showed lower scores on 3 cognitive tests than the group with normal vision: the digit span forward and backward tests (ß = -0.8 [95% confidence interval (CI), -1.5 to -0.2] and ß = -0.7 [95% CI, -1.3 to -0.1], respectively) and the logical memory test with immediate recall (ß = -1.3 [95% CI, -2.4 to -0.2]). Activity levels statistically significantly mediated the relationship between glaucoma and the digit span forward test (P = 0.043; percentage of the total effect mediated, 17%). CONCLUSIONS: People with glaucoma showed lower scores on cognitive tests that may depend on verbal working memory and encoding. If confirmed in longitudinal studies, interventions should be developed that are appropriate for a visually impaired population to slow this cognitive decline.

Fear of falling and its association with life-space mobility of older adults: a cross-sectional analysis using data from five international sites.

Background: fear of falling (FOF) is a major health concern among community-dwelling older adults that could restrict mobility. Objective: to examine the association of FOF with life-space mobility (i.e. the spatial area a person moves through in daily life) of community-dwelling older adults from five diverse sites. Methods: in total, 1,841 older adults (65-74 years) were recruited from Kingston, Canada; Saint-Hyacinthe, Canada; Tirana, Albania; Manizales, Colombia and Natal, Brazil. FOF was assessed using the Fall Efficacy Scale-International (FES-I total score), and the life space was quantified using the Life-Space Assessment (LSA), a scale that runs from 0 (minimum life space) to 120 (maximum life space). Results: the overall average LSA total score was 68.7 (SD: 21.2). Multiple-linear regression analysis demonstrated a significant relationship of FOF with life-space mobility, even after adjusting for functional, clinical and sociodemographic confounders (B = -0.15, 95% confidence interval (CI) -0.26 to -0.04). The FOF × site interaction term was significant with a stronger linear relationship found in the Canadian sites and Tirana compared with the South American sites. After adjusting for all confounders, the association between FOF with LSA remained significant at Kingston (B = -0.32, 95% CI -0.62 to -0.01), Saint-Hyacinthe (B = -0.81, 95% CI -1.31 to -0.32) and Tirana (B = -0.57, 95% CI -0.89 to -0.24). Conclusion: FOF is an important psychological factor that is associated with reduction in life space of older adults in different social and cultural contexts, and the strength of this association is site specific. Addressing FOF among older adults would help improve their mobility in local communities, which in turn would improve social participation and health-related quality of life.

Self-care tools to treat depressive symptoms in patients with age-related eye disease: a randomized controlled clinical trial.

BACKGROUND: Depression is very common in people with age-related eye disease. Our goal was to determine if self-care tools plus limited telephone support could reduce depressive symptoms in patients with age-related macular degeneration or diabetic retinopathy. DESIGN: A single-blind randomized controlled clinical trial was conducted at Maisonneuve-Rosemont Hospital in Montreal, Canada. PARTICIPANTS: Eighty participants were recruited. METHODS: To be eligible, participants must have had either late stage age-related macular degeneration or diabetic retinopathy, at least mild depressive symptoms, and visual acuity better than 20/200. Half were randomized to the intervention arm and half to delayed intervention/usual care. The intervention consisted of large print written and audio tools incorporating cognitive-behavioral principles plus three 10-minute telephone calls from a lay coach. Eight-week follow-up data were collected by telephone. MAIN OUTCOME MEASURES: The primary outcome was the 8-week change in depressive symptoms as measured by the Patient Health Questionnaire-9. Secondary outcomes included anxiety, life space and self-efficacy. RESULTS: The baseline mean logMAR visual acuity was 0.37 (SD = 0.20), and the baseline mean Patient Health Questionnaire-9 score was 9.5 (SD = 3.9) indicating moderate depressive symptoms. After adjusting for baseline imbalances in visual acuity, the intervention reduced depressive symptoms by 2.1 points more than usual care (P = 0.040). The intervention was not associated with the secondary outcomes (P > 0.05). CONCLUSIONS: Self-care tools plus telephone coaching led to a modest improvement in depressive symptoms in patients with age-related eye disease. Additional research on how to maximize their effect is necessary.

[The Management of Depression in Older Adults and Their Family Caregivers: Findings from a Research Program in Quebec]. / La gestion de la dépression chez les aînés et leurs aidants naturels : résultats d'un programme de recherche au Québec.

Objectives A research group based at St. Mary's Research Centre, St. Mary's Hospital, Montreal, has conducted a research program over the past two decades that aims to inform improvements in the management of depression in primary care and general medical settings, among older adults. This paper reviews the findings from this research program, discusses the findings in the context of other research, and highlights the implications for practice and health policy.Methods Narrative review and synthesis of 25 published articles, that included: 4 systematic reviews, 10 observational studies, 9 intervention trials, and 2 consensus conference reports.Results The results pertain to 4 research areas: detection of depression in primary care and general medical settings; collaborative care of depression; depression self-care interventions; and the role of family and friends in supporting depression self-care interventions.Conclusions We propose six recommendations for improving the management of depression in the target population. 1) Depression detection and treatment can be improved through collaborative care models that involve primary care physicians, mental health specialists and non-physician mental health workers who are trained to assist with the detection of depression, with the delivery of brief, low-intensity psychological interventions and with self-care support. More research and evaluation are necessary to determine the factors that enhance the effectiveness, cost-efficiency, and consumer-centeredness of these interventions. 2) Supported depression self-care (and other low-intensity interventions such as short problem-solving therapy) offered by telephone or via internet, either as part of collaborative or usual care are feasible treatment options but more research is necessary to determine their effectiveness in different clinical populations. Some populations (e.g., those aged 75 and over, with visual and/or mild cognitive impairment) are likely to need greater or face-to-face support. 3) As most family physicians are unlikely to have the necessary time or interest to support depression self-care interventions, other sustainable programmatic contexts are needed for delivery of these interventions. Options include: nurses or other mental health workers in multidisciplinary family medicine groups; regional mental health programs; and voluntary organizations dedicated to assisting in the management of chronic illnesses. Research is needed on the feasibility and effectiveness of using peer support workers or volunteers to provide coaching of depression self-care interventions. 4) Involvement of family or friends in depression self-care may improve outcomes (e.g., dyadic interventions) but further research is necessary. 5) Further research should explore the potential of depression self-care interventions to prevent major depression and in depression relapse prevention in this population.

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis.

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and postmenopausal women. We used baseline data from 898 peri- and postmenopausal women recruited from multiple communities, ages 42-62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and postmenopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and postmenopausal women.

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.

OBJECTIVES: To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. METHODS: Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. RESULTS: Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047). CONCLUSIONS: Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.

Bayesian estimation of associations between identified longitudinal hormone subgroups and age at final menstrual period.

BACKGROUND: Although follicle stimulating hormone (FSH) is known to be predictive of age at final menstrual period (FMP), previous methods use FSH levels measured at time points that are defined relative to the age at FMP, and hence are not useful for prospective prediction purposes in clinical settings where age at FMP is an unknown outcome. This study is aimed at assessing whether FSH trajectory feature subgroups identified relative to chronological age can be used to improve the prediction of age at FMP. METHODS: We develop a Bayesian model to identify latent subgroups in longitudinal FSH trajectories, and study the relationship between subgroup membership and age at FMP. Data for our study is taken from the Penn Ovarian Aging study, 1996-2010. The proposed model utilizes mixture modeling and nonparametric smoothing methods to capture hypothesized latent subgroup features of the FSH longitudinal trajectory; and simultaneously studies the prognostic value of these latent subgroup features to predict age at FMP. RESULTS: The analysis identified two FSH trajectory subgroups that were significantly associated with FMP age: 1) early FSH class (15%), which displayed initial increases in FSH shortly after age 40; and 2) late FSH class (85%), which did not have a rise in FSH until after age 45. The use of FSH subgroup memberships, along with class-specific characteristics, i.e., level and rate of FSH change at class-specific pre-specified ages, improved prediction of FMP age by 20-22% in comparison to the prediction based on previously identified risk factors (BMI, smoking and pre-menopausal levels of anti-mullerian hormone (AMH)). CONCLUSIONS: To the best of our knowledge, this work is the first in the area to demonstrate the existence of subgroups in FSH trajectory patterns relative to chronological age and the fact that such a subgroup membership possesses prediction power for age at FMP. Earlier ages at FMP were found in a subgroup of women with rise in FSH levels commencing shortly after age 40, in comparison to women who did not exhibit an increase in FSH until after 45 years of age. Periodic evaluations of FSH in these age ranges are potentially useful for predicting age at FMP.

Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements.

OBJECTIVE: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. STUDY DESIGN: We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). RESULTS: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). CONCLUSION: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect.

Effect modification by sex of genetic associations of vitamin C related metabolites in the Canadian Longitudinal study on aging.

Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions. Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite. Results: Two genome-wide statistically significant (p value < 5 × 10-8) interaction effects and several suggestive (p value < 10-5) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2, associated with sex hormones, and AGRP, associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues. Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.

Visual impairment, employment status, and reduction in income: the Canadian Longitudinal Study on Aging.

OBJECTIVE: To examine the employment status of those with and without visual impairment and eye disease and to examine the association between visual impairment and eye disease and a reduction in income over a 3-year period. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 12,174 nonretired participants aged 45-64 years old in the Canadian Longitudinal Study on Aging. METHODS: Visual impairment was defined if binocular presenting or pinhole-corrected monocular visual acuity in the better eye was worse than 20/40 at baseline. Self-reported diagnoses of age-related macular degeneration (AMD) and glaucoma were collected. Employment status (employed, not employed due to sickness or disability, or unemployed) was based on questions on labour force participation. Income reduction was defined as household income <$50,000 per year at follow-up when household income was ≥$50,000 at baseline. Multinomial and logistic regressions were used to adjust for demographic and health variables. RESULTS: Visual impairment using binocular presenting visual acuity (odds ratio [OR] = 2.09; 95% CI, 1.21-3.62) and pinhole-corrected visual acuity (OR = 2.99; 95% CI, 1.54-5.83) were associated with a higher odds of not being employed due to sickness or disability after adjustment. AMD (OR = 1.82; 95% CI, 1.11-3.01) and glaucoma (OR = 2.05; 95% CI, 1.28-3.28) at baseline were both associated with reductions in income over a 3-year period after adjustment. CONCLUSION: Individuals with visual impairment experienced lower employment, and those with AMD or glaucoma were more likely to have their incomes decline over 3 years. Policies to improve workplace participation by those with vision loss are needed.

Exploring ethnic and racial differences in intraocular pressure and glaucoma: The Canadian Longitudinal Study on aging.

Purpose: To determine whether self-reported race/ethnicity is associated with intraocular pressure (IOP) and glaucoma and to explore whether any associations are due to social, behavioral, genetic, or health differences. Design: Cross-sectional analysis of population-based data. Methods: We used the Canadian Longitudinal Study on Aging Comprehensive Cohort, which consists of 30,097 adults aged 45-85 years. Race/ethnicity was self-reported. Corneal-compensated intraocular pressure (IOP) was measured in mmHg using the Reichert Ocular Response Analyzer. Participants were asked to report if they have ever had a diagnosis of glaucoma and whether they used eye care in the past year. A glaucoma polygenic risk score (PRS) was calculated. Logistic and linear regression models were used. Results: Black individuals had higher mean IOP levels (beta coefficient (ß) = 1.46; 95% confidence interval [CI], 0.62, 2.30) while Chinese, Japanese and Korean (ß = -1.00; 95% CI, -1.63, -0.38) and Southeast Asian and Filipino individuals (ß = -1.56; 95% CI, -2.68, -0.43) had lower mean IOP levels as compared to White individuals after adjustment for sociodemographic, behavioral, genetic, and health-related variables. Black people were more likely to report glaucoma as compared to White people after adjustment (odds ratio [OR] = 2.43; 95% CI, 1.27, 4.64). Conclusion: Racial and ethnic differences in IOP and glaucoma were identified. Adjusting for sociodemographic, behavioral, genetic, and health-related variables did not fully explain these differences. Longitudinal research is needed to further explore the reasons for these differences and to understand their relevance to disease pathogenesis and progression.

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Clinical subtypes of core premenstrual disorders: a Delphi survey.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

ISPMD consensus on the management of premenstrual disorders.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

Air pollution and the onset of balance problems: The Canadian longitudinal study on aging.

PURPOSE: To understand the relationship between ambient air pollution and the onset of balance problems. DESIGN: Population-based prospective cohort study. METHODS: Baseline and 3-year follow-up data were used from the Canadian Longitudinal Study on Aging. The Comprehensive Cohort included adults aged 45-85 years old recruited from 11 sites across 7 provinces. Data on air pollution came from the Canadian Urban Environmental Health Research Consortium. Annual mean levels of ozone, fine particulate matter (PM2.5), and sulfur dioxide for each participant's postal code were estimated from satellite data. Balance was measured at both time points using the one-leg balance test with those who could not stand on one leg for at least 60 s defined as failing the balance test. Our outcome was the new development of failing the balance test at follow-up in those who passed the balance test at baseline. Logistic regression was used. RESULTS: Of the 12,158 people who could stand for 60 s on one leg at baseline, 18% were unable to do so 3 years later. In single pollutant models, living in an area with higher ozone levels was associated with the 3-year onset of balance problems (odds ratio (OR) = 1.13 per interquartile range of ozone, 95% CI 1.02, 1.24) after adjustment for demographic, lifestyle, and health variables. In a multipollutant model, the association with ozone increased slightly (OR = 1.16, 95% CI 1.04, 1.30). There were no associations with PM2.5 or sulfur dioxide. CONCLUSION: Our findings provide longitudinal evidence that higher ozone levels are associated with the odds of developing balance problems over a 3-year period. Further work should attempt to confirm our findings and explore the potential mechanism of action.

A Systematic Review and Meta-analysis of Systemic Antihypertensive Medications With Intraocular Pressure and Glaucoma.

PURPOSE: We synthesized the literature on the association between systemic antihypertensive medications with intraocular pressure (IOP) and glaucoma. Antihypertensive medications included ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. DESIGN: Systematic review and meta-analysis. METHODS: Databases were searched for relevant articles until December 5, 2022. Studies were eligible if they examined (1) the association between systemic antihypertensive medications with glaucoma or (2) the association between systemic antihypertensive medications with IOP in those without glaucoma or ocular hypertension. The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews; registration ID: CRD42022352028). RESULTS: A total of 11 studies were included in the review and 10 studies in the meta-analysis. The 3 studies on IOP were cross-sectional, whereas the 8 studies on glaucoma were primarily longitudinal. In the meta-analysis, ß-blockers were associated with a lower odds of glaucoma (odds ratio: 0.83, 95% CI: 0.75-0.92, 7 studies, n = 219,535) and lower IOP (ß: -0.53, 95% CI: -1.05 to -0.02, 3 studies, n = 28,683). Calcium channel blockers were associated with a higher odds of glaucoma (odds ratio: 1.13, 95% CI: 1.03-1.24, 7 studies, n = 219,535) but not with IOP (ß: -0.11, 95% CI: -0.25 to 0.03, 2 studies, n = 20,620). There were no consistent associations between angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or diuretics with glaucoma or IOP. CONCLUSIONS: Systemic antihypertensive medications have heterogeneous effects on glaucoma and IOP. Clinicians should be aware that systemic antihypertensive medications may mask elevated IOP or positively or negatively affect the risk of glaucoma.