Linda S. Kahn

The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD)

Currently it is estimated that 3-8% of women of reproductive age meet strict criteria for premenstrual dysphoric disorder (PMDD). Assessment of published reports demonstrate that the prevalence of clinically relevant dysphoric premenstrual disorder is probably higher. 13-18% of women of reproductive age may have premenstrual dysphoric symptoms severe enough to induce impairment and distress, though the number of symptoms may not meet the arbitrary count of 5 symptoms on the PMDD list. The impairment and lowered quality of life for PMDD is similar to that of dysthymic disorder and is not much lower than major depressive disorder. Nevertheless, PMS/PMDD is still under-recognized in large published epidemiological studies, as well as assessments of burden of disease. It is demonstrated here that the burden of PMS/PMDD as well as the disability adjusted life years (DALY) lost due to this repeated-cyclic disorder is in the same magnitude as major recognized disorders. Appropriate recognition of the disorder and its impact should lead to treatment of more women with PMS/PMDD. Efficacious treatments are available. They should reduce individual suffering and impact on family, society, and economy.

Role of estrogen in the aetiology and treatment of mood disorders.

Worldwide, the prevalence of depression in women is significantly greater than in men. Available data suggest that estrogen, or its absence, is strongly implicated in the regulation of mood and behaviour, as well as in the pathobiology of mood disorders.The multiple effects of estrogens and their complex interactions with the CNS and endocrine system have been well documented, although the specific, multifaceted role of estrogen in each dysphoric state has yet to be elucidated. Several facts suggest that estrogen plays a vital role in the precipitation and course of mood disorders in women. Gender differences in the prevalence of depression first appear after menarche, continue through reproductive age, and dissipate after perimenopause. Periods of hormonal fluctuations or estrogen instability (i.e. premenstrually, postpartum, perimenopausally) have been associated with increased vulnerability to depression among susceptible women. It is plausible that the phenotype of these depressions is distinguishable from those that are not associated with reproductive events or that occur in men.Based on current knowledge, estrogen treatment for affective disorders may be efficacious in two situations: (i) to stabilise and restore disrupted homeostasis — as occurs in premenstrual, postpartum or perimenopausal conditions; and (ii) to act as a psychomodulator during periods of decreased estrogen levels and increased vulnerability to dysphoric mood, as occurs in postmenopausal women. There is growing evidence suggesting that estrogen may be efficacious as a sole antidepressant for depressed perimenopausal women. It is still unclear whether estrogen is efficacious as an adjunct to selective serotonin reuptake inhibitors or as one of the paradigms to manage treatment-resistance depression in menopausal women, but such efficacy is plausible.

Bipolar disorder and metabolic syndrome: an international perspective.

INTRODUCTION The ubiquity and hazards posed by abnormal body composition and metabolic parameters in the bipolar population are a priority research and clinical issue. Herein, we summarize and synthesize international studies describing the rate of US National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III])- and International Diabetes Federation (IDF)-defined metabolic syndrome and its criterion components in individuals with bipolar disorder. METHODS We conducted a PubMed search of all English-language articles published between January 2005 and July 2009 with the following search terms: metabolic syndrome and bipolar disorder, mania and manic-depression. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. RESULTS The rate of metabolic syndrome in individuals with bipolar disorder is increased relative to the general population. Disparate estimates are reported ranging from comparability to approximately twofold greater than the general population. The increased hazard for metabolic syndrome amongst bipolar individuals is now documented in twelve countries from Europe, Australia, Asia, North and South America. The co-occurrence of metabolic syndrome in the bipolar population is associated with a more complex illness presentation, less favourable response to treatment, and adverse course and outcome. The association between metabolic syndrome and bipolar disorder is mediated/moderated by both iatrogenic and non-iatrogenic factors. DISCUSSION The increased hazard for metabolic syndrome in bipolar populations is due to the clustering of traditional (and emerging) risk factors as well as iatrogenic and health systems factors. Extant data support recommendations for prioritizing, surveillance, prevention, diagnosis and management of metabolic syndrome as routine care of the bipolar patient.

Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects.

The association between elevated prolactin levels and conventional antipsychotics is well-established. The novel antipsychotic, risperidone, has also been shown to elevate prolactin levels. Patients undergoing treatment with these medications are at high risk for developing hyperprolactinemia, which is associated with decreased bone mineral density, osteoporosis, menstrual disruptions and infertility, galactorrhea, breast cancer, cardiovascular disorders, and sexual impairment. Patients treated with conventional antipsychotics and risperidone should be routinely screened for hyperprolactinemia, and monitored for known sequelae. Optimally, patients with hyperprolactinemia secondary to antipsychotic drug treatment should be switched to a prolactin-sparing antipsychotic. This review will briefly highlight the regulation and function of prolactin secretion, discuss clinical effects of antipsychotic-induced hyperprolactinemia, and suggest a course of treatment.

Improving Chronic Kidney Disease Care in Primary Care Practices: An Upstate New York Practice-based Research Network (UNYNET) Study

Background: With the prevalence of chronic kidney disease (CKD) in the United States rising from 10% to 13%, implementation of the evidence-based Kidney Disease Outcomes Quality Initiative guidelines, which were developed for the delay of progression of CKD, is of increasing importance in primary care offices. Previous studies have shown limited knowledge and uptake of Kidney Disease Outcomes Quality Initiative guidelines by primary care physicians. CKD and its complications are still largely under-diagnosed and under-treated. A multifaceted quality improvement study was undertaken to test if these guidelines could be implemented to improve CKD care in underserved practices. Methods: Using a combination of practice enhancement assistants, computer decision-making support, and academic detailing, we sought to increase physician awareness and care of CKD in 2 inner-city practices. Using these 3 modalities, a rapid-cycle quality improvement process was implemented. Results: One hundred eighty-one patients met the inclusion criteria of having a glomerular filtration rate <60. This represented a 100% sample of patients with CKD at baseline. Recognition of CKD improved significantly from 30 (21%) to 114 (79%) (P < .001). Diagnosis of anemia also increased significantly from 26 (33%) to 53 (67%) (P < .001). Angiotensin-converting enzyme inhibitor and aspirin use did not change significantly (P = .31 and P = .233, respectively). Changes in medications that did show significance were metformin use, which decreased 50% from 12 to 6 patients (P < .001), and nonsteroidal anti-inflammatory drug use, which decreased 41% from 23 to 14 patients (P < .001). Mean glomerular riltration rate increased significantly from 45.75 to 47.34 (P < .001). Discussion: Recognition and treatment of CKD and its complications can be markedly improved in primary care offices using a combination of practice enhancement assistants, computer decision-making support, and academic detailing. A significant rise in glomerular riltration rate, although small, was a surprising and encouraging result. Larger studies in a more geographically spread region are needed to confirm these preliminary results.

Oral contraceptives and mood

The past 40 years of research on the mood and behavioural effects of combined oral contraceptives (OCs) have yielded inconclusive results due to dramatic changes in the compounds and to methodological flaws inherent in studies undertaken to assess the effects of OCs. Since the late 1960s, the dosages of oestrogen and progestin in marketed OCs significantly declined and novel progestins were developed to deliver higher levels of progestogenic activity with a lower risk of adverse oestrogenic and androgenic effects. This review evaluates controlled, comparative studies that have focused on the efficaciousness of OCs as treatment for premenstrual syndrome (PMS) and those examining whether OCs may cause negative mood. It is suggested that the mood and behavioural effects of OCs might be attributed to different progestin compounds and possibly, their oestrogen ratios. There is a great need for more longitudinal, randomised, placebo-controlled studies to further clarify the mood and behavioural effects of OCs.

Selective oestrogen receptor modulators--current and future brain and behaviour applications.

Selective oestrogen receptor modulators (SERMs) are compounds that act as oestrogen agonists on selected targets while being oestrogen antagonists on others. The main targets of SERMs are oestrogen agonist activity on bone metabolism and several functions of the cardiovascular system, as well as oestrogen antagonism in the breast and uterus. They are indicated for the treatment and/or prevention of breast and endometrial cancer, osteoporosis and coronary heart disease. The extensive documentation of the multiple oestrogen effects on the CNS, greater understanding of the mechanisms of action, and especially the discovery of a second oestrogen receptor with differentiated distribution and mechanisms, have all led the way to the possibility of specific CNS-targeted SERMs. The demonstration that oestrogen selectively improves cognition, delays the appearance of Alzheimer’s dementia, improves the feeling of well-being, as well as the response to antidepressant medications, provides targeted CNS indications for SERMs. The CNS effects of the currently marketed SERMs are not sufficiently explored yet. However, in postmenopausal women, tamoxifen and raloxifene probably show the most oestrogen agonist CNS effects. In women of reproductive age, competition with oestrogen probably exists, resulting in antagonist effects. Activity in men is still mostly unknown. It is quite safe to predict that the recent accumulation of knowledge, combined with the large, thirsty anticipated market for these ‘designer oestrogens’, will lead to clinical trials of CNS-targeted SERMs in the very near future.

Diabetes self-management in a low-income population: impacts of social support and relationships with the health care system

Objectives: This article reports on results of a qualitative study of social supports and institutional resources utilized by individuals living with diabetes in a high-poverty urban setting. The goal was to examine how access to social capital among low-income populations facilitates and impedes their self-efficacy in diabetes self-management. Methods: Semi-structured interviews were conducted with 34 patients with diabetes from a safety net primary care practice in Buffalo, New York. Results: Facilitators and barriers to successful self-management were identified in three broad areas: (1) the influence of social support networks; (2) the nature of the doctor–patient relationship; and (3) the nature of patient–health care system relationship. Patients’ unmet needs were also highlighted across these three areas. Discussion: Participants identified barriers to effective diabetes self-management directly related to their low-income status, such as inadequate insurance, and mistrust of the medical system. It may be necessary for patients to activate social capital from multiple social spheres to achieve the most effective diabetes management.

Improving evidence-based primary care for chronic kidney disease: study protocol for a cluster randomized control trial for translating evidence into practice (TRANSLATE CKD)

BackgroundChronic kidney disease (CKD) and end stage renal disease (ESRD) are steadily increasing in prevalence in the United States. While there is reasonable evidence that specific activities can be implemented by primary care physicians (PCPs) to delay CKD progression and reduce mortality, CKD is under-recognized and undertreated in primary care offices, and PCPs are generally not familiar with treatment guidelines. The current study addresses the question of whether the facilitated TRANSLATE model compared to computer decision support (CDS) alone will lead to improved evidence-based care for CKD in primary care offices.Methods/DesignThis protocol consists of a cluster randomized controlled trial (CRCT) followed by a process and cost analysis. Only practices providing ambulatory primary care as their principal function, located in non-hospital settings, employing at least one primary care physician, with a minimum of 2,000 patients seen in the prior year, are eligible. The intervention will occur at the cluster level and consists of providing CKD-specific CDS versus CKD-specific CDS plus practice facilitation for all elements of the TRANSLATE model. Patient-level data will be collected from each participating practice to examine adherence to guideline-concordant care, progression of CKD and all-cause mortality. Patients are considered to meet stage three CKD criteria if at least two consecutive estimated glomerular filtration rate (eGFR) measurements at least three months apart fall below 60 ml/min. The process evaluation (cluster level) will determine through qualitative methods the fidelity of the facilitated TRANSLATE program and find the challenges and enablers of the implementation process. The cost-effectiveness analysis will compare the benefit of the intervention of CDS alone against the intervention of CDS plus TRANSLATE (practice facilitation) in relationship to overall cost per quality adjusted years of life.DiscussionThis study has three major innovations. First, this study adapts the TRANSLATE method, proven effective in diabetes care, to CKD. Second, we are creating a generalizable CDS specific to the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for CKD. Additionally, this study will evaluate the effects of CDS versus CDS with facilitation and answer key questions regarding the cost-effectiveness of a facilitated model for improving CKD outcomes. The study is testing virtual facilitation and Academic detailing making the findings generalizable to any area of the country.Trial registrationRegistered as NCT01767883 on clinicaltrials.gov NCT01767883

Identifying barriers and facilitating factors to improve screening mammography rates in women diagnosed with mental illness and substance use disorders.

ABSTRACT Little is known about screening mammography rates among women diagnosed with mental illness–even though some studies have suggested that this population might be particularly vulnerable to breast cancer. The purpose of this pilot study was to identify facilitators and barriers to mammography among women diagnosed with mental illness and/or substance use disorders. Four focus groups were conducted, with a total of 26 women, ages 40–65 years, with mental illness and/or substance use disorders. Analysis was performed using the grounded-theory editing approach. Several major themes emerged from the transcripts: (1) motivators for obtaining mammograms, (2) fears and concerns, (3) shame and embarrassment, (4) the clinical environment, (5) provider-patient communication, and (6) the need for increased patient education. A family history of breast cancer and/or cancer was the most powerful motivator among focus group participants for obtaining a mammogram. Doctor recommendations and referrals were also identified as key facilitating factors. The overall knowledge of mammography and breast cancer among these women suggested educational deficiencies—despite extensive breast cancer screening and awareness campaigns. The findings highlight the importance of patient education as well as the positive effects of physician recommendations to encourage patients to receive breast cancer screening.