Intercountry assessment of the impact of severe premenstrual disorders on work and daily activities.

We explored the effects of premenstrual symptoms in women suffering from moderate-to-severe premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD) on work productivity, absenteeism, and daily life activities in a large, worldwide exploratory study. Women aged 15-45 years from 19 countries in North America, Latin America, Europe, Asia, and Australia were screened for suspected PMS and PMDD and invited to participate in this 2-month web-based survey. Overall, 4,032 women completed all administered questionnaires and represent the analysis set. Women suffering from moderate-to-severe PMS/PMDD had increased work absenteeism and work productivity impairment due to premenstrual symptoms relative to those with mild PMS/no perceived symptoms.

The impact of spina bifida on caregivers.

INTRODUCTION: Neural tube defects (NTDs) are the second most common birth defects. Spina bifida (SB) and anencephaly make up approximately 90% of total NTDs. Given the number of infants born with an NTD each year, anyone who provides unpaid care for the child (especially caregivers) is affected. This literature review explores the humanistic burden on caregivers of people with SB, specifically myelomeningocele. METHODS: A search using PubMed, PsycINFO, and Embase was performed to find studies from 1976 to 2010. Interpretative phenomenological analysis was performed on qualitative data and relevant extracts from the data were collated to form master themes. RESULTS: A total of 168 abstracts met the inclusion and exclusion criteria. Of these, 25 articles related to caregivers of individuals with SB. Four master themes emerged: initial diagnosis, living with an individual with SB, social support, and coping. Different aspects of caregivers' lives were found to be affected by caring for a child with SB, including activities of daily living, work impact, time consumption, parental responsibilities, confidence, feelings and emotions, mental health, stress, social impact, psychological adjustment, and relationships. CONCLUSION: NTDs, such as SB, present a multitude of issues to caregivers. Issues that affect caregivers of individuals with SB must be addressed in order to reduce the considerable burden that SB places on the caregiver. Continued and enhanced support from health services and patient advocacy groups is needed. For example, providing additional information, support, and empathy can help parents prepare themselves for dealing with the needs of a child with SB over their lifetime.

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States.

OBJECTIVE: The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. STUDY DESIGN: A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. RESULTS: The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. CONCLUSION: Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

The burden of moderate/severe premenstrual syndrome and premenstrual dysphoric disorder in a cohort of Latin American women.

OBJECTIVES: The aim of this study was to investigate the relationship between symptom severity, cost, and impairment in women with moderate/severe premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) in a Latin American setting. METHODS: A model was constructed based on analysis of an observational dataset. Data were included from four Latin American countries. Responder-level data were analysed according to four categories of symptom severity: Category 1 comprised Daily Record of Severity of Problems score 21 to 41.9, Category 2 score was 42 to 62.9, Category 3 score was 63 to 83.9, and Category 4 was a score of 84 or higher. Burden was estimated in terms of impact on job and activities using the modified work productivity and impairment questionnaire and affect on quality of life using the SF-12 questionnaire. Costs were estimated in Brazilian reals from a Brazilian private health care and societal perspective. The outputs of the analysis were estimates of burden, mean annual cost and affect on quality of life (as measured by quality adjusted life years) by symptom severity. Confidence intervals around key outcomes were generated through nonparametric bootstrapping. RESULTS: Analysis suggests a significant cost burden associated with moderate/severe PMS and PMDD with mean per patient annual costs estimated at 1618 BRL (95% confidence interval 957-2,481). Although the relationship between cost, quality of life, and severity was not clear, analysis showed a consistent relationship between disease severity and measures of disease burden (job and daily activity). Burden on activities increased with disease severity. CONCLUSIONS: Our analysis, conducted from a Latin American perspective, suggests a significant burden and an increasing impairment associated with moderate/severe PMS and PMDD.

Economic burden of neural tube defects and impact of prevention with folic acid: a literature review.

Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most countries. To understand the economic burden of NTDs and the economic impact of preventing NTDs with folic acid, a systematic review was performed on relevant studies. A total of 14 cost of illness studies and 10 economic evaluations on prevention of NTDs with folic acid were identified. Consistent findings were reported across all of the cost of illness studies. The lifetime direct medical cost for patients with NTDs is significant, with the majority of cost being for inpatient care, for treatment at initial diagnosis in childhood, and for comorbidities in adult life. The lifetime indirect cost for patients with spina bifida is even greater due to increased morbidity and premature mortality. Caregiver time costs are also significant. The results from the economic evaluations demonstrate that folic acid fortification in food and preconception folic acid consumption are cost-effective ways to reduce the incidence and prevalence of NTDs. This review highlights the significant cost burden that NTDs pose to healthcare systems, various healthcare payers, and society and concludes that the benefits of prevention of NTDs with folic acid far outweigh the cost. Further intervention with folic acid is justified in countries where the full potential of folic acid to reduce the risk of NTDs has not been realized.

A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease.

RATIONALE: Roflumilast is an oral, once-daily phosphodiesterase IV (PDE4) inhibitor under investigation for chronic obstructive pulmonary disease (COPD). This study investigated the cost effectiveness of roflumilast in patients with severe to very severe COPD from the perspective of the UK society and UK NHS. METHODS: The analysis was conducted alongside a 1-year, randomised, double-blind, placebo-controlled, multinational trial. The trial included 1514 COPD patients aged >or=40 years with a post-bronchodilator forced expiratory volume in 1 second (FEV1) % predicted

In vivo identification of the mitogen-activated protein kinase cascade as a central pathogenic pathway in experimental mesangioproliferative glomerulonephritis.

Evidence was recently provided for the activation of extracellular signal-regulated kinase (ERK), the best characterized mitogen-activated protein kinase, as an intracellular convergence point for mitogenic stimuli in animal models of glomerulonephritis (GN). In this study, in vivo ERK activity was blocked, with a pharmacologic inhibitor (U0126) of the ERK-activating kinase, in rats with mesangioproliferative GN. After injection of the monoclonal anti-Thy1.1 antibody (OX-7), the rats were treated (days 3 to 6) with low (10 mg/kg body wt) or high (100 mg/kg body wt) doses of U0126 administered intraperitoneally twice daily. On day 6 after induction of the disease, whole cortical tissue and isolated glomeruli were examined by using kinase activity assays, Western blot analyses, and immunohistochemical assays. Treatment with U0126 significantly reduced glomerular stimulation of ERK in anti-Thy1 GN. In the high dose-treated group, this downregulation was accompanied by a reduction in the number of glomerular mitotic figures, back to healthy control levels, and significant decreases in the numbers of total (P < 0.05) and 5-bromo-2'-deoxyuridine-positive (P < 0.05) glomerular cells. Immunohistochemical double-staining of renal sections demonstrated that mesangial cells were the major glomerular targets of U0126 in anti-Thy1 GN. These observations point to ERK as a putative intracellular mediator of the proliferative response in GN and suggest that pharmacologic treatments that interfere with the activation of ERK may be of potential therapeutic interest.

Differential activation of mitogen-activated protein kinases in experimental mesangioproliferative glomerulonephritis.

Multiple extracellular mitogens are involved in the pathogenesis of proliferative forms of glomerulonephritis (GN). In vitro studies demonstrate the pivotal role of mitogen-activated protein (MAP) kinases in the regulation of cellular proliferation. This study was conducted to examine whether these kinases, as a convergence point of mitogenic stimuli, are activated in mesangioproliferative GN in vivo. Therefore, anti-Thy1 GN was induced in rats using a monoclonal anti-Thy1.1 antibody (OX-7). Whole cortical tissue as well as isolated glomeruli were examined at different time points using kinase activity assays and Western blot analysis. A maximal increase in the number of glomerular mitotic figures (9.7-fold) was demonstrated 6 d after injection of the anti-Thy1.1 antibody. In parallel with this finding, a significant increase in cortical, and more dramatically glomerular, activity of extracellular signal-regulated kinase (ERK) was detected. Maximal activation of ERK was detectable on day 6. This activation of ERK was accompanied by an increase in the expression of MEK (MAP kinase/ERK kinase), the ERK-activating kinase. A marked induction of glomerular apoptosis at 2 h after injection of the anti-Thy1.1 antibody, which subsided subsequently, was demonstrated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay as well as staining for single-stranded DNA. However, no significant activation of stress-activated protein kinase or p38 MAP kinase, both MAP kinases that are suggested to induce apoptosis and to inhibit cellular growth, was detectable at this early time point. Rather, on day 6 a dramatic decrease in the activity of p38 MAP kinase, which might have contributed to the overshooting glomerular cellular proliferation, was observed. Treatment of rats with heparin blunted glomerular proliferation as well as ERK activation and restored p38 MAP kinase activity. These observations point to ERK and p38 MAP kinase as putative mediators of the proliferative response in mesangioproliferative GN and suggest that upregulation of MEK is involved in the long-term regulation of ERK in vivo.