Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members.

OBJECTIVE: Endometriosis constitutes a significant burden on the quality of life of women, their families and healthcare systems. The objective of this study is to describe the real-world epidemiology of endometriosis in an unselected low-risk population in Israel. DESIGN: Retrospective population-based study. SETTING AND SAMPLE: The computerised databases of Maccabi Healthcare Services (MHS), a 2-million-member healthcare provider representing a quarter of the Israeli population. METHODS: The crude point prevalence (31 December 2015; diagnosed since 1998) and annual incidence (2000-2015) rates of diagnosed endometriosis (ICD-9-CM 617.xx) were assessed among women aged 15-55 years. Prevalent patients were characterised in terms of sociodemographic and clinical characteristics, including validated MHS infertility and chronic disease registries. MAIN OUTCOME MEASURES: Prevalence and incidence of diagnosed endometriosis in MHS. RESULTS: The point prevalence of endometriosis [n = 6146, mean age 40.4 ± 8.0 years (SD)] was 10.8 per 1000 (95% CI 10.5-11.0). Women aged 40-44 years had the highest prevalence rate of 18.6 per 1000 (95% CI 17.7-19.5). Infertility was documented in 37% of patients. A total of 6045 patients were included in the cohort of newly-diagnosed endometriosis (mean age 34.0 ± 8.1 years), corresponding to an average annual incidence rate of 7.2 per 10 000 (95% CI 6.5-8.0). CONCLUSIONS: We observed a substantially lower prevalence of diagnosed endometriosis compared with previous reports in high-risk populations, in line with population-based estimates from European databases (range 0.8-1.8%). Further characterisation of this cohort may help to understand what affects the prevalence of endometriosis in Israel, and to promote earlier diagnosis and improve management in clinical practice. TWEETABLE ABSTRACT: Endometriosis diagnosed in 1% of women, according to a large population-based study in a community setting.

Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real-world data from a large healthcare provider.

Treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD ± RBV), was the first interferon-free direct-acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3-F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD ± RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2-million-member health plan in Israel. The study population included adults who initiated OPrD ± RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run-out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12-week post-treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naïve to prior HCV treatment, and 95.6% were treated with a 12-week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1-99.1) and 346/348 (99.4%; 95% CI 97.9-99.9), respectively. GT1b patients on 12-week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD ± RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities.

Effects of concurrent perioperative use of marbofloxacin and cimicoxib or carprofen in dogs.

OBJECTIVES: To investigate possible interactions visible on electroencephalogram recordings caused by concomitant administration of marbofloxacin and carprofen or cimicoxib in dogs without central nervous system disease. METHODS: Totally 21 client-owned dogs undergoing different surgeries were included in a randomised, blinded, clinical study. Each dog was assigned to one of two groups treated with either carprofen or cimicoxib pre- and postoperatively. After anaesthetic induction both groups received marbofloxacin intravenously while recording an electroencephalogram. Offline electroencephalogram analysis included qualitative evaluation and Fast Fourier Transformation. Postoperative analgesia was evaluated for 24 hours and after 10 days with the short-form Glasgow Composite Measure Pain Scale. Statistical analysis included Wilcoxon signed rank test, Mann-Whitney U test and Student's t-test with α set at 5%. RESULTS: Marbofloxacin injection caused no effects on quantitative and qualitative electroencephalogram parameters in both groups. No differences in postoperative pain scoring were found between treatment groups. CLINICAL SIGNIFICANCE: Concurrent use of marbofloxacin with either cimicoxib or carprofen did not induce neuroexcitatory activities in dogs without CNS disease directly after administration.

Stroop Color-Word Interference Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Stroop Test across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Stroop Test, as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 14-36% of the variance in Stroop Word scores, 12-41% of the variance in the Stoop Color, 14-36% of the variance in the Stroop Word-Color scores, and 4-15% of variance in Stroop Interference scores. Although t-tests showed significant differences between men and women on the Stroop test, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the Stoop Test in a Spanish-Speaking sample. This study will therefore have important implications for the future of neuropsychology research and practice throughout the region.

Symbol Digit Modalities Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Symbol Digit Modalities Test (SDMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the SDMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 29-56% of the variance in SDMT scores. Although there were gender differences on the SDMT in Mexico, Honduras, Paraguay, and Guatemala, none of the four countries had an effect size greater than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the SDMT; this study will have an impact on the future practice of neuropsychology throughout the global region.

Brief Test of Attention: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Brief Test of Attention (BTA) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the BTA as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 11-41% of the variance in BTA scores. Although men had higher scores on the BTA in Honduras, there were no other significant gender differences, and this one effect size was small. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the BTA; this study will have an impact on the future practice of neuropsychology throughout Latin America.

Adherence to statins and the risk of psoriasis: a population-based cohort study.

BACKGROUND: Statins have been shown to downregulate immune mechanisms activated in psoriasis. However, previous studies on their potential role in preventing psoriasis have yielded conflicting results. OBJECTIVES: To assess the relationship between adherence to statins and the risk of psoriasis. METHODS: This retrospective cohort study included 205,820 health plan enrollees in Israel (mean age 55 years; 54·1% women) who initiated statin treatment from January 1998 through to September 2009. Adherence to statins, measured by the proportion of days covered (PDC), throughout the entire follow-up period (mean 6·2 years) was recorded. Diagnosis codes of psoriasis were assigned by a dermatologist or rheumatologist, or at discharge from hospital. RESULTS: During 1·28 million person-years (PY) of follow-up (median 5·74 years per person; interquartile range 3·78-8·36), 5615 cases of psoriasis (incidence density rate 4·4 per 1000 PY) were recorded. Compared with patients who did not adhere to statins (PDC < 20%), patients covered by statins for 40-59% of the time had a significantly lower risk of psoriasis (P < 0·05), with hazard ratios (HRs) of 0·84 and 0·74 among men and women, respectively. Among patients who adhered better to statins (PDC ≥ 80%), HRs were 0·88 (95% CI 0·79-0·98) and 1·00 (95% CI 0·90-1·11) among men and women, respectively. CONCLUSIONS: The results of the current study suggest that high and long-term adherence to statins is not associated with a meaningful reduction in the risk of developing psoriasis.

[Toxicity and efficacy of intermittent docetaxel chemotherapy for hormone refractory prostate cancer]. / Toxizität und Effektivität wiederholter Docetaxel-therapie des hormonrefraktären Prostatakarzinoms.

BACKGROUND: Until today, docetaxel is the only EMEA and FDA approved active agent in hormone refractory prostate cancer (HRPC). In the absence of other effective and approved drugs we evaluated the toxicity and efficacy of intermittent-docetaxel-chemotherapy in patients whose cancers progressed after successful first-line docetaxel therapy. METHODS: 46, 18, and 5 patients with HRPC received 1, 2, or 3 cycles of docetaxel based chemotherapy. Toxicity, PSA response and general condition were evaluated systematically. SPSS 15.0 was applied for statistic analysis. RESULTS: 26 (56 %) patients achieved a PSA response of > 50 %, another 10 (22 %) patients of up to 50 %; 10 (22 %) patients were progressive under docetaxel. The median overall survival of the whole cohort calculated from the first docetaxel application was 16 (3-60 +) months. Tolerance, toxicity and general condition were crucial for the administration of a second cycle (n = 18); in contrast, age or the degree of the PSA decline in cycle 1 did not seem to be of importance. The -median overall survival of all patients who -received at least two blocks was 35 months; more-over, 13 / 18 patients achieved a biochemical response in cycle 2. Toxicity did not rise significantly. Five patients were given a third docetaxel cycle, three of whom responded. Higher frequencies of -grade 3 / 4 stomatitis, skin toxicity and leukocytopaenia were observed. CONCLUSION: Intermittent docetaxel therapy is well tolerated and shows high response rates in the sec-ond and third sequences of treatment in select-ed HRPC patients who presented with low docetaxel toxicity, good clinical condition and responded to prior docetaxel-based treatment.

Effect of refeeding on IGFI, IGFII, IGF receptors, FGF2, FGF6, and myostatin mRNA expression in rainbow trout myotomal muscle.

Fish endure long periods of fasting and demonstrate an extensive capacity for rapid and complete recovery after refeeding. The underlying mechanisms through which nutrient intake activates an increase in somatic growth and especially in muscle growth is poorly understood. In this study we examined the expression profile of major muscle growth regulators in trout white muscle 4, 12, and 34 days after refeeding, using real-time quantitative RT-PCR. Mean insulin-like growth factor I (IGFI) mRNA level in muscle increased dramatically 8- and 15-fold, 4 and 12 days, respectively, after refeeding compared to fasted trout. This declined thereafter. Conversely, only a weak but gradual increase in mean insulin-like growth factor II (IGFII) mRNA level was observed during refeeding. Inversely to IGFI, mean IGF receptor Ia (IGFRIa) mRNA level declined after ingestion of food. In contrast, IGF receptor Ib (IGFRIb) mRNA level was not affected by refeeding. Mean fibroblast growth factor 2 (FGF2) mRNA level increased by 2.5-fold both 4 and 12 days after refeeding, whereas fibroblast growth factor 6 (FGF6) and myostatin mRNA levels were unchanged. Subsequent to IGFI and FGF2 gene activation, an increase in myogenin mRNA accumulation was observed at 12 days post-refeeding suggesting that an active differentiation of myogenic cells succeeds their proliferation. In conclusion, among the potential growth factors we examined in this study, IGFI and FGF2 were identified as candidate genes whose expression may contribute to muscle compensatory growth induced by refeeding.

In vitro action of leptin on FSH and LH production in rainbow trout (Onchorynchus mykiss) at different stages of the sexual cycle.

The short-term effect of recombinant human leptin (rhleptin) on FSH and LH production (release+intracellular content) was studied in vitro using pituitary cells from male and female rainbow trout during the first gametogenesis cycle. In our rearing conditions, we found a direct action of rhleptin at the pituitary level, which depends on the sexual stage of the fish. No effect of rhleptin on FSH or LH release and cellular content could be detected in immature fish and post-ovulatory females. However, throughout the process of spermatogenesis and ovogenesis, high concentrations (0.5 and 1 x 10(-6)M) of rhleptin stimulated FSH and LH release, without observable action on intracellular content of gonadotropins. A relatively constant response to rhleptin for FSH was observed throughout gonad maturation, while LH response tended to be higher at the first stages of gametogenesis (beginning of spermatogenesis and endogenous vitellogenesis). Preliminary results on the potential interaction of rhleptin and salmon GnRH (sGnRH) suggest a possible synergistic effect of high concentration of rhleptin (10(-6)M) and sGnRH only at restricted phases of gonadal development when the gametogenetic process was already fully started (full spermatogenesis and early vitellogenesis). The direct action of leptin on FSH and LH release, evident only when gametogenesis had already started suggests that leptin is not the unique signal for the activation of the gonadotropic axis but requires a combined action with other promoting factors.

Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer.

BACKGROUND: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin (A) combination therapy in women with advanced breast cancer. To define a dose range of A for use in AT. PATIENTS AND METHODS: The effect of cumulative A dose on risk of congestive heart failure (CHF) and alterations of myocardial contractility (left ventricular ejection fraction [LVEF] decrease > or = 20% or to <50%) was estimated from pooled data from 10 trials of AT. RESULTS: Thirty-one of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6) after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3 months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was < or = 5% at a total A dose < or = 380 mg/m2. In patients who received a total A dose > 440 mg/m2, the incidence of CHF was >25% but similar to that of A monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy at a dose < or = 380 mg/m2 (2%-3%). LVEF progressively decreased in patients who received AT, especially at a cumulative A dose > 380 mg/m2. LVEF decreases were more frequent in patients who later developed CHF, but the majority of CHF patients did not experience LVEF alterations prior to symptoms. LVEF recovered after discontinuation of A in 25 of 67 women who developed LVEF < 50%. CONCLUSION: The reported cardiac effects are consistent with anthracycline-related cardiotoxicity. AT is associated with a cardiac risk similar to that of A monotherapy up to a cumulative A dose of 340-380 mg/m2.

Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial.

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m(2) followed 24 hours later by paclitaxel 220 mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non-anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P =.032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P =.034]; overall survival 23.3 months v 18.3 months [P =.013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P <.001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Exploring hope in patients with end stage renal disease on chronic hemodialysis.

The purpose of this qualitative study was to explore the definitions and sources of hope in patients with end stage renal disease (ESRD) receiving chronic hemodialysis. A convenience sample was recruited from a population of chronic hemodialysis patients from two dialysis centers in a rural area of the Pacific northwest. Study participants consisted of 9 men and 5 women between the ages of 43 and 81 (M = 62.5) who had been on chronic hemodialysis an average of 8.3 years. The data collection process consisted of an audiotaped interview guided by the pre-established research questions. The results of this study provide examples of the experience of hope in patients with ESRD on chronic hemodialysis. Hope is a multifaceted human response. The participants in this study were able to adapt to situational changes by attaching their hopes to reality consideration, therefore developing a cognitive process for maintaining hope.

Transposition of maize Ac/Ds transposable elements in the yeast Saccharomyces cerevisiae.

Excision by transposons is associated with chromosome breaks; generally, host-cell proteins repair this damage, often introducing mutations. Many transposons also use host proteins in the transposition mechanism or in regulation. Transposition in systems lacking host factors that influence the behaviour of these transpositions is useful in determining what those factors are and how they work. In addition, features of transposition and regulation intrinsic to the element itself can be determined. Maize Activator/Dissociation (Ac/Ds) elements transpose in a wide variety of heterologous plants, but their characteristics in these other systems differ from those in maize, including their response to increasing genetic dosage and the types of repair products recovered following excision. Two Arabidopsis thaliana mutants (iae1 and iae2) show increased Ac transposition frequencies. These mutants, and the differences mentioned above, suggest the involvement of host proteins in Ac/Ds activity and potential differences between these proteins among plant species. Here we report that Ac/Ds elements, members of the hAT (hobo, Ac, Tam3) superfamily, transpose in the yeast Saccharomyces cerevisiae, an organism lacking class II ('cut and paste') transposons. This demonstrates that plant-specific proteins are not essential for Ac/Ds transposition. The yeast system is valuable for dissecting the Ac/Ds transposition mechanism and identifying host factors that can influence transposition and the repair of DNA damage induced by Ac/Ds. Mutations caused by Ds excision in yeast suggest formation of a DNA-hairpin intermediate, and reinsertions occur throughout the genome with a frequency similar to that in plants. The high proportion of Ac/Ds reinsertions also makes this system an in vivo mutagenesis and reverse genetics tool in yeast and, presumably, other eukaryotic systems.

The maize LAG1-O mutant suggests that reproductive cell lineages show unique gene expression patterns early in vegetative development.

Patterns of transposable element activity often provide useful information about how and when organisms regulate gene expression. The maize lowered Ac/Ds germinal reversion 1 (LAG1)-O mutation causes unusually low rates of germinal reversion by Ac/Ds-induced alleles even though these same alleles revert frequently and early in somatic development. LAG1-O suppresses Ds transposition at multiple, unlinked loci, and does not affect Spm elements, indicating that the mutation acts in trans and may be specific to Ac/Ds elements. Our data suggest that LAG1-O suppression gradually reduces Ac/Ds activity in the meristem and newly formed leaves until, by the floral transition, transposition is undetectable even with PCR-based assays. This suppression persists during tassel development and does not appear to be released until some point after meiosis. Competitive RT-PCR results show no difference in Ac transposase mRNA levels between LAG1-O and lag1(+) tassels, suggesting that suppression is post-transcriptional. The pattern of LAG1-O expression is consistent with a model in which at least some gene expression specific to those meristem cells that will ultimately give rise to floral tissue and therefore gametes begins very early in plant development, and then persists throughout development.

The relationship between psychosocial factors and asthma morbidity in inner-city children with asthma.

OBJECTIVE: Children living in the inner city are affected disproportionately by asthma morbidity and mortality. Previous research has shown that behavioral and psychosocial factors affect asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated the factors that contribute to asthma morbidity among inner-city children. This article examines the relationship between psychosocial factors and asthma morbidity in this population. METHODS: A total of 1528 English- and Spanish-speaking children 4 to 9 years of age with asthma and their primary caretakers were recruited from 8 research centers in 7 metropolitan inner-city areas in the United States. Psychosocial variables were assessed at baseline and included measures of child and caretaker mental health, caretaker's problems with alcohol, life stress, social support, and parenting style. Morbidity measures were evaluated at baseline and at 3-, 6-, and 9-month follow-up intervals. These included number of hospitalizations and unscheduled visits for asthma in the past 3 months and number of days of wheeze and functional status in the previous 2-week period. RESULTS: Of the psychosocial variables assessed, mental health had the strongest relationship to children's asthma morbidity. Children whose caretakers had clinically significant levels of mental health problems were hospitalized for asthma at almost twice the rate as children whose caretakers did not have significant mental health problems. Children with clinically significant behavior problems had significantly more days of wheeze and poorer functional status in the follow-up period. CONCLUSION: Psychosocial factors, particularly the mental health of children and caretakers, are significant factors in predicting asthma morbidity. They may need to be included in intervention programs aimed at decreasing asthma morbidity in inner-city children with asthma in order for these programs to be successful.

Phase II study of oral platinum drug JM216 as first-line treatment in patients with small-cell lung cancer.

PURPOSE: This multicenter phase II trial was performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease received JM216 120 mg/m(2)/d for 5 consecutive days every 3 weeks. Individual dose escalation to 140 mg/m(2)/d was allowed if toxicity was