ANTI-THYROID ANTIBODIES AND THE GONADOTROPHINS PROFILE (LH/FSH) IN EUTHYROID POLYCYSTIC OVARIAN SYNDROME WOMEN.

Context: The current study aimed to determine association of anti-TPO with LH/FSH in PCOS women. Design: Current case control study included 33 diagnosed PCOS women and 32 age matched healthy women and were analysed for body mass index (BMI) and waist to hip ratio (WHR), fasting blood glucose (FBG), free T3 (FT3), free T4 (FT4), Thyroid stimulating hormone (TSH), dehydroepiandrostenedione (DHEA-S), total testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and anti thyroperoxidase antibodies (anti-TPO). Data was statistically analysed by Student's t - test and Pearson's correlation analysis. Results: Of the total PCOS women, 45% were obese and 34.37% had raised anti-TPO. The biochemical profile of obese PCOS women showed significantly raised FBG (p<0.0001), LH (p<0.0001), Testosterone (p<0.0001) and DHEA-S (p=0.0021) as compared to non-obese PCOS women. The LH/FSH ratio was significantly raised in PCOS women as compared to control (p<0.0001). Pearson's correlation analysis showed a significant association of anti-TPO with FBS, testosterone, LH and LH/FSH in obese PCOS and with Testosterone and LH in non-obese PCOS women using SPSS 21. Conclusion: The current study shows a high prevalence of AITD in euthyroid PCOS women and suggests a strong link of euthyroid obese PCOS women to autoimmunity due to the hyper-anderogenism and a higher LH/FSH ratio.

CRISPR/Cas-New Molecular Scissors in Diagnostics and Therapeutics of COVID-19.

The current pandemic of COVID-19, with its climbing number of cases and deaths, has us searching for tools for rapid, reliable, and affordable methods of detection on one hand, and novel, improved therapeutic strategies on the other. The currently employed RT-PCR method, despite its all-encompassing utility, has its shortcomings. Newer diagnostic tools, based on the Clustered Regularly Interspaced Short Palindromic Repeats/Cas(CRISPR-Cas) system, with its better diagnostic accuracy measures, have come up to fill that void. These assay platforms are expected to slowly take up the place of COVID-19 diagnostics. Further, the current therapeutic options focus mainly on counteracting the viral proteins and components and their entry into host cells. The CRISPR-based system, especially through the RNA-guided Cas13 approach, can identify the genomic characteristics of SARS-CoV-2 and provide a novel inhibition strategy for coronaviruses. In this mini-review, we have discussed the available and upcoming CRISPR-based diagnostic assays and the potential of the CRISPR/Cas system as a therapeutic or prevention strategy in COVID-19. CRISPR-Cas system shows promise in both diagnostics as well as therapeutics and may as well change the face of molecular diagnosis and precision medicine.

Self-management and adherence in childhood-onset systemic lupus erythematosus: what are we missing?

OBJECTIVES: The aims of this study are (1) to characterize factors influencing self-management behaviors and quality of life in adolescent and young adult (AYA) patients with childhood-onset systemic lupus erythematosus (cSLE) and (2) to identify barriers and facilitators of treatment adherence via focus groups. METHODS: AYAs with cSLE ages 12-24 years and primary caregivers of the adolescents participated in this study. Recruitment occurred during pediatric rheumatology clinic visits at a Midwestern children's hospital or the hospital's cSLE active clinic registry. Information about disease severity was obtained from patient health records. Pain and fatigue questionnaires were administered. Descriptive statistics were used to analyze data. RESULTS: Thirty-one AYA patients and caregivers participated in six focus groups. Ten major themes emerged from sessions; four were expressed both by the AYA and caregiver groups: knowledge deficits about cSLE, symptoms limiting daily function, specifically mood and cognition/learning, barriers and facilitators of adherence, and worry about the future. Themes unique to AYA participants included symptoms limiting daily functioning-pain/fatigue, self-care and management, impact on personal relationships, and health care provider communication/relationship. For caregiver groups unique themes included need for school advocacy, disruption of family schedule, and sense of normalcy for their adolescent. CONCLUSION: AYAs with cSLE face a lifelong disease characterized by pervasive pain, fatigue, organ damage, isolation-social and/or physical-and psycho-socioeducational challenges. This study confirmed that continued psychosocial support, health information education, adherence interventions, and personalized treatment plans are necessary to increase self-management and autonomy in AYAs with cSLE.

The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study.

The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. INTRODUCTION: This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. METHODS: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. RESULTS: The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥ 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. CONCLUSIONS: The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.

Frequency of discontinuation of injectable osteoporosis therapies in US patients over 2 years.

Little is known about treatment patterns with injectable osteoporosis therapies. At 12 months, the probability of discontinuation was 69.1% among patients using ibandronate, followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment. The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation. INTRODUCTION: This study was designed to assess the frequency of treatment discontinuation over time among patients who initiate injectable osteoporosis therapies. METHODS: This retrospective observational study utilized an administrative claims database to measure discontinuation of injectable osteoporosis therapy, reported at 6-month intervals over 2 years. Eligible patients were aged ≥55 years, had newly initiated injectable osteoporosis therapy between January 2008 and June 2012, and were continuously enrolled in the health plan for ≥1 year prior to and ≥1.5 years after the date the first injectable medication was received (the index date). Follow-up time ranged from 18 to 24 months. Injectable osteoporosis treatments included in the analysis were denosumab, ibandronate, teriparatide, and zoledronic acid. Discontinuation was assessed using Kaplan-Meier survival analysis and was defined at each time point as the percentage of patients who did not receive the dose scheduled for that time point. A 90-day grace period was allowed to accommodate flexibility in the scheduling of post-index re-administrations. Sensitivity analyses assessed discontinuation using grace periods of 60 and 30 days. RESULTS: A total of 4756 patients met the inclusion criteria for the study, with 617 utilizing denosumab, 233 ibandronate, 778 teriparatide, and 3128 zoledronic acid. At 12 months, discontinuation was highest among patients using ibandronate (69.1%), followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment: 87.5% for ibandronate, 87.9% for teriparatide, 79.8% for zoledronic acid, and 64.3% for denosumab. CONCLUSIONS: The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation.

Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS).

The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. INTRODUCTION: The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. METHODS: MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. RESULTS: Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P ≤ 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. CONCLUSIONS: The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.

Cost and health care resource use associated with noncompliance with oral bisphosphonate therapy: an analysis using Danish health registries.

We estimated the rate of compliance with oral bisphosphonates among Danish women and examined its association with health care resource use and cost. Approximately 30 % of Danish females aged >55 who take bisphosphonates are noncompliant, and noncompliance is significantly associated with increased health care resource use and cost. INTRODUCTION: Two objectives of this study were to estimate the rate of oral bisphosphonate compliance among Danish women and to examine the association of noncompliance with health care resource use and cost. METHODS: Women ≥55 with an index prescription claim for an oral bisphosphonate were identified from Danish national health registries between 2003 and 2008. Compliance was measured as the medication possession ratio (MPR) during the first 12 months post-index. Cost and health care resource use were collected for the following 12 months. RESULTS: Among the 38,234 women meeting the study inclusion criteria, 29.9 % were noncompliant (MPR <70 %). Younger age was associated with higher odds of compliance (OR [95 % CI] 1.22 [1.15-1.29] for ages 55-64 and 1.18 [1.12-1.24] for ages 65-74; reference age group ≥75 years). Rates of all-cause health care resource use were significantly higher in noncompliant subjects: 28.9 versus 23.0 % had inpatient admissions, 16.5 versus 13.0 % had emergency room visits, and 48.7 versus 43.3 % used outpatient services (P < 0.001 for all comparisons). The total mean (SD) all-cause cost per patient (excluding office visits) was €626 (2344) and €4178 (7854), respectively. The mean (SD) osteoporosis-related cost per patient (excluding office visits) was €572 (2085) and €754 (2857) for compliant and non-compliant subjects, respectively. The compliant subjects accrued significantly lower all-cause and OP-related cost than noncompliant subjects, regardless of whether the total cost or medical cost only was considered. CONCLUSIONS: Approximately 30 % of Danish females aged 55 or older who take bisphosphonates are noncompliant. Noncompliance is significantly associated with increased health care resource use and cost.

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study.

SUMMARY: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. INTRODUCTION: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. METHODS: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0-22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0-100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0-1; OPAQ-SV, score 0-100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. RESULTS: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1% of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, -0.43; OPSAT-Q, -5.68; EQ-5D, -0.04 (new users) and -0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, -4.17 (experienced users); emotional status, -4.28 (new users) and -5.68 (experienced users); back pain, -5.82 (new users) and -11.33 (experienced users), all P < 0.01. CONCLUSIONS: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms.

Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women.

BACKGROUND: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. METHODS: This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis). RESULTS: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85-86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics. CONCLUSIONS: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation.

Post-fracture pharmacotherapy for women with osteoporotic fracture: analysis of a managed care population in the USA.

UNLABELLED: Pharmacologic therapy is recommended to reduce future fracture risk. We examined osteoporosis medications dispensed to older women after first fracture. Only 23 % received therapy during the first year post-fracture. Prior osteoporosis therapy, a prior osteoporosis diagnosis, and older age were good predictors of post-fracture osteoporosis therapy. INTRODUCTION: Pharmacologic therapy is recommended after osteoporotic fracture to reduce future fracture risk. The objective of this retrospective study was to examine osteoporosis therapy dispensed to women post-fracture. METHODS: We identified women ≥50 years old in a large administrative claims database from 2003 to mid-2012 who were continuously enrolled 2 years before (baseline) and 1 year after first osteoporotic fracture. Exclusions were Paget's disease or malignant neoplasm. Pre- and post-fracture osteoporosis therapies (oral and parenteral) were assessed overall and by fracture site. RESULTS: A total of 47,171 women of mean (SD) age of 63 (10) years were eligible; fractures included 8 % hip, 17 % vertebral, 73 % non-hip/non-vertebral, and 3 % multiple fracture sites. Only 18 % received osteoporosis therapy within 90 days and 23 % within 1 year post-fracture. Overall, 19 % of women had a prior osteoporosis diagnosis; 20 % had received osteoporosis therapy during baseline. Of 37,649 (80 %) women without baseline therapy, only 9 % initiated pharmacologic therapy within 1 year. The adjusted odds ratio (OR) of therapy within 1 year post-fracture was significantly greater for women who had received baseline osteoporosis therapy (versus none) and who had vertebral (OR 12.7, 95 % confidence interval (CI) 11.2-14.5), hip (15.2, 12.5-18.7), or non-hip/non-vertebral fracture (34.4, 31.7-37.3). Other significant predictors included pre-fracture osteoporosis diagnosis (1.6, 1.4-1.7) and older age (OR range, 1.3-1.7). Treatment adherence was significantly better among women with baseline osteoporosis diagnosis. CONCLUSIONS: The substantial post-fracture treatment gap represents an important unmet need for women with osteoporotic fractures. Fracture liaison or adherence programs could lead to improved post-fracture treatment rates.

Prevalence of renal impairment among osteoporotic women in the USA, NHANES 2005-2008: is treatment with bisphosphonates an option?

UNLABELLED: Bisphosphonates are the first-line treatment for osteoporotic (OP) women; however, therapy is not recommended in severe renal impairment (RI). This study examined RI prevalence among OP women. Nearly a quarter of women had moderate RI, and 3.59% would not be recommended for bisphosphonates, demonstrating a need for better therapeutic alternatives. INTRODUCTION: Bisphosphonates are the recommended first-line treatment for postmenopausal women with OP. However, bisphosphonates are cleared through the kidney, and therapy is not recommended in severe RI due to adverse treatment effects observed with intravenous formulations. The objective of this study was to examine the prevalence of RI among women with OP aged ≥50 years in the USA. METHODS: Women with OP aged ≥50 years were identified using the 2005-2008 National Health and Nutrition Examination Survey (NHANES) data. OP was defined as prior OP diagnosis, previous hip or spine fracture, or measured lumbar spine/femoral neck bone mineral density (BMD) T-score <-2.5. The 2005 Modification of Diet in Renal Disease (MDRD) formula was used to calculate the glomerular filtration rate (GFR). Moderate and severe RI was defined as GFR 30-59 and 15-29 mL/min, respectively. Bisphosphonate therapy was considered not recommended among women with OP if GFR was <35 mL/min. RESULTS: The prevalence of OP among women in USA aged ≥50 years was 27% (12.7 million). Nearly a quarter of women with OP (23.54 ± 2.02%; 2.9 million) had moderate RI and 1.88 ± 0.28% (230,000) had severe RI. Correspondingly, bisphosphonate therapy would not be recommended for an estimated 439,000 women with OP (3.59 ± 0.73%). CONCLUSIONS: Nearly a quarter of postmenopausal women with OP have moderate RI, and over 3% would not be recommended for bisphosphonate treatment. These data reveal a need for better therapeutic alternatives that can be used in this patient population.

Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results.

BACKGROUND: Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk. PATIENTS AND METHODS: Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points. RESULTS: At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334). CONCLUSIONS: Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340.

Ongoing outbreak of Shigella flexneri serotype 3a in men who have sex with men in England and Wales, data from 2009-2011.

Diagnoses of Shigella flexneri in the United Kingdom (UK) are usually travel-related. However, since 2009, there has been an overall increase in UK-acquired cases. The Health Protection Agency has been investigating a national outbreak of S. flexneri detected in 2011 and which is still ongoing. Cases occurred mostly in men who have sex with men and were of serotype 3a. The investigation aimed at obtaining epidemiological data to inform targeted outbreak management and control.

Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

BACKGROUND: Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. METHODS: Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. RESULTS: Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. CONCLUSIONS: The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes.

Visioning a food system for equitable transition towards sustainable diets.

The Global Goals to end hunger requires interpretation of problems, and change across multiple domains. We facilitated a workshop aimed at understanding how stakeholders problematise sustainable diet transition (SDT) among a previously-marginalised social group. Using the systems thinking approach, three sub-systems, access to dietary diversity, sustainable beneficiation of natural capital, and 'food choice for well-being', highlighted the main forces governing the current context, and future interventions. Moreover, when viewed as co-evolving processes within the multi-level perspective, our identified microlevel leverage points - multi-faceted literacy, youth empowerment, deliberative policy-making, promotion of sustainable diet aspirations - can be linked and developed through existing national macrolevel strategies. Thus, by reconsidering knowledge use in the pursuit sustainability, transformational SDT can streamline multiple outcomes to restructure socio-technical sectors, reconnect people to nature-based solutions and, support legitimate aspirations. The approach could be applied in countries having complex socio-political legacy and to bridge the local-global goals coherently.