A Comparative Analysis of Naïve Exosomes and Enhanced Exosomes with a Focus on the Treatment Potential in Ovarian Disorders.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes", a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HtrA1, PAM, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified the altered expression of various miRNAs, such as miR-125b-5p and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

Fertility protection: a novel approach using pretreatment with mesenchymal stem cell exosomes to prevent chemotherapy-induced ovarian damage in a mouse model.

BACKGROUND: Primary ovarian insufficiency refers to the loss of ovarian function before the age of 40 years and leads to amenorrhea and infertility. Primary ovarian insufficiency has diverse causes, but a common cause is exposure to gonadotoxic chemotherapy used in cancer treatment. Because of the risk for developing primary ovarian insufficiency, patients who want to preserve their fertility may consider various procedures for fertility preservation. However, current fertility preservation options are highly invasive, carry substantial risks, and have uncertain success rates. Recent studies from our group and others reported that mesenchymal stem cells and mesenchymal stem cell-derived exosomes can restore ovarian function in preclinical models of primary ovarian insufficiency by restoring damaged cells and inhibiting apoptosis. Although the restorative effect of mesenchymal stem cell-derived exosomes has been well reported in previous studies, the potential of mesenchymal stem cell-derived exosomes in preventing ovarian damage has not been fully elucidated. OBJECTIVE: This study hypothesized that the antiapoptotic potential of mesenchymal stem cell-derived exosomes may protect ovarian tissue from chemotherapy-induced damage. STUDY DESIGN: In this study, we delivered mesenchymal stem cell-derived exosomes directly into the ovaries of mice before administration of chemotherapy. A total of 60 mice were divided into 3 groups (20 per group), which were labeled the control, chemotherapy, and fertility protection groups. Only the fertility protection group mice received exosomes, whereas the control and chemotherapy group mice received saline. After exosome injection, the chemotherapy and fertility protection groups of mice were subjected to chemotherapy to induce ovarian damage. After chemotherapy, we evaluated the protective effects of exosome treatment on ovarian function, such as estrous cyclicity, serum hormone levels, and the fertility rate, by comparing these outcomes between the chemotherapy and fertility protection groups. These outcomes were also compared with those of the control group for comparison with outcomes under healthy conditions. RESULTS: After intraovarian injection of exosomes before chemotherapy, the mice were able to maintain their estrous cycle (4- to 5-day cyclicity), serum anti-müllerian hormone level (66.06±26.40 ng/mL, not significantly different from that of the healthy controls), folliculogenesis (32.2±11.3 in the chemotherapy group vs 46.4±14.1 in the fertility protection group; P<.05), expression of the steroidogenic acute regulatory protein gene (a the steroidogenesis marker) (0.44±0.11-fold expression in the chemotherapy group and 0.88±0.31-fold expression in the fertility protection group; P<.05), and fertility (2 of 8 in the chemotherapy group and 5 of 8 in the fertility protection group), thereby showing prevention of chemotherapy-induced damage. We found that exosome treatment before chemotherapy can preserve ovarian function and protect fertility through the overexpression of ATP synthase-binding cassette transporters, such as ABCB1b (10.17±17.75-fold expression in the chemotherapy group and 44.14±33.25-fold expression in the fertility protection group; P<.05) and ABCC10 (3.25±0.59-fold expression in the chemotherapy group and 5.36±1.86-fold expression in the fertility protection group; P<.05). CONCLUSION: In this study, we present a novel fertility protection method using mesenchymal stem cell-derived exosomes. We concluded that mesenchymal stem cell-derived exosomes are a promising and simple treatment option for fertility protection in reproductive-aged patients who are receiving gonadotoxic chemotherapy.

Developing interfaith interventions to address hesitancy towards COVID-19 vaccination: protocol for a focus group-based, exploratory qualitative study.

INTRODUCTION: The COVID-19 pandemic demonstrated how vaccine hesitancy impacts are translated nationally and internationally. A predictor of vaccine hesitancy is religious beliefs (eg, the body being sacred and should be healed by God). Additionally, the perceived content of vaccines can conflict with religious dietary restrictions. Despite the main faith organisations in the UK endorsing COVID-19 vaccination, vaccine hesitancy remains a challenge. Most faith-based research and interventions have been investigated in individual faiths, in isolation from others. Therefore, the aim of our research is to inform the development of interfaith interventions to address COVID-19 vaccine hesitancy, following the identification of potential facilitators and barriers and codesign of interfaith intervention(s). METHODS AND ANALYSIS: We will facilitate six face-to-face focus groups in London, each comprising eight participants. There will also be the option of joining an online focus group. A semistructured topic guide will include questions on experiences around interfaith, vaccine hesitancy, facilitators and barriers, and potential interfaith interventions to increase vaccine acceptance. Focus group participants will be invited to join a subsequent interfaith codesign workshop where the researchers will share the tentative findings and facilitate discussion to develop one or more interventions. Purposive sampling will be used to recruit 48 participants from different faith groups, ethnicities and backgrounds to capture diversity in the sample. Reflexive thematic analysis will guide a systematic process of constant comparison, coding data into categories and refining into overarching themes. ETHICS AND DISSEMINATION: The University College London (UCL) Research Ethics Committee granted ethics approval (Project ID 4359.006) on 3 May 2022. Minor amendments to the study were approved on 15 May 2023 to accommodate participants' requests for online or face-to-face focus groups at a UCL venue. Informed consent is required from all participants. The findings will be disseminated in journals and to the public and key stakeholders.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles to Treat PCOS.

Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in women. Previously, we suggested that human mesenchymal stem cells (MSCs) can reverse the PCOS condition by secreting factors. Here, we evaluated the therapeutic capability of MSC-derived extracellular vesicles (EVs), also known as exosomes, in both in vitro and in vivo PCOS models. Exosomes were used to treat androgen-producing H293R cells and injected in a mouse model through intraovarian and intravenous injection into a letrozole (LTZ)-induced PCOS mouse model. We assessed the effects of the exosomes on androgen-producing cells or the PCOS mouse model by analyzing steroidogenic gene expression (quantitative real-time polymerase chain reaction (qRT-PCR)), body weight change, serum hormone levels, and fertility by pup delivery. Our data show the therapeutic effect of MSC-derived EVs for reversing PCOS conditions, including fertility issues. Interestingly, intravenous injection was more effective for serum glucose regulation, and an intraovarian injection was more effective for ovary restoration. Our study suggests that MSC-derived exosomes can be promising biopharmaceutics for treating PCOS conditions as a novel therapeutic option. Despite the fact that we need more validation in human patients, we may evaluate this novel treatment option for PCOS with the following clinical trials.

Comparison of the therapeutic effects between stem cells and exosomes in primary ovarian insufficiency: as promising as cells but different persistency and dosage.

BACKGROUND: Primary ovarian insufficiency (POI) refers to the loss of ovarian function under the age of 40 and results in amenorrhea and infertility. Our previous studies have shown that transplantation of mesenchymal stem cells (MSCs) and MSC-derived exosomes in chemotherapy-induced POI mouse ovaries can reverse the POI and eventually achieve pregnancy. Based on our recent studies, MSC-derived exosomes have almost equal therapeutic potentials as transplanted MSCs. However, it is still unclear whether exosomes can completely replace MSCs in POI treatment. For the reliable application of cell-free treatment for POI patients using exosomes, there is a need to understand whether there is any outcome and effectiveness difference between MSC and MSC-derived exosome treatment. METHODS: Comparing the therapeutic effect of intravenous injection using MSCs and equal amounts of exosomes in a POI mouse model will reveal the difference between the two therapeutic resources. In this study, we induced POI in C57/BL6 mice by chemotherapy (CXT) using a standard protocol. We then injected four different doses of MSCs or equal amounts of commercialized MSC-derived exosomes by retro-orbital injection post-CXT. RESULT: After MSC/exosome treatment, tissue and serum samples were harvested to analyze molecular changes after treatment, while other mice in parallel experiments underwent breeding experiments to compare the restoration of fertility. Both the MSC- and exosome-treated groups had a restored estrous cycle and serum hormone levels compared to untreated POI mice. The pregnancy rate in the MSC-treated group was 60-100% after treatment, while the pregnancy rate in the exosome-treated group was 30-50% after treatment. Interestingly, in terms of long-term effects, MSC-treated mice still showed a 60-80% pregnancy rate in the second round of breeding, while the exosome-treated group became infertile again in the second round of breeding. CONCLUSIONS: Although there were some differences in the efficacy between MSC treatment and exosome treatment, both treatments were able to achieve pregnancy in the POI mouse model. In conclusion, we report that MSC-derived exosomes are a promising therapeutic option to restore ovarian function in POI conditions similar to treatment with MSCs.

Candidate biomarkers in psychiatric disorders: state of the field.

The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety. This review highlights a critical gap in the biomarker validation process. An enormous societal investment over the past 50 years has identified numerous candidate biomarkers. However, to date, the overwhelming majority of these measures have not been proven sufficiently reliable, valid and useful to be adopted clinically. It is time to consider whether strategic investments might break this impasse, focusing on a limited number of promising candidates to advance through a process of definitive testing for a specific indication. Some promising candidates for definitive testing include the N170 signal, an event-related brain potential measured using electroencephalography, for subgroup identification within autism spectrum disorder; striatal resting-state functional magnetic resonance imaging (fMRI) measures, such as the striatal connectivity index (SCI) and the functional striatal abnormalities (FSA) index, for prediction of treatment response in schizophrenia; error-related negativity (ERN), an electrophysiological index, for prediction of first onset of generalized anxiety disorder, and resting-state and structural brain connectomic measures for prediction of treatment response in social anxiety disorder. Alternate forms of classification may be useful for conceptualizing and testing potential biomarkers. Collaborative efforts allowing the inclusion of biosystems beyond genetics and neuroimaging are needed, and online remote acquisition of selected measures in a naturalistic setting using mobile health tools may significantly advance the field. Setting specific benchmarks for well-defined target application, along with development of appropriate funding and partnership mechanisms, would also be crucial. Finally, it should never be forgotten that, for a biomarker to be actionable, it will need to be clinically predictive at the individual level and viable in clinical settings.

Circadian rhythm biomarker from wearable device data is related to concurrent antidepressant treatment response.

Major depressive disorder (MDD) is associated with circadian rhythm disruption. Yet, no circadian rhythm biomarkers have been clinically validated for assessing antidepressant response. In this study, 40 participants with MDD provided actigraphy data using wearable devices for one week after initiating antidepressant treatment in a randomized, double-blind, placebo-controlled trial. Their depression severity was calculated pretreatment, after one week and eight weeks of treatment. This study assesses the relationship between parametric and nonparametric measures of circadian rhythm and change in depression. Results show significant association between a lower circadian quotient (reflecting less robust rhythmicity) and improvement in depression from baseline following first week of treatment (estimate = 0.11, F = 7.01, P = 0.01). There is insufficient evidence of an association between circadian rhythm measures acquired during the first week of treatment and outcomes after eight weeks of treatment. Despite this lack of association with future treatment outcome, this scalable, cost-effective biomarker may be useful for timely mental health care through remote monitoring of real-time changes in current depression.

Fertility Protection, A Novel Concept: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Protect against Chemotherapy-Induced Testicular Cytotoxicity.

Currently, there is no viable option for fertility preservation in prepubertal boys. Experimentally, controlled vitrification of testicular tissue has been evaluated and found to cause potential structural damage to the spermatogonial stem cell (SSC) niche during cryopreservation. In this report, we leveraged the regenerative effect of human umbilical cord-derived Mesenchymal stem cell exosomes (h-UCMSC-Exo) to protect against testicular damage from the cytotoxic effects of polychemotherapy (CTX). A chemotherapy-induced testicular dysfunctional model was established by CTX treatment with cyclophosphamide and Busulfan in vitro (human Sertoli cells) and in prepubescent mice. We assessed the effects of the exosomes by analyzing cell proliferation assays, molecular analysis, immunohistochemistry, body weight change, serum hormone levels, and fertility rate. Our data indicates the protective effect of h-UCMSC-Exo by preserving the SSC niche and preventing testicular damage in mice. Interestingly, mice that received multiple injections of h-UCMSC-Exo showed significantly higher fertility rates and serum testosterone levels (p < 0.01). Our study demonstrates that h-UCMSC-Exo can potentially be a novel fertility protection approach in prepubertal boys triaged for chemotherapy treatment.

Stem Cell Therapy: From Idea to Clinical Practice.

Regenerative medicine is a new and promising mode of therapy for patients who have limited or no other options for the treatment of their illness. Due to their pleotropic therapeutic potential through the inhibition of inflammation or apoptosis, cell recruitment, stimulation of angiogenesis, and differentiation, stem cells present a novel and effective approach to several challenging human diseases. In recent years, encouraging findings in preclinical studies have paved the way for many clinical trials using stem cells for the treatment of various diseases. The translation of these new therapeutic products from the laboratory to the market is conducted under highly defined regulations and directives provided by competent regulatory authorities. This review seeks to familiarize the reader with the process of translation from an idea to clinical practice, in the context of stem cell products. We address some required guidelines for clinical trial approval, including regulations and directives presented by the Food and Drug Administration (FDA) of the United States, as well as those of the European Medicine Agency (EMA). Moreover, we review, summarize, and discuss regenerative medicine clinical trial studies registered on the Clinicaltrials.gov website.

Rare osteoarticular complications on [18F]FDG-PET/CT - following intravesical BCG immunotherapy for bladder cancer.

This case illustrates rare osteoarticular complications of Bacillus Calmette-Guérin (BCG) immunotherapy in a 55-year-old male with high-risk non-muscle-invasive bladder cancer (NMIBC). The patient was referred for 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) to rule out bone metastases suspected on prior post-gadolinium magnetic resonance imaging (MRI). Although metastases were excluded, nearly symmetrical uptakes were detected in the costovertebral and costotransverse joints. Medical history revealed that the patient had been receiving intravesical instillations of BCG, the first-line therapy for high-risk NMIBC. The patient was diagnosed with reactive arthritis (ReA), a rare autoimmune complication of BCG, that was successfully treated with a nonsteroidal anti-inflammatory drug (NSAID).

Risk of Upstaging Due to Oncofertility Treatment Mimicking Pelvic Lymphoma on 18F-FDG PET/CT.

ABSTRACT: A 23-year-old woman with primary mediastinal large B-cell lymphoma was referred to 18F-FDG PET/CT for staging. Besides the large mediastinal FDG-avid tumor, another FDG-avid lesion with an SUV higher than expected in corpus luteum cysts was found in the pelvis, raising suspicion for tumor. However, gynecologic ultrasound and review of patient chart revealed history of oncofertility treatment with GNRH analog. This prior treatment was responsible for the intense 18F-FDG uptake within the left ovary, way above the SUV levels commonly associated with menstrual cycle. In this case, the disease was downgraded to stage II, resulting in a less aggressive treatment.

Gradient boosting decision-tree-based algorithm with neuroimaging for personalized treatment in depression.

Introduction: Pretreatment positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and magnetic resonance spectroscopy (MRS) may identify biomarkers for predicting remission (absence of depression). Yet, no such image-based biomarkers have achieved clinical validity. The purpose of this study was to identify biomarkers of remission using machine learning (ML) with pretreatment FDG-PET/MRS neuroimaging, to reduce patient suffering and economic burden from ineffective trials. Methods: This study used simultaneous PET/MRS neuroimaging from a double-blind, placebo-controlled, randomized antidepressant trial on 60 participants with major depressive disorder (MDD) before initiating treatment. After eight weeks of treatment, those with ≤ 7 on 17-item Hamilton Depression Rating Scale were designated a priori as remitters (free of depression, 37%). Metabolic rate of glucose uptake (metabolism) from 22 brain regions were acquired from PET. Concentrations (mM) of glutamine and glutamate and gamma-aminobutyric acid (GABA) in anterior cingulate cortex were quantified from MRS. The data were randomly split into 67% train and cross-validation (n = 40), and 33% test (n = 20) sets. The imaging features, along with age, sex, handedness, and treatment assignment (selective serotonin reuptake inhibitor or SSRI vs. placebo) were entered into the eXtreme Gradient Boosting (XGBoost) classifier for training. Results: In test data, the model showed 62% sensitivity, 92% specificity, and 77% weighted accuracy. Pretreatment metabolism of left hippocampus from PET was the most predictive of remission. Conclusions: The pretreatment neuroimaging takes around 60 minutes but has potential to prevent weeks of failed treatment trials. This study effectively addresses common issues for neuroimaging analysis, such as small sample size, high dimensionality, and class imbalance.

Magnitude and factors associated with child abuse in a mega city of developing country pakistan.

OBJECTIVE: Child abuse is one of the major challenges for health care providers. This study was conducted to determine the burden of child abuse (physical & emotional) and the factors associated with it in an urban city of Pakistan. METHODS: This cross-sectional study was conducted in primary care clinics affiliated with a tertiary care hospital in Karachi, Pakistan between March to December 2010. Mothers with children aged between 6 and 12 years were included in the study. Those mothers' suffering from any acute illness like high grade fever, were excluded. A total of 412 mothers were recruited through consecutive sampling and written informed consent was taken. A pre-tested questionnaire was used to seek information about child abuse. Data was analyzed using SPSS version 19 and multivariable logistic regression was used to identify the factors (age, gender of child, family structure, educational status of parents, and mother's perception of her home environment) associated with child abuse. FINDINGS: Of the total 412 mothers, final analysis was conducted on 379 mothers. In all, 32.5% of children had been abused, 25.5% physically and 17.9% emotionally. Abuse was reported more among children whose mothers had minimal or no schooling (P=0.02), who were abused by their husbands (P<0.001), not satisfied with their marital life (P<0.001), and stressful home environment (P=0.02). In the multivariate analysis, the factors found to be independently associated with child abuse were mothers abused by their husbands (AOR=4.2; 95%CI: 2.2-7.9) and child being a girl (AOR=8.7; 95%CI: 4.5-16.8). CONCLUSION: The prevention of child abuse can be achieved through comprehensive, multifaceted and integrated approaches requiring joint efforts by the government, policy makers, stake holders, social workers, educationists, and public health practitioners.

Factors associated with intimate partner violence against women in a mega city of South-Asia: multi-centre cross-sectional study.

OBJECTIVES. To assess the proportion of women subjected to intimate partner violence and the associated factors, and to identify the attitudes of women towards the use of violence by their husbands. DESIGN. Cross-sectional study. SETTING. Family practice clinics at a teaching hospital in Karachi, Pakistan. PARTICIPANTS. A total of 520 women aged between 16 and 60 years were consecutively approached to participate in the study and interviewed by trained data collectors. Overall, 401 completed questionnaires were available for analysis. Multivariate logistic regression analysis was used to identify the association of various factors of interest. RESULTS. In all, 35% of the women reported being physically abused by their husbands in the last 12 months. Multivariate analysis showed that experiences of violence were independently associated with women's illiteracy (adjusted odds ratio=5.9; 95% confidence interval, 1.8-19.6), husband's illiteracy (3.9; 1.4-10.7), smoking habit of husbands (3.3; 1.9-5.8), and substance use (3.1; 1.7-5.7). CONCLUSION. It is imperative that intimate partner violence be considered a major public health concern. It can be prevented through comprehensive, multifaceted, and integrated approaches. The role of education is greatly emphasised in changing the perspectives of individuals and societies against intimate partner violence.

Medical management for chronic atherosclerotic peripheral arterial disease.

The generalized term 'peripheral vascular disease' (PVD) may be used to refer to vascular disorders in any non-coronary arterial bed. The more specific term 'peripheral arterial disease' (PAD) is used to refer to a more specific process, atherosclerotic disease of the lower extremities. PAD is common. Conservative estimates suggest more than 8 million Americans may be affected by PAD. Since atherosclerosis is a systemic process, PAD should be identified as a coronary heart disease risk equivalent. However, PAD remains an under-diagnosed and under-recognized risk for cardiovascular morbidity and mortality. PAD symptoms may range from non-specific ambulatory leg complaints, to typical symptoms of intermittent claudication to critical limb ischaemia with rest pain, gangrene or ulceration. These symptoms directly impact quality of life and may affect functional capacity. There are two therapeutic goals for patients with PAD: first, to reduce the risk of cardiovascular events and second, to manage the lower extremity symptoms. This manuscript reviews the medical management of patients with PAD, briefly discussing the goals of cardiovascular risk factor modification and then focusing on pharmacological management strategies for patients with intermittent claudication and critical limb ischaemia.

Focused abdominal CT scan for acute appendicitis in children: can it help in need?

OBJECTIVE: To evaluate the focused abdominal CT scan [FACT] in clinically equivocal cases of acute appendicitis in paediatric population. METHODS: A cross-sectional study was conducted at the Radiology Department of Aga Khan Hospital, from August 2007 to November 2008. A total of 84 patients (42 males & 42 females) with clinically equivocal signs and symptoms of acute appendicitis referred to radiology department for CT evaluation were studied. CT findings were compared with histopathology and clinical follow-up. RESULTS: The sensitivity of focused CT for acute appendicitis was 91%; specificity was 69% and accuracy of 76% while PPV and NPV were 58%, 94% respectively. CONCLUSION: Focused unenhanced CT is a quick, accurate and non invasive modality for the assessment of clinically equivocal cases of acute appendicitis for ruling out patients and reducing negative appendectomies.

Sclerosing mesenteritis as a cause of abdominal mass and discomfort in an elderly patient: a case report and literature review.

Sclerosing mesenteritis is a rare benign process that involves inflammation, fat necrosis, and fibrosis of the mesentery. The disease poses great diagnostic challenge due to its nonspecific clinical and diagnostic findings. We report the case of a 75-year-old man who presented with vague abdominal discomfort associated with an intra-abdominal mass. With suspicion of a bowel carcinoid tumor on computed tomography scans, the patient underwent diagnostic laparoscopy. A diagnosis of sclerosing mesenteritis was made on histological examination. The patient's symptoms responded to a combination of immunosuppressive drugs, with no interval change in the size of the mass on radiological examination after fifteen months.

Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone.

CONTEXT: Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes. OBJECTIVE: To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States. DESIGN, SETTING, AND PATIENTS: Nationwide, observational, retrospective, inception cohort of 227,571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation. MAIN OUTCOME MEASURES: Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference. RESULTS: A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12-1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year. CONCLUSION: Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older.

Frequency of endometriosis among infertile women and association of clinical signs and symptoms with the laparoscopic staging of endometriosis.

OBJECTIVE: The study aimed to determine the frequency of endometriosis in women who underwent diagnostic laparoscopy for evaluation of infertility and the association of clinical, ultrasonographic and laparoscopic findings of endometriosis with the laparoscopic stages of the disease. METHOD: It was a retrospective study of women presenting to gynaecologic clinics of the Aga Khan University Hospital from January 1999 to December 2005 with primary complaint of primary or secondary infertility and were diagnosed with endometriosis through laparoscopy. Relevant demographic and clinical information was entered and analyzed in SPSS version 14.0. RESULTS: The frequency of endometriosis in women with primary compliant of infertility was found to be 16.8%. Statistically significant associations was found between staging of the disease and thin built (p=0.007) and restricted uterine mobility on pelvic examination (p=0.035). The patients' ultrasound and laparoscopic examination showed significant association with staging of the disease with the presence of cysts on ultrasound (p-value < 0.0001) and adhesions on laparoscopy (p value <0.00001). CONCLUSION: The variability of the definition and inconsistency in diagnostic methods makes the prevalence of endometriosis difficult to determine and we might underestimate the true burden of the disease. Most of the signs and symptoms of endometriosis do not correlate with the severity (staging) of the disease. Hence, Laparoscopy remains the gold standard for diagnosis as well as staging of endometriosis.