Adolopment of clinical practice guidelines and creation of referral pathways for psychiatric conditions in Pakistan.

Psychiatric disorders are highly prevalent in Pakistan and burdens the scarce number of psychiatrists present in the country. The establishment of evidence-based clinical practice guidelines (EBCPGs) and primary-care referral pathways within the local context is imperative to make the process efficient. In this Health Policy, we aimed to develop EBCPGs and primary-care referral pathways that are specific to Pakistan's primary-care setting, with the aim of facilitating the management of psychiatric conditions. Ten EBCPGs were created through the GRADE-ADOLOPMENT process; two recommendations were adopted with minor changes, 43 were excluded, and all others were adopted without any changes. Ten primary-care referral pathways for managing ten psychiatric disorders were created and 23 recommendations were added which will help to bridge the gap in care provision. These psychiatric referral pathways and EBCPGs will bring Pakistan's healthcare system a step closer to achieving optimal health outcomes for patients.

GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context.

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis. PURPOSE: Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan. METHODS: The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). RESULTS: The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. CONCLUSION: The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis.Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan.The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

GRADE-ADOLOPMENT of clinical practice guidelines and creation of clinical pathways for the primary care management of chronic respiratory conditions in Pakistan.

INTRODUCTION: In Pakistan, chronic respiratory conditions contribute a large burden of morbidity and mortality. A major reason for this is the lack of availability of local evidence-based clinical practice guidelines (EBCPGs) in Pakistan, particularly at the primary care level. Thus, we developed EBCPGs and created clinical diagnosis and referral pathways for the primary care management of chronic respiratory conditions in Pakistan. METHODS: The source guidelines were selected by two local expert pulmonologists after a thorough literature review on PubMed and Google Scholar from 2010 to December 2021. The source guidelines covered idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disorders, and bronchiectasis. The GRADE-ADOLOPMENT process consists of three key elements: adoption (using recommendations as is or with minor changes), adaptation (effective context-specific changes to recommendations) or additions (including new recommendations to fill a gap in the EBCPG). We employed the GRADE-ADOLOPMENT process to adopt, adapt, adopt with minor changes, or exclude recommendations from a source guideline. Additional recommendations were added to the clinical pathways based on a best-evidence review process. RESULTS: 46 recommendations were excluded mainly due to the unavailability of recommended management in Pakistan and scope beyond the practice of general physicians. Clinical diagnosis and referral pathways were designed for the four chronic respiratory conditions, explicitly delineating the role of primary care practitioners in the diagnosis, basic management, and timely referral of patients. Across the four conditions, 18 recommendations were added (seven for IPF, three for bronchiectasis, four for COPD, and four for asthma). CONCLUSION: The widespread use of the newly created EBCPGs and clinical pathways in the primary healthcare system of Pakistan can help alleviate the morbidity and mortality related to chronic respiratory conditions disease in the country.

Development of Evidence-Based COVID-19 Management Guidelines for Local Context: The Methodological Challenges.

Background: The coronavirus disease 2019 (COVID-19) pandemic has presented as a therapeutic challenge for clinicians worldwide due to its rapid spread along with evolving evidence and understanding of the disease. Internationally, recommendations to guide the management of COVID-19 have been created and updated continuously by the WHO and CDC, which have been locally adapted by different countries. Similarly, Pakistan's National Command Operation Center (NCOC), in its national COVID-19 management strategy, generated guidelines for national implementation. Keeping the guidelines updated has proved challenging globally and locally. Here, we present a summary of the process to assess the evidence, including a time-restricted systematic review based on NCOC Clinical Management Guidelines for COVID-19 Infections v4 published on 11th December 2020 version, correlating it with current recommendations and with input one of the guidelines authors, particularly noting the methodological challenges. Methods: We conducted a systematic review synthesizing global research on treatment options for COVID-19 hospitalized patients, limiting it to pharmacological interventions for hospitalized COVID-19 patients included in Pakistan's NCOC's national guidelines v4 published on 11th December 2020. Each treatment recommendation's strength and quality of evidence was assessed based on the grading of recommendations assessment, development, and evaluation (GRADE) methodology. These were then compared to the most current living WHO COVID-19 pharmacological treatment guidelines v7.1. One of the authors of the NCOC guidelines reviewed and commented on the findings as well. Results: We note that the data from our systematic review strongly supports corticosteroids use in treating severe and critically ill COVID-19 hospitalized patients correlating with WHO v7.1 guidelines 24 September 2021. However, evidence from our review and WHO v7.1 for the use of tocilizumab had some conflicting evidence, with data from our review until December 2020 supporting only a weak recommendation for its use, compared to the strong recommendation by the WHO for the use of tocilizumab in patients with severe or critical COVID-19 infection. Regarding the use of antibiotics and ivermectin use in treating COVID-19 hospitalized patients, data from our review and WHO v 7.1 recommend against their use. Conclusion: Research data about the efficacy and safety of pharmacological interventions to treat hospitalized patients with COVID-19 are rapidly evolving, and based on it, the evidence for or against recommendations changes accordingly. Our study illustrates the challenges of keeping up with the evidence; the recommendations were based on studies up till December 2021, and we have compared our recommendations with the WHO v7.1, which showed some significant changes in the use of pharmacological treatment options.

Efficacy and Safety Profile of 25-Gauge Pars Plana Vitrectomy in Rhegmatogenous Retinal Detachment in Pakistan: A Multicenter Retrospective Study.

Introduction This study aims to evaluate the primary anatomical success and visual outcomes of 25-gauge pars plana vitrectomy (25g PPV) in patients with rhegmatogenous retinal detachment (RRD) in Pakistan. Design This is a five-year retrospective, interventional cohort study conducted at tertiary care hospitals in Pakistan from October 2013 to October 2018. Methods This is a retrospective, interventional cohort study of 418 consecutive patients with RRD who underwent 25g PPV. All surgeries were performed by two experienced surgeons at tertiary care hospitals in Pakistan. Consecutive patients who underwent 25g PPV surgery as the treatment for RRD from October 2013 to October 2018 were included. We excluded patients who had a history of previous retinal surgery or did not complete the 4-8 weeks of primary outcome visit. We used the Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM Corporation, Armonk, NY, USA) for statistical analysis. A p-value of <0.05 was considered significant. Results We identified 452 patients through the coding system of our hospitals who underwent 25g PPV surgery for RRD during the study period. A total of 441 patient files were reviewed for the study, of which 418 patients met the criteria for final analysis. The mean age was 49 ± 15.8 years. There was a higher number of males (n = 284, 67.9%). In our study, 186 (44.4%) patients were phakic at the time of presentation. The macula was detached in 361 (86.4%) patients. At the primary outcome visit (4-8 weeks of follow-up), the primary anatomical success rate was 89.47%. The most common cause of failure was proliferative vitreoretinopathy (PVR) (n = 20), followed by missed breaks (n = 5). Conclusions The surgical outcomes of RRD with 25g PPV surgery in our study were similar to the outcomes reported in the developed world. We propose a prospective multicenter national study to prospectively evaluate the risk factors for RRD surgical failure in the Pakistani population.

Comparison between the values of intra-ocular pressure measured by Goldmann applanation tonometer and Air-Puff non-contact tonometer and their relationship with central corneal thickness.

Glaucoma is a sight threatening disorder in which measuring intra-ocular pressure (IOP) with accuracy plays a fundamental role. This study aimed to compare the IOP values air-puff of non-contact tonometer(APT) and Goldmann applanation tonometer (GAT) along with their relationship to central corneal thickness (CCT), in various IOP groups. Three hundred and eleven patients were enrolled using convenience sampling in this cross-sectional, prospective study. IOP was measured with Keeler 3000 APT and GAT along with CCT using TOMEY EM-4000. Data was analysed using Bland-Altman, Spearman's and intra-class correlation analysis of APT, GAT and CCT on SPSS 24.0. The median IOP by APT and GAT was 14 mmHg (range:37) and 12 mmHg (range:16) whereas the median CCT was 534µ (range: 44), respectively. At low (<10 mmHg) and normal IOP (10-20 mmHg) both the instruments showed similar results but GAT was found to be more accurate (p£0.001) at higher IOP (21-30 mmHg). However, at moderate and higher groups of IOP, APT revealed overestimation of IOP compared to GAT. CCT also plays a significant role.

Quality of reporting of randomised controlled trials of artificial intelligence in healthcare: a systematic review.

OBJECTIVES: The aim of this study was to evaluate the quality of reporting of randomised controlled trials (RCTs) of artificial intelligence (AI) in healthcare against Consolidated Standards of Reporting Trials-AI (CONSORT-AI) guidelines. DESIGN: Systematic review. DATA SOURCES: We searched PubMed and EMBASE databases for studies reported from January 2015 to December 2021. ELIGIBILITY CRITERIA: We included RCTs reported in English that used AI as the intervention. Protocols, conference abstracts, studies on robotics and studies related to medical education were excluded. DATA EXTRACTION: The included studies were graded using the CONSORT-AI checklist, comprising 43 items, by two independent graders. The results were tabulated and descriptive statistics were reported. RESULTS: We screened 1501 potential abstracts, of which 112 full-text articles were reviewed for eligibility. A total of 42 studies were included. The number of participants ranged from 22 to 2352. Only two items of the CONSORT-AI items were fully reported in all studies. Five items were not applicable in more than 85% of the studies. Nineteen per cent (8/42) of the studies did not report more than 50% (21/43) of the CONSORT-AI checklist items. CONCLUSIONS: The quality of reporting of RCTs in AI is suboptimal. As reporting is variable in existing RCTs, caution should be exercised in interpreting the findings of some studies.

To assess the aggressiveness of oral squamous cell carcinoma in the young population.

Objectives: To assess the recurrence and disease-free survival in oral squamous cell carcinoma patients, and to compare them between two age groups. METHODS: Data were extracted from Patel hospital cancer registry database of patients admitted from January 1st2008 to December 31st 2018 based on retrospective diagnosed with oral squamous cell carcinoma. Patient stratified in to two groups i.e. patients with less than or more than 40 years. Various etiological factors, staging, treatment, site of the tumor and recurrence and mortality were assessed. RESULTS: Of the 450 patients, 124(27.5%) were in group A and 327(72.5%) were in group B. There were 101(81%) males in group A and 240(73.4%) males in group B. The overall mean age was 43.63±10.75 years (range: 22-70 years). The most common site of the tumour was cheek 232(51.5%). Recurrence of tumour was 45(36%) in group A and 120(37%) in group B (p=0.653). Overall mortality in group A was 67(54%) compared to 168(51%) in group B (p=0.811). CONCLUSIONS: Mortality and disease recurrence in both age groups was almost the same. Cheek was the most common site of presentation.

Risk factors associated with disease recurrence in patients with T4 staged Squamous Cell Carcinoma of the Oral Cavity treated with surgery and postoperative radiotherapy.

Objective: To determine the association of clinical and pathological parameters on recurrence of treated stage T4squamous cell carcinoma of oral cavity patients managed with surgery followed by concomitant chemo and radiation therapy. METHODS: The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with oral squamous cell carcinoma and admitted between January 1, 2014, and January 30, 2019. Patients of either gender aged 20-80 years who had a minimum follow-up of one year were included. Data was collected using the Head and Neck Cancer registry form and the medical record files. The subjects were also contacted by telephone when needed. The study end-points were disease-free survival and overall survival. Data was analysed using SPSS 21. RESULTS: Out of the 83 patients, 65(78%) were male. The overall median(range) age was 46(20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 15(18%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. Overall survival was 42.2% with the median(range) follow-up time was 14(9-21) months and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13(7-19). The factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043). Conclusion: Among T4 oral squamous cell carcinoma patients treated with surgery and adjuvant therapy, the rate of disease recurrence was found to be high. Tumours with a high cervical nodal disease burden and/or margin involved were at substantially higher risk of recurrence.

A rare case of three years disease free survival in a locally advanced parathyroid carcinoma successfully excised by complete surgical resection.

Parathyroid carcinoma (PC) is one of the rarest malignancies making approximately 0.005% of all cancers. It may arise sporadically or less commonly, in conjunction with genetic endocrine syndromes. Due to the rarity of the disease, no general consensus or definitive guidelines exist for its pre-operative diagnosis, management, or follow up. Surgical tumor removal is the gold standard treatment to prevent its recurrence. Parathyroid carcinoma has a high recurrence rate ranging from 40 to 60% in recent literature. We report a case of a seventy-year-old elderly female with locally advanced parathyroid carcinoma successfully surgically excised completely with a 3 year disease free survival period without adjuvant chemotherapy or radiotherapy.

A case report of Munchausen syndrome presenting with bleeding from ear: a rare factitious disorder.

Munchausen syndrome is a rare psychiatric illness that includes mimicking a group of medical conditions, in which a person repeatedly harms him or herself or falsely misinterprets any medical condition when he or she is not actually sick, in order to achieve health care attention. Underdiagnosis of this syndrome leads to irrelevant use of medical assets. Here, we document an interesting and rare case of a young girl presented in the outpatient department of the Otolaryngology department of Patel Hospital with episodes of bleeding from her ear, which is a rare presentation of Munchausen syndrome. Her complete physical, otolar yngological, haematological and radiological examination failed to reveal any clue towards a particular diagnosis. Hence a diagnosis of Munchausen syndrome was made by exclusion of other possibilities of ear bleeding, and it was considered as a case report after taking duly signed written consent from the patient. This report will help in increasing the self-knowledge and perception of different clinical based presentations of this syndrome in medical practitioners, in order to avoid overlooking such cases. Further exploratory work is required in this regard to discover the etiology and predisposing factors and to develop new treatment strategies.

Clinical symptoms that predict the presence of Obstructive Sleep Apnea.

OBJECTIVE: To determine if a set of clinical symptoms can help in determining the presence and severity of OSA. SETTING: Tertiary urban pediatric hospital. METHODS: Parents of children undergoing an overnight PSG answered a 56 item questionnaire based on their child's symptoms. The responses to the questionnaire were compared between patients with different severities of OSA (s determined by PSG) and those without OSA. Responses to questionnaire were also analyzed between obese and non-obese patients. RESULTS: 235 children were included (140 male and 95 female) with a mean age of 5.76 ± 2.78 years. The mean Apnea Hypopnea Index (AHI) was 7.78 ± 14.50 events/hour (range 0-110 events/h). 74 (31.5%) children had mild-OSA (AHI between 1 and 4.99 events/h), 31 (13.19%) had moderate-OSA (AHI between 5 and 9.99 events/h), 58 (24.7%) had severe-OSA (AHI≥10events/h) and the remaining 72 (30.64%) had No-OSA (AHI≤1event/h). 87 (37%) patients were obese. Eight clinical symptoms in non-obese and six clinical symptoms in obese patients predicted the mild to severe OSA. Sixteen symptoms in non-obese patients and nine symptoms in obese patients predicted the presence of severe OSA in these patients. CONCLUSION: Clinical symptoms reported in this study are useful to predict the presence of and the severity of OSA in children. Clinical symptoms can also predict the presence and severity of OSA in children who are obese, however, the symptoms required to make the prediction are different in obese children.

Impact of short sleep on metabolic variables in obese children with obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: To analyze the association between sleep duration, metabolic variables, and insulin resistance in obese children with and without obstructive sleep apnea. The decline in sleep duration has paralleled a dramatic increase in the prevalence of obesity and diabetes, suggesting a mechanistic relationship. STUDY DESIGN: Retrospective, case series. METHODS: Consecutive obese patients 3 to 12 years of age who underwent polysomnography (PSG) and a metabolic panel and who completed a 14-item sleep questionnaire were analyzed. All laboratory testing was conducted within 3 months of PSG. Total sleep times were obtained from the PSG and confirmed by the questionnaire. RESULTS: A total of 171 patients (55.0% male) were studied. All patients were obese (body mass index [BMI] z score > 95th percentile). Patients were categorized into three groups: short sleepers, borderline sleepers, and optimal sleepers. Eighty-six (50.3%) patients were short sleepers, 71 (41.5%) were borderline sleepers, and 14 (8.2%) were optimal sleepers. The mean BMI z score was 3.13 ± 1.3 in short sleepers, 3.3 ± 1.1 in borderline sleepers, and 3.5 ± 1.5 in optimal sleepers (P = .39). There was no statistical difference in high- and low-density lipoprotein levels (P = .21 and P = .76, respectively) and total cholesterol (P = .43) among subgroups. Triglycerides, blood glucose, insulin, and homeostasis model assessment-insulin resistance were significantly higher in short sleepers when compared to borderline or normal sleepers (P = .008, P < .001, P < .001, and P < .001, respectively). CONCLUSIONS: Short sleep duration was correlated with alterations in metabolic variables and insulin resistance in obese patients. This raises concern for development of comorbid conditions that can persist into adulthood. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:2176-2181, 2017.

Cochlear implantation of solid organ transplant patients receiving immunosuppressive therapy.

OBJECTIVE: To evaluate the incidence of infectious complications and healing problems in cochlear implant (CI) patients receiving immunosuppressive therapy following solid organ transplant. STUDY DESIGN: IRB-approved retrospective chart review of implanted patients. SETTING: Tertiary care children's hospital. METHODS: Seven patients of the more than 1000 implanted during the time period between 1991 and 2014 underwent cochlear implantation while on immunosuppressive therapy after having received a solid organ transplant. Their charts were reviewed for demographic and medical information pre- and post-implantation. The 4 males and 3 females ranged in age at CI from 2.4 to 18.8 years, with a mean of 9.0 years. Postimplant follow-up averaged 3.9 years (range: 0.1-13.1). Main outcome measures were occurrence of wound healing, infectious complications, whether open-set word recognition was achieved, and communication mode(s). RESULTS: No wound infections or delayed healing, mastoiditis, or bacterial meningitis occurred after cochlear implantation. All seven patients had received at least one pneumococcal vaccination prior to implantation. Five of 6 (83%) developed open-set speech perception, of whom 4 (67%) use only oral communication. CONCLUSION: In our series of patients receiving immunosuppressive therapy following solid organ transplantation, none developed wound healing or infectious complications after cochlear implantation. History of solid organ transplantation alone should not be a contraindication to cochlear implant candidacy which would deprive the child of the potential benefits of hearing, including language development.

Metabolic alterations in adolescents with obstructive sleep apnea.

IMPORTANCE: Obesity is one of the leading health concerns in developed and in developing countries. The risk of obstructive sleep apnea (OSA) is greatly increased by obesity. Obesity is known to be associated with the Metabolic Syndrome and cardiovascular disease in adults. This same association in children is not well defined. Understanding the relationship of obesity, OSA, and metabolic alterations in children would improve understanding of the risks of cardiovascular disease into adulthood. OBJECTIVE: To evaluate the association of OSA and metabolic outcomes, including lipid variables and insulin resistance, in obese adolescents. METHODS: Retrospective, case-control series at a tertiary care children's hospital. Obese adolescents aged 12-18 years who underwent overnight polysomnography (PSG) and routine laboratory testing for lipid levels, fasting glucose, and insulin from January 1, 2006 to December 31, 2012. RESULTS: A total of 42 patients with a mean age of 14.1±1.9 years were analyzed. Nineteen (45.2%) were male. The mean body mass index (BMI) z score was 2.23±0.86, and all patients were obese (BMI z score >95th percentile). Triglyceride, fasting blood glucose, insulin, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were significantly higher in patients with OSA when compared to those with No-OSA (p<0.01). There was incremental worsening of insulin and HOMA-IR with greater severity of OSA. The apnea-hypopnea index (AHI) was positively and significantly correlated with blood glucose and HOMA-IR (p=0.01and p<0.001, respectively). Multiple linear regression analysis showed that the AHI was a predictor of blood glucose (p=0.04) and HOMA-IR (p=0.01) independent of age, gender, total sleep time and BMI z score. Logistic regression analysis showed that elevated levels of blood glucose predicted severe OSA (p=0.02) independent of gender and BMI z score. Elevation in HOMA-IR predicted severe OSA (p=0.004). CONCLUSION: OSA severity is associated with increased fasting insulin, blood glucose and HOMA-IR even after controlling for the age, and BMI z score in adolescents.

Anti-miR182 reduces ovarian cancer burden, invasion, and metastasis: an in vivo study in orthotopic xenografts of nude mice.

High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely because of widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long-term benefits for patients with cancer. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment, which is emerging as a potential modality for cancer therapy. MicroRNA-182 (miR182) overexpression contributes to aggressive ovarian cancer, largely by its negative regulation of multiple tumor suppressor genes involved in tumor growth, invasion, metastasis, and DNA instability. In this study, we examined the therapeutic potential of anti-miR182 utilizing the animal orthotopic model to mimic human ovarian cancer using ovarian cancer cells SKOV3 (intrabursal xenografts) and OVCAR3 (intraperitoneal injection). These models provide a valuable model system for the investigation of ovarian cancer therapy in vivo. Through a combination of imaging, histological, and molecular analyses, we found that anti-miR182 treatment can significantly reduce tumor burden (size), local invasion, and distant metastasis compared with its control in both models. The bases of anti-miR182 treatment are mainly through the restoration of miR182 target expression, including but not limited to BRCA1, FOXO3a, HMGA2, and MTSS1. Overall, our results strongly suggest that anti-miR182 can potentially be used as a therapeutic modality in treating HGSOC.