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 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.

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.

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.

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.

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.

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.

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.