Development of palliative care clinical practice guidelines and referral care pathways for primary care practitioners in Pakistan.

BACKGROUND: Despite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan. METHODS: A GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The "National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021" was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either "Adopt," "Adapt" or "Exclude". The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines. RESULTS: Twenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made. CONCLUSION: The described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.

Diagnostic accuracy of tests for tuberculous pericarditis: A network meta-analysis.

Tuberculous pericarditis (TBP) is a relatively uncommon but potentially fatal extrapulmonary manifestation of tuberculosis. Despite its severity, there is no universally accepted gold standard diagnostic test for TBP currently. The objective of this study is to compare the diagnostic accuracy of the most commonly used tests in terms of specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV), and provide a summary of their diagnostic accuracies. A comprehensive literature review was performed using Scopus, MEDLINE, and Cochrane central register of controlled trials, encompassing studies published from start to April 2022. Studies that compared Interferon Gamma Release Assay (IGRA), Xpert MTB/RIF, Adenosine Deaminase levels (ADA), and Smear Microscopy (SM) were included in the analysis. Bayesian random-effects model was used for statistical analysis and mean and standard deviation (SD) with 95% confidence intervals were calculated using the absolute risk (AR) and odds ratio (OR). Rank probability and heterogeneity were determined using risk difference and Cochran Q test, respectively. Sensitivity and specificity were evaluated using true negative, true positive, false positive, and false negative rates. Area under the receiver operating characteristic (AUROC) was calculated for mean and standard error. A total of seven studies comprising 16 arms and 618 patients were included in the analysis. IGRA exhibited the highest mean (SD) sensitivity of 0.934 (0.049), with a high rank probability of 87.5% for being the best diagnostic test, and the AUROC was found to be 94.8 (0.36). On the other hand, SM demonstrated the highest mean (SD) specificity of 0.999 (0.011), with a rank probability of 99.5%, but a leave-one-out analysis excluding SM studies revealed that Xpert MTB/RIF ranked highest for specificity, with a mean (SD) of 0.962 (0.064). The diagnostic tests compared in our study exhibited similar high NPV, while ADA was found to have the lowest PPV among the evaluated methods. Further research, including comparative studies, should be conducted using a standardized cutoff value for both ADA levels and IGRA to mitigate the risk of threshold effect and minimize bias and heterogeneity in data analysis.

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.

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.

The CalculAuthor: determining authorship using a simple-to-use, fair, objective, and transparent process.

Authorship determination on a research article remains a largely subjective process. Existing guidelines on authorship taxonomy lack objectivity and are more useful in determining who deserves authorship rather than determining the order of authors. To promote best practices in authorship taxonomy, we developed an authorship rubric that provides a fair, objective, and transparent means of crediting authorship. We christened this tool the "CalculAuthor". The following steps are to be undertaken to create a scoring system based on the requirements of the projects: determining creditable criteria, assigning credit weightages, deciding levels of contribution, determining each author's contribution, calculating authorship scores and ranking. These must be performed by or in close collaboration with the primary investigator (PI), with conflicts being resolved at the PI's discretion. All team members should be informed about the authorship determination process early in the project and their agreement regarding its use must be obtained. While the CalculAuthor was developed to be used in medical research, its customizability enables it to be employed in any field of academia. We recommend that the CalculAuthor be piloted within institutions before its mainstream adoption, and any institution-specific factors should be considered to make the process more efficient and suitable.

The tendency of segmental distribution of hepatic metastasis according to couinaud classification: a comparison of portal versus systemic route of metastatis due to primary colorectal and breast tumors.

Objective: The liver is the commonest site of metastatic disease for patients with colorectal cancer (CRC), with at least 25% of patients developing liver metastasis (LM) during their illness. About 50% of patients diagnosed with metastatic breast cancer develop LM, and 5-12% of these patients develop LM as the main site of breast cancer recurrence. This study aims to determine the frequency of segmental distribution of LM seeding from portal versus systemic routes of dissemination due to primary CRC and breast carcinoma, respectively. Material and methods: This retrospective study was conducted in a tertiary care teaching hospital in Pakistan. Ethical approval was taken from the institutional review board. A total of 587 patients were included in the study with 297 CRC patients with LM and 300 breast carcinoma patients with LM. Segment I involvement was excluded from the calculation because of the dual blood supply. Patients' detailed demographics and other information were collected on a predesigned proforma. The authors evaluated axial and multiplanar reformatted computed tomography images for LM and CRC metastasis. Data analysis was done using SPSS version 25. P value less than or equal to 0.05 was considered statistically significant. Results: A study population of 587 patients was employed that comprised 287 CRC and 300 breast carcinoma patients. There were 179 (30.5%) male and 408 (69.5%) female patients. The mean age of patients was 54.9±13.3. The study revealed that 204 (34.8%) CRC patients showed right lobe (V, VI, VII, VIII) and 83 (14.1%) CRC patients showed left lobe involvement of metastasis while 192 (32.7%) breast carcinoma patients showed right lobe involvement and 108 (18.4%) breast carcinoma patients showed left lobe involvement in metastasis (P=0.02). We also found 40 (6.8%) colorectal and 55 (9.4%) breast carcinoma patients showed left lateral segment (II, III) involvement. Medial segment involvement (IV) was seen in 43 (7.3%) CRC patients and 53 (9%) breast carcinoma patients (P=0.03). Conclusion: The right hepatic lobe is the predominant site of metastasis independent of the portal or systemic route of dissemination in primary carcinoma. Moreover, in left lobe metastasis medial segment (IV) is more affected in CRC while the lateral segment (II, III) is more affected in breast carcinoma.

Comparative analysis of pinning techniques for supracondylar humerus fractures in paediatrics: A systematic review and meta-analysis of randomized controlled trials.

Purpose: Supracondylar humeral fractures (SCHFs) rank among the frequently observed fractures in children. Nonetheless, there exists a dearth of consensus regarding the optimal surgical approach. This meta-analysis aims to thoroughly evaluate and compare two distinct pinning techniques (cross pinning versus lateral pinning) for SCHFs, using data from Randomized controlled trials (RCTs). Methods: Literature review was done using PubMed, CINAHL, Scopus, and The Cochrane Library for RCTs comparing the two pinning methods and providing information on at least one of the following: Loss of Baumann's angle, loss of carrying angle, elbow function assessed based on Flynn criteria, pin tract infection, and iatrogenic ulnar nerve injury. Random effect model was used to calculate standardized mean difference or Odds Ratio (OR) for the outcomes. Review Manager 5.4.1. was used to perform quality assessment and statistical analysis. Results: A total of 22 RCTs were included. 20 studies reported data for iatrogenic ulnar nerve injury, the OR was calculated to be 3.76 (95% CI 1.75-8.06), showing a significantly lower risk of surgical ulnar nerve injury with the lateral technique. However, no significant difference was found between the pinning techniques in regard to the other outcomes. Conclusion: In comparison to lateral pinning, the utilization of cross pinning technique exposes the patient to a heightened susceptibility of iatrogenic nerve injury. Therefore, it is recommended that surgeons prioritize the implementation of the lateral pinning technique whenever feasible, as it offers greater protection against iatrogenic ulnar nerve injury. For the other intraoperative and postoperative outcomes, both surgical techniques yield comparable results.

Clinical outcomes of different revascularization approaches for patients with multi-vessel coronary artery disease: A network meta-analysis.

BACKGROUND: As surgical techniques continue to evolve, the optimal approach for revascularizing multi-vessel coronary artery disease (CAD) remains a matter of ongoing debate. Accordingly, our objective was to compare and contrast various surgical techniques utilized in the management of multi-vessel CAD. METHODS: A systematic literature review was performed using PubMed, Embase, and Cochrane central register of controlled trials from inception to May 2022. Random-effects network meta-analysis was performed for the primary outcome; target vessel revascularization (TVR), and secondary outcomes; mortality, major adverse cardiac and cerebrovascular events, postoperative myocardial infarction, new-onset atrial fibrillation, stroke, new-onset dialysis, in patients undergoing percutaneous coronary intervention (PCI) with a stent, off-pump coronary bypass graft, on-pump coronary artery bypass graft (ONCABG), hybrid coronary revascularization, minimally-invasive coronary artery bypass, or robot-assisted coronary artery bypass (RCAB) surgeries. RESULTS: A total of 8841 patients were included from 23 studies. The analysis showed that ONCABG had the highest freedom from TVR, with a mean (SD) absolute risk of 0.027 (0.029); although ONCABG was found to be superior to all other methods, it was only significantly better than first-generation stent PCI. While RCAB did not demonstrate significant superiority over other treatments, it showed a greater probability of preventing postoperative complications. Notably, no significant heterogeneity was calculated for any of the reported outcomes. CONCLUSIONS: ONCABG shows a better rank probability compared to all other techniques for preventing TVR, while RCAB offers greater freedom from most postoperative complications. However, given the absence of randomized controlled trials, these results should be interpreted with caution.

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.

Global geographic and gender disparities in stem cell-related surgical research: bibliometric review of the top 200 most-cited articles.

Objectives: The study aimed to identify geographic and gender disparities in the quality, academic impact, and media attention of the top-cited articles related to stem cell-related surgical research. METHODS: The following data was extracted for the top 200 most-cited articles (2011-2021): article- (including citation metrics and country of publication), journal- (including impact factor), and author-level (including corresponding author gender) variables. Article Altmetric Attention Score (AAS), a measure of mass mainstream and social media attention, was also recorded. RESULTS: Most articles originated from high-income countries (HICs: 175 [87.5%]), with only 7 (3.5%) from lower-middle-income countries. Articles from non-HIC were published in journals with significantly lower impact factors (6.66 [3.75-9.46] vs. 23.2 [7.3-32.5]; p < 0.001) and AAS (7 [3-14.5] vs. 30 [11-83]; p < 0.001). Only 44 (22%) of articles were authored by a female corresponding author, with these having significantly fewer citations than those authored by a male (289 [250-400] vs. 331.5 [267.25-451.25]; p=0.031). CONCLUSIONS: Even amongst the top-cited literature, our results demonstrate worrying disparities in the geographic origins of stem cell-related surgical research. The vast majority originates from HICs, with these articles being published in better journals and receiving greater media attention. We also identified significant gender disparities, with female representation being concerningly low and female-authored articles receiving significantly fewer citations.

Safety outcomes of anti-platelet therapy post coronary artery bypass graft surgery: A systematic review and network meta-analysis of randomized control trials.

BACKGROUND: Antiplatelet therapy is used to decrease the risk of graft failure post coronary artery bypass graft surgery. We aimed to compare dual antiplatelet therapy (DAPT) with monotherapy along with a comparison of Aspirin, Ticagrelor, Aspirin+Ticagrelor (A+T) and Aspirin+Clopidogrel (A+C) to determine the major and minor bleeding risk, risk of postoperative myocardial infarction (MI), stroke, and all-cause mortality (ACM). METHODS: Randomized Controlled Trials comparing the four groups were included. Odds ratio (OR) and Absolute Risk (AR) were employed to assess the mean and standard deviation (SD) with 95% confidence intervals (CI). The Bayesian random-effects model was used for statistical analysis. Risk difference and Cochran Q tests were used to calculate rank probability (RP) and heterogeneity, respectively. RESULTS: We included 10 trials, consisting of 21 arms and 3926 patients. For the risk of major and minor bleed, A + T and Ticagrelor showed the lowest mean value of 0.040 (0.043) and 0.067 (0.073), respectively, and the highest RP of being the safest group. While a direct comparison between DAPT and monotherapy resulted in an OR of 0.57 [0.34, 0.95] for the risk of minor bleed. A + T was found to have the highest RP and the lowest mean value in terms of ACM, MI, and stroke. CONCLUSION: No significant difference was found between monotherapy or dual-antiplatelet therapy for the major bleeding risk safety outcome, however DAPT was found to have a significantly higher rate of minor bleeding complications post-CABG. DAPT should be considered as the antiplatelet modality of choice post-CABG.

Termination of seizures in the paediatric age group, best benzodiazepine and route of administration: A network meta-analysis.

This network meta-analysis aims to compare various benzodiazepines and their route of administration using the data published exclusively in randomized controlled trials (RCTs). Two thousand two hundred sixty-three children presenting with an episode of seizure to ER or to a paramedic where they were administered a benzodiazepine as the first-line treatment were included. All the outcomes were measured for their mean with 95% CI and rank probability. The primary outcome was the number of successful seizure cessation. Secondary outcomes were the time interval between drug administration and seizure cessation, the time interval between patient arrival and seizure cessation and the number of episodes of seizure recurrence after drug administration. For the number of successful cessations, intramuscular midazolam showed the highest mean and best rank probability with a value of .881 (.065) and 57.9%, respectively. For the time of cessation, both intravenous lorazepam (IVL) and intravenous diazepam showed a mean of 3.30 (1.30) with IVL having the highest rank probability of 32%. For total time for cessation, intranasal midazolam showed the best mean and rank probability with a value of 4.3 (1.1) and 55%, respectively. Buccal midazolam showed the lowest mean with a value of .106 (.084) for rate of recurrence. Although there was no significant difference between the treatments, but based on the rank probability, IVL shows more promising results for patients who already have an established intravenous line, and for patients presenting in the ER without an intravenous line, the first line of treatment should be INM as it shows the highest rank probability in total time with second-highest successful cessation rate.

Adolopment of adult diabetes mellitus management guidelines for a Pakistani context: Methodology and challenges.

Introduction: Pakistan has the highest national prevalence of type 2 diabetes mellitus (T2DM) in the world. Most high-quality T2DM clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local T2DM CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of adult DM in Pakistan. Methods: We employed the GRADE-ADOLOPMENT approach utilizing the T2DM CPG of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes - 2021 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 document contained 243 recommendations, 219 of which were adopted without change, 5 with minor changes, and 18 of which were excluded in the newly created Pakistani guidelines. One recommendation was adapted: the recommended age to begin screening all individuals for T2DM/pre-diabetes was lowered from 45 to 30 years, due to the higher prevalence of T2DM in younger Pakistanis. Exclusion of recommendations were primarily due to differences in the healthcare systems of Pakistan and the US, or the unavailability of certain drugs in Pakistan. Conclusion: A CPG for the management of T2DM in Pakistan was created. Our newly developed guideline recommends earlier screening for T2DM in Pakistan, primarily due to the higher prevalence of T2DM amongst younger individuals in Pakistan. Moreover, the systematic methodology used is a significant improvement on pre-existing T2DM CPGs in Pakistan. Once these evidence based CGPs are officially published, their nationwide uptake should be top priority. Our findings also highlight the need for rigorous expanded research exploring the effectiveness of earlier screening for T2DM in Pakistan.