Delay in the Diagnosis of Pediatric Brain Tumors in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Vague symptoms and a lack of pathognomonic features hinder the timely diagnosis of pediatric brain tumors (PBTs). However, patients in low- and middle-income countries (LMICs) must also bear the brunt of a multitude of additional factors contributing to diagnostic delays and subsequently affecting survival. Therefore, this study aims to assess these factors and quantify the durations associated with diagnostic delays for PBTs in LMICs. METHODS: A systematic review of extant literature regarding children from LMICs diagnosed with brain tumors was conducted. Articles published before June 2023 were identified using PubMed, Google Scholar, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, and Web of Science. A meta-analysis was conducted using a random-effects model through R Statistical Software. Quality was assessed using the Newcastle Ottawa Scale. RESULTS: A total of 40 studies including 2483 patients with PBT from 21 LMICs were identified. Overall, nonspecific symptoms (62.5%) and socioeconomic status (45.0%) were the most frequently reported factors contributing to diagnostic delays. Potential sources of patient-associated delay included lack of parental awareness (45.0%) and financial constraints (42.5%). Factors contributing to health care system delays included misdiagnoses (42.5%) and improper referrals (32.5%). A pooled mean prediagnostic symptomatic interval was calculated to be 230.77 days (127.58-333.96), the patient-associated delay was 146.02 days (16.47-275.57), and the health care system delay was 225.05 days (-64.79 to 514.89). CONCLUSION: A multitude of factors contribute to diagnostic delays in LMICs. The disproportionate effect of these factors is demonstrated by the long interval between symptom onset and the definitive diagnosis of PBTs in LMICs, when compared with high-income countries. While evidence-based policy recommendations may improve the pace of diagnosis, policy makers will need to be cognizant of the unique challenges patients and health care systems face in LMICs.

Real-World Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated With Bortezomib/Cyclophosphamide/Dexamethasone and Bortezomib/Lenalidomide/Dexamethasone as Upfront Treatment.

Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current mainstay of treatment for patients with newly diagnosed MM (NDMM) is a triplet regimen with a proteasome inhibitor, immunomodulatory imide, and dexamethasone. The two most common of these triplet regimens are VLD (bortezomib/lenalidomide/dexamethasone) and VCD (bortezomib/cyclophosphamide/dexamethasone). This study aims to compare the outcomes between these two therapies in transplant-ineligible patients with NDMM. Methods We conducted a retrospective study at the Aga Khan University Hospital in Karachi, Pakistan. All NDMM transplant-ineligible patients either receiving VLD or VCD therapy between January 2015 and December 2022 were included in our study. Hematological parameters before and after treatment were obtained from hospital records. Response to treatment was classified according to the International Myeloma Working Group (IMWG) response criteria as either complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), or progressive disease (PD). The response to treatment as well as overall survival (OS) and progression-free survival (PFS) was compared between VCD and VLD therapy. A p-value of 0.05 or less was taken to be statistically significant. Results Twenty (23.8%) patients in the VCD group and 20 (23.0%) in the VLD group underwent complete remission. Seven (8.3%) patients experienced disease progression in the VCD group, while the figure stood at three (3.4%) in the VLD group. There was no statistically significant difference in the overall response rate between the VCD (58; 69.0%) and VLD (70; 80.5%) groups (p=0.086), a difference that was not statistically significant on the Chi-square test. OS was comparable between VCD (69.1 months, 95%CI: 61.3-77.0) and VLD (76.9 months, 95%CI: 69.0-85.0) therapies. Conclusions The study did not identify any statistically significant distinction in the treatment outcomes between the VCD and VLD regimens among NDMM patients ineligible for transplantation. Nevertheless, the study highlights the positive outcomes observed with both treatments in this specific patient cohort. This implies that either regimen could be deemed suitable as a treatment option for patients in low- and middle-income countries. Since both regimens demonstrate comparable effectiveness, assessing the cost-effectiveness of these regimens is crucial. Future research should also explore the economic aspects of the two treatment options.

Diagnostic Accuracy of Intraoperative Brain Smear: A Meta-Analysis of Studies from Resource-Limited Settings.

BACKGROUND: Intraoperative brain smear is an easy, rapid, and cost-effective technique for immediate diagnosis of brain tumors. Earlier studies have gauged its application on limited number of samples, but its diagnostic accuracy especially in low-resource settings, where its practice would be extremely helpful, is still undetermined. To investigate the diagnostic accuracy of intraoperative brain smear in resource-limited settings for diagnosis of brain tumors. METHODS: A systematic search was conducted on PubMed, Google Scholar, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase for all articles utilizing intraoperative brain smears that were extracted. Studies from low- and middle-income countries (LMICs) with test performance characteristics were selected and subsequent values were summarized using a hierarchical summary receiver operating characteristic (ROC) curve via STATA and pooled using a random-effects model on MetaDiSc 2.0. RESULTS: Twelve studies consisting of 1124 patients were identified. Six studies included both adult and pediatric population groups, while 4 investigated adults and 2 included pediatric patients. The pooled diagnostic odds ratio (OR) was calculated to be 212.52 (CI: [104.27-433.13]) of Bivariable pooled specificity and sensitivity were 92% (CI: [86%-96%]) and 96% (CI: [93%-98%]), respectively. CONCLUSIONS: Our study shows that intraoperative brain smear is not only an accurate and sensitive diagnostic modality in resource-rich settings, but it is also equally useful in resource-limited settings, making it an ideal method for rapid diagnosis.

Perception of Neurosurgery as a Career Choice Among Early Career Doctors in Pakistan: A Nationwide Cross-Sectional Survey.

BACKGROUND: A low neurosurgeon-to-patient ratio persists in many developing nations including Pakistan. We aimed to investigate the perceptions of medical students regarding neurosurgery as a first step toward recognizing this problem and potentially suggesting ways to solve it. METHODS: A questionnaire was designed comprising 3 sections: 1) demographics, 2) possible challenges and perceptions regarding neurosurgery as a profession, and 3) general perceptions about neurosurgery. Statistical analysis was conducted, and a P value < 0.05 was considered significant. RESULTS: Of 387 responses received, 44.4% of male respondents and 50.6% of female respondents revealed intent to consider opting for neurosurgery as a profession. Regression analysis revealed inadequate dexterity (P = 0.001) and inability to carry out private practice (P = 0.002) were responsible for increased likelihood of opting out of neurosurgery by medical students. CONCLUSIONS: This study identified the perceptions that may influence the decision to pursue neurosurgical training among physicians early in their careers. Interventions including availability of day care facilities for children and introduction of curricula to promote neurosurgical knowledge in clinical training are expected to encourage the decision to pursue neurosurgery among medical students in Pakistan.

The role of angiotensin receptor blockers in treating epilepsy: a review.

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind.

Association of neutrophil-to-lymphocyte ratio with clinical, pathological, radiological, laboratory features and disease outcomes of invasive breast cancer patients: A retrospective observational cohort study.

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.

The Precedent set by Unprecedented Rainfall: Lessons to be Learnt From Disastrous Flooding in Pakistan.

Pakistan has suffered heavy losses due to the torrential monsoon rains of 2022. With obliterated infrastructure and rising disease burden, the nation is still reeling from the dismal aftermath. It is critical to understand that such catastrophes are not a 1-time calamity but are likely to become more frequent with growing severity of the climate crisis. These losses point to a more systemic problem that is a lack of preparedness, and without sustainable long-term measures in place, the nation remains just as vulnerable to the next 'unpredictable' weather contingency. Prior planning and effective allocation of resources can help develop a proactive response to future disasters of this magnitude.

Aiding gastrointestinal diagnostic laboratory by designing a device for the non invasive detection of peptic ulcer.

Peptic ulcer (PU) has been recognized as an utmost gastrointestinal problem that affects the lining of the stomach and duodenum, specifically triggering soreness. It is a life-threatening condition, while roots of the infection are not identified yet. There are various risk factors for the cause of peptic ulcer disease, but the most significant is "Helicobacter pylori" (H. pylori). The detection of this disease involves different invasive procedures which are painful and not feasible for everyone. The aim of this device is to identify the peptic ulcer non-invasively by unmasking the presence of H. Pylori bacterium by monitoring crucial parameters of the disease which include respiration rate, heart rate, ECG, pH of Saliva, and temperature. Multiple investigations related to PU authenticate the alteration in these physicochemical aspects of the body. The increase in the level of stomach acid in PU is responsible for belching and bloating. Heart rate, temperature, and respiratory rate are also elevated during peptic ulcers while the pH of Saliva is decreased toward the acidic side. The disturbance in the QRS complex of the ECG wave is also observed. These biosignals are examined as analog input from the body, sent into MCP3008, and converted into digital input signals. Then these digital inputs are directed toward Raspberry pi 3 which processes, received inputs, and shows output on the LCD. The values of parameters obtained are then compared with standard values and a conclusion is made that whether a patient has a peptic ulcer or not.

Managing and treating Sydenham chorea: A systematic review.

INTRODUCTION: Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan. METHODS: We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies. RESULTS: The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature. CONCLUSION: Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.

Comparative efficacy and safety of lemborexant 5 mg versus 10 mg for the treatment of insomnia: a systematic review.

INTRODUCTION: Insomnia is a common condition that may be caused by or coexist with other medical or psychological illnesses. Nearly a quarter of a billion people across the globe suffer from insomnia frequently. Lemborexant, a dual orexin receptor antagonist, is a recently authorized hypnotic-based medication for insomnia. The purpose of this systematic review is to further investigate its efficacy and safety profile, with the primary goal of comparing the effects of two FDA-approved doses of lemborexant, 5 mg and 10 mg (LEM5 and LEM10, respectively). MATERIALS AND METHODS: PubMed, Google Scholar, ClinicalTrials.gov, and Cochrane Central were searched for relevant literature, and studies were considered if they compared the efficacy and safety of lemborexant 5 mg to lemborexant 10 mg. This study comprised clinical trials. RESULTS: A total of 6 studies were evaluated for efficacy and safety of lemborexant therapy. They reported a significant betterment in values pertaining to sleep efficacy, sleep onset latency, wake after sleep onset, total sleep time, sleep quality, ISI score, and morning alertness. The results presented a dose-dependent pattern and showed slight variation with the different dosages. The most prevalent side effects noted were somnolence, headaches, and dizziness, with infections like UTIs and upper respiratory tract infections also being commonly reported. The incidence is rather ambiguous and not sincerely dose-dependent. The differences between results for LEM5 and LEM10 do not exhibit a wide variation, although slight dose-dependent alterations are noted. CONCLUSION: Lemborexant is well integrated with the amelioration of sleep disturbances in insomniac patients, as shown by a decrease in eSOL and sWASO and a rise in sSE, sTST, quality of sleep, and morning alertness. Effects last 12 months after therapy.

Efficacy and Safety of Vericiguat for Treatment of Heart Failure: A Systematic Review.

Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.

The battle against Thalassemia in Pakistan: Way to move forward.

Thalassemia, one of the most common genetic hemoglobinopathy, is yet still an economy-depriving disorder, prevalent throughout the world. Specifically in Pakistan, numerous factors have led to the ever-increasing numbers of the affected masses. Amidst its battle with other diseases, it is worthy to highlight that the country did not overlook this disorder and hence, significant work has been done to change the thalassemia status of the country. From the establishment of reforms to private philanthropic organizations, Pakistan is actively fighting against the disorder. However, some more practical working and well-devised planning can help the country, attain a thalassemic-free status.

SARS-CoV-2 Vaccination and Chilblain-like Lesions: What Do We Know so Far?

Introduction: The coronavirus pandemic has caused massive damage to global health care and the economy. The vaccination program has been paced around the globe to return as soon as possible to pre-COVID time. Although all the vaccines have been approved after the rigorous clinical and safety trials, some adverse effects have surfaced and are being reported from different parts of the world. One such side effect is chilblain-like lesions following the COVID vaccination. Chilblain lesions, also known as pernio, are an inflammatory condition usually affecting the acral regions of the body. It is mostly reported from cold and damp areas and has multiple causes associated with it. Objective: This study aims to review the publicly available data and to provide concise and comprehensive information as well as evaluate the potential pathology, clinical approach, and management of CLL post-vaccination. Methods: An extensive literature search over PubMed, Cochrane library, Google Scholar, and Clinicaltrails. gov from inception till 5th October 2021, without any restriction of language was carried out. All the recruited articles were reviewed, and their bibliographies were also screened for any relevant information. Results: 12 studies (10 case reports and 2 case series) were retrieved reporting the incidence of CLL post-vaccination. 8 studies reported incidence in female patients while 5 reported in males, with one study mentioning no gender. Moreover, most of them were either from Europe or the United States of America, except for two cases, reported from Turkey. Conclusions: Although the overall incidence of Chilblains following COVID-19 vaccination is low, there is still a strong need to find out the exact mechanism behind this to redefine the safety and administration criteria of the vaccines and to formulate a proper management protocol.

Postoperative cardiac troponin I as an indicator of surgical outcomes: A systematic review.

INTRODUCTION: Cardiac surgeries are generally associated with high morbidity and mortality. To prevent any adverse outcomes, it is crucial to identify patients at risk of developing postoperative complications and initiate relevant therapeutic interventions. Several biomarkers are used to determine postoperative myocardial injury but they either lack sensitivity and specificity or are elevated for a short time. In this systematic review, we evaluate postoperative troponin I as a predictor of postoperative myocardial infarction, mortality, and hospital and Intensive Care Unit stay. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. A thorough literature search was conducted over PubMed, clinicaltrials. gov, and the Cochrane library from inception till May 24, 2022 using relevant keywords, and only articles that met the pre-defined criteria were recruited. RESULTS: Following a comprehensive literature search, a total of 359 articles were obtained. Following a rigid screening and full-length review, only 13 studies met our inclusion criteria and were included. The recruited studies evaluated data from a total of 12,483 individuals and assessed troponin I as a predictor of at least one outcome. CONCLUSION: Troponin I has the potential to be used as a stand-alone predictor of surgical outcomes following coronary artery bypass grafting and valvular surgeries. However, supplementing it with other markers and scores offers the best chance at timely diagnosing any complications.

SARS-CoV-2 vaccination and uveitis: Are they linked?

In 2019, the discovery of a new strain of Coronavirus, later referred to as SARS-CoV2 took the world by storm, leading to a pandemic and shutting down all global activities. Several measures were taken adequately to combat the viral havoc, including developing numerous vaccines. All the vaccines currently available for the general population went through rigorous screenings and trials to ensure maximum safety and were only approved after that. However, once they were rolled out in the markets and administered to the population, some adverse reactions were reported, one of which included uveitis. It is an ocular inflammatory condition of the uveal tract, choroid, or iris. If untreated, it can lead to severe consequences, including blindness. It is further divided into four categories based on its anatomical location. Despite the rare incidence of uveitis following COVID-19 vaccination, it may contribute to vaccine hesitancy; hence addressing and digging into the pathophysiological cause is crucial. This study evaluates all the pathophysiological and demographical links between COVID-19 vaccination and uveitis, suggesting appropriate management plans.

Mysterious dengue-like virus: A case report from Pakistan.

Recently, in Pakistan, several cases of mysterious dengue-like illness are being reported, which has concerned the authorities and requires prompt action. We present a case of a 52-year-old female patient presenting with a history of continuous fever, documented up to 104 F, for 5 days. The symptoms were associated with headache, nausea, retro-orbital headache, arthralgia, and myalgia. Currently, to the best of our knowledge, this is the first reported case in the literature for the endemic mysterious virus and may serve as the groundwork for future studies.