Implementation of a clinical breast exam and referral program in a rural district of Pakistan.

BACKGROUND: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan. METHODS: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up. RESULTS: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community's breast cancer knowledge at the follow-up visits using the standardized post-test. CONCLUSIONS: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatment.

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.

Quality of life after robotic versus conventional minimally invasive cancer surgery: a systematic review and meta-analysis.

Optimizing postoperative quality of life (QoL) is an essential aspect of surgical oncology. Minimally invasive surgery (MIS) decreases surgical morbidity and improves QoL outcomes. This meta-analysis aimed to compare post-operative QoL after oncologic resections using different MIS modalities. The PubMed, Embase, Scopus, and CENTRAL databases were searched for articles that compared post-operative QoL in patients undergoing video-assisted thoracoscopic (VATS) or laparoscopic surgery (LS) versus robotic surgery (RS) for malignancy. Quality assessment was performed using the ROBINS-I and Cochrane Risk of Bias 2 (RoB-2) tools. Meta-analysis was performed using an inverse-variance random effects model. 27 studies met the inclusion criteria, including 5 randomized controlled trials (RCTs). 15 studies had a low risk of bias, while 11 had a moderate risk of bias and 1 had serious risk of bias. 8330 patients (RS: 5090, LS/VATS: 3240) from across 25 studies were included in the meta-analysis. Global QoL was significantly better after robotic surgery in the pooled analysis overall (SMD: - 0.28 [95% CI: - 0.49, - 0.08]), as well as in the prostatectomy and gastrectomy subgroups. GRADE certainty of evidence was low. Analysis of EPIC-26 subdomains also suggested greater sexual function after robotic versus laparoscopic prostatectomy. Robotic and conventional MIS approaches produce similar postoperative QoL after oncologic surgery for various tumor types, although advantages may emerge in some patient populations. Our results may assist surgeons in counseling patients who are undergoing oncologic surgery.

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.

Comparing redo surgery and stereotactic radiosurgery for recurrent, residual, and/or tumors showing progression in nonfunctioning pituitary adenomas: A systematic review and meta-analysis.

Background: Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with headaches, visual disorders, or cranial nerve deficits. NFPAs can recur, progress, or present as residual tumors. We, therefore, conducted this review to compare the effects of both revision surgery and stereotactic surgery on tumor size, visual status, endocrine status, and complications. Methods: A systematic review of published literature on recurrent, residual, or progressing NFPAs that underwent redo surgery or stereotactic radiosurgery from the inception till June 2020 was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen records (1209 patients) were included, and risk ratio (RR) and 95% confidence intervals (CIs) estimated from each study were pooled using a random-effects meta-analysis model. Results: Redo surgery was the preferred intervention in patients presenting with larger tumor sizes and was more effective in reducing the tumor size as compared to stereotactic radiosurgery (SRS) (risk ratio [RR] 56.14; 95% CI, 16.45-191.58). There was more visual loss with revision surgery as compared to SRS (risk ratio [RR] 0.08; 95% CI, 0.03-0.20). However, SRS was associated with fewer complications, such as new diabetes insipidus, as compared to the redo surgery (risk ratio [RR] 0.01; 95% CI 0.01-0.03). Conclusion: Redo surgery is the superior choice in the treatment of recurrent/residual or progressing NFPAs if the tumor size is large and an immediate reduction in tumor burden through debulking is warranted. However, redo surgery is associated with a higher risk of visual loss, new endocrinopathies, and other complications, in contrast to SRS.

Novel Journal Metrics in Cardiothoracic Surgery: How Different Are Contemporary Metrics From the Impact Factor?

OBJECTIVE: Despite shortcomings, impact factor (IF) remains the "gold standard" metric for journal quality. However, novel metrics including the h-index, g-index, and Altmetric Attention Score (AAS; mentions in mainstream/social media) are gaining traction. We assessed correlations between these metrics among cardiothoracic surgery journals. METHODS: For all cardiothoracic surgery journals with a 2021 Clarivate IF (N = 20), the 2-year IF (2019 to 2020) and 5-year IF (2016 to 2020), h-index, and g-index were obtained. Two-year journal-level AAS (2019 to 2020) was also calculated. Journal Twitter presence and activity was sourced from Twitter and the Twitter application programming interface. Correlations were assessed using Spearman correlation, and coefficients of determination were calculated. RESULTS: IF demonstrated a moderate-strong positive correlation with the h-index (rs = 0.48 to 0.77) and g-index (rs = 0.49 to 0.79) and a moderate correlation with AAS (rs = 0.53 to 0.58). The 2-year IF accounted for 25% to 49% of variability in the h-index, 27% to 55% of variability in the g-index, and 32% of variability in the AAS. Among journals with a Twitter account (N = 10), IF was strongly correlated with Twitter following (rs = 0.81 to 0.86), which was in turn strongly correlated with journal AAS (rs = 0.79). Article-level AAS was moderately correlated with citation count (rs = 0.47). CONCLUSIONS: IF accounted for only between 25% and 55% of variability in the h-index and g-index, indicating that these newer metrics measure unique dimensions of citation-based impact. Thus, the academic community must familiarize itself with these newer journal metrics. Social media attention may be associated with scholarly impact, although further work is needed to understand these relationships.

Socio-demographic characteristics of children and young people with primary brain tumours: comparison between a public and private sector tertiary hospital in Karachi, Pakistan.

Primary brain tumours (PBTs) are the commonest solid tumours in children and young people (CYP). A study was conducted at a private and a public sector hospital in Karachi, Pakistan, to determine the socio-demographic and tumour-related characteristics of CYP with PBTs between those presenting to the public and private hospitals. A total of 49 patients were included. The commonest PBT was pilocytic astrocytoma (29%). There were no differences in tumour-related characteristics between the two groups. However, parents of CYP with PBTs presenting to the public sector hospital were significantly less educated and had lower household incomes. No significant differences in age, gender, educational status, and ethnicity of CYP with PBTs were observed. Since CYP with PBTs presenting at the public sector hospital were from significantly lower socioeconomic backgrounds and their parents were less educated, it suggests socio-economic disparities in PBT care for CYPs in Karachi, Pakistan.

Factors associated with safe and successful postoperative day 1 discharge after lung operations: a systematic review and meta-analysis.

BACKGROUND: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection. METHODS: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model. RESULTS: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1. CONCLUSIONS: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions.

Hospital Resources and Practice Patterns for Congenital Cardiac Surgery in Pakistan: A Nationwide Status Report.

Objective: Low- and middle-income countries such as Pakistan bear the brunt of the global burden of congenital heart disease (CHD), This nationwide study assessed hospital resources and surgical practice patterns pertaining to CHD surgery across Pakistan. Methods: A nationwide hospital facility survey was conducted, targeting all health centers performing CHD surgery in Pakistan. Descriptive data analysis was performed, with categorical variables being presented as frequencies and percentages and continuous variables being reported as means and standard deviations. Results: Seventeen surgeons across 17 different centers participated in the study. Eight of 17 (47%) surgeons were under 45 years of age, while the rest were older than 45 years. More respondents were employed at public/government-owned hospitals (11/17, 65%) and at specialized cardiac centers (13/17, 76%), with a majority of centers reported as having a special ICU designated for congenital cardiac patients (11/17, 65%). With regard to operative volume, 7 of 17 (41%) centers reported more than 350 cases per year, with 7 of 17 reported >10 neonatal cases per year (6/12, 50%). Only one center reported national and international collaborations for research, most centers carrying out less than five research projects in a year. Conclusion: This study has identified key areas that require the attention of local administrative bodies as well as international organizations and societies. The existing centers in Pakistan are unable to meet the demands of the population, leaving a large number of untreated patients, especially for neonatal lesions.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer.

BACKGROUND: In patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. METHODS: We queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. RESULTS: The inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. CONCLUSIONS: Neoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.

Bailout Surgery for Difficult Gallbladders: Surgical Approach and Outcomes.

INTRODUCTION: Inflammation in acute cholecystitis may cause a cholecystectomy to be more challenging. Due to the difficult dissection, conversion to subtotal cholecystectomy via laparoscopic or open procedure may be required. This is done to reduce the risk of bile duct injury and hemorrhage. We sought to describe the incidence and risk factors, safety, morbidity, and outcomes associated with bailout procedures. METHODS: A single academic center, retrospective review of laparoscopic cholecystectomies that resulted in bailout procedures performed between January 2015 and December 2020. Data collected from the chart review included demographics, comorbidities, length of presenting symptoms, vital signs, laboratory and imaging, intraoperative findings, length of surgery, and outcome. RESULTS: A total of 1892 cholecystectomies were performed with 147 bailout procedures. For bailout 92 (63.4%) were converted to open, with 66% resulting in complete cholecystectomy. Hypertension and diabetes were the most common comorbidities. The median duration of symptoms was 4 days. Difficult anatomy in the hepatocystic triangle (66%) and dense adhesions (31%) were the most common reasons for bailout. The mean duration of surgery was 145.76 (SD 102.94) minutes. There were 2 bile duct injuries, both in open total cholecystectomy subgroup. Bile leak occurred in 23.8% with majority in subtotal cholecystectomy group. There was no difference in hospital length of stay, surgical site infection, or mortality among different bailout procedures. CONCLUSIONS: Subtotal cholecystectomy represents a safe alternative to total cholecystectomy during challenging cases to avoid damaging surrounding structures. The choice of laparoscopic or open subtotal approach is dependent on the surgeons' expertise.

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.

From emissions to incisions and beyond: the repercussions of climate change on surgical disease in low- and-middle-income countries.

Climate change has far-reaching repercussions for surgical healthcare in low- and middle-income countries. Natural disasters cause injuries and infrastructural damage, while air pollution and global warming may increase surgical disease and predispose to worse outcomes. Socioeconomic ramifications further strain healthcare systems, highlighting the need for integrated climate and healthcare policies.

Operating Ethically: A Review of Surgical Ethics in Pakistan and Recommendations for the Way Forward.

Medical ethics underpin the moral framework that delineates the professional relationship between physicians and their patients and thereby is an integral part of making patient-centric healthcare decisions. The concept of ethics is deeply embedded in the field of surgery as surgeons confront a myriad of dilemmas as a part of their routine, whether it be in a preoperative or postoperative environment. The current review aims to describe the state of surgical ethics in Pakistan, with the intent of encouraging dialogues about the ethical considerations relevant to the field surgery that will identify actionable areas for improvement. While most surgeons are aware of the traditional principles of ethics and their practice, their surgical and clinical decisions may fall short of these standards because of time constraints and prevailing cultural and religious beliefs and taboos. The rigorous application of ethical principles in areas of patient-related communication, such as consenting, trainee education, palliative and end-of-life care, and surgical innovation and research, will have significant implications for patients, surgeons, and society. Our review has identified the lack of formal bioethics education and insufficient oversight and ethical regulations to be at the core of inadequate ethical practices in Pakistan and has highlighted actionable areas to be addressed in the future.

Anastomotic stenosis of bioengineered trachea grafts is driven by transforming growth factor ß1-induced signaling, proinflammatory macrophages, and delayed epithelialization.

Objective: Anastomotic stenosis caused by hypertrophic granulation tissue often develops in response to orthotopically implanted bioengineered tracheal grafts. To determine mechanisms responsible for the development and persistence of this granulation tissue, we looked for changes in gene expression from tissue specimens from the graft-native interface. Methods: RNA was isolated from paraffin-embedded tissue samples of the anastomotic sites of orthotopically implanted bioengineered tracheal grafts of 9 animals. Tissue samples were binned into 3 groups based on degree of stenosis: no stenosis (<5%), mild stenosis (25%-50%), and moderate and severe stenosis (≥75%). Sections of healthy trachea tissue were used as control. The expression levels of ∼200 genes related to wound healing, plus several endogenous controls, were measured with a pathway-focused predesigned primer array. Results: Expression of ARG2, IL4, RPL13 A, TGFBR3, and EGFR decreased, whereas expression of RUNX2 was increased in stenotic wounds compared with nonstenotic tissue. Based on the cell types present in the trachea and wound healing, this expression profile indicates a lack of M2 anti-inflammatory macrophages, absent epithelial cells, and transforming growth factor ß1-induced signaling. Conclusions: These findings represent a significant step for tracheal tissue engineering by identifying several key mechanisms present in stenotic granulation tissue. Further research must be conducted to determine what modifications of the graft substrate and which coadministered therapeutics can be used to prevent the development of hypertrophic granulation tissue.

Clinical and psychosocial factors associated with quality of life in patients with head and neck cancer: an analytical cross-sectional study from a lower-middle-income country.

INTRODUCTION: The disease course of head and neck (H&N) cancer can severely impair patients' quality of life (QoL). In Pakistan, a South Asian lower-middle-income country (LMIC), psychosocial factors may impact QoL. We aimed to assess QoL and associated factors amongst patients with H&N cancer in Pakistan. METHODS: An analytical cross-sectional study was conducted amongst adult (≥ 18 years) patients with H&N cancer who were ≥ 4 weeks post-initiation of treatment. The survey assessed QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires), anxiety and depression (Hospital Anxiety and Depression Scale), and social support (Enriched Social Support Instrument). Multivariable linear regression was performed for analysis. RESULTS: A total of 250 patients (mean age: 51.6 years) were included. The majority of patients were married (87%) and living with multigenerational/extended family households (53%). On multivariable linear regression, ongoing cancer treatment (beta coefficient: -13.93), having a tracheostomy (-10.02), and receiving adjuvant chemoradiotherapy (-8.17) were significantly associated with poorer global QoL. Additionally, poorer QoL was associated with depression (-24.37) and anxiety (-13.34). However, having more household family members was associated with better global QoL (0.34). CONCLUSION: The QoL of patients with H&N cancer in Pakistan is affected by both the nature of cancer treatment as well as sociocultural factors such the number of household family members. Given that poorer QoL is associated with worse mental health outcomes, there is a need to develop and implement psychosocial interventions to improve the QoL of patients with H&N cancer in Pakistan, particularly during active treatment.

Socio-demographic and antenatal risk factors of brain tumor in children and young people: A matched case-control study from Karachi, Pakistan.

Background: Brain tumors are a common cause of morbidity, disability, cognitive deterioration and mortality in children, even after treatment. Little is know about the specific causes. The study aimed to assess potential socio-demographic and antenatal factors in primary brain tumor (PBTs) in children and young people (CYP) in Karachi, Pakistan. Designs and methods: A single center hospital based matched case control study in Karachi, Pakistan. Cases were defined as CYP aged between 5 and 21 years with any histological type and grade of primary brain tumor of any histology, stage or grade. Data were collected from parents of 244 patients at the selected center between 2017 and 2021 via telephonic interview. Controls were 5-21 years old CYP admitted with non-oncological diagnoses matched on age and sex. Matched Odds Ratios for predictors of brain tumor in children were derived. Those of statistical significance were included in a multivariable logistic regression model. Results: In the adjusted model, lower paternal education (matched adjusted odds ratio (maOR) 2.46; 95% CI 1.09-5.55), higher household monthly income (maOR 3.4; 95% CI 1.1-10.2), antenatal paternal use of addictive substances (maOR 19.5; 95% CI 2.1-179.8), and antenatal maternal use of analgesics during pregnancy (maOR 3.0; 95% CI 1.2-7.9) were all independently predictive of brain tumors. Conclusion: This matched case-control study found novel associations between maternal use of analgesics, paternal use of addictive substances, higher household income, and lower paternal education and Primary Brain Tumors in Children and Young People. Longitudinal multicenter studies will be required to test these associations prospectively.