Zavegepant for Acute Treatment of Migraine: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks. METHODS: A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs. RESULTS: Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72). CONCLUSION: Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.

Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy.

Introduction VMA21 -related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. Method Here, we describe a case of genetically confirmed VMA21 -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. Results A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3' splice site of intron 2 of the VMA21 gene (c.164-7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. Conclusion This report expands the phenotypic and genotypic profile of VMA21 -related myopathy, with a yet unreported mutation in India.

The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature.

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients.

Self-medication prevalence and associated factors among adult population in Northern India: A community-based cross-sectional study.

Objectives: This study aimed to determine self-medication prevalence and its associated factors. Methods: A community-based cross-sectional study was conducted in the urban and rural catchment areas of Uttar Pradesh, India, among 440 adults using a pretested, semistructured questionnaire. The Chi-square test and logistic regression were used to determine the association of self-medication prevalence with various independent variables. The associations were reported as adjusted odds ratios and 95% confidence intervals. Results: The prevalence of medication use was 66.4%. The majority of participants (45%) took medicine for fever, cough (40.1%), and cold (31.8%). Allopathy (83.2%) was the most common medicine system used for self-medication. More than half reported taking medicine such as paracetamol (52%), followed by cough syrup (21%) and antihistaminic (17%). Convenience (46%) and lack of time (35.3%) were commonly cited reasons for self-medication. Also, 64.4% of the respondents practiced self-medication on the pharmacist's recommendation. Urban participants (adjusted odds ratio: 9.85, 95% confidence interval: 5.32-18.23), females (adjusted odds ratio: 2.32, 95% confidence interval: 1.18-4.57), skilled workers (adjusted odds ratio: 5.62, 95% confidence interval: 1.80-17.5), and those who completed primary school (adjusted odds ratio: 2.48, 95% confidence interval: 1.16-5.25) were more likely to self-medicate than rural, male, unemployed, and illiterate participants, respectively. Also, participants whose income was 30,000 Indian rupees (adjusted odds ratio: 3.21, 95% confidence interval: 1.00-10.21) were more likely to self-medicate than those whose income was less than 4000. Conclusions: A high prevalence of self-medication was found, particularly in urban areas. Convenience and lack of time were commonly cited reasons for self-medication. Allopathy was the most widely used medicine system for self-medication. Antipyretics, cough syrups, and antiallergics were most commonly self-medicated. Gender, education, and income were associated with self-medication. The study highlighted the increased usage among females which could be further explored and role of pharmacists' recommendation as a major driver for self-medication.

Qualitative and Quantitative Electrocardiogram Parameters in a Large Cohort of Children with Duchenne Muscle Dystrophy in Comparison with Age-Matched Healthy Subjects: A Study from South India.

Background: Electrocardiography (ECG) remains an excellent screening tool for cardiac assessment in Duchenne muscular dystrophy (DMD), but an accurate interpretation requires comparison with age-matched healthy controls. Objective: We examined various ECG parameters in children with DMD, in comparison with age-matched controls. Methods: Standard 12-lead ECG tracings of serial patients were screened for quality and selected. Controls were healthy, age-matched school-going children. Both quantitative and qualitative ECG parameters were analyzed. Results: After screening, ECGs from 252 patients with DMD (8.32 ± 3.12 years, 2-21 years) and ECGs from 151 age-matched healthy controls (9.72 ± 2.23, 4-19 years) were included. A significantly higher heart rate, shorter R-R interval, and taller R wave in V1 were seen across all age group of DMD in comparison to controls, with the difference increasing with age. While QT prolongation was seen in all age groups of DMD, QTc prolongation was seen only at 10 years or more. Incomplete right bundle branch block (RBBB) and pathological Q waves in inferolateral leads were exclusive in DMD, with the latter declining with age. Evidence for left ventricular (LV) pathology, such as tall R in V5/V6, increase in SV1 + RV6 height, and QRS complex duration, were seen only in the age group of 10 years or more. Conclusion: Stratification based on age and comparison with age-matched healthy subjects showed that several ECG parameters were influenced by age, and it also identified age-dependent evidence for LV pathology and QTc prolongation in DMD.

Myotonic Dystrophy Type 1 (DM1): Clinical Characteristics and Disease Progression in a Large Cohort.

BACKGROUND: DM1 is a multisystem disorder caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK. Neuropsychological consequences and sleep abnormalities are important associations in DM1. OBJECTIVE: To describe the clinical phenotype, disease progression and characterize the sleep alterations and cognitive abnormalities in a sub-set of patients. MATERIALS AND METHODS: A retrospective study on 120 genetically confirmed DM1 cases. Findings in neuropsychological assessment and multiple sleep questionnaires were compared with 14 age and sex matched healthy individuals. All 120 patients were contacted through letters/telephonic consultation/hospital visits to record their latest physical and functional disabilities. RESULTS: The mean age at symptom onset was 23.1 ± 11.4 years, M: F = 3.8:1, mean duration of illness = 14.3 ± 9.5 years. Clinically 54.2% had adult onset form, juvenile = 27.5%, infantile = 10.8%, late adult onset = 7.5%. Paternal transmission occurred more frequently. The predominant initial symptoms were myotonia (37.5%), hand weakness (21.7%), lower limb weakness (23.3%) and bulbar (10%). Twenty patients completed sleep questionnaires (SQ). Abnormal scores were noted in Epworth sleepiness scale (55%); Pittsburgh sleep quality index (45%); Berlin SQ (30%); Rapid eye movement sleep Behaviour Disorder SQ (15%); Restless leg syndrome rating scale (10%). Neuropsychological assessment of 20 patients revealed frontal executive dysfunction, attention impairment and visuospatial dysfunction. Frontal lobe was most affected (72%) followed by parietal (16%) and temporal lobe (12%). CONCLUSIONS: The current study provides a comprehensive account of the clinical characteristics in Indian patients with DM1. Hypersomnolence was most commonly seen. Excessive daytime sleepiness and Sleep disordered breathing were the most common sleep related abnormality. Cognitive impairment comprised predominantly of frontal lobe dysfunction.

Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis.

Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system and can cause various types of pain including ongoing extremity pain, Lhermitte's phenomenon, trigeminal neuralgia, and mixed pain. Neuropathic pain is a major concern for individuals with multiple sclerosis as it is directly linked to myelin damage in the central nervous system and the management of neuropathic pain in multiple sclerosis is challenging as the options available have limited efficacy and can cause unpleasant side effects. The literature search was conducted across two databases, PubMed, and Google Scholar. Eligible studies included clinical trials, observational studies, meta-analyses, systematic reviews, and narrative reviews. The objective of this article is to provide an overview of literature on pharmacological and non-pharmacological strategies employed in the management of neuropathic pain in multiple sclerosis. Pharmacological options include cannabinoids, muscle relaxants (tizanidine, baclofen, dantrolene), anticonvulsants (benzodiazepines, gabapentin, phenytoin, carbamazepine, lamotrigine), antidepressants (duloxetine, venlafaxine, tricyclic antidepressants), opioids (naltrexone), and botulinum toxin variants, which have evidence from various clinical trials. Non-pharmacological approaches for trigeminal neuralgia may include neurosurgical methods. Non-invasive methods, physical therapy, and psychotherapy (cognitive behavioral therapy, acceptance and commitment therapy and mindfulness-based stress reduction) may be recommended for patients with neuropathic pain in multiple sclerosis. The choice of treatment depends on the severity and type of pain as well as other factors, such as patient preferences and comorbidities. There is a pressing need for healthcare professionals and researchers to prioritize the development of better strategies for managing multiple sclerosis-induced neuropathic pain.

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives.

Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

Foodborne Outbreak by Salmonella enterica Serovar Weltevreden in West Bengal, India.

Foodborne gastroenteritis outbreaks owing to Salmonella enterica serovar Weltevreden (Salmonella Weltevreden) represent a significant global public health problem. In the past two decades, Salmonella Weltevreden has emerged as a dominant foodborne pathogen, especially in South-East Asian countries. This report describes a community foodborne outbreak of gastroenteritis caused by Salmonella Weltevreden in August 2022 following consumption of panipuri from a street vendor in the Polba block in Hooghly district, West Bengal, India. This food item was consumed by 185 people, of whom 129 had acute watery diarrhea with other clinical symptoms and 65 of them were admitted to different District hospitals for treatment. Stool specimens collected from hospitalized cases were positive for S. enterica, and further serotyped as Salmonella Weltevreden. All the Salmonella Weltevreden strains possessed the Salmonella pathogenicity islands associated genes (invA/E, orgA, ttrc, ssaQ, mgtC, misL, spi4D), the enterotoxin (stn), and hyperinvasive locus gene (hilA). Except erythromycin, all the strains were susceptible for commonly used antimicrobials in the treatment of diarrhea. The XbaI-based pulsed-field gel electrophoresis analysis indicated that all the isolates responsible for the recent outbreak were similar, but diverged from other Salmonella Weltevreden that were previously reported in West Bengal. This report indicates that foodborne infection is a major public health concern in India and demands to strengthen capacity-building measures at the local health care levels for linking causative agents of outbreaks.

Clinical spectrum, biochemical profile and disease progression of Kennedy disease in an Indian cohort.

BACKGROUND: Kennedy disease (KD) is a slowly progressive lower motor neuron degenerative disease. The prevalence of KD is unknown in India. AIM: To describe the phenotypic and laboratory features of an Indian cohort of KD patients. METHODS: A retrospective study was done on seven genetically confirmed KD patients based on demographic, clinical and laboratory details. RESULTS: Mean age at onset and presentation was 37 ± 11.9 and 44.6 ± 13.5 years respectively. Progressive asymmetric proximal and distal limb weakness was the commonest symptom (57.1%). All patients had motor symptoms along with non-specific symptoms such as cramps from the onset. Easy fatigability, decremental response along with ptosis were noted in two patients, which was a novel finding. Gynaecomastia and tongue wasting with fasciculations were universal findings. All five patients with nerve conduction studies showed sensorimotor neuropathy. Magnetic resonance imaging muscle done in two patients showed a prominent moth-eaten appearance in the thigh and posterior leg compartment in one patient. The mean cytosine-adenine-guanine repeats were 44 ± 3.7, and there was no association between age of onset or severity with repeat length. Only one patient required an assistive device for ambulation after 15 years of symptom onset. CONCLUSIONS: This study showed phenotypic heterogeneity in the Indian cohort. The age of onset was earlier with a slowly progressive indolent course as compared with other ethnic cohorts. This highlights the importance of considering the KD diagnosis in patients with the indolent course and suspected ALS diagnosis even with ptosis and fatigability in an appropriate clinical context.

Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.

Congenital myasthenic syndromes (CMS) are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and ß2 adrenergic receptor agonists. In this study, we identified and genetically characterized the largest cohort of CMS patients from India to date. Genetic testing of clinically suspected patients evaluated in a South Indian hospital during the period 2014-19 was carried out by standard diagnostic gene panel testing or using a two-step method that included hotspot screening followed by whole-exome sequencing. In total, 156 genetically diagnosed patients (141 families) were characterized and the mutational spectrum and genotype-phenotype correlation described. Overall, 87 males and 69 females were evaluated, with the age of onset ranging from congenital to fourth decade (mean 6.6 ± 9.8 years). The mean age at diagnosis was 19 ± 12.8 (1-56 years), with a mean diagnostic delay of 12.5 ± 9.9 (0-49 years). Disease-causing variants in 17 CMS-associated genes were identified in 132 families (93.6%), while in nine families (6.4%), variants in genes not associated with CMS were found. Overall, postsynaptic defects were most common (62.4%), followed by glycosylation defects (21.3%), synaptic basal lamina genes (4.3%) and presynaptic defects (2.8%). Other genes found to cause neuromuscular junction defects (DES, TEFM) in our cohort accounted for 2.8%. Among the individual CMS genes, the most commonly affected gene was CHRNE (39.4%), followed by DOK7 (14.4%), DPAGT1 (9.8%), GFPT1 (7.6%), MUSK (6.1%), GMPPB (5.3%) and COLQ (4.5%). We identified 22 recurrent variants in this study, out of which eight were found to be geographically specific to the Indian subcontinent. Apart from the known common CHRNE variants p.E443Kfs*64 (11.4%) and DOK7 p.A378Sfs*30 (9.3%), we identified seven novel recurrent variants specific to this cohort, including DPAGT1 p.T380I and DES c.1023+5G>A, for which founder haplotypes are suspected. This study highlights the geographic differences in the frequencies of various causative CMS genes and underlines the increasing significance of glycosylation genes (DPAGT1, GFPT1 and GMPPB) as a cause of neuromuscular junction defects. Myopathy and muscular dystrophy genes such as GMPPB and DES, presenting as gradually progressive limb girdle CMS, expand the phenotypic spectrum. The novel genes MACF1 and TEFM identified in this cohort add to the expanding list of genes with new mechanisms causing neuromuscular junction defects.

Monomelic Amyotrophy/Hirayama Disease: Surgical Outcome in a Large Cohort of Indian Patients.

BACKGROUND: Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. METHODS: Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. RESULTS: Age at onset and duration of illness were 12-31 years (mean, 18 ± 2.7) and 1-96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. CONCLUSIONS: ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated.

A Novel Mutation in Frabin (FGD4) Causing a Mild Phenotype of CMT4H in an Indian Patient.

Charcot-Marie-Tooth disease 4H(CMT4H) is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. CMT4H is characterized by early onset and slowly progressing motor and sensory deficits in the distal extremities, along with foot deformities. We describe a patient with CMT4H who presented with rapidly progressing flaccid quadriparesis during the postpartum period, which improved significantly with steroid therapy. Magnetic resonance imaging and ultrasonography demonstrated considerable nerve thickening with increased cross-sectional area in the peripheral nerves. A nerve biopsy revealed significant demyelination and myelin outfolding. This is the first report of an Indian patient with a novel homozygous nonsense c.1672C>T (p.Arg558Ter) mutation in the FGD4 gene, expanding the mutational and phenotypic spectrum of this disease.

An overview of the therapeutic strategies for neoplastic meningitis due to breast cancer: when and why?

INTRODUCTION: Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options. AREAS COVERED: This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer. EXPERT OPINION: Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease.

Silico-tuberculosis amidst COVID-19 pandemic: global scenario and Indian perspective.

Inhalation of crystalline silica-rich dust particles can result in the deadly occupational lung disorder called silicosis. The risk of contracting tuberculosis (TB) and the potential for lung cancer increase due to silicosis. This review article aims to bring to light the state of silicosis and TB scenario in the world and India for evaluating hurdles in the present and future to achieve the elimination road map and assess these conditions in the backdrop of the COVID-19 pandemic. A patient with silicosis has a 2.8-2.9 times higher risk of developing pulmonary TB and 3.7 times that of extrapulmonary TB. Incidences of missed cases when TB was misdiagnosed with silicosis due to indifferent clinical manifestations of the two in the initial stages are not uncommon. The duration of silica exposure and silicosis severity are directly related to the propensity to develop TB. As per a study, an average gap of 7.6 years has been noticed in a South African population for silico-tuberculosis to develop post-silicosis. In a study done on mine workers at Jodhpur, Rajasthan, it was seen that there is no definitive relation between patients with silicosis and the possibility of having COVID-19. There is a significant need to integrate the Silicosis control program with the TB elimination program for the government. A few steps can include assessing the workplaces, periodic monitoring of the workers' health, active case surveillance, identification of hotspots, and introducing reforms to curb the spread of dust and particulate matter from industrialised areas be taken in this regard.

Genetics and Genomics of Chronic Pancreatitis with a Focus on Disease Biology and Molecular Pathogenesis.

Chronic pancreatitis is a long-term fibroinflammatory condition of the pancreas with varying incidences across countries. The recent increase in its occurrence implies the involvement of genetic, hereditary, and unconventional risk factors. However, there is a lack of updated literature on recent advances in genetic polymorphisms of chronic pancreatitis. Therefore, this review aims to present recent findings on the genetic implications of chronic pancreatitis based on individual gene mechanisms and to discuss epigenetics and epistasis involved in the disease. Four mechanisms have been implicated in the pathogenesis of chronic pancreatitis, including premature activation of proteases, endoplasmic reticulum stress, ductal pathway dysfunction, and inflammatory pathway dysfunction. These mechanisms involve genes such as PRSS1, PRSS2, SPINK, CEL, PNLIP, PNLIPRP2, CFTR, CaSR, CLDN2, Alpha 1 antitrypsin, and GGT1 . Studying genetic polymorphisms on the basis of altered genes and their products may aid clinicians in identifying predispositions in patients with and without common risk factors. Further research may also identify associations between genetic predispositions and disease staging or prognosis, leading to personalized treatment protocols and precision medicine.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.