High Burden Research Articles

A case of double‐negative prostate cancer with BRCA2 mutation and high tumor mutation burden treated sequentially with olaparib and pembrolizumab

IntroductionDouble‐negative prostate cancer, an androgen receptor–independent prostate cancer without features of neuroendocrine tumors, is refractory to treatment but could be an ideal candidate for individualized treatment.Case presentationAn 85‐year‐old patient with metastatic castration‐resistant prostate cancer without prostate‐specific antigen progression presented with local recurrence and liver and lung metastases 6 months after orchiectomy and apalutamide. A liver tumor biopsy led to a diagnosis of double‐negative prostate cancer. FoundationOne® CDx showed BRCA2 mutation and high tumor mutation burden. Olaparib and pembrolizumab were administered sequentially, and the patient responded to each treatment for 5 months until radiographic progression.ConclusionSequential use of olaparib and pembrolizumab may be effective for double‐negative prostate cancer with BRCA2 mutations and high tumor mutation burden.

Host-Pathogen Interaction and Resistance Mechanisms in Dermatophytes

Dermatophytes are widely distributed in the environment, with an estimated prevalence of 20–25% of the the global population yearly. These fungi are keratinophilic and keratinolytic and cause the infection of keratin-rich structures such as skin, hair, and nails. The pattern of this infectious disease covers a wide spectrum from exposed individuals without symptoms to those with acutely inflammatory or non-inflammatory, chronic to invasive, and even life-threatening symptoms. This review summarizes current information on the pathogenicity, virulence factors, and drug resistance mechanisms associated with dermatophytes. A greater number of virulence factors of these fungi are important for the occurrence of infection and the changes that occur, including those regarding adhesins, the sulfite efflux pump, and proteolytic enzymes. Other virulence factors include mechanisms of evading the host defense, while the development of resistance to antifungal drugs is increasing, resulting in treatment failure. The investigation of host-pathogen interactions is essential for developing a more complete understanding of the mechanisms underlying dermatophyte pathogenesis and host response to inform the use of diagnostics methods and antifungal therapeutics to minimize the high fungal burden caused by dermatophytes and to control the spread of resistance.

Impact of mitigating obesity, smoking, and physical inactivity on type 2 diabetes mellitus burden in Oman: insights from mathematical modeling

IntroductionTo estimate the impact of reducing obesity, smoking, and physical inactivity (PIA) prevalence, and of introducing physical activity (PA) as an explicit intervention, on the prevalence, incidence, and mortality of...

Informal Employment and High Burden of Out-of-Pocket Healthcare Payments among Older Workers: Evidence from Longitudinal Ageing Study in India.

India's economy is among the fastest growing in the world. However, a large share of informal workforce is a common characteristic of country's economy, comprises a significant portion of most of its labour markets. This workforce often receives low wages and lacks benefits such as strong social security and health coverage for all. The majority of healthcare spending in India is private. As India's population ages and the informal sector expands, it is expected that many of these workers will continue to work beyond the retirement age to bear their own healthcare costs due to lack of savings, pensions and the precarious nature of their employment. In this context, this study estimates the burden of Out-of-Pocket (OOP) payments on India's informal older workers compared to their formal counterparts, using data from the first wave of the nationally representative Longitudinal Ageing Study in India. According to estimates from the Two-part regression model, informal older workers pay, on an average, INR 1113 (p<0.01) and INR 55 (p<0.05) less than their formal counterparts for inpatient and outpatient care, respectively. However, probit regression models revealed that the burden of combined (both inpatient and outpatient) OOP payments exceeding (by 40%, 20%, and 10%) of their income is significantly higher among informal older workers compared to formal older workers. The study underscores the need for strengthening of universal health insurance schemes to ensure everyone has access to medical services without experiencing financial hardship. It also advocates for policies specifically tailored towards informal workers, considering their unique challenges with regard to livelihoods and healthcare security. In particular, this encompasses bolstering the existing social security and healthcare system, and related policies for ensuring financial security against OOP payments, especially for informal workers and all the population in general.

Global burden of HIV among long-distance truck drivers: a systematic review and meta-analysis

ObjectivesThe purpose of this study was to systematically summarise the empirical evidence on the prevalence of HIV among long-distance truck drivers (LDTDs) from all parts of the world.DesignA systematic review...

Sexual orientation, gender identity and virologic failure among people with HIV: a cohort study in all of US research program

BackgroundSexual and gender minorities (SGMs) are at higher risk of HIV incidence compared to their heterosexual cisgender counterparts. Despite the high HIV disease burden among SGMs, there was limited data on whether they are at higher risk of virologic failure, which may lead to potential disease progression and increased transmission risk. The All of Us (AoU) Research Program, a national community-engaged program aiming to improve health and facilitate health equity in the United States by partnering with one million participants, provides a promising resource for identifying a diverse and large volunteer TGD cohort. Leveraging various data sources available through AoU, the current study aims to explore the association between sexual orientation and gender identity (SOGI) and longitudinal virologic failure among adult people with HIV (PWH) in the US.MethodsThis retrospective cohort study used integrated electronic health records (EHR) and self-reported survey data from the All of Us (AoU) controlled tier data, version 7, which includes participants enrolled in the AoU research program from May 31, 2017, to July 1, 2022. Based on participants’ sexual orientation, gender identity, and sex assigned at birth, their SOGI were categorized into six groups, including cisgender heterosexual women, cisgender heterosexual men, cisgender sexual minority women, cisgender sexual minority men, gender minority people assigned female at birth of any sexual orientation, and gender minority people assigned male at birth of any sexual orientation. Yearly virologic failure was defined yearly after one’s first viral load testing, and individuals with at least one viral load test > 50 copies/mL during a year were defined as having virologic failure at that year. Generalized linear mixed-effects models were used to explore the association between SOGI and longitudinal virologic failure while adjusting for potential confounders, including age, race, ethnicity, education attainment, income, and insurance type.ResultsA total of 1,546 eligible PWH were extracted from the AoU database, among whom 1,196 (77.36%) had at least one viral failure and 773 (50.00%) belonged to SGMs. Compared to cisgender heterosexual women, cisgender sexual minority women (adjusted Odds Ratio [aOR] = 1.85, 95% CI: 1.05–3.27) were at higher risk of HIV virologic failure. Additionally, PWH who were Black vs. White (aOR = 2.15, 95% CI: 1.52–3.04) and whose insurance type was Medicaid vs. Private insurance (aOR = 2.07, 95% CI: 1.33–3.21) were more likely to experience virologic failure.ConclusionsMaintaining frequent viral load monitoring among sexual minority women with HIV is warranted because it allows early detection of virologic failure, which could provide opportunities for interventions to strengthen treatment adherence and prevent HIV transmission. To understand the specific needs of subgroups of SGMs, future research needs to examine the mechanisms for SOGI-based disparities in virologic failure and the combined effects of multi-level psychosocial and health behavior characteristics.

Subcellular expression of CD30 in cutaneous mastocytosis-An important factor for targeted treatment.

The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin. Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns. Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis. CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden. Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis. Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.

Temporal trends of diarrheal diseases and associated treatment responses among children aged under five: Insight from the multiple Indicator Cluster surveys from 2006 to 2019

BackgroundDespite significant progress in its health sector, Bangladesh has a high burden of diarrheal mortality and morbidity in the South Asian region. Given recent major social and economic transitions in Bangladesh, it is important to examine how patterns of diarrhea and its treatment have evolved over the past few decades. The current study aims to assess the temporal changes in the frequency of diarrhea and identify the factors that influence whether affected children receive proper treatment. MethodsThe current study utilized data from three Bangladesh Multiple Indicator Cluster Surveys (MICS), 2006, 2012–13, and 2019, respectively. Binary logistic regressions were conducted, and the reported results included odds ratios (OR) and 95% confidence intervals (CIs). A p-value of <0.05 was considered statistically significant (α = 0.05). ResultsThe prevalence of diarrhea in Bangladesh declined from 7.05% in 2006 to 3.91% in 2012–13, but then increased to 8.78% in 2019. The proportion of children with diarrhea who received oral rehydration therapy (ORT) was 68.91%, 77.35%, and 70.59% respectively. Binary logistic regression indicated that older children (OR:0.54; CI:0.51–0.58), females (OR:0.92; CI:0.86–0.98), children from upper quintile families, and children from mothers having primary education (OR:0.9; CI:0.83–0.98) were less likely to suffer from diarrhea. However, the odds of receiving proper treatment with ORT were higher among older children (OR:1.45; CI:1.26–1.68), children from the rich and richest quintiles (OR:1.85; CI:1.47–2.32 and OR:1.7; CI:1.32–2.2 respectively). Also, it was the same for children from mothers with primary (OR:1.19; CI:1.01–1.41) and secondary or above education (OR:1.32; CI:1.12–1.56). ConclusionA targeted approach is needed to reduce diarrhea and promote the use of ORT. Maternal education can be an important intervention, and steps should be taken to reduce poverty. Future policies should consider strategies focusing on socioeconomic and environmental factors.

Faster steroid-free remission with tocilizumab compared to methotrexate in giant cell arteritis: a real-life experience in two reference centres.

Glucocorticoids (GCs) are still the mainstay of treatment of giant cell arteritis (GCA). Although GCs are highly effective in GCA, the high burden of toxicity of GCs as well as the disease relapse during GC tapering is well documented. To compare the efficacy and rapidity of TCZ and MTX as steroid-sparing agents in a real-life cohort of GCA patients. A retrospective analysis was conducted including patients with newly diagnosed GCA from the Rheumatology Units of Udine and Rome. The inclusion criterion was the treatment with TCZ or MTX as first steroid-sparing drug. 112 GCA patients (81 females) with a median age of 70 (IQ 65-75) years were collected. Thirty-one out of 112 (27.7%) patients were treated with TCZ (162mg/week), while 81/112 (72.3%) patients received MTX (up to 20mg/week) as a GC-sparing agent. At month 6 after GCA onset, 5/31 (16.1%) patients in TCZ group and none in MTX group were in GC-free sustained remission (p value = 0.001). Similarly, at month 12, 64.5% (20/31) and 11.1% (9/81) of patients were in sustained GC-free remission in TCZ and MTX group, respectively (p value <0.001). At month 24 of follow-up, at least one relapse of the disease occurred in 7/31 (22.6%) in TCZ-treated and 28/81 (34.6%) in MTX-treated patients, respectively (p value = 0.22). TCZ allowed a faster discontinuation of steroid therapy than MTX in GCA patients, without increasing the risk of relapse.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

Clinician Perspectives on the Implementation of the Lee Silverman Voice Treatment–BIG® Program

Abstract Date Presented 03/22/24 Lee Silverman Voice Treatment (LSVT)–BIG® clinicians provided feedback on their execution of the program, identifying high-frequency visits and high patient payment burden as barriers. Further research is needed to explore the differences in implementation. Primary Author and Speaker: Leah Botkin Contributing Authors: Rachel Proffitt

Nanotechnology-based Strategies for Molecular Imaging, Diagnosis, and Therapy of Organ Transplantation.

Organ transplantation is the preferred paradigm for patients with end-stage organ failures. Despite unprecedented successes, complications such as immune rejection, ischemia-reperfusion injury, and graft dysfunction remain significant barriers to long-term recipient survival after transplantation. Conventional immunosuppressive drugs have limited efficacy because of significant drug toxicities, high systemic immune burden, and emergence of transplant infectious disease, leading to poor quality of life for patients. Nanoparticle-based drug delivery has emerged as a promising medical technology and offers several advantages by enhancing the delivery of drug payloads to their target sites, reducing systemic toxicity, and facilitating patient compliance over free drug administration. In addition, nanotechnology-based imaging approaches provide exciting diagnostic methods for monitoring molecular and cellular changes in transplanted organs, visualizing immune responses, and assessing the severity of rejection. These noninvasive technologies are expected to help enhance the posttransplantation patient survival through real time and early diagnosis of disease progression. Here, we present a comprehensive review of nanotechnology-assisted strategies in various aspects of organ transplantation, including organ protection before transplantation, mitigation of ischemia-reperfusion injury, counteraction of immune rejection, early detection of organ dysfunction posttransplantation, and molecular imaging and diagnosis of immune rejection.

Palliative neurology

Palliative medicine represents the holistic multiprofessional treatment of severely and incurably ill people and their relatives, addressing their complex physical, psychological, social and spiritual needs. The central therapeutic goals are the quality of life and alleviation of suffering. In the course of many neurological diseases, high symptom burden, long and variable trajectories and unfavorable prognosis at times create aneed for palliative care even at an early stage, which is currently still inadequately met. This can be countered by qualified neuropalliative care. In addition to intensifying interdisciplinary collaboration, this requires neurologists to have core competencies in palliative care. These include ateam-oriented attitude, communication skills, expertise in symptom control and knowledge of biomedical ethics including palliative options at the end of life.

Impact of completely histological remission on reducing flare-ups in moderate-to-severe, biologics-experienced ulcerative colitis patients with endoscopic remission

Background/purposeEndoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. MethodsThis retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. ResultsA total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. ConclusionsFor moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.

Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the influence of T2D pPS on diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin or placebo arms. Associations were tested using general linear models and Cox regression adjusted for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at one year follow-up adjusted for baseline measures (effect per pPS standard deviation (SD) -0.04, P=9.6 x 10-7; -8.45 uU/mg, P=5.6 x 10-6, respectively) and with increased diabetes incidence adjusted for BMI at nominal significance (HR 1.10 per SD, P=0.035). The liver/lipid pPS was associated with reduced one-year baseline-adjusted triglyceride levels (effect per SD -4.37, P=0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.

Post-independence health research productivity in Portuguese-speaking African countries: A bibliometric analysis of 43 years of research and higher education in Mozambique

BackgroundAfrica has a high double burden of infectious and non-communicable diseases underscoring the critical need for robust scientific research. However, it is also associated with low scientific research productivity. Mozambique, which gained independence in 1975, serves as a poignant example. However, there remains a notable scarcity of evidence evaluating the country's trajectory in scientific and academic development. This study aims to evaluate 43 years of health-related scientific knowledge production through bibliometric analysis, focusing on key indicators. Additionally, it seeks to characterize the higher education institutions within the country. MethodsThe data was retrieved from the Web of Science Core Collection using an advanced search tool with Boolean research strategies, covering the period from 1976 to 2022 for all PALOP and 1976 to 2019 for Mozambique. To map Mozambican higher institutions, information was sourced from the Ministry of Science Technology and Higher Education database. Descriptive statistics were employed to summarize the findings, while the VOSviewer program version 1.6.19 was utilized to visualize distance-based bibliometric networks, focusing on co-authorship among institutions and keyword co-occurrence. ResultsPortuguese-speaking African countries (PALOP) contribute 2.5 % (10,933 out of 442,309) to Africa's total scientific output, with Mozambique leading at 63.6 % (6,951 publications) followed by Angola at 16.6 % (1,811 publications). All PALOP countries experienced decreased scientific productivity during the third year of the COVID-19 pandemic. In Mozambique, over 70 % (1,710 out of 2,380) of health-related publications from 2011 to 2019 were concentrated in this period. Key journals for health sciences include PLOS ONE, Malaria Journal, and Tropical Medicine & International Health, focusing on HIV, malaria, and tuberculosis. Higher education institutions in Mozambique show regional disparities, with 67.9 % in the South and only 8.9 % in the North, indicating significant inequality in their distribution across the country. ConclusionThis study highlights Mozambique's significant progress in health research productivity over 43 years, establishing it as a leader among PALOP countries. The substantial increase in publications, particularly after 2008, underscores the nation's growing research capacity and commitment to addressing critical health challenges such as HIV, malaria, and tuberculosis. However, regional disparities in higher education access and limited research contributions from private universities remain high in Mozambique.

The long-term effects of domestic and international tuberculosis service improvements on tuberculosis trends within the USA: a mathematical modelling study

For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. US Centers for Disease Control and Prevention.

Palliative care needs and integration in severe COPD and ILD: Protocol of a mixed method study (PCIntegCOPD-ILD)

Background and Aim Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) have high symptom burden, serious health-related suffering, and mortality that necessitate palliative care (PC) integration. There is an information gap on PC needs, symptom burden, anxiety and depression in COPD and ILD, and the feasibility of PC integration from low-middle-income countries (LMICs). The PCIntegCOPD-ILD study aims to identify PC needs, symptom burden, and psychological distress in severe COPD/ ILD and assess the feasibility of PC integration within standard care. It will also explore experiences and unmet needs relating to disease and PC services for patients and informal carers. Methods and Design This mixed-methods study will assess PC needs, symptom burden, and psychological distress in patients with severe COPD (stages C, D) and ILD (stages II, III). Assessment will be done at recruitment (T0) and third (T3) month (face-to-face) and first (T1) and second (T2) month (phone call). After initial recruitment, patients will be provided PC interventions as required. At T3, patients’ and informal carers’ experiences and unmet needs of disease and PC services will be explored through semi-structured interviews. Impact and feasibility of integration of PC within standard care will also be assessed. Discussion The PCIntegCOPD-ILD study will provide robust data on PC needs, symptom burden, psychological distress and understanding of patient and caregiver perspecitves in severe COPD and ILD. An objective information on feasibility of PC integration will inform development and evaluation of similar models in the management of other progressive chronic diseases in LMICs.

Global Case Fatality of Bacterial Meningitis During an 80-Year Period

The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. Case fatality ratios of bacterial meningitis. This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.