Postexposure prophylaxis for occupational exposure to selected pathogens for healthcare personnel.

PURPOSE OF REVIEW: Timely postexposure prophylaxis is important after an occupational exposure. Here we review select organisms, exposure opportunities in the healthcare setting, and postexposure prophylaxis regimens. RECENT FINDINGS: Needlestick injuries pose a risk of exposure to bloodborne pathogens, such as HIV, Hepatitis B, and Hepatitis C. Risk mitigation strategies should be reexamined in light of newer vaccines and therapeutics. Increased vaccine hesitancy and vaccine denialisms may foster the re-emergence of some infections that have become extremely uncommon because of effective vaccines. With increasing occurrences of zoonotic infections and the ease of global spread as evidenced by COVID-19 and mpox, healthcare exposures must also consider risks related to emerging and re-emerging infectious diseases. SUMMARY: Early recognition and reporting of occupational exposures to pathogens with available postexposure prophylaxis is key to mitigating the risk of transmission. Providers should be able to evaluate the exposure and associated risks to provide prompt and appropriate postexposure prophylaxis.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer.

AIM: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. METHODS: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. RESULTS: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. CONCLUSIONS: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.

Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer.

The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Lymphodepletion - an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle.

Lymphodepletion (LD) or conditioning is an essential step in the application of currently used autologous and allogeneic chimeric antigen receptor T-cell (CAR-T) therapies as it maximizes engraftment, efficacy and long-term survival of CAR-T. Its main modes of action are the depletion and modulation of endogenous lymphocytes, conditioning of the microenvironment for improved CAR-T expansion and persistence, and reduction of tumor load. However, most LD regimens provide a broad and fairly unspecific suppression of T-cells as well as other hematopoietic cells, which can also lead to severe side effects, particularly infections. We reviewed 1271 published studies (2011-2023) with regard to current LD strategies for approved anti-CD19 CAR-T products for large B cell lymphoma (LBCL). Fludarabine (Flu) and cyclophosphamide (Cy) (alone or in combination) were the most commonly used agents. A large number of different schemes and combinations have been reported. In the respective schemes, doses of Flu and Cy (range 75-120mg/m2 and 750-1.500mg/m2) and wash out times (range 2-5 days) differed substantially. Furthermore, combinations with other agents such as bendamustine (benda), busulfan or alemtuzumab (for allogeneic CAR-T) were described. This diversity creates a challenge but also an opportunity to investigate the impact of LD on cellular kinetics and clinical outcomes of CAR-T. Only 21 studies explicitly investigated in more detail the influence of LD on safety and efficacy. As Flu and Cy can potentially impact both the in vivo activity and toxicity of CAR-T, a more detailed analysis of LD outcomes will be needed before we are able to fully assess its impact on different T-cell subsets within the CAR-T product. The T2EVOLVE consortium propagates a strategic investigation of LD protocols for the development of optimized conditioning regimens.

Identification of a neural development gene expression signature in colon cancer stem cells reveals a role for EGR2 in tumorigenesis.

Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDHPositive CSCs from colon cancer patient-derived organoids (PDOs) and xenografts (PDXs) showed CSCs to be enriched for neural development genes. Functional analyses of genes differentially expressed in CSCs from PDO and PDX models demonstrated the neural crest stem cell (NCSC) regulator EGR2 to be required for tumor growth and to control expression of homebox superfamily embryonic master transcriptional regulator HOX genes and the neural stem cell and master cell fate regulator SOX2. These data support CSCs as the source of tumor neurogenesis and suggest that targeting EGR2 may provide a therapeutic differentiation strategy to eliminate CSCs and block nervous system driven disease progression.

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation.

The primary cilium constitutes an organelle that orchestrates signal transduction independently from the cell body. Dysregulation of this intricate molecular architecture leads to severe human diseases, commonly referred to as ciliopathies. However, the molecular underpinnings how ciliary signaling orchestrates a specific cellular output remain elusive. By combining spatially resolved optogenetics with RNA sequencing and imaging, we reveal a novel cAMP signalosome that is functionally distinct from the cytoplasm. We identify the genes and pathways targeted by the ciliary cAMP signalosome and shed light on the underlying mechanisms and downstream signaling. We reveal that chronic stimulation of the ciliary cAMP signalosome transforms kidney epithelia from tubules into cysts. Counteracting this chronic cAMP elevation in the cilium by small molecules targeting activation of phosphodiesterase-4 long isoforms inhibits cyst growth. Thereby, we identify a novel concept of how the primary cilium controls cellular functions and maintains tissue integrity in a specific and spatially distinct manner and reveal novel molecular components that might be involved in the development of one of the most common genetic diseases, polycystic kidney disease.

Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022.

On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.

Prevalence of metabolic syndrome among patients with schizophrenia in Ethiopia.

BACKGROUND: Globally, the prevalence of metabolic syndrome (MetS) is higher among patients with schizophrenia than the general population, and this leads to higher morbidity and mortality in this population. The aim of this study was to investigate the MetS prevalence among patients with schizophrenia in Ethiopia. METHODS: We conducted a cross-sectional analysis of baseline data of 200 patients with schizophrenia recruited from Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Lipid profile and blood glucose levels were measured using Roche Cobas 6000 clinical chemistry analyzer. The prevalence of MetS was assessed based on National Cholesterol Education Program Adult Treatment Panel III criteria. Patients' demographic information, clinical and laboratory data, lifestyle habits, particularly smoking and Khat chewing, were evaluated vis-à-vis MetS. RESULTS: The overall prevalence of MetS in patients with schizophrenia was 21.5% (17.1% male, 29.6% female) where Low HDL-cholesterol value was the most common metabolic disorders components in both males and females subgroups. In the multivariate analysis, the positive and negative symptoms score (PANSS, AOR = 1.03, 95% CI 1.001-1.054) was associated factors with MetS. CONCLUSION: In Ethiopia, patients with schizophrenia were found to have higher prevalence of MetS than the general population. Physicians/health care providers should routinely screen patients with schizophrenia for MetS and initiate timely management of those who develop the syndrome to reduce the health cost from caring for NCDs, improve the patients' quality of life, and prevent premature mortality.

Excessive polypharmacy and potentially inappropriate prescribing in 147 care homes: a cross-sectional study.

BACKGROUND: Care home residents often have multiple cognitive and physical impairments, and are at high risk of adverse drug events (ADEs). AIM: To describe excessive polypharmacy and potentially inappropriate prescribing predisposing care home residents to ADEs. DESIGN & SETTING: A cross-sectional analysis of all dispensed prescriptions for 147 care home residents in Tayside and Fife, Scotland. METHOD: Prevalence of excessive polypharmacy was examined using multilevel logistic regression, by modelling associations between individual and care home predictors with excessive polypharmacy (≥10 drugs). Prescribing of drugs known to increase the risk of eight clinically important ADE categories was examined. Drugs prescribed within each ADE category, for each resident, were counted. RESULTS: In total, 32.3% (n = 1444/4468) of residents had excessive polypharmacy, which was more common in residents aged 70-74 years (adjusted odds ratio [aOR] 1.86, 95% confidence interval [CI] = 1.04 to 3.34) and 80-84 years (aOR 1.75, 95% CI = 1.01 to 3.02), living in a residential care home (aOR 1.50, 95% CI = 1.19 to 1.88), and located in Fife (aOR 1.37, 95% CI = 1.09 to 1.71). Excessive polypharmacy was less common in residents with dementia (aOR 0.73, 95% CI = 0.64 to 0.84), and 8.9% (95% CI = 5.9% to 11.6%) of the variation was attributable to care home predictors. Potentially inappropriate prescribing of ≥2 drugs was seen across all ADE categories, with highest prevalence seen in drugs predisposing to constipation (35.8%), sedation (27.7%), and renal injury (18.0%). CONCLUSION: Excessive polypharmacy is common in care home residents and is associated with both individual and care home predictors. Potentially inappropriate prescribing of drugs that predisposed residents to all included ADE categories is common. Research is needed to support and evaluate safe care home prescribing practices.

Synthesis and pharmacological evaluation of [18F]PBR316: a novel PET ligand targeting the translocator protein 18 kDa (TSPO) with low binding sensitivity to human single nucleotide polymorphism rs6971.

Radiopharmaceuticals that target the translocator protein 18 kDa (TSPO) have been investigated with positron emission tomography (PET) to study neuroinflammation, neurodegeneration and cancer. We have developed the novel, achiral, 2-phenylimidazo[1,2-a]pyridine, PBR316 that targets the translocator protein 18 kDa (TSPO) that addresses some of the limitations inherent in current TSPO ligands; namely specificity in binding, blood brain barrier permeability, metabolism and insensitivity to TSPO binding in subjects as a result of rs6971 polymorphism. PBR316 has high nanomolar affinity (4.7-6.0 nM) for the TSPO, >5000 nM for the central benzodiazepine receptor (CBR) and low sensitivity to rs6971 polymorphism with a low affinity binders (LABs) to high affinity binders (HABs) ratio of 1.5. [18F]PBR316 was prepared in 20 ± 5% radiochemical yield, >99% radiochemical purity and a molar activity of 160-400 GBq µmol-1. Biodistribution in rats showed high uptake of [18F]PBR316 in organs known to express TSPO such as heart (3.9%) and adrenal glands (7.5% ID per g) at 1 h. [18F]PBR316 entered the brain and accumulated in TSPO-expressing regions with an olfactory bulb to brain ratio of 3 at 15 min and 7 at 4 h. Radioactivity was blocked by PK11195 and Ro 5-4864 but not Flumazenil. Metabolite analysis showed that radioactivity in adrenal glands and the brain was predominantly due to the intact radiotracer. PET-CT studies in mouse-bearing prostate tumour xenografts indicated biodistribution similar to rats with radioactivity in the tumour increasing with time. [18F]PBR316 shows in vitro binding that is insensitive to human polymorphism and has specific and selective in vivo binding to the TSPO. [18F]PBR316 is suitable for further biological and clinical studies.

RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence.

Recent data suggest that therapy-resistant quiescent cancer stem cells (qCSCs) are the source of relapse in colon cancer. Here, using colon cancer patient-derived organoids and xenografts, we identify rare long-term label-retaining qCSCs that can re-enter the cell cycle to generate new tumors. RNA sequencing analyses demonstrated that these cells display the molecular hallmarks of quiescent tissue stem cells, including expression of p53 signaling genes, and are enriched for transcripts common to damage-induced quiescent revival stem cells of the regenerating intestine. In addition, we identify negative regulators of cell cycle, downstream of p53, that we show are indicators of poor prognosis and may be targeted for qCSC abolition in both p53 wild-type and mutant tumors. These data support the temporal inhibition of downstream targets of p53 signaling, in combination with standard-of-care treatments, for the elimination of qCSCs and prevention of relapse in colon cancer.

Workforce Planning for Community-Based Palliative Care Specialist Teams Using Operations Research.

CONTEXT: Many countries have aging populations. Thus, the need for palliative care will increase. However, the methods to estimate optimal staffing for specialist palliative care teams are rudimentary as yet. OBJECTIVES: To develop a population-need workforce planning model for community-based palliative care specialist teams and to apply the model to forecast the staff needed to care for all patients with terminal illness, organ failure, and frailty during the next 20 years, with and without the expansion of primary palliative care. METHODS: We used operations research (linear programming) to model the problem. We used the framework of the Canadian Society of Palliative Care Physicians and the Nova Scotia palliative care strategy to apply the model. RESULTS: To meet the palliative care needs for persons dying across Nova Scotia in 2019, the model generated an estimate of 70.8 nurses, 23.6 physicians, and 11.9 social workers, a total of 106.3 staff. Thereby, the model indicated that a 64% increase in specialist palliative care staff was needed immediately, and a further 13.1% increase would be needed during the next 20 years. Trained primary palliative care providers currently meet 3.7% of need, and with their expansion are expected to meet 20.3% by 2038. CONCLUSION: Historical, current, and projected data can be used with operations research to forecast staffing levels for specialist palliative care teams under various scenarios. The forecast can be updated as new data emerge, applied to other populations, and used to test alternative delivery models.

Pooled Saliva Specimens for SARS-CoV-2 Testing.

We evaluated saliva (SAL) specimens for SARS-CoV-2 reverse transcriptase PCR (RT-PCR) testing by comparison of 459 prospectively paired nasopharyngeal (NP) or midturbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals (n = 380) and in the emergency department (ED) (n = 69). The percentages of positive and negative agreement of saliva compared to nasopharyngeal swab were 81.1% (95% confidence interval [CI], 65.8% to 90.5%) and 99.8% (95% CI, 98.7% to 100%), respectively. The percent positive agreement increased to 90.0% (95% CI, 74.4% to 96.5%) when considering only samples with moderate to high viral load (cycle threshold [CT ] for the NP, ≤34). Pools of five saliva specimens were also evaluated on three platforms, bioMérieux NucliSENS easyMAG with ABI 7500Fast (CDC assay), Hologic Panther Fusion, and Roche Cobas 6800. The average loss of signal upon pooling was 2 to 3 CT values across the platforms. The sensitivities of detecting a positive specimen in a pool compared with testing individually were 94%, 90%, and 94% for the CDC 2019-nCoV real-time RT-PCR, Panther Fusion SARS-CoV-2 assay, and Cobas SARS-CoV-2 test, respectively, with decreased sample detection trending with lower viral load. We conclude that although pooled saliva testing, as collected in this study, is not quite as sensitive as NP/MT testing, saliva testing is adequate to detect individuals with higher viral loads in an asymptomatic screening program, does not require swabs or viral transport medium for collection, and may help to improve voluntary screening compliance for those individuals averse to various forms of nasal collections.

Relationship between vasculitis and chronic lymphocytic leukaemia: a correlation without causation.

We report a novel case of a patient who presented with new diagnoses of both cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) positive vasculitis and chronic lymphocytic leukaemia (CLL). The patient was a 79-year-old man who presented with melena, haemoptysis, acute hypoxia and acute kidney injury. In the current literature, there are rare associations of c-ANCA vasculitis and malignancy, but very few, if any, relating c-ANCA vasculitis and CLL. This case is unique due to the presence of both pathologies and an uncommon presentation of the vasculitis. He presented with renal and pulmonary findings, unlike the dermal manifestations commonly seen with vasculitis. We think that this could be an easily overlooked combination of diseases and, therefore, the purpose of this case is to prevent delays in care that could affect patient outcomes and also to encourage further research into the relationship between these diseases.

Gene Expression Signatures of BRCAness and Tumor Inflammation Define Subgroups of Early-Stage Hormone Receptor-Positive Breast Cancer Patients.

PURPOSE: Patients with estrogen receptor- and/or progesterone receptor-positive, early breast cancer benefit from hormonal treatment, yet high global death burdens due to high prevalence and long-term recurrence risk call for biomarkers to guide additional treatment approaches. EXPERIMENTAL DESIGN: From a prospective, observational study of postmenopausal early breast cancer patients treated with tamoxifen or aromatase inhibitors, gene expression analyses of 612 tumors was performed using the NanoString Breast Cancer 360 panel to interrogate 23 breast cancer pathways. Candidate signatures associated with disease subtype and event-free survival (EFS) were obtained by cluster analysis, Cox modeling, and conditional inference trees, and were independently tested in 613 patients from BreastMark. Tumor-infiltrating lymphocytes (TIL) were assessed on tissue sections, and mutational burden was assessed in 36 tumors by whole-exome sequencing. RESULTS: PAM50-derived classification distinguished lower-risk (Luminal A) from higher-risk subtypes (Luminal B, P = 0.04; HER2, P = 0.006; Basal, P = 0.008). In higher-risk patients, shorter EFS was associated with low androgen receptor [HR = 3.61; 95% confidence interval (CI), 1.72-7.56; P = 0.001] or high BRCAness signature expression (HR = 3.58; 95% CI, 1.19-10.7; P = 0.023). BRCAness was independently confirmed as a predictor of shorter EFS (HR = 2.64; 95% CI, 1.31-5.34; P = 0.007). About 13%-15% of patients, enriched for high-grade, higher-risk subtypes (P ≤ 0.0001), had strong expression of the Tumor Inflammation Signature (TIS) suggestive of an inhibited antitumor immune response. TIS scores were strongly associated with TIL numbers (P < 1e-30) but not with tumor mutation status. CONCLUSIONS: BRCA-related DNA repair deficiency and suppressed tumor immune responses may be clinically relevant predictors of endocrine therapy complementing treatment options in subgroups of hormone-sensitive early breast cancer.

Establishing reliability and validity for mental health screening instruments in resource-constrained settings: Systematic review of the PHQ-9 and key recommendations.

Mental illness is one of the largest contributors to the global disease burden. The importance of valid and reliable mental health measures is crucial in order to accurately measure said burden, to capture symptom improvement, and to ensure that symptoms are appropriately identified and quantified. This is of particular importance in low and middle-income countries (LMICs), where the burden of mental illness is relatively high, and there is heterogeneity in linguistic, racial, and ethnic groups. Using the PHQ-9 as an illustrative example, this systematic review aims to provide an overview of existing work and highlight common validation and reporting practices. A systematic review of published literature validating the use of the PHQ-9 in LMICs as indexed in the PubMed and PsychInfo databases was conducted. The review included n = 49 articles (reduced from n = 2,349). This manuscript summarizes these results in terms of the frequency of reporting on important procedures and in regards to the types of reliability and validity measured. Then, building off of the existing literature, we provide key recommendations for measure validation in LMICs, which can be generalized for any type of measure used in a setting in which it was not initially developed.