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Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger containing (PIKfyve) inhibitor with favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis models. In this amyotrophic lateral sclerosis clinical trial, the safety, tolerability, CNS penetrance, and modulation of pharmacodynamic target engagement biomarkers were evaluated. This Phase 2a, randomized, double-blind, placebo-controlled, biomarker-endpoint clinical trial was conducted in four USA centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansion were randomly assigned (2:1) to receive twice-daily oral treatment of 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent adverse or serious adverse events attributable to study drug, and tolerability as trial completion on treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition (soluble glycoprotein nonmetastatic melanoma protein B [sGPNMB] upregulation) and disease-specific CNS target engagement (poly[GP]). Between Dec 16, 2021, and Jul 7, 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance (N=9 [90%] apilimod dimesylate; N=5 [100%] placebo). At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/mL (SD: 0.937). At Week 12, apilimod dimesylate increased plasma sGPNMB by > 2.5-fold (p < 0.001) indicating PIKfyve inhibition and lowered CSF poly(GP) protein levels by 73% (p < 0.001) indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker endpoints in this Phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to have the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials.
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PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aß-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aß-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aß- and Aß + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aß- from Aß + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.
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Doença de Alzheimer , Compostos de Anilina , Estilbenos , Humanos , Benzotiazóis , Amiloide/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismoRESUMO
Rhizobia are bacteria that form nitrogen-fixing nodules in legume plants. The sets of genes responsible for both nodulation and nitrogen fixation are carried in plasmids or genomic islands that are often mobile. Different strains within a species sometimes have different host specificities, while very similar symbiosis genes may be found in strains of different species. These specificity variants are known as symbiovars, and many of them have been given names, but there are no established guidelines for defining or naming them. Here, we discuss the requirements for guidelines to describe symbiovars, propose a set of guidelines, provide a list of all symbiovars for which descriptions have been published so far, and offer a mechanism to maintain a list in the future.
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Rhizobium , Simbiose , Fabaceae/microbiologia , Guias como Assunto , Fixação de Nitrogênio , Rhizobium/genética , Rhizobium/classificação , Nódulos Radiculares de Plantas/microbiologiaRESUMO
Opinion 129 addresses the status of Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980). The name has the category 'division' and was included in the Approved Lists of Bacterial Names, although that category had previously been removed from the International Code of Nomenclature of Bacteria (1975 revision onwards). When the category 'phylum' was introduced into the International Code of Nomenclature of Prokaryotes (ICNP) in 2021, equivalence between 'phylum' and 'division' was not stipulated. Since the definition of the taxonomic categories and their relative order is one of the principal tasks of every code of nomenclature, the inclusion of Firmicutes corrig. Gibbons and Murray 1978 in the Approved Lists was an error. The name is either not validly published or illegitimate because its category is not covered by the ICNP. If Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980) was a validly published phylum name, it would be illegitimate because it would contravene Rule 8, which does not permit any deviation from the requirement to derive a phylum name from the name of the type genus. Since Firmicutes corrig. Gibbons and Murray 1978 is also part of a 'misfitting megaclassification' recognized in Opinion 128, the name is rejected, without any pre-emption regarding a hypothetically validly published name Firmicutes at the rank of phylum. Gracilicutes Gibbons and Murray 1978 (Approved Lists 1980) and Anoxyphotobacteriae Gibbons and Murray 1978 (Approved Lists 1980) are also rejected. The validly published phylum names have a variety of advantages over their not validly published counterparts and cannot be replaced with ad hoc names suggested in the literature. To ease the transition, it is recommended to mention the not validly published phylum names which strongly deviate in spelling from their validly published counterparts along with the latter in publications during the next years.
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Ácidos Graxos , Hylobates , Animais , Filogenia , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Ácidos Graxos/química , FirmicutesRESUMO
Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.
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Rhodococcus , Terminologia como Assunto , Rhodococcus/classificaçãoRESUMO
INTRODUCTION: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. METHODS: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). RESULTS: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below -48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). CONCLUSION: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.
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Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Humanos , Hipercapnia/complicações , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Músculos Respiratórios , Diafragma/diagnóstico por imagem , Insuficiência Respiratória/etiologiaRESUMO
The UK government has recently committed to adopting a new policy-dubbed 'Martha's Rule'-which has been characterised as providing patients the right to rapidly access a second clinical opinion in urgent or contested cases. Support for the rule emerged following the death of Martha Mills in 2021, after doctors failed to admit her to intensive care despite concerns raised by her parents. We argue that framing this issue in terms of patient rights is not productive, and should be avoided. Insofar as the ultimate goal of Martha's Rule is the provision of a clinical service that protects patient safety, an approach that focuses on the obligations of the health system-rather than the individual rights of patients-will better serve this goal. We outline an alternative approach that situates rapid clinical review as part of a suite of services aimed at enhancing and protecting patient care. This approach would make greater progress towards addressing the difficult systemic issues that Martha's Rule does not, while also better engaging with the constraints of clinical practice.
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We suggest that in the particular context of medical education, ethics can be considered in a similar way to other kinds of knowledge that are categorised and shaped by academics in the context of wider society. Moreover, the study of medical ethics education is translational in a manner loosely analogous to the study of medical education as adjunct to translational medicine. Some have suggested there is merit in the idea that much as translational research attempts to connect the laboratory scientist's work to its implications for patient care, translational ethics focuses on bringing ethics scholarship into the sphere of personal and public action. We distinguish the term 'translational ethics' (the study of ethics being translated between academy, classroom and clinic) from other prominent definitions in the bioethics literature. To do this, we build off a notion of knowledge translation that focuses on the nonlinear movement of information that comes to professionals through multiple competing sources. We suggest that this knowledge, and particularly knowledge about ethics, becomes embodied by the individual. It is through a reflective practice that internally embedded ethics knowledge might be modified, and this work might be best carried out with a moral community that maintains a sense of practical wisdom. Applying this translational approach to the study of medical ethics education can be both academically relevant and practically useful. This view of translation can help bridge the evident, multidirectional relationships between research, education and performance. It might also create further opportunities to develop medical ethics education theory.
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Bioética , Educação Médica , Humanos , Ética Médica , Princípios Morais , Pesquisa Translacional BiomédicaRESUMO
BACKGROUND/OBJECTIVES: Randomized controlled trials that deliver physical activity interventions have demonstrated benefits for older adults across numerous health outcomes. However, too little attention has been directed to ensuring that such trials are measuring patient-relevant outcomes. To support outcome selection for future trials, the objective of this study was to understand what outcomes related to their physical activity participation older adults find important. METHODS: We conducted 12 semistructured interviews with adults aged 65 years and older and analyzed interview transcripts with a reflexive thematic analysis. RESULTS: Older adults desired diverse outcomes from their physical activity participation, ranging from generic (e.g., quality of life) to specific (e.g., leg strength). Relevant outcomes were classified under five themes: physical, clinical, social, psychological, and overarching, each with respective subthemes. CONCLUSIONS: The outcomes that older adults found important were plentiful and rooted in a desire to improve their quality of life. Some of the outcome themes have been reported frequently in past trials (e.g., physical), but others have not (e.g., social). Future researchers should be aware of, and responsive to, the priorities of older adults when designing trials and defining outcomes. Significance/Implications: This study will help to improve outcome selection for future trials of physical activity with older adults. In alignment with a patient-oriented research philosophy, this study will also ground future outcome selection in the priorities of older adults.
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Pyogenic granulomas are benign lesions commonly found on the skin and mucosal surfaces. Although the etiology of pyogenic granuloma is not well understood, some reports have suggested that PG may be caused by impaired wound healing following tissue injury. Rare cases of pyogenic granulomas in the setting of local foreign body have been reported in the literature. Although foreign body reactions have not been identified as a cause of pyogenic granuloma, these reports evidence the need to further investigate this association. We present a 33-year-old man who presented with a pyogenic granuloma on the scalp six years after a contralateral skull-penetrating gunshot wound that resulted in retained bullet fragments.
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Granuloma Piogênico , Ferimentos por Arma de Fogo , Humanos , Masculino , Granuloma Piogênico/etiologia , Ferimentos por Arma de Fogo/complicações , Adulto , Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/etiologia , Dermatoses do Couro Cabeludo/patologia , Corpos Estranhos/complicações , Traumatismos Cranianos Penetrantes/etiologiaRESUMO
OBJECTIVE: This study evaluated the racial and ethnic diversity of physician associate/assistant (PA) graduating cohorts during the profession's transition from a standard undergraduate degree to an entry-level master's degree. METHODS: Using all existing program reports from the Physician Assistant Education Association (1985-2019), we explored potential associations between changes in tuition, degree types offered, and racial/ethnic makeup of graduating cohorts. RESULTS: We observed a strong negative association between Black students and graduates versus increasing tuition and the rise of master's level programs. CONCLUSIONS: More equitable opportunities for joining the PA profession may be needed.
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Assistentes Médicos , Estudantes , Humanos , Escolaridade , Assistentes Médicos/educaçãoRESUMO
ABSTRACT: Skin cancer is the most common cancer in the United States, with an estimated 9,500 new diagnoses made each day. Dermoscopy (also called dermatoscopy) is an established clinical approach to improving skin cancer evaluation. However, only 8% to 9% of primary care physicians use it, and no data are available for physician associate/assistant or NP use. This article reports a dermoscopy algorithm that primary care providers can use to increase the detection of skin cancer and reduce unnecessary referrals and biopsies.
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Dermoscopia , Atenção Primária à Saúde , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Algoritmos , Encaminhamento e Consulta , Melanoma/diagnóstico por imagem , Melanoma/diagnóstico , Melanoma/patologia , Assistentes Médicos , Estados Unidos , Biópsia/métodosRESUMO
BACKGROUND: Toward development of a core outcome set for randomized controlled trials (RCTs) of physical activity (PA) interventions for older adults, the purpose of this study was to identify outcome domains and subdomains ('what' was measured) in previously published RCTs of PA for older adults. METHODS: We conducted a rapid review and searched Ovid MEDLINE for recently- published (2015-2021), English-language, RCTs of PA interventions for older adults (mean age 60+ yrs). We limited to articles published in Web of Science top-10 journals in general and internal medicine, geriatrics and gerontology, rehabilitation, and sports science. Two reviewers independently completed eligibility screening; two other reviewers abstracted trial descriptors and study outcomes. We classified study outcomes according to the standard outcome classification taxonomy endorsed by the Core Outcome Measures in Effectiveness Trials Initiative. RESULTS: Our search yielded 548 articles; 67 articles were eligible to be included. Of these, 82% were efficacy/effectiveness trials, 85% included both male and female participants, and 84% recruited community-dwelling older adults. Forty percent of articles reported on interventions that involved a combination of group and individual PAs, and 60% involved a combination of PA modes (e.g., aerobic, resistance). Trial sample size ranged from 14 to 2157 participants, with median (IQR) of 94 (57-517); 28,649 participants were included across all trials. We identified 21 unique outcome domains, spanning 4/5 possible core areas (physiological/clinical; life impact; resource use; adverse events). The five most commonly reported outcome domains were physical functioning (included in n=51 articles), musculoskeletal and connective tissue (n=30), general (n=26), cognitive functioning (n=16), and emotional functioning/wellbeing (n=14). Under these five outcome domains, we further identified 10 unique outcome subdomains (e.g., fall-related; body composition; quality of life). No outcome domains or subdomains were reported consistently in all RCTs. CONCLUSIONS: We found extensive variability in outcome domains and subdomains used in RCTs of PA for older adults, reflecting the broad range of potential health benefits derived from PA and also investigator interest to monitor a range of safety parameters related to adverse events. This study will inform development of a core outcome set to improve outcome reporting consistency and evidence quality.
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Exercício Físico , Qualidade de Vida , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The connectivity between somatosensory evoked potentials (SEPs) and cortical plasticity remains elusive due to a lack of supporting data. This study investigates changes in pathological latencies and amplitudes of SEPs caused by an acute stroke after 2 weeks of rehabilitation with functional electrical stimulation (FES). Furthermore, changes in SEPs and the efficacy of FES against foot drop (FD) stroke symptoms were correlated using the 10-m walk test and foot-ankle strength. METHODS: A randomised controlled two-period crossover design plus a control group (group C) was designed. Group A (n = 16) was directly treated with FES, while group B (n = 16) was treated after 2 weeks. The untreated control group of 20 healthy adults underwent repeated SEP measurements for evaluation only. RESULTS: The repeated-measures ANOVA showed a decrease in tibial nerve (TN) P40 and N50 latencies in group A after the intervention, followed by a decline in non-paretic TN SEP in latency N50 (p < 0.05). Moreover, compared to groups B and C from baseline to 4 weeks, group A showed a decrease in paretic TN latency P40 and N50 (p < 0.05). An increase in FD strength and a reduction in step cadence in group B (p < 0.05) and a positive tendency in FD strength (p = 0.12) and step cadence (p = 0.08) in group A were observed after the treatment time. The data showed a moderate (r = 0.50-0.70) correlation between non-paretic TN latency N50 and step cadence in groups A and B after the intervention time. CONCLUSION: The FES intervention modified the pathological gait in association with improved SEP afferent feedback. Registered on 25 February 2021 on ClinicalTrials.gov under identifier number: NCT04767360.
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Terapia por Estimulação Elétrica , Neuropatias Fibulares , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Adulto , Humanos , Neuropatias Fibulares/complicações , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Potenciais Somatossensoriais Evocados , Estimulação ElétricaRESUMO
Bullous impetigo is a variant of epidermal infection by Staphylococcus aureus, representing 30% of impetigo cases. Its clinical appearance may mimic certain autoimmune blistering dermatoses and other cutaneous infections, sometimes necessitating careful evaluation. Herein we present a patient with bullous impetigo in a striking and characteristic appearance and briefly overview the approach to diagnosis, treatment, and prevention.
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Doenças Autoimunes , Impetigo , Dermatopatias , Infecções Estafilocócicas , Masculino , Humanos , Impetigo/diagnóstico , Vesícula , AbdomeRESUMO
Cutaneous larva migrans (CLM) is a dermo-epidermal parasitic infection with a disproportionate incidence in developing countries, particularly in, and near tropical areas. It is characterized by erythematous, twisting, and linear plaques that can migrate to adjacent skin. Herein, we present an otherwise healthy 45-year-old woman who acquired a pruritic, erythematous, and serpiginous rash localized to her right medial ankle during a trip to New England. Oral ivermectin, the preferred first-line treatment for cutaneous larva migrans, was administered in combination with triamcinolone. This was followed by removal of the papular area via punch biopsy; treatment was successful with a one-week recovery. Although cutaneous larva migrans has traditionally been considered a tropical disease, clinicians should be cognizant of its expanding geographic spread.
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Exantema , Larva Migrans , Humanos , Feminino , Pessoa de Meia-Idade , Larva Migrans/diagnóstico , Larva Migrans/tratamento farmacológico , Larva Migrans/epidemiologia , Ivermectina/uso terapêutico , Pele/patologia , Epiderme , Exantema/patologiaRESUMO
BACKGROUND: The extent of population exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was uncertain in many African countries during the onset of the pandemic. METHODS: We conducted a cross-sectional study and randomly selected and surveyed general population and occupational groups from 6 July to 24 August 2020, in 3 cities in Mozambique. Anti-SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies were measured using a point-of-care rapid test. The prevalence was weighted for population (by age, sex, and city) and adjusted for test sensitivity and specificity. RESULTS: A total of 21 183 participants, including 11 143 from the general population and 10 040 from occupational groups, were included across all 3 cities. General population seropositivity (IgM or IgG) prevalence was 3.0% (95% confidence interval [CI], 1.0%-6.6%) in Pemba, 2.1% (95% CI, 1.2%-3.3%) in Maputo City, and 0.9% (95% CI, .1%-1.9%) in Quelimane. The prevalence in occupational groups ranged from 2.8% (95% CI, 1.3%-5.2%) to 5.9% (95% CI, 4.3%-8.0%) in Pemba, 0.3% (95% CI, .0%-2.2%) to 4.0% (95% CI, 2.6%-5.7%) in Maputo City, and 0.0% (95% CI, .0%-.7%) to 6.6% (95% CI, 3.8%-10.5%) in Quelimane, and showed variations between the groups tested. CONCLUSIONS: In the first representative COVID-19 serosurveys in Mozambique, in mid-2020, weighted and assay-adjusted seroprevalence in 3 provincial capitals of anti-SARS-CoV-2 ranged from 0.9% to 3.0%, whereas adjusted prevalence in occupational groups ranged from 0.0% to 6.6% with variation between groups. Exposure to SARS-CoV-2 was extensive during the first pandemic wave, and transmission may have been more intense among occupational groups. These data have been of utmost importance to inform public health intervention to control and respond to the pandemic in Mozambique.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/epidemiologia , Teste para COVID-19 , Cidades , Estudos Transversais , Humanos , Imunoglobulina G , Imunoglobulina M , Moçambique/epidemiologia , Prevalência , Estudos SoroepidemiológicosRESUMO
OBJECTIVE: The objective of this study was to assess the quality and accuracy of visual abstracts published in academic surgical journals. BACKGROUND: Visual abstracts are commonly used to disseminate medical research findings. They distill the key messages of a research article, presenting them graphically in an engaging manner so that potential readers can decide whether to read the complete manuscript. METHODS: We developed the Visual Abstract Assessment Tool based upon published guidelines. Seven reviewers underwent iterative training to apply the tool. We collected visual abstracts published by 25 surgical journals from January 2017 to April 2021; those corresponding to systematic reviews without meta-analysis, conference abstracts, narrative reviews, video abstracts, or nonclinical research were excluded. Included visual abstracts were scored on accuracy (as compared with written abstracts) and design, and were given a "first impression" score. RESULTS: Across 25 surgical journals 1325 visual abstracts were scored. We found accuracy deficits in the reporting of study design (35.8%), appropriate icon use (49%), and sample size reporting (69.2%), and design deficits in element alignment (54.8%) and symmetry (36.1%). Overall scores ranged from 9 to 14 (out of 15), accuracy scores from 4 to 8 (out of 8), and design scores from 3 to 7 (out of 7). No predictors of visual abstract score were identified. CONCLUSION: Visual abstracts vary widely in quality. As visual abstracts become integrated with the traditional components of scientific publication, they must be held to similarly high standards. We propose a checklist to be used by authors and journals to standardize the quality of visual abstracts.
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Publicações Periódicas como Assunto , Lista de Checagem , Humanos , Projetos de PesquisaRESUMO
BACKGROUND: Understanding the magnitude and causes of mortality at national and sub-national levels for countries is critical in facilitating evidence-based prioritization of public health response. We provide comparable cause of death data from Kisumu County, a high HIV and malaria-endemic county in Kenya, and compared them with Kenya and low-and-middle income countries (LMICs). METHODS: We analyzed data from a mortuary-based study at two of the largest hospital mortuaries in Kisumu. Mortality data through 2019 for Kenya and all LMICs were downloaded from the Global Health Data Exchange. We provided age-standardized rates for comparisons of all-cause and cause-specific mortality rates, and distribution of deaths by demographics and Global Burden of Disease (GBD) classifications. RESULTS: The all-cause age-standardized mortality rate (SMR) was significantly higher in Kisumu compared to Kenya and LMICs (1118 vs. 659 vs. 547 per 100,000 population, respectively). Among women, the all-cause SMR in Kisumu was almost twice that of Kenya and double the LMICs rate (1150 vs. 606 vs. 518 per 100,000 population respectively). Among men, the all-cause SMR in Kisumu was approximately one and a half times higher than in Kenya and nearly double that of LMICs (1089 vs. 713 vs. 574 per 100,000 population). In Kisumu and LMICs non-communicable diseases accounted for most (48.0 and 58.1% respectively) deaths, while in Kenya infectious diseases accounted for the majority (49.9%) of deaths. From age 10, mortality rates increased with age across all geographies. The age-specific mortality rate among those under 1 in Kisumu was nearly twice that of Kenya and LMICs (6058 vs. 3157 and 3485 per 100,000 population, respectively). Mortality from injuries among men was at least one and half times that of women in all geographies. CONCLUSION: There is a notable difference in the patterns of mortality rates across the three geographical areas. The double burden of mortality from GBD Group I and Group II diseases with high infant mortality in Kisumu can guide prioritization of public health interventions in the county. This study demonstrates the importance of establishing reliable vital registry systems at sub-national levels as the mortality dynamics and trends are not homogeneous.
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Países em Desenvolvimento , Carga Global da Doença , Causas de Morte , Criança , Feminino , Saúde Global , Humanos , Lactente , Quênia/epidemiologia , Masculino , MortalidadeRESUMO
BACKGROUND: For assessing the HIV epidemic in Kenya, a series of independent HIV indicator household-based surveys of similar design can be used to investigate the trends in key indicators relevant to HIV prevention and control and to describe geographic and sociodemographic disparities, assess the impact of interventions, and develop strategies. We developed methods and tools to facilitate a robust analysis of trends across three national household-based surveys conducted in Kenya in 2007, 2012, and 2018. METHODS: We used data from the 2007 and 2012 Kenya AIDS Indicator surveys (KAIS 2007 and KAIS 2012) and the 2018 Kenya Population-based HIV Impact Assessment (KENPHIA 2018). To assess the design and other variables of interest from each study, variables were recoded to ensure that they had equivalent meanings across the three surveys. After assessing weighting procedures for comparability, we used the KAIS 2012 nonresponse weighting procedure to revise normalized KENPHIA weights. Analyses were restricted to geographic areas covered by all three surveys. The revised analysis files were then merged into a single file for pooled analysis. We assessed distributions of age, sex, household wealth, and urban/rural status to identify unexpected changes between surveys. To demonstrate how a trend analysis can be carried out, we used continuous, binary, and time-to-event variables as examples. Specifically, temporal trends in age at first sex and having received an HIV test in the last 12 months were used to demonstrate the proposed analytical approach. These were assessed with respondent-specific variables (age, sex, level of education, and marital status) and household variables (place of residence and wealth index). All analyses were conducted in SAS 9.4, but analysis files were created in Stata and R format to support additional analyses. RESULTS: This study demonstrates trends in selected indicators to illustrate the approach that can be used in similar settings. The incidence of early sexual debut decreased from 11.63 (95% CI: 10.95-12.34) per 1,000 person-years at risk in 2007 to 10.45 (95% CI: 9.75-11.2) per 1,000 person-years at risk in 2012 and to 9.58 (95% CI: 9.08-10.1) per 1,000 person-years at risk in 2018. HIV-testing rates increased from 12.6% (95% CI: 11.6%-13.6%) in 2007 to 56.1% (95% CI: 54.6%-57.6%) in 2012 but decreased slightly to 55.6% [95% CI: 54.6%-56.6%) in 2018. The decrease in incidence of early sexual debut could be convincingly demonstrated between 2007 and 2012 but not between 2012 and 2018. Similarly, there was virtually no difference between HIV Testing rates in 2012 and 2018. CONCLUSIONS: Our approach can be used to support trend comparisons for variables in HIV surveys in low-income settings. Independent national household surveys can be assessed for comparability, adjusted as appropriate, and used to estimate trends in key indicators. Analyzing trends over time can not only provide insights into Kenya's progress toward HIV epidemic control but also identify gaps.