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1.
Nature ; 623(7985): 183-192, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853125

RESUMO

The DNA damage response is essential to safeguard genome integrity. Although the contribution of chromatin in DNA repair has been investigated1,2, the contribution of chromosome folding to these processes remains unclear3. Here we report that, after the production of double-stranded breaks (DSBs) in mammalian cells, ATM drives the formation of a new chromatin compartment (D compartment) through the clustering of damaged topologically associating domains, decorated with γH2AX and 53BP1. This compartment forms by a mechanism that is consistent with polymer-polymer phase separation rather than liquid-liquid phase separation. The D compartment arises mostly in G1 phase, is independent of cohesin and is enhanced after pharmacological inhibition of DNA-dependent protein kinase (DNA-PK) or R-loop accumulation. Importantly, R-loop-enriched DNA-damage-responsive genes physically localize to the D compartment, and this contributes to their optimal activation, providing a function for DSB clustering in the DNA damage response. However, DSB-induced chromosome reorganization comes at the expense of an increased rate of translocations, also observed in cancer genomes. Overall, we characterize how DSB-induced compartmentalization orchestrates the DNA damage response and highlight the critical impact of chromosome architecture in genomic instability.


Assuntos
Compartimento Celular , Cromatina , Dano ao DNA , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular , Cromatina/genética , Cromatina/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteína Quinase Ativada por DNA/metabolismo , Fase G1 , Histonas/metabolismo , Neoplasias/genética , Estruturas R-Loop , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(17): e2307216121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38621126

RESUMO

Uncontrolled fires place considerable burdens on forest ecosystems, compromising our ability to meet conservation and restoration goals. A poor understanding of the impacts of fire on ecosystems and their biodiversity exacerbates this challenge, particularly in tropical regions where few studies have applied consistent analytical techniques to examine a broad range of ecological impacts over multiyear time frames. We compiled 16 y of data on ecosystem properties (17 variables) and biodiversity (21 variables) from a tropical peatland in Indonesia to assess fire impacts and infer the potential for recovery. Burned forest experienced altered structural and microclimatic conditions, resulting in a proliferation of nonforest vegetation and erosion of forest ecosystem properties and biodiversity. Compared to unburned forest, habitat structure, tree density, and canopy cover deteriorated by 58 to 98%, while declines in species diversity and abundance were most pronounced for trees, damselflies, and butterflies, particularly for forest specialist species. Tracking ecosystem property and biodiversity datasets over time revealed most to be sensitive to recurrent high-intensity fires within the wider landscape. These megafires immediately compromised water quality and tree reproductive phenology, crashing commercially valuable fish populations within 3 mo and driving a gradual decline in threatened vertebrates over 9 mo. Burned forest remained structurally compromised long after a burn event, but vegetation showed some signs of recovery over a 12-y period. Our findings demonstrate that, if left uncontrolled, fire may be a pervasive threat to the ecological functioning of tropical forests, underscoring the importance of fire prevention and long-term restoration efforts, as exemplified in Indonesia.


Assuntos
Borboletas , Incêndios , Animais , Ecossistema , Solo , Florestas , Árvores , Biodiversidade
3.
Ann Neurol ; 95(2): 347-361, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37801480

RESUMO

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Feminino , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibrinolíticos/uso terapêutico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Hemorragia/complicações , Terapia Trombolítica/métodos , Resultado do Tratamento , Isquemia Encefálica/tratamento farmacológico
4.
N Engl J Med ; 385(11): 971-981, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34496173

RESUMO

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).


Assuntos
Ambulâncias , Serviços Médicos de Emergência , AVC Isquêmico/tratamento farmacológico , Unidades Móveis de Saúde , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Avaliação da Deficiência , Feminino , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Razão de Chances , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
5.
Am J Obstet Gynecol ; 231(2): 261.e1-261.e10, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38705225

RESUMO

BACKGROUND: The choice of midurethral sling type may impact efficacy and complications in women undergoing transvaginal native tissue repair of pelvic organ prolapse. OBJECTIVE: The primary aim was to determine if the single-incision sling is noninferior to retropubic sling for the management of stress urinary incontinence among patients undergoing reconstructive or obliterative native tissue vaginal repair. The secondary aims were to compare adverse events and surgeon ease of use with sling assignment. STUDY DESIGN: A multicenter, noninferiority, randomized trial of women with ≥ stage II pelvic organ prolapse and objectively confirmed stress urinary incontinence undergoing reconstructive or obliterative vaginal repair was performed. Women were randomized to concomitant single-incision (Altis sling, Coloplast Minneapolis, MN) with suprapubic sham incisions or retropubic slings. The primary dichotomous outcome was abnormal lower urinary tract function within 12 months postsurgery, defined as bothersome stress urinary incontinence symptoms (>1 Pelvic Floor Distress Inventory question no. 17); retreatment for stress urinary incontinence or treatment for urinary retention. Secondary outcomes were adverse events, Patient Global Impression of Improvement of bladder function, and surgeon ease of use (1, worst; 10, best). All subjects completed validated questionnaires and underwent a Pelvic Organ Prolapse Quantification, cough stress test, and postvoid residual preoperatively, at 6 weeks and 12 months postoperatively. Assuming a subjective cure rate for retropubic of 82%, 80% power, and 1-sided 5% significance level, we estimated that 127 patients in each arm were needed to declare noninferiority of the single-incision sling if the upper bound of the 95% confidence interval for the between-group difference per protocol in abnormal bladder function was <12%. Assuming a 10% loss to follow-up, the total enrollment goal was 280. RESULTS: Between December 2018 and January 2023, 280 subjects were enrolled across 7 sites, and 255 were randomized: 126 were for single-incision, and 129 were for retropubic sling. There were no preoperative or operative characteristic differences between groups. Overall, 81% had reconstructive, and 19% had obliterative native tissue repairs. The primary outcome, abnormal lower urinary tract function at 12 months, occurred in 29 (25%) of single-incision vs 24 (20%) of the retropubic sling group (risk difference, 0.04472 [95% confidence interval, -0.03 to 0.1133]; P=.001 for noninferiority). Bothersome stress urinary incontinence occurred in 20% vs 17% (P=.27) and was retreated in 4% vs 2% (P=.44) of single-incision vs retropubic groups, respectively. Adverse events were reported in 24 (16%) of single-incision vs 14 (9%) of the retropubic group (95% confidence interval, 0.95-3.29; P=.70) and included de novo or worsening urgency incontinence symptoms, urinary tract infection, mesh exposure, need for prolonged catheter drainage, and de novo pain, without differences between groups. Patient Global Impression of Improvement (very satisfied and satisfied) was 71% vs 67% (P=.43), and median surgeon ease of sling use was 8 (7-10) vs 9 (8-10), P=.03 in single-incision vs retropubic, respectively. CONCLUSION: For women undergoing vaginal repair, single-incision was noninferior to retropubic sling for stress urinary incontinence symptoms, and complications, including treatment for urinary retention, did not differ.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Humanos , Feminino , Incontinência Urinária por Estresse/cirurgia , Pessoa de Meia-Idade , Idoso , Prolapso Uterino/cirurgia , Procedimentos Cirúrgicos em Ginecologia/métodos , Prolapso de Órgão Pélvico/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Retenção Urinária/etiologia
6.
Environ Sci Technol ; 58(26): 11482-11491, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38889081

RESUMO

There is a longstanding debate about the role of nitrogen (N) vs phosphorus (P) in limiting primary production in lakes and whether co-nutrient limitation should be considered for managing eutrophication. We evaluated nutrient limitation and eutrophication at a subcontinental scale. Using U.S. Environmental Protection Agency National Lakes Assessment data, we assessed broad-scale patterns in nutrient limitation and compared samples of all surveyed lakes and lakes resurveyed in multiple surveys. We found that N correlated more strongly with productivity in the western U.S., while P correlated more strongly in the eastern U.S. The aggregated subcontinental effect suggests the importance of factors like N-deposition, terrestrial vegetation, underlying geology, and land use for understanding drivers of nutrient dynamics in lakes. Our study showed how patterns can aggregate across subcontinental scales yet still demonstrate considerable variation when more deeply examined on an individual lake level. Overall, we found that nutrient limitation is dynamic over space and time, with most lakes being co-limited. The prevalence of co-limitation also increased from 2007 to 2017. Trophic states within each limitation category varied substantially. Our findings underscore the need for combined N and P reductions to mitigate accelerated eutrophication.


Assuntos
Eutrofização , Lagos , Nitrogênio , Nutrientes , Fósforo , Estados Unidos , Monitoramento Ambiental
8.
Int Urogynecol J ; 35(1): 31-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38117297

RESUMO

This article explores the current landscape of clinical education in obstetrics and gynecology for medical students, residents, and fellows who identify as male. Academic, clinical instruction should be inclusive for the betterment of the training experience for all, but most importantly, for the betterment of women's health.


Assuntos
Ginecologia , Internato e Residência , Obstetrícia , Feminino , Masculino , Humanos , Ginecologia/educação , Obstetrícia/educação , Saúde da Mulher
9.
Int Urogynecol J ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066810

RESUMO

INTRODUCTION AND HYPOTHESIS: Women undergoing surgery for apical pelvic organ prolapse have several medically sound options for specific surgical approaches. METHODS: We review the principles of shared decision-making as they pertain to surgery for prolapse. We review the literature supporting the superior sacrocolpopexy as a durable treatment for prolapse and the factors that may differentiate it from other repairs in risk and benefit. RESULTS: We emphasize the importance of collaboration between patients and surgeons in surgical decision-making. CONCLUSION: All medically appropriate patients who desire reconstructive surgery for prolapse should be offered sacrocolpopexy.

10.
Int Urogynecol J ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073630

RESUMO

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy is the gold standard for the surgical management of apical prolapse. Over the years, surgical advancements have transformed the procedure from a laparotomy with a hospital stay of several days to a minimally invasive approach with a much shorter hospital stay. One recent innovation has the potential to transform minimally invasive sacrocolpopexy. METHODS: The da Vinci single-port robotic platform has allowed urological procedures to generate improved recovery, pain control, and cosmesis, with no differences in complications rates. RESULTS: Although the data with respect to sacrocolpopexy are more limited owing to the novelty of this application, the results appear to be similar to those of urological procedures such as prostatectomy. CONCLUSIONS: We present our surgical technique for completing single-port robotic sacrocolpopexy, with and without a hysterectomy, as well as a review of the relevant literature.

11.
BMC Public Health ; 24(1): 1887, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010030

RESUMO

Khat, a naturally growing stimulant, has seen a significant increase in both consumption and cultivation in eastern Ethiopia. This reliance on khat in the region comes despite its known physiological complications, with users unable to restrict khat use due to its pervasive impact on their livelihood. This qualitative study sought to understand the meaning that those in eastern Ethiopia attribute to khat and explore their firsthand experiences with the substance. In June and July of 2023, six unstructured interviews were conducted among residents of the Haramaya District in Ethiopia. To promote a holistic comprehension of the participants' lived experiences, an interpretative phenomenological analysis approach was employed when collecting and analyzing the data. Participant responses were coded independently from one another by two different researchers identifying superordinate and corresponding subordinate themes. Among the participants, six superordinate themes were captured: economic backbone of the region, market disruption & fluctuation, pesticide use, societal relationships around khat, applications of khat, and access to healthcare. The participants' responses indicated that the normalization of khat use, coupled with the downplaying of its addictive potential, has established a framework where khat consumption is not only allowed but, in some cases, even encouraged. The unique interplay between communal practice and individual preservation creates a cyclical effect of using khat to supplement energy to farm khat and then sell or stimulate further work on their farm. This study illuminates the transitionfrom what was once the traditional or spiritual use of khat, to a more practical use for ensuring economic livelihood.


Assuntos
Catha , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Substâncias , Humanos , Etiópia , Masculino , Adulto , Feminino , Transtornos Relacionados ao Uso de Substâncias/psicologia , Pessoa de Meia-Idade , Adulto Jovem , Entrevistas como Assunto , Acessibilidade aos Serviços de Saúde
12.
BMC Pediatr ; 23(Suppl 2): 657, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977945

RESUMO

BACKGROUND: The emergence of COVID-19 precipitated containment policies (e.g., lockdowns, school closures, etc.). These policies disrupted healthcare, potentially eroding gains for Sustainable Development Goals including for neonatal mortality. Our analysis aimed to evaluate indirect effects of COVID-19 containment policies on neonatal admissions and mortality in 67 neonatal units across Kenya, Malawi, Nigeria, and Tanzania between January 2019 and December 2021. METHODS: The Oxford Stringency Index was applied to quantify COVID-19 policy stringency over time for Kenya, Malawi, Nigeria, and Tanzania. Stringency increased markedly between March and April 2020 for these four countries (although less so in Tanzania), therefore defining the point of interruption. We used March as the primary interruption month, with April for sensitivity analysis. Additional sensitivity analysis excluded data for March and April 2020, modelled the index as a continuous exposure, and examined models for each country. To evaluate changes in neonatal admissions and mortality based on this interruption period, a mixed effects segmented regression was applied. The unit of analysis was the neonatal unit (n = 67), with a total of 266,741 neonatal admissions (January 2019 to December 2021). RESULTS: Admission to neonatal units decreased by 15% overall from February to March 2020, with half of the 67 neonatal units showing a decline in admissions. Of the 34 neonatal units with a decline in admissions, 19 (28%) had a significant decrease of ≥ 20%. The month-to-month decrease in admissions was approximately 2% on average from March 2020 to December 2021. Despite the decline in admissions, we found no significant changes in overall inpatient neonatal mortality. The three sensitivity analyses provided consistent findings. CONCLUSION: COVID-19 containment measures had an impact on neonatal admissions, but no significant change in overall inpatient neonatal mortality was detected. Additional qualitative research in these facilities has explored possible reasons. Strengthening healthcare systems to endure unexpected events, such as pandemics, is critical in continuing progress towards achieving Sustainable Development Goals, including reducing neonatal deaths to less than 12 per 1000 live births by 2030.


Assuntos
COVID-19 , Mortalidade Infantil , Análise de Séries Temporais Interrompida , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/mortalidade , Recém-Nascido , Tanzânia/epidemiologia , Quênia/epidemiologia , Mortalidade Infantil/tendências , Malaui/epidemiologia , Nigéria/epidemiologia , Admissão do Paciente/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal , Hospitalização/estatística & dados numéricos , Pandemias , Lactente
13.
Ecol Lett ; 26(12): 2077-2086, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787116

RESUMO

Resource quantity controls biodiversity across spatial scales; however, the importance of resource quality to cross-scale patterns in species richness has seldom been explored. We evaluated the relationship between stream basal resource quantity (periphyton chlorophyll a) and invertebrate richness and compared this to the relationship of resource quality (periphyton stoichiometry) and richness at local and regional scales across 27 North American streams. At the local scale, invertebrate richness peaked at intermediate levels of chlorophyll a, but had a shallow negative relationship with periphyton C:P and N:P. However, at the regional scale, richness had a strong negative relationship with chlorophyll a and periphyton C:P and N:P. The divergent relationships of periphyton chlorophyll a and stoichiometry with invertebrate richness suggest that autochthonous resource quantity limits diversity more than quality, consistent with patterns of eutrophication. Collectively, we provide evidence that patterns in resource quantity and quality play important, yet differing roles in shaping freshwater biodiversity across spatial scale.


Assuntos
Ecossistema , Rios , Animais , Clorofila A , Invertebrados , Biodiversidade
14.
J Muscle Res Cell Motil ; 44(2): 39-52, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36131170

RESUMO

Fibrosis-driven solid organ failure is a major world-wide health burden with few therapeutic options. Spiny mice (genus: Acomys) are terrestrial mammals that regenerate severe skin wounds without fibrotic scars to evade predators. Recent studies have shown that spiny mice also regenerate acute ischemic and traumatic injuries to kidney, heart, spinal cord, and skeletal muscle. A common feature of this evolved wound healing response is a lack of formation of fibrotic scar tissue that degrades organ function, inhibits regeneration, and leads to organ failure. Complex tissue regeneration is an extremely rare property among mammalian species. In this article, we discuss the evidence that Acomys represents an emerging model organism that offers a unique opportunity for the biomedical community to investigate and clinically translate molecular mechanisms of scarless wound healing and regeneration of organ function in a mammalian species.


Assuntos
Pele , Cicatrização , Animais , Pele/metabolismo , Cicatrização/fisiologia , Murinae/fisiologia , Fibrose , Músculo Esquelético/fisiologia
15.
Anim Cogn ; 26(4): 1147-1159, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36864246

RESUMO

The use of 2-dimensional representations (e.g. photographs or digital images) of real-life physical objects has been an important tool in studies of animal cognition. Horses are reported to recognise objects and individuals (conspecifics and humans) from printed photographs, but it is unclear whether image recognition is also true for digital images, e.g. computer projections. We expected that horses trained to discriminate between two real-life objects would show the same learnt response to digital images of these objects indicating that the images were perceived as objects, or representations of such. Riding-school horses (N = 27) learnt to touch one of two objects (target object counterbalanced between horses) to instantly receive a food reward. After discrimination learning (three consecutive sessions of 8/10 correct trials), horses were immediately tested with on-screen images of the objects over 10 image trials interspersed with five real object trials. At first image presentation, all but two horses spontaneously responded to the images with the learnt behaviour by contacting one of the two images, but the number of horses touching the correct image was not different from chance (14/27 horses, p > 0.05). Only one horse touched the correct image above chance level across 10 image trials (9/10 correct responses, p = 0.021). Our findings thus question whether horses recognise real-life objects from digital images. We discuss how methodological factors and individual differences (i.e. age, welfare state) might have influenced animals' response to the images, and the importance of validating the suitability of stimuli of this kind for cognitive studies in horses.


Assuntos
Cognição , Aprendizagem , Humanos , Cavalos , Animais , Aprendizagem por Discriminação/fisiologia , Reconhecimento Psicológico , Tato
16.
BMC Pediatr ; 23(Suppl 2): 632, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098013

RESUMO

BACKGROUND: Small and sick newborn care (SSNC) is critical for national neonatal mortality reduction targets by 2030. Investment cases could inform implementation planning and enable coordinated resource mobilisation. We outline development of an investment case for Tanzania to estimate additional financing for scaling up SSNC to 80% of districts as part of health sector strategies to meet the country's targets. METHODS: We followed five steps: (1) reviewed national targets, policies and guidelines; (2) modelled potential health benefits by increased coverage of SSNC using the Lives Saved Tool; (3) estimated setup and running costs using the Neonatal Device Planning and Costing Tool, applying two scenarios: (A) all new neonatal units and devices with optimal staffing, and (B) half new and half modifying, upgrading, or adding resources to existing neonatal units; (4) calculated budget impact and return on investment (ROI) and (5) identified potential financing opportunities. RESULTS: Neonatal mortality rate was forecast to fall from 20 to 13 per 1000 live births with scale-up of SSNC, superseding the government 2025 target of 15, and close to the 2030 Sustainable Development Goal 3.2 target of <12. At 85% endline coverage, estimated cumulative lives saved were 36,600 by 2025 and 80,000 by 2030. Total incremental costs were estimated at US$166 million for scenario A (US$112 million set up and US$54 million for running costs) and US$90 million for scenario B (US$65 million setup and US$25 million for running costs). Setup costs were driven by infrastructure (83%) and running costs by human resources (60%). Cost per capita was US$0.93 and the ROI is estimated to be between US$8-12 for every dollar invested. CONCLUSIONS: ROI for SSNC is higher compared to other health investments, noting many deaths averted followed by full lifespan. This is conservative since disability averted is not included. Budget impact analysis estimated a required 2.3% increase in total government health expenditure per capita from US$40.62 in 2020, which is considered affordable, and the government has already allocated additional funding. Our proposed five-step SSNC investment case has potential for other countries wanting to accelerate progress.


Assuntos
Mortalidade Infantil , Desenvolvimento Sustentável , Recém-Nascido , Humanos , Tanzânia
17.
BMC Pediatr ; 23(Suppl 2): 568, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968606

RESUMO

BACKGROUND: Thirty million small and sick newborns worldwide require inpatient care each year. Many receive antibiotics for clinically diagnosed infections without blood cultures, the current 'gold standard' for neonatal infection detection. Low neonatal blood culture use hampers appropriate antibiotic use, fuelling antimicrobial resistance (AMR) which threatens newborn survival. This study analysed the gap between blood culture use and antibiotic prescribing in hospitals implementing with Newborn Essential Solutions and Technologies (NEST360) in Kenya, Malawi, Nigeria, and Tanzania. METHODS: Inpatient data from every newborn admission record (July 2019-August 2022) were included to describe hospital-level blood culture use and antibiotic prescription. Health Facility Assessment data informed performance categorisation of hospitals into four tiers: (Tier 1) no laboratory, (Tier 2) laboratory but no microbiology, (Tier 3) neonatal blood culture use < 50% of newborns receiving antibiotics, and (Tier 4) neonatal blood culture use > 50%. RESULTS: A total of 144,146 newborn records from 61 hospitals were analysed. Mean hospital antibiotic prescription was 70% (range = 25-100%), with 6% mean blood culture use (range = 0-56%). Of the 10,575 blood cultures performed, only 24% (95%CI 23-25) had results, with 10% (10-11) positivity. Overall, 40% (24/61) of hospitals performed no blood cultures for newborns. No hospitals were categorised as Tier 1 because all had laboratories. Of Tier 2 hospitals, 87% (20/23) were District hospitals. Most hospitals could do blood cultures (38/61), yet the majority were categorised as Tier 3 (36/61). Only two hospitals performed > 50% blood cultures for newborns on antibiotics (Tier 4). CONCLUSIONS: The two Tier 4 hospitals, with higher use of blood cultures for newborns, underline potential for higher blood culture coverage in other similar hospitals. Understanding why these hospitals are positive outliers requires more research into local barriers and enablers to performing blood cultures. Tier 3 facilities are missing opportunities for infection detection, and quality improvement strategies in neonatal units could increase coverage rapidly. Tier 2 facilities could close coverage gaps, but further laboratory strengthening is required. Closing this culture gap is doable and a priority for advancing locally-driven antibiotic stewardship programmes, preventing AMR, and reducing infection-related newborn deaths.


Assuntos
Antibacterianos , Hemocultura , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Estudos Transversais , Quênia , Pacientes Internados , Malaui , Tanzânia , Nigéria , Hospitais
18.
BMC Pediatr ; 23(Suppl 2): 566, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968613

RESUMO

BACKGROUND: High-quality neonatal care requires sufficient functional medical devices, furniture, fixtures, and use by trained healthcare workers, however there is lack of publicly available tools for quantification and costing. This paper describes development and use of a planning and costing tool regarding furniture, fixtures and devices to support scale-up of WHO level-2 neonatal care, for national and global newborn survival targets. METHODS: We followed a systematic process. First, we reviewed planning and costing tools of relevance. Second, we co-designed a new tool to estimate furniture and device set-up costs for a default 40-bed level-2 neonatal unit, incorporating input from multi-disciplinary experts and newborn care guidelines. Furniture and device lists were based off WHO guidelines/norms, UNICEF and national manuals/guides. Due to lack of evidence-based quantification, ratios were based on operational manuals, multi-country facility assessment data, and expert opinion. Default unit costs were from government procurement agency costs in Kenya, Nigeria, and Tanzania. Third, we refined the tool by national use in Tanzania. RESULTS: The tool adapts activity-based costing (ABC) to estimate quantities and costs to equip a level-2 neonatal unit based on three components: (1) furniture/fixtures (18 default but editable items); (2) neonatal medical devices (16 product categories with minimum specifications for use in low-resource settings); (3) user training at device installation. The tool was used in Tanzania to generate procurement lists and cost estimates for level-2 scale-up in 171 hospitals (146 District and 25 Regional Referral). Total incremental cost of all new furniture and equipment acquisition, installation, and user training were US$93,000 per District hospital (level-2 care) and US$346,000 per Regional Referral hospital. Estimated cost per capita for whole-country district coverage was US$0.23, representing 0.57% increase in government health expenditure per capita and additional 0.35% for all Regional Referral hospitals. CONCLUSION: Given 2.3 million neonatal deaths and potential impact of level-2 newborn care, rational and efficient planning of devices linked to systems change is foundational. In future iterations, we aim to include consumables, spare parts, and maintenance cost options. More rigorous implementation research data are crucial to formulating evidence-based ratios for devices numbers per baby. Use of this tool could help overcome gaps in devices numbers, advance efficiency and quality of neonatal care.


Assuntos
Decoração de Interiores e Mobiliário , Morte Perinatal , Lactente , Recém-Nascido , Feminino , Humanos , Tanzânia , Quênia , Nigéria
19.
J Hum Nutr Diet ; 36(5): 1621-1635, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37158099

RESUMO

BACKGROUND: Cystic fibrosis diabetes (CFD) is a very common co-morbidity affecting the lives of people with cystic fibrosis. Surprisingly, minimal research has been undertaken to understand the experiences of people with CFD and how they self-mange this condition. METHODS: Using interpretative phenomenological analysis, the present study examined the self-management experiences of people with CFD. In-depth semi-structure interviews were conducted with eight people who had CFD. RESULTS: The following three superordinate themes were identified: forming a relationship with CFD, balancing the CFD self-management triad, and the unmet need for information and support. CONCLUSIONS: The findings suggest that the management of CFD is challenging and, although people with CFD experience many adaptation and management processes similar to people with type 1 diabetes, they struggle with the additional complexity of balancing CF and CFD. The provision of appropriate education, support and person-centred care needs to be addressed.


Assuntos
Fibrose Cística , Diabetes Mellitus Tipo 1 , Autogestão , Humanos , Fibrose Cística/terapia , Diabetes Mellitus Tipo 1/terapia , Comportamentos Relacionados com a Saúde , Pesquisa Qualitativa
20.
Palliat Support Care ; : 1-12, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36847132

RESUMO

OBJECTIVES: Chronically ill adolescent and young adult (AYA) patients experience barriers to accessing psychosocial care. AYAs who receive palliative and psychosocial care experience numerous benefits from these services. However, we still lack research investigating age-appropriate programs targeting AYAs' psychosocial needs that are delivered virtually and extend beyond the hospital setting. Streetlight is a palliative care program designed for chronically ill AYAs that offers the Streetlight Gaming League (SGL), an online health community (OHC) combining peer-based support, online gaming, and community events. We evaluated the usefulness, acceptability, and potential effectiveness of SGL through an assessment of chronically ill AYAs' lived experiences. METHODS: We used a qualitative evaluation approach grounded in hermeneutic phenomenology. Questionnaires and interviews were conducted with 9 chronically ill AYAs to elicit in-depth accounts of their lived experiences of using SGL. Descriptive statistical analysis was performed on questionnaire data. Phenomenological data analysis, informed by hermeneutic analysis, was used to analyze interviews. RESULTS: AYAs reported positive experiences with SGL and valued the ability to engage in various content while having few participation expectations. They also described psychosocial benefits, including reprieve from illness, sense of community, and solidarity through mutual understandings and shared experiences. SIGNIFICANCE OF THE RESULTS: Findings highlight the usefulness and acceptability of a virtual palliative psychosocial care program for chronically ill AYAs. Findings also suggest the effectiveness of SGL and support using an OHC to meet the psychosocial needs of AYAs. This study can guide future programming and implementation of online palliative psychosocial care programs in other hospital settings, resulting in similar beneficial and meaningful experiences.

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