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1.
Lancet Respir Med ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33844996

RESUMO

BACKGROUND: Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. METHODS: We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 800 µg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. FINDINGS: From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned-73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the budesonide group and one (1%) of 69 participant in the usual care group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0-50] vs 50% [15-71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference -0·12, 95% CI -0·21 to -0·02 [p=0·016]; FLUPro mean difference -0·10, 95% CI -0·21 to -0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. INTERPRETATION: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. FUNDING: National Institute for Health Research Biomedical Research Centre and AstraZeneca.

2.
PLoS Pathog ; 17(3): e1009402, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33705489

RESUMO

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen.

5.
Bull World Health Organ ; 98(12): 886-893, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33293749

RESUMO

Globally, dietary factors are responsible for about one in five deaths. In many low- and middle-income countries different forms of malnutrition (including obesity and undernutrition) can co-exist within the same population. This double burden of malnutrition is placing a disproportional strain on health systems, slowing progress towards universal health coverage (UHC). Poor nutrition also impedes the growth of local economies, ultimately affecting the global economy. In this article, we argue that comprehensive primary health care should be used as a platform to address the double burden of malnutrition. We use a conceptual framework based on human rights and the Astana Declaration on primary health care to examine existing recommendations and propose guidance on how policy-makers and providers of community-oriented primary health care can strengthen the role of nutrition within the UHC agenda. Specifically, we propose four thematic areas for action: (i) bridging narratives and strengthening links between the primary health care and the nutrition agenda with nutrition as a human rights issue; (ii) encouraging primary health-care providers to support local multisectoral action on nutrition; (iii) empowering communities and patients to address unhealthy diets; and (iv) ensuring the delivery of high-quality promotive, preventive, curative and rehabilitative nutrition interventions. For each theme we summarize the available strategies, policies and interventions that can be used by primary health-care providers and policy-makers to strengthen nutrition in primary health care and thus the UHC agenda.

7.
PLoS One ; 15(12): e0243948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373366

RESUMO

BACKGROUND: Studies from high-income countries reported reduced life expectancy in children with cerebral palsy (CP), while no population-based study has evaluated mortality of children with CP in sub-Saharan Africa. This study aimed to estimate the mortality rate (MR) of children with CP in a rural region of Uganda and identify risk factors and causes of death (CODs). METHODS AND FINDINGS: This population-based, longitudinal cohort study was based on data from Iganga-Mayuge Health and Demographic Surveillance System in eastern Uganda. We identified 97 children (aged 2-17 years) with CP in 2015, whom we followed to 2019. They were compared with an age-matched cohort from the general population (n = 41 319). MRs, MR ratios (MRRs), hazard ratios (HRs), and immediate CODs were determined. MR was 3952 per 100 000 person years (95% CI 2212-6519) in children with CP and 137 per 100 000 person years (95% CI 117-159) in the general population. Standardized MRR was 25·3 in the CP cohort, compared with the general population. In children with CP, risk of death was higher in those with severe gross motor impairments than in those with milder impairments (HR 6·8; p = 0·007) and in those with severe malnutrition than in those less malnourished (HR = 3·7; p = 0·052). MR was higher in females in the CP cohort, with a higher MRR in females (53·0; 95% CI 26·4-106·3) than in males (16·3; 95% CI 7·2-37·2). Age had no significant effect on MR in the CP cohort, but MRR was higher at 10-18 years (39·6; 95% CI 14·2-110·0) than at 2-6 years (21·0; 95% CI 10·2-43·2). Anaemia, malaria, and other infections were the most common CODs in the CP cohort. CONCLUSIONS: Risk of premature death was excessively high in children with CP in rural sub-Saharan Africa, especially in those with severe motor impairments or malnutrition. While global childhood mortality has significantly decreased during recent decades, this observed excessive mortality is a hidden humanitarian crisis that needs to be addressed.


Assuntos
Paralisia Cerebral/mortalidade , Mortalidade Prematura , Adolescente , Paralisia Cerebral/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Fatores de Risco , População Rural , Uganda/epidemiologia
8.
Glob Health Sci Pract ; 8(4): 858-862, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33361248

RESUMO

Oxygen therapy is an essential medicine and core component of effective hospital systems. However, many hospitals in low- and middle-income countries lack reliable oxygen access-a deficiency highlighted and exacerbated by the coronavirus disease (COVID-19) pandemic. Oxygen access can be challenged by equipment that is low quality and poorly maintained, lack of clinical and technical training and protocols, and deficiencies in local infrastructure and policy environment. We share learnings from 2 decades of oxygen systems work with hospitals in Africa and the Asia-Pacific regions, highlighting practical actions that hospitals can take to immediately expand oxygen access. These include strategies to: (1) improve pulse oximetry and oxygen use, (2) support biomedical engineers to optimize existing oxygen supplies, and (3) expand on existing oxygen systems with robust equipment and smart design. We make all our resources freely available for use and local adaptation.


Assuntos
/epidemiologia , Países em Desenvolvimento , Oxigenoterapia/métodos , Oxigenoterapia/estatística & dados numéricos , Oxigênio/provisão & distribução , /terapia , Acesso aos Serviços de Saúde , Administração Hospitalar/estatística & dados numéricos , Humanos , Oximetria , Pandemias
9.
Int J Chron Obstruct Pulmon Dis ; 15: 3003-3012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33239872

RESUMO

Purpose: For exercise testing of COPD patients, a standard endurance test (ET) with constant workload is recommended. The test suffers from large inter-individual variability and need for large sample sizes in order to evaluate treatment effects. Methods: A new protocol for ET in COPD was designed. In contrast to the standard ET, the new ET involved an increasing workload in order to reduce the standard deviation of endurance time. Two new ETs were compared with the standard ET. In Study A, the new ET started at 75% of the patient's maximum workload (WMAX) and increased stepwise with 3%/2 min until exhaustion. Study B started at 70% of WMAX and increased linearly with 1%/min. Results: In Study A, that included 15 patients, the standard deviation and range for endurance time and work capacity were narrower for the new versus the standard ET. However, the higher mean workload at end and the low mean work capacity relative to the standard ET indicated that the stepwise increase was too aggressive. In Study B, that included 18 patients, with a modified protocol, the averages for endurance time, workload at end and work capacity were similar for new and standard ET, while the standard deviations and ranges for endurance time and work capacity were kept more narrow in the new ET. The variances for endurance time were not equal between the standard ET and the two new ETs (p<0.05 for both according to Levene's test). Conclusion: The new ET reduced the number of patients with extreme endurance times (short and long) compared to the standard test. The new test showed a significant lower variance for endurance time, which potentially can lead to fewer patients needed in comparative studies. The overall best results were observed with a low linear increase during endurance.

10.
Respir Med ; 173: 106175, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33032168

RESUMO

BACKGROUND: Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients. METHODS: In this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations. FINDINGS: At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size. INTERPRETATION: COPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.

11.
Global Health ; 16(1): 106, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109214

RESUMO

BACKGROUND: Peer supervision improves health care delivery by health workers. However, in rural Uganda, self-supervision is what is prescribed for licensed private drug sellers by statutory guidelines. Evidence shows that self-supervision encourages inappropriate treatment of children less than 5 years of age by private drug sellers. This study constructed a model for an appropriate peer supervisor to augment the self-supervision currently practiced by drug sellers at district level in rural Uganda. METHODS: In this qualitative study, six Key informant interviews were held with inspectors while ten focus group discussions were conducted with 130 drug sellers. Data analysis was informed by the Kathy Charmaz constructive approach to grounded theory. Atlas ti.7 software package was used for data management. RESULTS: A model with four dimensions defining an appropriate peer supervisor was developed. The dimensions included; incentives, clearly defined roles, mediation and role model peer supervisor. While all dimensions were regarded as being important, all participants interviewed agreed that incentives for peer supervisors were the most crucial. Overall, an appropriate peer supervisor was described as being exemplary to other drug sellers, operated within a defined framework, well facilitated to do their role and a good go-between drug sellers and government inspectors. CONCLUSION: Four central contributions advance literature by the model developed by our study. First, the model fills a supervision gap for rural private drug sellers. Second, it highlights the need for terms of reference for peer supervisors. Third, it describes who an appropriate peer supervisor should be. Lastly, it elucidates the kind of resources needed for peer supervision.

13.
J Pharm Policy Pract ; 13: 55, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944257

RESUMO

Background: Regulatory inspection of private drug shops in Uganda is a mandate of the Ministry of Health carried out by the National Drug Authority. This study evaluated how this mandate is being carried out at national, district, and drug shop levels. Specifically, perspectives on how the inspection is done, who does it, and challenges faced were sought from inspectors and drug sellers. Methods: Six key informant interviews (KIIs) were held with inspectors at the national and district level, while eight focus group discussions (FGDs) were conducted among nursing assistants, and two FGDs were held with nurses. The study appraised current methods of inspecting drug sellers against national professional guidelines for licensing and renewal of class C drug shops in Uganda. Transcripts were managed using Atlas ti version 7 (ATLAS.ti GmbH, Berlin) data management software where the thematic content analysis was done. Results: Five themes emerged from the study: authoritarian inspection, delegated inspection, licensing, training, and bribes. Under authoritarian inspection, drug sellers decried the high handedness used by inspectors when found with expired or no license at all. For delegated inspection, drug sellers said that sometimes, inspectors send health assistants and sub-county chiefs for inspection visits. This cadre of people is not recognized by law as inspectors. Inspectors trained drug sellers on how to organize their drug shops better and how to use new technologies such as rapid diagnostic tests (RDTs) in diagnosing malaria. Bribes were talked about mostly by nursing assistants who purported that inspectors were not interested in inspection per se but collecting illicit payments from them. Inspectors said that the facilitation they received from the central government were inadequate for a routine inspection. Conclusion: The current method of inspecting drug sellers is harsh and instills fear among drug sellers. There is a need to establish a well-recognized structure of inspection as well as establish channels of dialogue between inspectors and drug sellers if meaningful compliance is to be achieved. The government also needs to enhance both human and financial resources if meaningful inspection of drug sellers is to take place.

15.
BMC Pregnancy Childbirth ; 20(1): 497, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854629

RESUMO

BACKGROUND: Delivery in a facility with a skilled health provider is considered the most important intervention to reduce maternal and early newborn deaths. Providing care close to people's homes is an important strategy to facilitate equitable access, but many women are known to bypass the closest delivery facility for a higher level one. The aim of this study was to investigate to what extent mothers in rural Uganda bypassed their nearest facility for childbirth care and the determinants for their choice. METHODS: The study used data collected as part of the Expanded Quality Management Using Information power (EQUIP) study in the Mayuge District of Eastern Uganda between 2011 and 2014. In this study, bypassing was defined as delivering in a health facility that was not the nearest childbirth facility to the mother's home. Multilevel logistic regression was used to model the relationship between bypassing the nearest health facility for childbirth and the different independent factors. RESULTS: Of all women delivering in a health facility, 45% (499/1115) did not deliver in the nearest facility regardless of the level of care. Further, after excluding women who delivered in health centre II (which is not formally equipped to provide childbirth care) and excluding those who were referred or had a caesarean section (because their reasons for bypassing may be different), 29% (204/717) of women bypassed their nearest facility to give birth in another facility, 50% going to the only hospital of the district. The odds of bypassing increased if a mother belonged to highest wealth quintile compared to the lowest quintile (AOR 2.24, 95% CI: 1.12-4.46) and decreased with increase of readiness of score of the nearest facility for childbirth (AOR = 0.84, 95% CI: 0.69-0.99). CONCLUSIONS: The extent of bypassing the nearest childbirth facility in this rural Ugandan setting was 29%, and was associated primarily with the readiness of the nearest facility to provide care as well as the wealth of the household. These results suggest inequalities in bypassing for better quality care that have important implications for improving Uganda's maternal and newborn health outcomes.

16.
Malar J ; 19(1): 270, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711582

RESUMO

BACKGROUND: Support supervision improves performance outcomes among health workers. However, the national professional guidelines for new licenses and renewal for Class C drug shops in Uganda prescribe self-supervision of licensed private drug sellers. Without support supervision, inappropriate treatment of malaria, pneumonia and diarrhoea among children under 5 years of age continues unabated. This study assessed experiences of drug sellers and peer supervisors at the end of a peer supervision intervention in Luuka District in East Central Uganda. METHODS: Eight in-depth interviews (IDIs) were held with peer supervisors while five focus group discussions (FGDs) were conducted among registered drug sellers at the end of the peer supervision intervention. The study assessed experiences and challenges of peer supervisors and drug sellers regarding peer supervision. Transcripts were imported into Atlas.ti 7 qualitative data management software where they were analysed using thematic content analysis. RESULTS: Initially, peer supervisors were disliked and regarded by drug sellers as another extension of drug inspectors. However, with time a good relationship was established between drug sellers and peer supervisors leading to regular, predictable and supportive peer supervision. This increased confidence of drug sellers in using respiratory timers and rapid diagnostic tests in diagnosing pneumonia symptoms and uncomplicated malaria, respectively, among children under 5 years. There was also an improvement in completing the sick child register which was used for self-assessment by drug sellers. The drug shop association was mentioned as a place where peer supervision should be anchored since it was a one-stop centre for sharing experiences and continuous professional development. Drug sellers proposed including community health workers in monthly drug shop association meetings so that they may also gain from the associated benefits. Untimely completion of the sick child registers by drug sellers and inadequate financial resources were the main peer supervision challenges mentioned. CONCLUSION: Drug sellers benefitted from peer supervision by developing a good relationship with peer supervisors. This relationship guaranteed reliable and predictable supervision ultimately leading to improved treatment practices. There is need to explore the minimum resources needed for peer supervision of drug sellers to further inform practice and policy.

18.
Eur J Epidemiol ; 35(6): 537-547, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32350689

RESUMO

We consider disease mapping of early- and late-stage cancer, in order to identify and monitor inequalities in early detection. Our method is demonstrated by mapping cancer incidence at high geographical resolution using data on 10,302 cutaneous malignant melanoma (CMM) cases within the 3.7 million population of South-West Sweden. The cases were geocoded into small-areas, each with a population size between 600 and 2600 and accessible socio-demographic data. Using the disease mapping application Rapid Inquiry Facility (RIF) 4.0, we produced regional maps to visualise spatial variations in stage I, II and III-IV CMM incidences, complemented by local maps to explore the variations within two urban areas. Pronounced spatial disparities in stage I CMM incidence were revealed by the regional and local maps. Stage I CMM incidence was markedly higher in wealthier small-areas, in particular within each urban area. A twofold higher stage I incidence was observed, on average, in the wealthiest small-areas (upper quintile) than in the poorest small-areas (lower quintile). We identified in the regional map of stage III-IV CMM two clusters of higher or lower than expected late-stage incidences which were quite distinct from those identified for stage I. In conclusion, our analysis of CMM incidences supported the use of this method of cancer stage incidence mapping for revealing geographical and socio-demographic disparities in cancer detection.


Assuntos
Detecção Precoce de Câncer , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Classe Social , Fatores Socioeconômicos , Suécia/epidemiologia
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