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1.
Breast Cancer Res Treat ; 199(2): 401-413, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37010652

RESUMO

BACKGROUND: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women. METHODS: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates. RESULTS: A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma. CONCLUSION: The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Quênia/epidemiologia , Linfócitos do Interstício Tumoral , Prognóstico
2.
Value Health ; 26(9): 1296-1300, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37244416

RESUMO

OBJECTIVES: There are inconsistencies in the South Africa HIV mortality data reported by Institute of Health Metrics and Evaluation (IHME), Joint United Nations Programme on HIV/AIDS (UNAIDS), and Statistics South Africa (StatsSA) platforms. Between 2006 and 2016, these global data sets (IHME and UNAIDS) show that HIV-related mortalities were improving in South Africa, whereas StatsSA argues the opposite. We explain the causes of this differing stands and highlight areas that may be improved to address such inconsistencies. METHODS: This observational analysis uses data from IHME, UNAIDS, and StatsSA platforms. RESULTS: We demonstrate that IHME and UNAIDS data sets are based on a mathematical compartmental model, which is not dynamic to all HIV epidemiological aspects. Such limitation may cause inflated improvement in HIV mortality outcomes that are not in line with HIV mortality evidence recorded at the household level as demonstrated by StatsSA. CONCLUSION: There is a need to streamline the IHME, UNAIDS, and StatsSA data on HIV to improve the quality of HIV research and programming in South Africa.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , África do Sul/epidemiologia , Características da Família
3.
BMC Pulm Med ; 23(1): 321, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658386

RESUMO

INTRODUCTION: Obstructive sleep apnea (OSA) is a type of breathing problem during sleep caused by the blockage of the upper airway, which can cause cessation of airflow. There is limited research on the prevalence of OSA in hypertensive patients in sub-Saharan Africa (SSA). The study aimed to describe the prevalence and clinical characteristics of OSA among hypertensive patients at a tertiary hospital in Nairobi, Kenya. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital in Nairobi, Kenya. Two hundred and fifty-one hypertensive patients were screened for OSA risk using the STOP-Bang questionnaire (SBQ). Patients with a SBQ score of ≥ 4 were categorized as high risk for OSA. Descriptive statistics were employed to describe both categorical and continuous variables and binary logistic regression to assess factors associated with the high risk of OSA. RESULTS: The study reported that 78.5% of the participants had high-risk OSA. The median age and body mass index (BMI) were 57.0 years (IQR: 50.0-64.0) and 28.3 kg/m2, respectively. Age, neck circumference, gender, and BMI were significantly higher in the high-risk OSA group as compared to the low-risk group. CONCLUSION: The study highlights the importance of screening hypertensive patients for OSA using the SBQ in clinical settings, particularly in low-and middle-income countries (LMICs). Healthcare providers can use patient characteristics such as age, gender, neck circumference, and BMI to identify those at greater risk of developing OSA. Further research could focus on developing effective OSA prevention and treatment interventions in hypertensive patients.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Quênia/epidemiologia , Estudos Transversais , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Sono , Índice de Massa Corporal
4.
Behav Med ; : 1-8, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37489805

RESUMO

Discrimination and abuse of healthcare workers (HCWs) by patients and their relatives remains a pressing and prevalent problem in various healthcare settings, negatively affecting professional outcomes. Despite this, little has been reported about discrimination and abuse in many low- and middle-income countries such as Kenya. We conducted a cross-sectional survey study between May - August 2021 among healthcare workers at a hospital in Kenya. Email invitations were sent, and the survey was in English, and the data was collected through and online survey. Discrimination based on gender was reported by 24.9% of all HCWs; 39.9% of doctors, 17.2% of nurses, and 10.9% of allied staff whereas racial discrimination was reported by 28.8% of all HCWs; 49.0% of doctors, 18.9% of nurses, and 8.9% of allied staff. Verbal or emotional abuse was the most common form of abuse and was reported by 56.8% of all HCWs while physical abuse was reported by 4.9% of all HCWs. For those that reported discrimination based on gender, 77.4% reported patient and their family members as the main source, whereas 81.2% of those that reported discrimination based on race reported the main source was from patient and their family members. Despite strict laws against discrimination and abuse, a significant portion of healthcare providers suffer from discrimination and abuse primarily from patients and their family members. In addition to education programs and policies to curb such behavior in the work environment, coping mechanisms should be actively sought to help healthcare providers deal with such actions.

5.
Epilepsia ; 63(9): 2225-2241, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35729725

RESUMO

OBJECTIVE: Despite the high prevalence of epilepsy in Africa, evaluation of epilepsy research trends on the continent is lacking. Without establishing effective research, improvement in care for people with epilepsy cannot be effectively strategized or targeted. METHODS: A scoping review of the peer-reviewed literature on epilepsy from Africa (1989-2019) was conducted. The aim was to understand from this what areas are well researched versus underresearched based on published epilepsy topics. RESULTS: A total of 1227 publications were identified and assessed. A significant increase in publications occurred over the 30 years assessed. African author leadership was evident in most reports. Nine countries had >50 publications identified; the remaining 45 countries had <50 or no publications. Research studies were typically of lower quality (case series and observational studies). Research themes were more focused on clinical epilepsy (descriptive observational studies) and social aspects (qualitative surveys). However, there were a number of unique and strong themes, specifically for neurocysticercosis and nodding syndrome, where strong research collaborations were evident, basic science understandings were explored, and interventional models were established. SIGNIFICANCE: Despite Africa being the continent with the most countries, it is lacking in the quantity, quality, and for some areas, relevance of research on epilepsy. Targeted approaches are needed to upskill the strength of research undertaken with more basic science, interventional, and randomized controlled studies. Themes of research need to promote those with unique African content but also to align with current international research areas that have impact on care delivery, such as epilepsy surgery and epilepsy genetics. For this to be possible, it is important to strengthen research hubs with collaborations that empower Africa to own its epilepsy research journey.


Assuntos
Epilepsia , Comitês Consultivos , África/epidemiologia , Criança , Atenção à Saúde , Epilepsia/epidemiologia , Epilepsia/terapia , Humanos , Relatório de Pesquisa
6.
Support Care Cancer ; 30(2): 1557-1567, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34537888

RESUMO

INTRODUCTION: Metastatic breast cancer (MBC) patients have several unmet needs. The needs and quality of life of MBC women living in sub-Saharan Africa (SSA) are understudied. Facilitating the interaction of various caregivers is beneficial in addressing the needs. Internet-based resources play an important role in reaching out to these patients. We aimed to bring the various stakeholders into a joint network force, create a web-based portal, understand the needs of MBC patients, and assess the utilization of web-based resources for women from Kenya. METHODS: A network of various stakeholders considered crucial in the care of Kenyan women with MBC was created. We conducted educational camps and assessed their needs, quality of life (QoL), and knowledge. We assessed the impact of utilizing web-based resources by MBC patients from here. RESULTS: We formed a network involving partners and launched the first dedicated website for MBC from Kenya. The website has received 13,944 visits and 310,379 hits in 2 years. One hundred fourteen women living with MBC were interviewed, and our findings show that psychological needs (63%), physical support needs (60%), and health care system needs (55%) are leading areas of needs that increase with rural residence (p = 0.001), less education (p = 0.003), and aggressive treatments (p = 0.008). Quality of life (QoL) confirmed better scores with urban residence (p = 0.002), internet access (p = 0.010), and stable disease (p = 0.042). CONCLUSIONS: Creating a network of caregivers provides opportunities for cohesive efforts in understanding the psychosocial and medical needs of patients with MBC. Internet-based resources are an effective way of reaching out to them. Kenyan patients show extremely good uptake of internet-based resources.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/terapia , Escolaridade , Feminino , Humanos , Quênia
7.
BMC Nephrol ; 22(1): 225, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34139998

RESUMO

BACKGROUND: Chronic kidney disease is highly prevalent across the globe with more than 2 million people worldwide requiring renal replacement therapy. Interdialytic weight gain is the change in body weight between two sessions of haemodialysis. Higher interdialytic weight gain has been associated with an increase in mortality and adverse cardiovascular outcomes. It has long been questioned whether using a lower dialysate sodium concentration during dialysis would reduce the interdialytic weight gain and hence prevent these adverse outcomes. METHODS: This study was a single blinded cross-over study of patients undergoing twice weekly haemodialysis at the Aga Khan University Hospital, Nairobi and Parklands Kidney Centre. It was conducted over a twelve-week period and patients were divided into two groups: dialysate sodium concentration of 137 meq/l and 140 meq/l. These groups switched over after a six-week period without a washout period. Univariate analysis was conducted using Fisher's exact test for categorical data and Mann Whitney test for continuous data. RESULTS: Forty-one patients were included in the analysis. The mean age was 61.37 years, and 73% were males. The mean duration for dialysis was 2.53 years. The interdialytic weight gain was not significantly different between the two groups (2.14 for the 137 meq/l group and 2.35 for the 140 meq/l group, p = 0.970). Mean blood pressures were as follows: pre-dialysis: DNa 137 meq/l: systolic 152.14 ± 19.99, diastolic 78.99 ± 12.20, DNa 140 meq/l: systolic 156.95 ± 26.45, diastolic 79.75 ± 11.25 (p = 0.379, 0.629 respectively). Post-dialysis: DNa 137 meq/l: systolic 147.29 ± 22.22, diastolic 77.85 ± 12.82 DNa 140 meq/l: systolic 151.48 ± 25.65, diastolic 79.66 ± 15.78 (p = 0.569, 0.621 respectively). CONCLUSION: There was no significant difference in the interdialytic weight gain as well as pre dialysis and post dialysis systolic and diastolic blood pressures between the two groups. Therefore, using a lower dialysate sodium concentration does not appear useful in altering the interdialytic weight gain or blood pressure although further studies are warranted with a larger sample size, taking into account residual renal function and longer duration for impact on blood pressures.


Assuntos
Soluções para Diálise/química , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Sódio/análise , Aumento de Peso , Pressão Sanguínea , Estudos Cross-Over , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
8.
J Surg Oncol ; 122(6): 1145-1151, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32734604

RESUMO

BACKGROUND: Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS: The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS: White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P < .001), primary tumor resection (P < .001), and experienced increased 90-day mortality (P < .014). CONCLUSION: cPNET and pPNET are rare and aggressive malignancies that tend to arise in White males. Multimodal treatment including surgery, chemotherapy, and radiation is conventional. Patients with cPNET more often receive radiation and primary tumor resection with increased 90-day mortality.


Assuntos
Bases de Dados Factuais , Tumores Neuroectodérmicos Primitivos/mortalidade , Tumores Neuroectodérmicos Primitivos/terapia , Adulto , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Masculino , Tumores Neuroectodérmicos Primitivos/epidemiologia , Tumores Neuroectodérmicos Primitivos/patologia , Prognóstico , Taxa de Sobrevida , Estados Unidos/epidemiologia
9.
BMC Bioinformatics ; 20(Suppl 24): 673, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861984

RESUMO

BACKGROUND: With the rise of metabolomics, the development of methods to address analytical challenges in the analysis of metabolomics data is of great importance. Missing values (MVs) are pervasive, yet the treatment of MVs can have a substantial impact on downstream statistical analyses. The MVs problem in metabolomics is quite challenging and can arise because the metabolite is not biologically present in the sample, or is present in the sample but at a concentration below the lower limit of detection (LOD), or is present in the sample but undetected due to technical issues related to sample pre-processing steps. The former is considered missing not at random (MNAR) while the latter is an example of missing at random (MAR). Typically, such MVs are substituted by a minimum value, which may lead to severely biased results in downstream analyses. RESULTS: We develop a Bayesian model, called BayesMetab, that systematically accounts for missing values based on a Markov chain Monte Carlo (MCMC) algorithm that incorporates data augmentation by allowing MVs to be due to either truncation below the LOD or other technical reasons unrelated to its abundance. Based on a variety of performance metrics (power for detecting differential abundance, area under the curve, bias and MSE for parameter estimates), our simulation results indicate that BayesMetab outperformed other imputation algorithms when there is a mixture of missingness due to MAR and MNAR. Further, our approach was competitive with other methods tailored specifically to MNAR in situations where missing data were completely MNAR. Applying our approach to an analysis of metabolomics data from a mouse myocardial infarction revealed several statistically significant metabolites not previously identified that were of direct biological relevance to the study. CONCLUSIONS: Our findings demonstrate that BayesMetab has improved performance in imputing the missing values and performing statistical inference compared to other current methods when missing values are due to a mixture of MNAR and MAR. Analysis of real metabolomics data strongly suggests this mixture is likely to occur in practice, and thus, it is important to consider an imputation model that accounts for a mixture of missing data types.


Assuntos
Teorema de Bayes , Metabolômica/métodos , Algoritmos , Animais , Viés , Camundongos , Método de Monte Carlo
10.
Nicotine Tob Res ; 21(1): 101-110, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085294

RESUMO

Introduction: Smokeless tobacco products such as snuff and snus are used worldwide. However, little is known about the systemic and cardiovascular toxicity of smokeless tobacco exposure. Methods: Biomarkers of endothelial activation and injury, immune functions, platelet activation and insulin resistance were measured in 8-week old male C57BL/6 mice exposed to commercial snuff, CRP-2 reference snuff, commercial snus, CRP-1 reference snus, and nicotine in drinking water (100 µg/mL) for 4, 12, and 24 weeks. Results: Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased the levels of circulating Flk+/Sca+ endothelial progenitor cells. Twelve and 24 weeks of exposure to all the smokeless tobacco products and nicotine significantly decreased the levels of circulating CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD11b+ monocytes, whereas 4 weeks of exposure to Camel snus and Copenhagen snuff significantly depleted the levels of peripheral blood CD19+ B cells and CD11b+ monocytes. Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased plasma IFNγ levels. However, plasma TNFα levels were significantly increased in mice exposed to Copenhagen snuff or nicotine for 24 weeks. This was accompanied by a five to sevenfold increase in the hepatic expression of TNFα. Neither smokeless products nor nicotine affected plasma lipoproteins, platelet activation, or systemic insulin sensitivity. Conclusions: Chronic exposure to snuff and snus suppresses circulating levels of EPCs, endothelial microparticles and immune cells, but increases plasma TNF-α levels. These effects of smokeless tobacco products are attributable, at least in part, to nicotine. Implications: Exposure to smokeless tobacco products results in the depletion of endothelial progenitor cells, which may impair the endothelium repair. Suppression of the circulating levels of immune cells upon exposure to smokeless tobacco products may increase the susceptibility to secondary infection. Increased formation of proinflammatory cytokines such as TNFα by nicotine or Copenhagen snuff may lead to vascular inflammation and thereby exacerbate atherogenesis.


Assuntos
Biomarcadores/análise , Endotélio Vascular/patologia , Imunidade Celular/efeitos dos fármacos , Resistência à Insulina , Ativação Plaquetária/efeitos dos fármacos , Trombose/patologia , Tabaco sem Fumaça/toxicidade , Animais , Endotélio Vascular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Trombose/induzido quimicamente
11.
Am J Physiol Endocrinol Metab ; 315(5): E1005-E1018, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153066

RESUMO

Hepatic glutathione S-transferases (GSTs) are dysregulated in human obesity, nonalcoholic fatty liver disease, and diabetes. The multifunctional GST pi-isoform (GSTP) catalyzes the conjugation of glutathione with acrolein and inhibits c-Jun NH2-terminal kinase (JNK) activation. Herein, we tested whether GSTP deficiency disturbs glucose homeostasis in mice. Hepatic GST proteins were downregulated by short-term high-fat diet in wild-type (WT) mice concomitant with increased glucose intolerance, JNK activation, and cytokine mRNAs in the liver. Genetic deletion of GSTP did not affect body composition, fasting blood glucose levels, or insulin levels in mice maintained on a normal chow diet; however, compared with WT mice, the GSTP-null mice were glucose intolerant. In GSTP-null mice, pyruvate intolerance, reflecting increased hepatic gluconeogenesis, was accompanied by elevated levels of activated JNK, cytokine mRNAs, and glucose-6-phosphatase proteins in the liver. Treatment of GSTP-null mice with the JNK inhibitor 1,9-pyrazoloanthrone (SP600125) significantly attenuated pyruvate-induced hepatic gluconeogenesis and significantly altered correlations between hepatic cytokine mRNAs and metabolic outcomes in GSTP-null mice. Collectively, these findings suggest that hepatic GSTP plays a pivotal role in glucose handling by regulating JNK-dependent control of hepatic gluconeogenesis. Thus, hepatic GSTP-JNK dysregulation may be a target of new therapeutic interventions during early stages of glucose intolerance to prevent the worsening metabolic derangements associated with human obesity and its relentless progression to diabetes.


Assuntos
Gluconeogênese/fisiologia , Intolerância à Glucose/metabolismo , Glutationa Transferase/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/metabolismo , Animais , Antracenos/farmacologia , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Gluconeogênese/efeitos dos fármacos , Intolerância à Glucose/genética , Glutationa Transferase/genética , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Fígado/efeitos dos fármacos , Camundongos , Camundongos Knockout
12.
BMC Bioinformatics ; 18(1): 114, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28219348

RESUMO

BACKGROUND: High throughput metabolomics makes it possible to measure the relative abundances of numerous metabolites in biological samples, which is useful to many areas of biomedical research. However, missing values (MVs) in metabolomics datasets are common and can arise due to both technical and biological reasons. Typically, such MVs are substituted by a minimum value, which may lead to different results in downstream analyses. RESULTS: Here we present a modified version of the K-nearest neighbor (KNN) approach which accounts for truncation at the minimum value, i.e., KNN truncation (KNN-TN). We compare imputation results based on KNN-TN with results from other KNN approaches such as KNN based on correlation (KNN-CR) and KNN based on Euclidean distance (KNN-EU). Our approach assumes that the data follow a truncated normal distribution with the truncation point at the detection limit (LOD). The effectiveness of each approach was analyzed by the root mean square error (RMSE) measure as well as the metabolite list concordance index (MLCI) for influence on downstream statistical testing. Through extensive simulation studies and application to three real data sets, we show that KNN-TN has lower RMSE values compared to the other two KNN procedures as well as simpler imputation methods based on substituting missing values with the metabolite mean, zero values, or the LOD. MLCI values between KNN-TN and KNN-EU were roughly equivalent, and superior to the other four methods in most cases. CONCLUSION: Our findings demonstrate that KNN-TN generally has improved performance in imputing the missing values of the different datasets compared to KNN-CR and KNN-EU when there is missingness due to missing at random combined with an LOD. The results shown in this study are in the field of metabolomics but this method could be applicable with any high throughput technology which has missing due to LOD.


Assuntos
Algoritmos , Pesquisa Biomédica , Metabolômica , Biologia Computacional , Humanos
13.
Arterioscler Thromb Vasc Biol ; 35(11): 2468-77, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26293462

RESUMO

OBJECTIVES: Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. APPROACH AND RESULTS: In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). CONCLUSIONS: Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways.


Assuntos
Antígenos CD/sangue , Automóveis , Células Progenitoras Endoteliais/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Glicoproteínas/sangue , Mediadores da Inflamação/sangue , Peptídeos/sangue , Características de Residência , Emissões de Veículos , Antígeno AC133 , Adulto , Biomarcadores/sangue , Contagem de Células , Estudos Transversais , Células Progenitoras Endoteliais/imunologia , Células Progenitoras Endoteliais/metabolismo , Feminino , Humanos , Kentucky , Masculino , Pessoa de Meia-Idade , Regulação para Cima
15.
Am J Physiol Endocrinol Metab ; 307(3): E262-77, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24918202

RESUMO

Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇(O2), V̇(CO2), and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity.


Assuntos
Gordura Abdominal/metabolismo , Adiposidade , Autofagia , Metabolismo Energético , Regulação Enzimológica da Expressão Gênica , Dinâmica Mitocondrial , Obesidade/metabolismo , Gordura Abdominal/patologia , Gordura Abdominal/ultraestrutura , Animais , Tamanho Celular , Citrato (si)-Sintase/metabolismo , Ciclo do Ácido Cítrico , Dieta Hiperlipídica/efeitos adversos , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hipertrofia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/patologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
16.
J Pain Symptom Manage ; 67(1): 12-19.e1, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37709176

RESUMO

INTRODUCTION: Advance care directives (AD) are instructions from patients regarding the care they would prefer if they could not make medical decisions in the future. It is widely recognized that racial and ethnic as well as sex differences, particularly in the West, can influence AD. However, to the best of our knowledge, there is limited understanding of how these factors impact AD in sub-Saharan Africa. METHODS: This prospective cross-sectional study was conducted at the Aga Khan University Hospital, Nairobi. We enrolled patients above the age of 18 years who were admitted to the general medical wards. The data were collected using a structured questionnaire that consisted of questions based on demographics and AD. Descriptive statistics were used to summarize the data, including frequencies and percentages, as well as medians and interquartile ranges. RESULTS: The study involved 286 participants, with a median age of 44.0 years (IQR: 37.0 - 52.0). Roughly half of the participants were male (51.7%), and the majority identified themselves as Christians (77.3%) and of African ethnicity (78.3%). Upon further analysis, it was discovered that only 35.3% had an awareness of AD. Notably, individuals from the Hindu religion and Asian ethnicity demonstrated significantly higher knowledge of AD. Furthermore, more males reported having a living will and believed that AD are crucial for patients who could not make independent medical decisions compared to females. CONCLUSION: This study indicated a lower awareness and knowledge of AD among the participants. Hindus and Asians exhibited higher levels of awareness regarding AD. Considering the diverse religious and cultural backgrounds in our setting, there is a pressing need for strategies to increase awareness surrounding AD.


Assuntos
Assistência Terminal , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Centros de Atenção Terciária , Quênia , Estudos Transversais , Estudos Prospectivos
17.
Infect Prev Pract ; 6(1): 100333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38222856

RESUMO

Background: Surgical site infection is a common healthcare-associated infection that affects maternal health, yet it can be prevented or controlled. Caesarian sections are most likely to develop surgical site infections. The rates of delivery by caesarian section in reported to be higher that the acceptable rates in some healthcare facilities. Risk factors for surgical site infections can be identified and modified to reduce the occurrence of surgical site infections. This study aims to determine the risk factors that contribute to surgical site infections post caesarian section in a tertiary teaching hospital in Kenya. Methods: This was a retrospective case-control (1:2 matched) study conducted between 1st November 2021 to 31st October 2022 at a tertiary hospital in Nairobi. Data was extracted on surgical site risk factors as per World Health Organization's recommended preoperative measures, for both cases and controls. Descriptive statistics was used to summarize the variables and the Chi-squared test and Fisher's Exact test were used for group comparisons. Results: A total of 1,262 caesarian deliveries were performed, 2.1% (27/1262) of which developed surgical site infections post caesarian section. The risk factors identified were not significantly associated with surgical site infection development (gestational age P=0.152, body mass index P=0.615, premature rupture of membranes P=0.253, and antibiotic prophylaxis P=0.108). Conclusions: There was no significant association of exposure to surgical site infection risk factors with surgical site infection despite a positive trend. Other prospective methods should also be used in addition to chart reviews to determine the level of effect each risk factor has on surgical site infection.

18.
Can J Kidney Health Dis ; 11: 20543581241227015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38292818

RESUMO

Background: Corona Virus Disease 2019 (COVID-19), an infection caused by the SARS-CoV-2 virus, has been the largest global pandemic since the turn of the 21st century. With emerging research on this novel virus, studies from the African continent have been few. Corona Virus Disease 2019 has been shown to affect various organs including the lungs, gut, nervous system, and the kidneys. Acute kidney injury (AKI) is an independent risk factor for mortality and increases the health care burden for patients with persistent kidney dysfunction and maintenance dialysis. Sub-Saharan Africa has a high number of poorly controlled chronic illnesses, economic inequalities, and health system strains that may contribute to higher cases of kidney injury in patients with COVID-19 disease. Objectives: The objective of this study was to determine the incidence, associated factors, and outcomes of AKI in patients hospitalized with COVID-19 in Kenya. Methods: This retrospective cohort study included 1366 patients with confirmed COVID-19 illness hospitalized at the Aga Khan University Hospital in Nairobi, Kenya, between April 1, 2020 and October 31, 2021. Data were collected on age, sex, the severity of COVID-19 illness, existing pregnancy and comorbid conditions including human immunodeficiency virus (HIV), diabetes mellitus, hypertension, and functioning kidney transplant patients. Univariate analysis was carried out to determine the association of clinical and demographic factors with AKI. To determine independent associations with AKI incidence, a logistic regression model was used and the relationship was reported as odds ratios (ORs) with a 95% confidence interval (CI). The outcomes of AKI including the in-hospital mortality rate, renal recovery rate at hospital discharge, and the duration of hospital stay were reported and stratified based on the stage of AKI. Results: The median age of study patients was 56 years (interquartile range [IQR] = 45-68 years), with 67% of them being male (914 of 1366). The AKI incidence rate was 21.6% (n = 295). Patients with AKI were older (median age = 64 years vs 54 years; P < .001), majority male (79% of men with AKI vs 63.6% without AKI; P < .001), and likely to have a critical COVID-19 (OR = 8.03, 95% CI = 5.56-11.60; P < .001). Diabetes and hypertension, with an adjusted OR of 1.75 (95% CI = 1.34-2.30; P < .001) and 1.68 (95% CI = 1.27-2.23; P < .001), respectively, were associated with AKI occurrence in COVID-19. Human immunodeficiency virus, pregnancy, and a history of renal transplant were not significantly associated with increased AKI risk in this study. Patients with AKI had significantly higher odds of mortality, and this effect was proportional to the stage of AKI (OR = 11.35, 95% CI = 7.56-17.03; P < .001). 95% of patients with stage 1 AKI had complete renal recovery vs 33% of patients with stage 3 AKI. Of the patients with stage 3 AKI (n = 64), 10 underwent hemodialysis, with 1 recovery in renal function and 3 patients requiring ongoing dialysis after discharge. Conclusions: This study was conducted at a single private tertiary-level health care facility in Kenya and only up to the time of hospital discharge. It is one of the first large studies from sub-Saharan Africa looking at the associated factors and outcomes of AKI in COVID-19 and forms a foundation for further analysis on the long-term consequences of COVID-19 on the kidneys. A major limitation of the study is the lack of baseline pre-admission creatinine values for most patients; thus, the impact of chronic kidney disease/baseline creatinine values on the incidence of AKI could not be established.

19.
Value Health Reg Issues ; 41: 48-53, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38237329

RESUMO

OBJECTIVES: There are irregularities in investment cases generated by the Mental Health Compartment Model. We discuss these irregularities and highlight the costing techniques that may be introduced to improve mental health investment cases. METHODS: This analysis uses data from the World Bank, the World Health Organization Mental Health Compartment Model, the United Nations Development Program, the Kenya Ministry of Health, and Statistics from the Kenyan National Commission of Human Rights. RESULTS: We demonstrate that the Mental Health Compartment Model produces irrelevant outcomes that are not helpful for clinical settings. The model inflated the productivity gains generated from mental health investment. In some cases, the model underestimated the economic costs of mental health. Such limitation renders the investment cases poor in providing valuable intervention points from the perspectives of both the users and the providers. CONCLUSIONS: There is a need for further calibration and validation of the investment case outcomes. The current estimated results cannot be used to guide service provision, research, and mental health programming comprehensively.


Assuntos
Países em Desenvolvimento , Serviços de Saúde Mental , Humanos , Serviços de Saúde Mental/economia , Quênia , Saúde Mental/estatística & dados numéricos , Investimentos em Saúde/estatística & dados numéricos , Investimentos em Saúde/tendências
20.
eNeurologicalSci ; 33: 100484, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38020076

RESUMO

Background: There is severe shortage of neurologists in sub-Saharan Africa. Tele-neurology consultations (TNC) can bridge this service gap, but there is very little published evidence on TNC in our setting, which we addressed through our study. Methods: We prospectively enrolled patients at our neurology outpatients from October 2020 to October 2021. We administered a post-TNC questionnaire which captured satisfaction/acceptability using Likert scales. A sub-group of participants who also did in-person consultations (IPC) were additionally administered post-IPC questionnaires. Statistical comparisons were made using the paired student t-test, and descriptive data expressed as median (inter-quartile range). Results: From 219 enrolled patients, 66.7% participants responded: 74.0% had both IPC and TNC; 63.0% were female; age was 40.9 (30.6-55.2) years; and 2.7% were from neighbouring countries. The commonest presentations were headache (30.8%), seizures (26.0%) and neurodegenerative disorders (15.1%). For TNC, >90% found it: (i) as comfortable as IPC (p = 0.35); (ii) didn't violate their privacy; (iii) saved time [3.0 (2.0-4.0) hours], travel [11.0 (7.2-21.1) km] and cost [$9.09 (4.55-18.18)]; and (iv) addressed their concerns satisfactorily such that they would use TNC again. Conversely, 15.1% didn't agree with TNC being as effective as IPC, and felt the neurologist did not satisfactorily identify all of their health problems (p = 0.03). In total, our TNC service saved our patients $6167, 1143 h, and 25,506 km of travel, translating to 3.5 t (equivalent to 21 newly-planted trees) of carbon dioxide emissions. Conclusions: Our study demonstrates that TNC is an acceptable, efficient, effective, and environmentally-sustainable care delivery model.

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