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OBJECTIVE: To develop a practical and psychometrically sound tool to evaluate caregiver knowledge of their child's asthma action plan (AAP). METHODS: A pilot study was conducted in a sample of 40 caregivers of children with asthma to assess the content validity, item difficulty, and item discrimination of the Asthma Action Plan Questionnaire (AAPQ). The inter-rater and intra-rater agreement of the AAPQ's scoring rubric were also examined. Subsequently, a large-scale study was conducted in a sample of 80 caregivers of children with asthma and 40 caregivers of children without current asthma and no prior exposure to patients with asthma to evaluate the internal consistency, test-retest reliability, and known-groups validity of the AAPQ. RESULTS: The 7-item AAPQ demonstrated acceptable content validity (a scale-content validity index of 0.98) and internal consistency (Cronbach's alpha =.63 and mean inter-item correlation coefficient of.20) and very strong test-retest reliability over a two-to-four-week period (r = .88, p < .001). The AAPQ discriminated between caregivers of children with asthma and caregivers of children without asthma (M ± SD 8.3 ± 1.6 vs. 4.3 ± 1.7, p < .001, respectively). CONCLUSION: The AAPQ is a valid and reliable questionnaire that provides an assessment of caregivers' knowledge of their child's AAP and can guide educational interventions by healthcare providers.
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BACKGROUND: Academic achievement is essential for all students seeking a successful career. Studying habits and routines is crucial in achieving such an ultimate goal. OBJECTIVES: This study investigates the association between study habits, personal factors, and academic achievement, aiming to identify factors that distinguish academically successful medical students. METHODS: A cross-sectional study was conducted at the College of Medicine, King Saud University, Riyadh, Saudi Arabia. The participants consisted of 1st through 5th-year medical students, with a sample size of 336. The research team collected study data using an electronic questionnaire containing three sections: socio-demographic data, personal characteristics, and study habits. RESULTS: The study results indicated a statistically significant association between self-fulfillment as a motivation toward studying and academic achievement (p = 0.04). The results also showed a statistically significant correlation between recalling recently memorized information and academic achievement (p = 0.05). Furthermore, a statistically significant association between preferring the information to be presented in a graphical form rather than a written one and academic achievement was also found (p = 0.03). Students who were satisfied with their academic performance had 1.6 times greater chances of having a high-grade point average (OR = 1.6, p = 0.08). CONCLUSION: The results of this study support the available literature, indicating a correlation between study habits and high academic performance. Further multicenter studies are warranted to differentiate between high-achieving students and their peers using qualitative, semi-structured interviews. Educating the students about healthy study habits and enhancing their learning skills would also be of value.
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Éxito Académico , Hábitos , Motivación , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Estudios Transversales , Masculino , Femenino , Arabia Saudita , Adulto Joven , Encuestas y Cuestionarios , Educación de Pregrado en Medicina , Adulto , Satisfacción PersonalRESUMEN
In this work, we successfully integrated fluorescent nanodiamonds (FNDs) and lanthanide ion-doped upconversion nanoparticles (UCNPs) in a nanocomposite structure for simultaneous optical temperature sensing. The effective integration of FND and UCNP shells was confirmed by employing high-resolution TEM imaging, X-ray diffraction, and dual-excitation optical spectroscopy. Furthermore, the synthesized ND@UCNP nanocomposites were tested by making simultaneous optical temperature measurements, and the detected temperatures showed excellent agreement within their sensitivity limit. The simultaneous measurement of temperature using two different modalities having different sensing physics but with the same composite nanoparticles inside is expected to greatly improve the confidence of nanoscale temperature measurements. This should resolve some of the controversy surrounding nanoscale temperature measurements in biological applications.
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Upconversion nanoparticles (UCNPs) and carbon quantum dots (CQDs) have emerged as promising candidates for enhancing both the stability and efficiency of perovskite solar cells (PSCs). Their rising prominence is attributed to their dual capabilities: they effectively passivate the surfaces of perovskite-sensitive materials while simultaneously serving as efficient spectrum converters for sunlight. In this work, we synthesized UCNPs doped with erbium ions as down/upconverting ions for ultraviolet (UV) and near-infrared (NIR) light harvesting. Various percentages of the synthesized UCNPs were integrated into the mesoporous layers of PSCs. The best photovoltaic performance was achieved by a PSC device with 30% UCNPs doped in the mesoporous layer, with PCE = 16.22% and a fill factor (FF) of 74%. In addition, the champion PSCs doped with 30% UCNPs were then passivated with carbon quantum dots at different spin coating speeds to improve their photovoltaic performance. When compared to the pristine PSCs, a fabricated PSC device with 30% UCNPs passivated with CQDs at a spin coating speed of 3000 rpm showed improved power conversion efficiency (PCE), from 16.65% to 18.15%; a higher photocurrent, from 20.44 mA/cm2 to 22.25 mA/cm2; and a superior fill factor (FF) of 76%. Furthermore, the PSCs integrated with UCNPs and CQDs showed better stability than the pristine devices. These findings clear the way for the development of effective PSCs for use in renewable energy applications.
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Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.
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Trastornos Mieloproliferativos , Mielofibrosis Primaria , Humanos , Médula Ósea/patología , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/patología , Trastornos Mieloproliferativos/genética , Mutación , Pronóstico , Janus Quinasa 2/genética , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Despite significant decline in the past two decades, malaria is still a major public health concern in Tanzania; with over 93% of the population still at risk. Community knowledge, attitudes and practices (KAP), and beliefs are key in enhancing uptake and utilization of malaria control interventions, but there is a lack of information on their contribution to effective control of the disease. This study was undertaken to determine KAP and beliefs of community members and service providers on malaria, and how they might be associated with increased risk and persistence of the disease burden in North-western and Southern regions of Tanzania. METHODS: This was an exploratory study that used qualitative methods including 16 in-depth interviews (IDI) and 32 focus group discussions (FGDs) to collect data from health service providers and community members, respectively. The study was conducted from September to October 2017 and covered 16 villages within eight districts from four regions of mainland Tanzania (Geita, Kigoma, Mtwara and Ruvuma) with persistently high malaria transmission for more than two decades. RESULTS: Most of the participants had good knowledge of malaria and how it is transmitted but some FGD participants did not know the actual cause of malaria, and thought that it is caused by bathing and drinking un-boiled water, or consuming contaminated food that has malaria parasites without warming it. Reported barriers to malaria prevention and control (by FGD and IDI participants) included shortage of qualified health workers, inefficient health financing, low care-seeking behaviour, consulting traditional healers, use of local herbs to treat malaria, poverty, increased breeding sites by socio-economic activities and misconceptions related to the use of bed nets and indoor residual spraying (IRS). Among the misconceptions, some participants believed that bed nets provided for free by the government came with bedbugs while others reported that free bed nets caused impotence among men. CONCLUSION: Despite good knowledge of malaria, several risk factors, such as socio-economic and behavioural issues, and misconceptions related to the use of bed nets and IRS were reported. Other key factors included unavailability or limited access to health services, poor health financing and economic activities that potentially contributed to persistence of malaria burden in these regions. Relevant policies and targeted malaria interventions, focusing on understanding socio-cultural factors, should be implemented to reduce and finally eliminate the disease in the study regions and others with persistent transmission.
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Conocimientos, Actitudes y Práctica en Salud , Malaria , Masculino , Humanos , Tanzanía , Control de Mosquitos/métodos , Malaria/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Urinary tract infection (UTI) is considered one of the most prevalent infections that may lead to many renal complications. They account for almost 10% of all infections in Saudi Arabia, making them the second most common cause of emergency department admissions. Bacterial pathogens, primarily Escherichia coli, Klebsiella spp., Enterococcus spp., Proteus spp., and Staphylococcus spp. are the most causative agents of UTI. This study aims to evaluate the prevalence and antimicrobial susceptibility patterns of uropathogens in adult patients from Madinah, Saudi Arabia. METHODS: A retrospective cross-sectional study was performed using data collected from patients who visited King Fahad General Hospital in Madinah, Saudi Arabia. Data included 16,803 urine bacterial cultures and their antimicrobial susceptibility profiles collected between January 2019 and October 2021. RESULTS: Among the 16,803 tested samples, 3937 (23.4%) showed positive results for urine bacterial cultures. UTI prevalence was slightly higher in women (52.1%) than men (47.9%). Escherichia coli (29.8%) was the most prevalent, followed by Klebsiella spp. (23.2%) and Pseudomonas spp. (8.4%). As for Gram-positive bacteria, Enterococcus spp. (10.8%) were most common, followed by Streptococcus spp. (8%) and Staphylococcus spp. (3.3%). Gram-negative bacteria exhibited high resistance rates toward aztreonam (> 83.3%), ampicillin (78.8%), and cephalexin (68.5%). Enterococcus spp. displayed elevated resistance rates (> 62.3%) against ciprofloxacin, gentamicin, and tetracycline. Conversely, Streptococcus spp. showed substantial resistance rates (> 76.6%) toward colistin and trimethoprim/sulfamethoxazole. CONCLUSION: To optimize therapy and minimize the risk of multidrug-resistant uropathogenic infections, physicians should consider the local epidemiological trends and antimicrobial resistance patterns of prevalent uropathogens prior to initiating any empirical antibacterial therapy.
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Antibacterianos , Enterococcus , Masculino , Humanos , Adulto , Femenino , Arabia Saudita/epidemiología , Estudios Transversales , Prevalencia , Estudios Retrospectivos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coliRESUMEN
BACKGROUND: COVID-19 is no longer a global public health emergency, but it still affects numerous diseases and needs further research. Diabetic COVID-19 patients with major complications or intensive care had high mortality rates. This review provides pathophysiological descriptive data on diabetes mellitus type 2 and shows how COVID-19 infection in Saudi Arabia predicts disease severity and prognosis. METHODS: This review was conducted through online research on MEDLINE/PubMed databases, Scopus, and Web of Science based on links between COVID-19 and diabetes mellitus type 2 patients. By using the keywords 'COVID-19', 'diabetes', ' correlation', and impact on 'population' from December 2022 to February 2023. The full texts of the articles that were retrieved were accessed. RESULTS: The COVID-19 epidemic has affected the community, especially diabetics, and their daily life. According to our research on prior studies, most COVID-19 patients in Saudi Arabia had diabetes as a comorbidity. CONCLUSIONS: We underline the necessity of thorough study to better understand COVID-19 and its association with diabetes to design and implement evidence-based initiatives and policies in Saudi Arabia, where diabetes is a major health issue.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , COVID-19/epidemiología , Comorbilidad , Pronóstico , Arabia Saudita/epidemiologíaRESUMEN
OBJECTIVE: This study aimed to compare two methods of wound skin closure-staples versus vertical mattress nylon sutures-in patients undergoing primary total hip (THR) and total knee replacements (TKR). The comparison was for wound complications as a primary outcome, and satisfaction of patient and nurse as secondary outcomes. METHOD: A prospective cohort study was conducted at an academic teaching hospital. All the patients who were admitted for either primary THR or TKR from September 2018 to September 2019 were included. Revision surgeries, patients >85 years of age, and those who were on steroid therapy were excluded. Patients were divided into two groups (staples and sutures) to compare the two methods of wound closure. Patients in each group were assessed for characteristics such as age, sex, weight, height, comorbidities, smoking status, postoperative wound complications, reoperation and patient/nurse satisfaction. RESULTS: A total of 100 patients met the inclusion criteria. In the staples group (n=50), 26 patients underwent THR while 24 patients underwent TKR. In the sutures group (n=50), 23 patients underwent THR and 27 patients underwent TKR. Overall, there was no significant difference between the two groups (staples versus sutures) in terms of wound complications (p=0.401), patient satisfaction (p=0.357) and nurse satisfaction (p=0.513). Further analysis compared THR and TKR subgroups (THR staples versus THR sutures and TKR staples versus TKR sutures). The results showed no significant difference between the staples and sutures subgroups of THR and TKR in terms of wound complications, patient satisfaction and nurse satisfaction. CONCLUSION: In THR and TKR, there was no significant difference between either vertical mattress nylon sutures or staples primary skin closure in terms of wound complications and patient satisfaction in this study. The decision on wound closure method should be based on the availability of resources in the institution/country.
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Artroplastia de Reemplazo de Rodilla , Humanos , Técnicas de Sutura , Estudios Prospectivos , Nylons , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Suturas , Infección de la Herida Quirúrgica/etiologíaRESUMEN
PURPOSE: There are limited data regarding hospital and intensive care unit (ICU) outcomes in patients with hepatopulmonary syndrome (HPS) following liver transplantation (LT). METHODS: Data were retrospectively collected from consecutive HPS adult patients who underwent LT and were immediately admitted to the ICU at three transplant centers with shared management protocols, from 2002 to 2018. Demographic, clinical, surgical, laboratory, and outcome data were extracted. RESULTS: We identified 137 patients (74 male, 54%), with a median age at LT of 58 years (IQR: 52-63). One hundred and 31 (95.6%) patients were admitted to the ICU on invasive mechanical ventilation (MV). The median time on invasive MV in the ICU was 12 hours (IQR: 5-28) and 97 patients (74%) were extubated within 24 hours of ICU admission. The median highest positive end expiratory pressure and fraction of inspired oxygen (FiO2) were 7 (IQR: 5-8) and 0.6 (IQR: 0.5-0.7), respectively. 7 patients (5%) developed severe post-transplant hypoxemia. Of all patients, 42 (30.4%) required vasopressors and the median ICU and hospital length of stay (LOS) were 3 (IQR: 1-5) and 10 (IQR: 7-20) days, respectively. The in-hospital mortality rate was 3.6% (5/137). HPS severity was not associated with hospital mortality. CONCLUSION: Most HPS patients have short durations of MV, ICU, and hospital LOS post-LT. HPS severity does not impact hospital mortality.
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Síndrome Hepatopulmonar , Unidades de Cuidados Intensivos , Trasplante de Hígado , Adulto , Femenino , Síndrome Hepatopulmonar/etiología , Síndrome Hepatopulmonar/cirugía , Mortalidad Hospitalaria , Hospitales , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios RetrospectivosRESUMEN
SIGNIFICANCE: Logarithmic reading charts provide standardized measures of reading performance. Here we show that existing charts provide equivalent assessments of visual aspects of reading that are in good agreement with traditional measures of visual acuity and seem uninfluenced by cognitive (linguistic) factors. PURPOSE: The aims of this study were to (1) determine the equivalence of logarithmic charts of sentence and word reading, (2) evaluate the relationship between reading chart performance and more traditional measures of visual assessment, and (3) establish the influence of linguistic factors on reading chart performance. METHODS: In a sample of 82 normally sighted participants, we determined performance on the reading measures (e.g., reading acuity, reading speed, critical print size) of the following logarithmic charts of sentence and word reading: The Colenbrander English Continuous Text Near Vision Card, Radner Reading Chart, Minnesota Reading Acuity Chart, and Smith-Kettlewell Reading Chart. In doing so, we compared performance on reading measures between charts and with performance on more traditional measures of visual assessment (uncrowded and crowded letter acuity, stereoacuity, accommodation) and cognitive measures of word knowledge and ability (Wechsler Adult Intelligence Scale Vocabulary Subtest, National Adult Reading Test). RESULTS: Factor analysis confirmed that performance on the reading measures (reading acuity, reading speed, critical print size) was equivalent across charts. Reading test performance was also related to more traditional measures of vision, the most consistent of which were significant associations between reading acuity and acuity for single-letter optotypes. There were no significant associations between reading chart performance and cognitive measures of word knowledge and ability. CONCLUSIONS: The findings presented here suggest that logarithmic charts composed of sentences and words represent an alternative to traditional letter acuity testing. This is particularly the case for measures of reading acuity.
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Lectura , Pruebas de Visión , Acomodación Ocular , Adulto , Humanos , Lenguaje , Agudeza VisualRESUMEN
Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their antimicrobial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future. HighlightsA series of new N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised targeting the multidrug efflux pump (MATE) guided by the pharmacophoric features of the co-crystallized native inhibitor of the target protein.The newly synthesised compounds were assessed through in vitro, in vivo, and in silico approaches.Using the agar well diffusion assay, the antibacterial activities of the synthesised compounds were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas, their antifungal activities were screened against C. albicans.The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the synthesised compounds were investigated on variable microbial species.Compounds (4h and 4i) -as the broader and superior members regarding their antimicrobial effects- were further evaluated via in vivo testing using bio-chemical analysis and liver/kidney histological examination.A molecular docking study and ADMET in silico studies were performed.A structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.
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Antiinfecciosos , Staphylococcus aureus , Antibacterianos/química , Antiinfecciosos/farmacología , Antifúngicos/química , Candida albicans , Escherichia coli , Ligandos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Pseudomonas aeruginosa , Relación Estructura-ActividadRESUMEN
Upconversion nanoparticles (UCNPs) and carbon quantum dots (CQDs) have recently received a lot of attention as promising materials to improve the stability and efficiency of perovskite solar cells (PSCs). This is because they can passivate the surfaces of perovskite-sensitive materials and act as a spectrum converter for sunlight. In this study, we mixed and added both promising nanomaterials to PSC layers at the ideal mixing ratios. When compared to the pristine PSCs, the fabricated PSCs showed improved power conversion efficiency (PCE), from 16.57% to 20.44%, a higher photocurrent, and a superior fill factor (FF), which increased from 70% to 75%. Furthermore, the incorporation of CQDs into the manufactured PSCs shielded the perovskite layer from water contact, producing a device that was more stable than the original.
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Nanopartículas , Puntos Cuánticos , Carbono , Luz SolarRESUMEN
INTRODUCTION: Low awareness and lack of adequate services for cervical cancer screening and treatment of premalignant lesions of the cervix have been identified as some of the reasons for the high burden of cervical cancer in Sub-Saharan Africa. Women living with HIV infection are at a higher risk of developing cervical cancer than HIV negative women. OBJECTIVE: The study sought to assess the awareness of cervical cancer and screening services among women living with HIV in a HIV treatment centre. Factors that affect uptake of screening were also explored. METHODS: It was a qualitative study conducted from 26th August to 9th September 2019, in a HIV treatment centre in Zaria. A total of 61 HIV positive women participated in ten focus group discussions. Two key informant interviews were conducted with health care providers in the center. RESULTS: Majority of the participants have heard about cervical cancer and cervical cancer screening during routine health talk in the clinic, however, most of them were not aware of the increased risk of cervical cancer among women living with HIV. Uptake of screening was low. Stigma, cost and lack of screening facility within the treatment center were the main barriers to screening uptake. CONCLUSION: From our study, uptake of cervical cancer screening among women living with HIV was low. There is need to integrate cervical cancer screening services within the compact of care offered to all women living with HIV within HIV treatment centres.
INTRODUCTION: La faible sensibilisation et le manque de services adéquats pour le dépistage du cancer du col de l'utérus et le traitement des lésions précancéreuses du col de l'utérus ont été identifiés comme certaines des raisons du fardeau élevé du cancer du col de l'utérus en Afrique subsaharienne. Les femmes vivant avec le VIH sont plus à risque de développer un cancer du col de l'utérus que les femmes séronégatives. OBJECTIF: L'étude visait à évaluer la connaissance du cancer du col de l'utérus et des services de dépistage chez les femmes vivant avec le VIH dans un centre de traitement du VIH. Les facteurs qui affectent le recours au dépistage ont également été explorés. MÉTHODES: Il s'agit d'une étude qualitative menée du 26 août au 9 septembre 2019, dans un centre de traitement du VIH à Zaria. Au total, 61 femmes séropositives ont participé à dix discussions de groupe. Deux entretiens avec des informateurs clés ont été menés avec des prestataires de soins de santé du centre. RÉSULTATS: La majorité des participants ont entendu parler du cancer du col de l'utérus et du dépistage du cancer du col de l'utérus lors de discussions de routine sur la santé à la clinique, cependant, la plupart d'entre eux n'étaient pas au courant du risque accru de cancer du col de l'utérus chez les femmes vivant avec le VIH. Le recours au dépistage était faible. La stigmatisation, le coût et le manque d'installations de dépistage au sein du centre de traitement étaient les principaux obstacles à l'adoption du dépistage. CONCLUSION: D'après notre étude, le recours au dépistage du cancer du col de l'utérus chez les femmes vivant avec le VIH était faible. Il est nécessaire d'intégrer les services de dépistage du cancer du col de l'utérus dans le cadre des soins offerts à toutes les femmes vivant avec le VIH dans les centres de traitement du VIH. Mots clés: Sensibilisation au cancer du col de l'utérus, Dépistage du cancer du col de l'utérus, Femmes vivant avec le VIH.
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Infecciones por VIH , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Tamizaje Masivo , Nigeria/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.
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Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.
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Telangiectasia Hemorrágica Hereditaria , Administración Intravenosa , Bevacizumab/uso terapéutico , Hemorragia/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológicoRESUMEN
OBJECTIVES: To develop and validate on a simulator a learnable technique to decrease deviation of biopsied cores from the template schema during freehand, side-fire systematic prostate biopsy (sPBx) with the goal of reducing prostate biopsy (PBx) false-negatives, thereby facilitating earlier sampling, diagnosis and treatment of clinically significant prostate cancer. PARTICIPANTS AND METHODS: Using a PBx simulator with real-time three-dimensional visualization, we devised a freehand, pitch-neutral (0°, horizontal plane), side-fire, transrectal ultrasonography (TRUS)-guided sPBx technique in the left lateral decubitus position. Thirty-four trainees on four Canadian and US urology programmes learned the technique on the same simulator, which recorded deviation from the intended template location in a double-sextant template as well as the TRUS probe pitch at the time of sampling. We defined deviation as the shortest distance in millimeters between a core centre and its intended template location, template deviation as the mean of all deviations in a template, and mastery as achieving a template deviation ≤5.0 mm. RESULTS: All results are reported as mean ± sd. The mean absolute pitch and template deviation before learning the technique (baseline) were 8.2 ± 4.1° and 8.0 ± 2.7 mm, respectively, and after mastering the technique decreased to 4.5 ± 2.7° (P = 0.001) and 4.5 ± 0.6 mm (P < 0.001). Template deviation was related to mean absolute pitch (P < 0.001) and increased by 0.5 mm on average with each 1° increase in mean absolute pitch. Participants achieved mastery after practising 3.9 ± 2.9 double-sextant sets. There was no difference in time to perform a double-sextant set at baseline (277 ± 102 s) and mastery (283 ± 101 s; P = 0.39). CONCLUSION: A pitch-neutral side-fire technique reduced template deviation during simulated freehand TRUS-guided sPBx, suggesting it may also reduce PBx false-negatives in patients in a future clinical trial. This pitch-neutral technique can be taught and learned; the University of Florida has been teaching it to all Urology residents for the last 2 years.
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Próstata/patología , Neoplasias de la Próstata/diagnóstico , Entrenamiento Simulado , Urología/educación , Biopsia con Aguja Gruesa/métodos , Competencia Clínica , Reacciones Falso Negativas , Humanos , Biopsia Guiada por Imagen/métodos , Internado y Residencia , Masculino , Posicionamiento del Paciente , Práctica Psicológica , Entrenamiento Simulado/métodosRESUMEN
BACKGROUND: Pseudomonas aeruginosa is a Gram-negative bacteria that causes a large range of human infections such as lung infection (cystic ï¬brosis) and urinary tract infection. Even worse, antibiotic resistant bacteria have become a serious health care problem throughout the last decade, and there is a need for a clear approach to regulate and prevent the spread of pseudomonas aeruginosa resistance. METHODS: A complete analysis of Pseudomonas aeruginosa proteomics data showed that 25% of proteins are hypothetical proteins (HPs) whose function is not precisely defined. HP gene sequence analysis offers a framework for defining sequence-function relationships with a deeper understanding of organisms' molecular mechanisms at the system level. In the current research, we used the power of different bioinformatics tools to assign the potential roles for the HPs based on protein family association, amino acid function, motifs, and pathway analysis. RESULTS: The current findings show that 30 HPs have well-defined functions and are classified as enzymes, DNA binding, periplasmic binding protein, transport, etc. Seven HPs showed virulence characteristics that is to be expected to be essential for Pseudomonas aeruginosa and pathogenesis survival. CONCLUSIONS: This study's findings may encourage a better understanding of virulence mechanisms, drug resistance, pathogenesis, and drug discovery to treat Pseudomonas aeruginosa infections.
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Fibrosis Quística , Infecciones por Pseudomonas , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/genética , VirulenciaRESUMEN
Vancomycindosing error and inappropriate monitoring is a common problem in hospital daily practice. In King Abdulaziz Medical City (KAMC) in Jeddah, a high percentage of abnormal vancomycin trough levels is still detected despite using the recommended dose. Therefore, the current research objective is to study the major causes of vancomycin dosing errors. This retrospective, single-center, cross-sectional study was carried out at KAMC hospital in Jeddah from January 1st until December 31st 2019. All adult patients (≥15 years) who received vancomycin and had an initial abnormal trough level at the measured steady-state were included in this study. 472 patients have met the study inclusion criteria. The current study evaluated the factors that play a role in causing vancomycin trough level abnormalities such as sampling time, vancomycin dosing, and patient's pharmacokinetic and pharmacodynamic variations. In this study, we found that pharmacokinetic and pharmacodynamic variability was attributed to 65% of vancomycin's abnormal trough level. Also, the result showed a significantly increased odds of the low trough in the non-elderly group (OR 6, 95% CI 2.48 - 14.9, P < 0.001) and febrile neutropenic patients (OR 2.21, 95% CI 1.119 - 4.365, P < 0.05). However, the odds of high trough levels were significantly elevated among patients who have CrCl < 50 ml/min (OR 5, 95% CI 1.262-20.539, P < 0.05). In addition, the present investigation revealed that the occurrence of abnormal vancomycin levels was not affected by daily duty time or working days (p > 0.05). The current study indicated that vancomycin dosing errors were common in KAMC patients; thus, there is an unmet need to evaluate the causes of vancomycin abnormal trough level and optimize a strategy that would enhance the therapeutic effectiveness and minimize the potential toxicity.
RESUMEN
BACKGROUND: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction. METHODS: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay]. RESULTS: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores). CONCLUSIONS: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment.