Profile, performance, and perception of pharmacist preparedness for the COVID-19 pandemic.

INTRODUCTION: The lack of human resources for disease prevention and control is evident in times of health crisis, such as the COVID-19 pandemic. In public health emergencies, the capacity for adequate assistance and guaranteed access to pharmacological treatment are fundamental and contribute to impact reduction. We aimed to analyze the profile, performance, and characteristics related to the self-perception of preparedness among pharmacists who responded to the COVID-19 pandemic in Brazil. METHOD: A cross-sectional study was conducted in two stages: content validation of a questionnaire and its application to a representative sample of pharmacists in Rio de Janeiro. The snowball technique was used to recruit participants. A logistic regression model was adjusted to determine the effects of the factors on the probability of a pharmacist feeling prepared to act during the pandemic. RESULTS: Six experts approved and validated the questionnaire, and 376 pharmacists were included in the study, 60.6 % of whom were in places specially designated by health authorities to diagnose and treat COVID-19. Professionals participated in various activities related to pandemic demands, including medication management and population guidance. Postgraduate degrees increased the odds of participants feeling prepared to act during the pandemic. Furthermore, pharmacists who worked in reference facilities were more likely to feel ready than those who worked in other places. Professionals who knew treatment guidelines were almost three times more likely to feel prepared than the ones without the knowledge of treatment guidelines. Training or guidance on how to act during the pandemic increased pharmacists' odds of feeling prepared by 2.58 times. CONCLUSION: Pharmacists actuated from diagnosis to treatment and participated in the health activities required during the pandemic. Factors contributing to the self-perception of preparedness were identified. Such factors can be targets for interventions to promote the preparedness of the workforce for future health emergencies.

Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines.

Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eight months. The resistance and parental cells were evaluated for cell viability and functional assays. Protein expression was analyzed by Western blot and human cell surface panel by lyoplate. The mutational profile and copy number alterations (CNA) were analyzed using whole-exome sequencing (WES) and the NanoString platform. FaDu resistant clones exhibited at least two-fold higher IC50 compared to the parental cell line. WES showed relevant mutations in several cancer-related genes, and the comparative mRNA expression analysis showed 36 differentially expressed genes associated with EGFR tyrosine kinase inhibitors resistance, RAS, MAPK, and mTOR signaling. Importantly, we observed that overexpression of KRAS, RhoA, and CD44 was associated with cetuximab resistance. Protein analysis revealed EGFR phosphorylation inhibition and mTOR increase in resistant cells. Moreover, the resistant cell line demonstrated an aggressive phenotype with a significant increase in adhesion, the number of colonies, and migration rates. Overall, we identified several molecular alterations in the cetuximab resistant cell line that may constitute novel biomarkers of cetuximab response such as mTOR and RhoA overexpression. These findings indicate new strategies to overcome anti-EGFR resistance in HNSCC.

Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review.

The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters.There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics.Age ≥ 50 years (OR = 3.22, 95% CI = 2.30-4.51, p < 0.001) and alcohol consumption (OR = 1.60, 95% CI = 1.13-2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumours were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B.Individuals aged ≥ 50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.

Abordagem fisioterapêutica na reabilitação da musculatura do assoalho pélvico em mulheres com prolapso genital / Physiotherapy approach in the rehabilitation of pelvic floor musculature in women with genital prolapse

Introdução: O assoalho pélvico tem como objetivo sustentar órgãos internos, principalmente o útero, a bexiga e o reto, porém qualquer alteração na cavidade pélvica pode resultar em disfunção dessa região e descida patológica dos órgãos, características dos prolapsos genitais. A fisioterapia melhora os sintomas relacionados ao prolapso genital, bem como a força muscular do assoalho. Objetivo: Identificar os procedimentos fisioterapêuticos mais utilizados e de melhor eficácia comprovada no tratamento dos prolapsos. Métodos: Foi realizado um levantamento de artigos científicos e teses em bancos de dados, nos quais foram encontrados 716 estudos. Destes, 9 foram selecionados, sendo 3 do tipo ensaio clínico randomizado controlado, 1 quaseexperimental do tipo antes e depois e 5 do tipo revisão, publicados nos últimos 20 anos e relacionados ao tema proposto. Resultados: Participaram dos estudos clínicos 430 mulheres no total, que foram submetidas a intervenções como: cinesioterapia, exercícios hipopressivos e eletroestimulação transvaginal. Os estudos de revisão mencionam os efeitos do biofeedback e da cinesioterapia no manejo dos prolapsos. Conclusão: Das abordagens analisadas a cinesioterapia e os exercícios hipopressivos são os mais efetivos para o tratamento do prolapso genital, porém mais estudos são necessários para avaliar o real impacto desses recursos. (AU)

Introduction: The pelvic floor is intended to support internal organs, especially the uterus, bladder and rectum. However, any alteration in the pelvic cavity may result in dysfunction of the pelvic floor and pathological falling of the organs, characteristic of genital prolapses. Physical therapy improves symptoms related to genital prolapse as well as muscle strength of the floor. Objective: The aim of this study was to identify the most widely used physiotherapeutic procedures with proven efficacy in the treatment of prolapses. Methods: A survey of scientific articles and theses in databases was carried out, in which 716 studies were found. Of these, 9 were selected, 3 of which were randomized controlled clinical trials, 1 quasi-experimental and 5 reviews, published in the last 20 years. Results: A total of 430 women participated in the clinical studies, who underwent interventions such as: kinesiotherapy, hipopressive exercises and transvaginal electrostimulation. The review studies mention the effects of biofeedback and kinesiotherapy in the management of prolapses. Conclusion: From the approaches analyzed kinesiotherapy and hipopressive exercises are the most effective for the treatment of genital prolapse, but more studies are necessary to evaluate the real impact of these resources. (AU)

Early discontinuation of empirical antibacterial therapy in febrile neutropenia: the ANTIBIOSTOP study.

INTRODUCTION: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin (FUO). OBJECTIVES: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia. METHODS: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37). RESULTS: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia. CONCLUSIONS: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.

Osteoarticular manifestations of celiac disease and non-celiac gluten hypersensitivity.

Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at least in part, of increasing interest in gluten-free diet in the general population.

Experiences of four parents with physical therapy and early mobility of their children in a pediatric critical care unit: A case series.

PURPOSE: The aim of this study was to conduct a preliminary investigation into parents' experiences of physical therapy and early mobility (EM) for their children in a pediatric critical care unit (PCCU). METHODS: We conducted a series of four qualitative case studies using in-depth semi-structured face-to-face interviews. We recruited parents of children who had undergone surgery and received at least one EM physical therapy intervention while intubated. We conducted a thematic analysis of transcribed interviews to illuminate the factors that influenced EM experiences. RESULTS: Four parents participated in the study. We developed an overview of Parental Experiences with Physical Therapy and Early Mobility in a PCCU, which includes four themes that parents believed influenced their experiences: (1) environmental factors; (2) awareness of physical therapist and health care professional (HCP) roles; (3) communication among parents and HCPs; and (4) parental participation in their child's EM, within the overarching parental experiences in the PCCU. CONCLUSION: This study affords a preliminary understanding of parents' experiences with physical therapy and EM in a PCCU setting. Results provide an important foundation for future research on mobility in the context of pediatric critical care research and practice.

Water-related factors and childhood diarrhoea in African informal settlements. A cross-sectional study in Ouagadougou (Burkina Faso).

Improved access to water is a key factor in reducing diarrhoeal diseases, a leading cause of death among children in sub-Saharan Africa. In terms of water access, sub-Saharan African cities are some of the worst off in the world, with 20% of populations supplied by an unimproved water source. This situation is even worse in informal settlement areas. Using cross-sectional data on access to water from a survey implemented in three informal neighbourhoods of the Ouagadougou Health and Demographic Surveillance System, logistic regressions are modelled to test the effect of different modalities of access to water on childhood diarrhoea. Our results show that the prevalence of diarrhoea in children is high: one-third of households with a child under 10 experienced an episode of childhood diarrhoea during the 2 weeks preceding the survey, even though 91% of the households surveyed have access to an improved water source. The results show that efforts to reduce childhood morbidity would be greatly enhanced by strengthening piped water access in informal settlement areas in Africa. In addition, this study confirms that, beyond the single measure of the main access to water, accurate variables that assess the accessibility to water are needed.

Use of health care among febrile children from urban poor households in Senegal: does the neighbourhood have an impact?

Urban malaria is considered a major public health problem in Africa. The malaria vector is well adapted in urban settings and autochthonous malaria has increased. Antimalarial treatments prescribed presumptively or after rapid diagnostic tests are also highly used in urban settings. Furthermore, health care strategies for urban malaria must comply with heterogeneous neighbourhood ecosystems where health-related risks and opportunities are spatially varied. This article aims to assess the capacity of the urban living environment to mitigate or increase individual or household vulnerabilities that influence the use of health services. The data are drawn from a survey on urban malaria conducted between 2008 and 2009. The study sample was selected using a two-stage randomized sampling. The questionnaire survey covered 2952 households that reported a case of fever episode in children below 10 years during the month before the survey.Self-medication is a widespread practice for children, particularly among the poorest households in Dakar. For rich households, self-medication for children is more a transitional practice enabling families to avoid opportunity costs related to visits to health facilities. For the poorest, it is a forced choice and often the only treatment option. However, the poor that live in well-equipped neighbourhoods inhabited by wealthy residents tend to behave as their rich neighbours. They grasp the opportunities provided by the area and adjust their behaviours accordingly. Though health care for children is strongly influenced by household socio-economic characteristics, neighbourhood resources (facilities and social networks) will promote health care among the poorest and reduce access inequalities. Without being a key factor, the neighbourhood of residence-when it provides resources-may be of some help to overcome the financial hurdle. Findings suggest that the neighbourhood (local setting) is a relevant scale for health programmes in African cities.

Environmental factors and childhood Fever in areas of the Ouagadougou Health and Demographic Surveillance System, Burkina Faso.

Using data on 825 under-5 children from the Ouagadougou Health and Demographic Surveillance System collected in 2010, this article examines the effects of aspects of the immediate environment on childhood fever. Logit regression models were estimated to assess the effects of the quality of the local environment on the probability that a child is reported to have had a fever in the two weeks preceding the survey, after controlling for various demographic and socioeconomic variables. While the estimated impact of some environmental factors persisted in the full models, the effects of variables such as access to water and type of household waste management decreased in the presence of demographic, socioeconomic and neighbourhood factors. The management of waste water was found to significantly affect the occurrence of childhood fever. Overall, the results of the study call for more efforts to promote access to tap water to households at prices that are affordable for the local population, where the threats to child health appears to be greatest.

Evaluation of the effectiveness of malaria vector control measures in urban settings of Dakar by a specific anopheles salivary biomarker.

Standard entomological methods for evaluating the impact of vector control lack sensitivity in low-malaria-risk areas. The detection of human IgG specific to Anopheles gSG6-P1 salivary antigen reflects a direct measure of human-vector contact. This study aimed to assess the effectiveness of a range of vector control measures (VCMs) in urban settings by using this biomarker approach. The study was conducted from October to December 2008 on 2,774 residents of 45 districts of urban Dakar. IgG responses to gSG6-P1 and the use of malaria VCMs highly varied between districts. At the district level, specific IgG levels significantly increased with age and decreased with season and with VCM use. The use of insecticide-treated nets, by drastically reducing specific IgG levels, was by far the most efficient VCM regardless of age, season or exposure level to mosquito bites. The use of spray bombs was also associated with a significant reduction of specific IgG levels, whereas the use of mosquito coils or electric fans/air conditioning did not show a significant effect. Human IgG response to gSG6-P1 as biomarker of vector exposure represents a reliable alternative for accurately assessing the effectiveness of malaria VCM in low-malaria-risk areas. This biomarker tool could be especially relevant for malaria control monitoring and surveillance programmes in low-exposure/low-transmission settings.

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal.

BACKGROUND: Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low. METHODS: One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district. RESULTS: Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts. CONCLUSIONS: Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.

Asymptomatic carriage of plasmodium in urban Dakar: the risk of malaria should not be underestimated.

INTRODUCTION: The objective of this study was to measure the rate of asymptomatic carriage of plasmodium in the Dakar region two years after the implementation of new strategies in clinical malaria management. METHODOLOGY: Between October and December 2008, 2952 households selected in 50 sites of Dakar area, were visited for interviews and blood sampling. Giemsa-stained thick blood smears (TBS) were performed for microscopy in asymptomatic adult women and children aged 2 to 10 years. To ensure the quality of the microscopy, we performed a polymerase chain reaction (PCR) with real time qPCR in all positive TBS by microscopy and in a sample of negative TBS and filter paper blood spots. RESULTS: The analysis has concerned 2427 women and 2231 children. The mean age of the women was 35.6 years. The mean age of the children was 5.4 years. The parasite prevalence was 2.01% (49/2427) in women and 2.15% (48/2231) in children. Parasite prevalence varied from one study site to another, ranging from 0 to 7.41%. In multivariate analysis, reporting a malaria episode in 2008 was associated with plasmodium carriage (OR = 2.57, P = 0.002) in women; in children, a malaria episode (OR = 6.19, P<0.001) and a travel out of Dakar during last 3 months (OR = 2.27, P = 0.023) were associated with plasmodium carriage. Among the positive TBS, 95.8% (93/97) were positive by plasmodium PCR. Among the negative TBS, 13.9% (41/293) were positive by PCR. In blood spots, 15.2% (76/500) were positive by PCR. We estimated at 16.5% the parasite prevalence if PCR were performed in 4658 TBS. CONCLUSION: Parasite prevalence in Dakar area seemed to be higher than the rate found by microscopy. PCR may be the best tool for measuring plasmodium prevalence in the context of low transmission. Environmental conditions play a major role in the heterogeneity of parasite prevalence within sites.