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Introduction: Moderate-to-high physical activity participation is associated with a reduced risk of infertility. Yet, exercise interventions that target cardiorespiratory fitness, independent of weight loss, are lacking in obesity and female fertility research. Purpose: The primary objective of the PRO-FIT-CARE (PROmoting FITness for CArdiometabolic & REproductive Health) study was to assess the feasibility of a moderate-to-high-intensity online exercise program for persons with obesity and female infertility. Methods: Feasibility, safety, acceptability, and efficacy were assessed by examining: (1) recruitment and consent rate, (2) study retention, (3) adverse events, (4) participant satisfaction, (5) adherence, and (6) cardiorespiratory fitness. Results: Eleven of thirty-two women contacted agreed to participate in the program (34.4% consent rate). Eight participants (72.7%) completed the study. One musculoskeletal injury was reported. There was a 30% adherence rate based on prescribed exercise intensity (60%-80% of heart rate maximum). One of eleven participants attended 80% of the exercise intervention. Based on a weekly satisfaction survey, the program had an overall high level of satisfaction. Compared to sex and age normative data, post-intervention, two of eight participants improved their cardiorespiratory fitness percentile rank. Conclusion: The study highlights challenges with adherence to an online exercise program. While the program was safe and participants reported high levels of program satisfaction, approaches to improve adherence must be incorporated.
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AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.
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Tumores Neuroendocrinos , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Tumores Neuroendocrinos/patología , Medicina de Precisión , Octreótido/uso terapéutico , Imagen Molecular , Receptores de Péptidos , RadioisótoposRESUMEN
BACKGROUND: Myogenic Arthrogryposis Multiplex Congenita type 3 (AMC-3), is a rare congenital condition characterized by severe hypotonia, club feet, and multiple joint contractures often affecting both arms and legs which start prior to birth. CASE PRESENTATION: We report a full-term neonate born to first-degree cousins from fourth-generation consanguineous families, who had with antenatal history of reduced fetal movements. At birth, he was noticed to have bilateral club feet, arthrogryposis, severe hypotonia, and absent deep tendon reflexes. The patient developed difficulty in breathing probably attributed to his generalized severe hypotonia, necessitating mechanical ventilation. His creatinine-phospho-kinase, electromyogram, and brain magnetic resonance imaging were normal. Whole-exome sequencing (WES) was requested for the genetic diagnosis of the case. WES identified a novel homozygous variant c.23415-3799C > G p. in the synaptic nuclear envelope protein1 [SYNE1] gene. Seven out of 20 bioinformatic in silico programs predicted a pathogenic effect for this variant. Segregation analysis of the variant in the parents and siblings revealed that both parents and one sibling were heterozygous for the same mutation which proved the variant significance and its autosomal recessive pattern of inheritance. CONCLUSIONS: AMC3 should be suspected in patients with decreased fetal movements, severe hypotonia, absent deep tendon reflexes, and arthrogryposis. SYNE1 gene mutations can be the underlying genetic defect and molecular genetic testing can prove the diagnosis.
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Artrogriposis , Pie Equinovaro , Artrogriposis/diagnóstico , Artrogriposis/genética , Proteínas del Citoesqueleto/genética , Femenino , Humanos , Recién Nacido , Hipotonía Muscular , Mutación , Proteínas del Tejido Nervioso/genética , Membrana Nuclear/patología , Linaje , Embarazo , Arabia SauditaRESUMEN
BACKGROUND: Thromboembolic events are a common complicated health problem. Although anticoagulants have several positive effects on these conditions, they also have several characteristics that strongly affect compliance and satisfaction. The purpose of this investigation is to explore the association between treatment satisfaction and self-efficacy in a sample of patients using anticoagulation therapy and determine the influence of sociodemographic and clinical factors on both aspects. METHODS: This was a cross-sectional exploratory study carried out in Palestine. The Arabic version of the Anti-Coagulant Treatment Satisfaction Scale (ACTS) assessed treatment satisfaction. In addition, the Arabic version of the 6-Item Self-Efficacy for Managing Chronic Diseases (SES6C) was used to assess self-efficacy. RESULTS: A total of 300 patients using anticoagulants (average age 51.95 and SD 17.98) were included. There is a modest correlation between treatment satisfaction and self-efficacy (r = 0.345; p < 0.001). The mean and median self-efficacy scores were 38.41 ± 9.88 and 39.00 (interquartile range: 33.00-46.00), respectively. Overall, patients reported a moderate burden and benefit score. The mean and median of the acting burden were 43.30 ± 10.45, and 43.30 (interquartile range: 36.00 to 51.00), respectively. The results showed that young age, higher education, employment, use of fewer medications, and having fewer diseases were significantly associated with higher self-efficacy behaviors. The results also showed that new oral anti-coagulants (NOACs) had a higher degree of self-efficacy and ACTS benefit scores (41.00 (33.75-47.00), p = 0.002; 13.00 (12.00-15.00), p < 0.001, respectively), than vitamin k antagonists (VKA). CONCLUSIONS: The results demonstrated a significant relationship between treatment satisfaction and self-efficacy, and certain sociodemographic and clinical characteristics influence both. We found that there is a higher degree of self-efficacy and treatment satisfaction among patients who use NOACs than those who use UFH / VKA. Therefore, patients should be motivated to increase their knowledge about anticoagulant therapy. Healthcare providers should play an active role in educating patients, increasing their self-esteem, and awareness about anticoagulant drugs. Importantly, this study was an explanatory one, and it includes a low proportion of patients with venous thromboembolism. This encourages future research on a large scale of patients, considering the indications of anticoagulant therapy.
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INTRODUCTION: To examine the mean differences between patient beliefs about medicine with reference to adherence and glycemic control. METHODS: This study utilized a cross-sectional questionnaire-based approach. Adherence to medication was measured with the Morisky Green Levine Medication Adherence Scale (MGLS); glycemic control as the last HbA1c test value; and beliefs about medicine with the Beliefs about Medicines Questionnaire (BMQ). RESULTS: According to MGLS scale, 220 (57.9%) of the diabetic patients were classified as high adherent to their medications and 160 (42.1%) were classified as low adherent. Patients had strong believes in their medication, the mean necessity score was significantly outweighed the mean concerns score (17.7 vs 14.4; P < .001). Low adherent patients had significantly more concerns about long term effect of medications (14.4 vs 13.8; P < .008). No significant mean differences were found between glycemic controlled and uncontrolled group regarding necessity or concern domains. CONCLUSION: Assessing beliefs about medicine is crucial for recognizing patients at risk of low adherence, which offers a way to help patients with diabetes to achieve a better glycemic control.
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Diabetes Mellitus Tipo 2 , Control Glucémico , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Medio Oriente , Encuestas y CuestionariosRESUMEN
OBJECTIVES: This study had the goal of evaluating the role of treatment satisfaction among diabetic patients in the context of health-related quality of life (QoL) and medication adherence. METHODS: This study, which utilized a cross-sectional design, was conducted at the Primary Healthcare Unit in the Ministry of Health in Ramallah between Feb. and May 2019. Medication adherence was evaluated with the 4-item Morisky Green-Levine (MGL) questionnaire, treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM 1.4), and health-related quality of life with the European Quality of Life scale (EQ-5D-3L). RESULTS: Study participants consisted of 380 diabetic patients, of which 220 (57.9%) had high adherence to their medications and 160 (42.1%) had low adherence. Based on the classification of patient responses among the EQ-5D domains, pain/discomfort was the most influenced dimension, with 173 patients (36.1%) reporting problems, (36.1%). Also prominent were anxiety and depression (128 patients, 33.7%) and Mobility (115 patients, 30.3%). A significant relation was observed between QoL and treatment satisfaction (73.8 vs. 69.8; P = 0.016). Treatment satisfaction also had a significant association with the anxiety domain (39.4 vs. 28.7; P = 0.031). CONCLUSION: Participants expressed moderate satisfaction with their treatments; more satisfied patients showed greater medication adherence and had better QoL. Anxiety has been shown to be associated with reduced medication adherence and lower QoL.
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Diabetes Mellitus Tipo 2/psicología , Hipoglucemiantes/uso terapéutico , Satisfacción del Paciente , Calidad de Vida/psicología , Adulto , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Medio OrienteRESUMEN
AIMS: Strong evidence indicates that drugs reduce blood lipids and improve cardiovascular end-points, leading to their wide usage. However, the success of these drugs can be affected by poor patient's adherence to prescribed medication. This study aimed to evaluate medication adherence in patients with dyslipidaemia in association with patient beliefs about medicines. METHODS: The study was conducted from January 2019 to July 2019 at the middle governmental primary healthcare clinics in Ramallah and Bethlehem cities, and used a cross-sectional design. Adherence was determined using the 4-item Morisky medication adherence scale, while beliefs were determined using the Beliefs about Medicines Questionnaire. RESULTS: Of 220 patients, 185 agreed to participate in the study, resulting in a response rate of 84.1%. Of the participants, 106 (57.3%) were men, and almost half (88, 46.5%) were ≥56 years. Medication non-adherence was high (47.6%), but a majority (65.5%) reported believing their treatment to be necessary for their continued good health. Accordingly, the mean necessity score (17.3, SD 3.7) significantly outweighed (P < .001) the mean concerns score (14.0, SD 3.5). Multivariate regression demonstrated four variables to be significantly correlated with non-adherence: illiterate (OR = 2.52; CI: 0.9-4.3; P = .03), polypharmacy (OR = 3.18; CI: 1.9-5.7; P = .007), having comorbidity (OR = 3.10; CI: 2.2-4.6; P = .005) and having concerns about side effects (OR = 2.89; CI: 1.1-4.6, P = .04). CONCLUSION: Non-adherence among patients taking lipid-lowering agents was high despite most holding positive beliefs regarding medication necessity. This may be due to concern also being high. Physicians should identify and target high-risk patients and individualise their treatment plans in order to achieve adequate control of dyslipidaemia.
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Conocimientos, Actitudes y Práctica en Salud , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Cooperación del Paciente/psicología , Adulto , Anciano , Estudios Transversales , Quimioterapia/psicología , Femenino , Humanos , Hiperlipidemias/psicología , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Cooperación del Paciente/estadística & datos numéricos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
OBJECTIVES: This review surveys current pharmacotherapies available for the treatment of diabetic peripheral neuropathy (DPN), emphasising their mechanisms of action. METHODS: A comprehensive literature review focusing on the 'pharmacotherapy and treatment of diabetic peripheral neuropathy' was conducted. The Database of International Pharmaceutical Abstracts, EMBASE, PubMed, OVID, Scopus, Google and Google Scholar were searched, and reference lists of relevant articles were also included. KEY FINDINGS: Diabetic peripheral neuropathy is often inadequately treated, and the role of improving glycaemic control specifically in type-2 diabetes remains unclear. It is crucial to explore the mechanisms of action and effectiveness of available therapies. Major international clinical guidelines for the management of DPN recommend several symptomatic treatments. First-line therapies include tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and anticonvulsants that act on calcium channels. Other therapies include opioids and topical agents such as capsaicin and lidocaine. The objectives of this paper are to review current guidelines for the pharmacological management of DPN and to discuss research relevant to the further development of pharmacological recommendations for the treatment of diabetic neuropathy. SUMMARY: Diabetic neuropathy is a highly prevalent, disabling condition, the management of which is associated with significant costs. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. All current guidelines advise a personalised approach with a low-dose start that is tailored to the maximum response having the least side effects or adverse events.
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Neuropatías Diabéticas/tratamiento farmacológico , Administración del Tratamiento Farmacológico , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: Acne vulgaris (AV) is a common dermatological disease affecting almost 85% of teenagers. Patients with AV usually present at community pharmacies during the early stages of their disease. AIM: The aim of this study was to assess community pharmacists' knowledge, attitudes, and practice toward AV management in West Bank in Palestine. METHODS: This study was a cross-sectional questionnaire-based study. The questionnaire included four sections: 1) demographic, 2) knowledge, 3) attitude and practice items related causes, and 4) treatment options and counseling during management of patients with AV. A convenience sampling method was implemented in this study. Parametric and non-parametric tests were used to compare different issues as appropriate. P < 0.05 were considered significant. RESULT: A total of 270 community pharmacists were interviewed, and more than half (54.1%) were males. The study revealed that community pharmacists had an inadequate level of knowledge on management of AV; only 7.7% had high levels of knowledge. Pharmacists have positive attitude regarding AV management, but inadequate knowledge was reflected on their treatment practices; only 10% of participants independently dealt with AV without referral. Pharmacists with a low level of knowledge showed five times more referrals than those with a high level of knowledge (OR: 5.3; P < 0.001), and those with a bachelor degree showed three times more referrals than postgraduates (OR: 3.3; P < 0.001). CONCLUSION: There is a demand to update dermatological knowledge of community pharmacists and encourage them to attend structured training programs about the management of AV.
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Acné Vulgar/tratamiento farmacológico , Actitud del Personal de Salud , Competencia Clínica/estadística & datos numéricos , Servicios Comunitarios de Farmacia/estadística & datos numéricos , Farmacéuticos/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medio Oriente , Farmacéuticos/psicología , Derivación y Consulta/estadística & datos numéricos , Adulto JovenRESUMEN
Asthma is a clinical problem with social, psychological and economic burdens. To improve patient disease management, different education programmes have been developed. Challenges in asthma management may be partially attributed to non-adherence or improper use of inhalers. This study aimed to implement and assess hospital-based pharmaceutical care services for asthmatic patients. A 12-month, single-centre, randomized, controlled study was initiated in asthmatic adult patients who had been divided into either a control or intervention group. Patients in the control group received the usual care, and patients in the intervention group received patient counselling per study protocol that covered asthma knowledge, control, adherence to treatment and inhalation techniques. The main variables compared measurements at baseline with those at 6 and 12 months. A total of 192 patients completed the study protocol: 90 in the control group and 102 in the intervention group. The control group included 90 patients, and the intervention group included 102 patients. Over the course of the 12-month follow-up period, a significant difference was observed between intervention and control groups with respect to asthma control (38.2% vs 10.0%; P < .001), mean correct inhalation technique (confidence interval [CI]: 8.1, 7.8-8.5 vs CI: 6.1; 5.6-6.6; P = .01) and good medication adherence (60.7% vs 50.0%, P = .02). There were 34% and 25% decreases in emergency room visits and hospital admissions, respectively, in the intervention group compared to the control group. This study emphasizes the importance of patient counselling in asthma management and the significant contribution that the pharmacist's intervention can have on asthma control.
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Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Cumplimiento de la Medicación , Servicio de Farmacia en Hospital/organización & administración , Administración por Inhalación , Adolescente , Adulto , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Educación del Paciente como Asunto/métodos , Farmacéuticos/organización & administración , Rol Profesional , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: This study aims to assess the views and attitudes of the general public towards the current role of pharmacists in Jordan. METHODS: This study is a cross-sectional quantitative questionnaire-based study. After a thorough literature review on public perspectives of pharmaceutical care services, a draft questionnaire was designed. This questionnaire was examined and discussed in a focus group of invited public members and was amended accordingly to reach the final draft. The questionnaire was administered using a structured interview technique in which members of the public were asked a series of questions by a trained pharmacist. The study took a place over a period of six months, from January to June 2013. Individuals were recruited from urban and rural areas of Jordan. RESULTS: A total of 1214 respondents were interviewed during the study. Of the respondents, 67.8% were female. Most of the respondent were married (64%) and had a university degree (88.5%). Approximately half of the respondents (55.1%) had no previous knowledge of pharmaceutical care. A relative majority of respondents considered the most important activity performed by pharmacists to be dispensing medications (46.2%), followed by patient counseling (34.6%). The majority of respondents (86.4%) believed that pharmacists have a role in providing healthcare services, and 68% of respondents reported that in order to serve their needs, a pharmacist must consider the patient's needs and engage patients in determining medication timing and options. CONCLUSIONS: The plurality of respondents believed in the importance of pharmacists in providing pharmaceutical care services. However, respondents expected much from pharmacists and felt that their current role was unsatisfying.
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Objective: This study aims to assess the views and attitudes of the general public towards the current role of pharmacists in Jordan. Methods: This study is a cross-sectional quantitative questionnaire-based study. After a thorough literature review on public perspectives of pharmaceutical care services, a draft questionnaire was designed. This questionnaire was examined and discussed in a focus group of invited public members and was amended accordingly to reach the final draft. The questionnaire was administered using a structured interview technique in which members of the public were asked a series of questions by a trained pharmacist. The study took a place over a period of six months, from January to June 2013. Individuals were recruited from urban and rural areas of Jordan. Results: A total of 1214 respondents were interviewed during the study. Of the respondents, 67.8% were female. Most of the respondent were married (64%) and had a university degree (88.5%). Approximately half of the respondents (55.1%) had no previous knowledge of pharmaceutical care. A relative majority of respondents considered the most important activity performed by pharmacists to be dispensing medications (46.2%), followed by patient counseling (34.6%). The majority of respondents (86.4%) believed that pharmacists have a role in providing healthcare services, and 68% of respondents reported that in order to serve their needs, a pharmacist must consider the patient's needs and engage patients in determining medication timing and options. Conclusions: The plurality of respondents believed in the importance of pharmacists in providing pharmaceutical care services. However, respondents expected much from pharmacists and felt that their current role was unsatisfying
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Humanos , Masculino , Femenino , Servicios Farmacéuticos/organización & administración , Servicios Comunitarios de Farmacia/organización & administración , Jordania/epidemiología , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Demografía , Rol ProfesionalRESUMEN
An ethanol oxidation reaction (EOR) in alkaline medium was carried out at palladium (Pd) or platinum (Pt) nanoparticles/poly 1,8-diaminonaphthalene (p1,8-DAN) composite catalyst electrodes. Pd and Pt were incorporated onto a p1,8-DAN/GC electrode by a cyclic voltammetry (CV) strategy. The obtained Pd/p1,8-DAN/GC, Pt/p1,8-DAN/GC, Pt/Pd/p1,8-DAN/GC and Pd/Pt/p1,8-DAN/GC modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and cyclic voltammetry (CV) techniques. Electrode surface areas (ESAs) of the obtained catalysts were calculated by carbon monoxide (CO) adsorption using differential electrochemical mass spectroscopy (DEMS). The electrocatalytic oxidation of ethanol (EtOH) at the catalyst electrodes was considered in 0.5 M NaOH solutions by CV and chronoamperometric techniques. The catalyst electrodes significantly enhanced the catalytic efficiency for EOR compared to a bare glassy carbon (GC) electrode. Bimetallic catalyst electrodes demonstrate improved catalytic activity, superior durability and higher tolerance to (CO) poison generated in the development of EOR compared with Pd/p1,8-DAN and Pt/p1,8-DAN catalysts, giving priority to Pt/Pd/p1,8-DAN/GC electrodes. Viability parameters, such as NaOH and EtOH concentrations, scan rate and upper potential limits, were examined and analyzed. This study suggests that the prepared catalysts have pronounced potential applications in direct EOR in fuel cells.
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AIMS: Inappropriate use of antibiotics is one of the most important factors contributing to the emergence of drug resistant pathogens. The purpose of this study was to measure the clinical impact of antimicrobial stewardship programme (ASP) interventions on hospitalized patients at the Intensive care unit at Palestinian Medical Complex. METHODS: A prospective audit with intervention and feedback by ASP team within 48-72 h of antibiotic administration began in September 2015. Four months of pre-ASP data were compared with 4 months of post-ASP data. Data collected included clinical and demographic data; use of antimicrobials measured by defined daily doses, duration of therapy, length of stay, readmission and all-cause mortality. RESULTS: Overall, 176 interventions were made the ASP team with an average acceptance rate of 78.4%. The most accepted interventions were dose optimization (87.0%) followed by de-escalation based on culture results with an acceptance rate of 84.4%. ASP interventions significantly reduces antimicrobial use by 24.3% (87.3 defined daily doses/100 beds vs. 66.1 defined daily doses/100 beds P < 0.001). The median (interquartile range) of length of stay was significantly reduced post ASP [11 (3-21) vs. 7 (4-19) days; P < 0.01]. Also, the median (interquartile range) of duration of therapy was significantly reduced post-ASP [8 (5-12) days vs. 5 (3-9); P = 0.01]. There was no significant difference in overall 30-day mortality or readmission between the pre-ASP and post-ASP groups (26.9% vs. 23.9%; P = 0.1) and (26.1% vs. 24.6%; P = 0.54) respectively. CONCLUSIONS: Our prospective audit and feedback programme was associated with positive impact on antimicrobial use, duration of therapy and length of stay.
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Antibacterianos/administración & dosificación , Programas de Optimización del Uso de los Antimicrobianos/métodos , Hospitalización , Unidades de Cuidados Intensivos , Anciano , Anciano de 80 o más Años , Retroalimentación , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Estudios ProspectivosRESUMEN
Reactive oxygen species generate some 20,000 base lesions per human cell per day. The vast majority of these potentially mutagenic or cytotoxic lesions are subject to base excision repair (BER). Although chromatin remodelers have been shown to enhance the excision of oxidized bases from nucleosomes in vitro, it is not clear that they are recruited to and act at sites of BER in vivo. To test the hypothesis that cells possess factors that enhance BER in chromatin, we assessed the capacity of nuclear extracts from human cells to excise thymine glycol (Tg) lesions from exogenously added, model nucleosomes. The DNA glycosylase NTHL1 in these extracts was able to excise Tg from both naked DNA and sites in nucleosomes that earlier studies had shown to be sterically accessible. However, the same extracts were able to excise lesions from sterically-occluded sites in nucleosomes only after the addition of Mg2+/ATP. Gel mobility shift assays indicated that nucleosomes remain largely intact following the Mg2+/ATP -dependent excision reaction. Size exclusion chromatography indicated that the NTHL1-stimulating activity has a relatively low molecular weight, close to that of NTHL1 and other BER glycosylases; column fractions that contained the very large chromatin remodeling complexes did not exhibit this same stimulatory activity. These results indicate that cells possess a factor(s) that promotes the initiation of BER in chromatin, but differs from most known chromatin remodeling complexes.
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Ensamble y Desensamble de Cromatina , Daño del ADN , Reparación del ADN , Desoxirribonucleasa (Dímero de Pirimidina)/metabolismo , Nucleosomas/metabolismo , Timina/análogos & derivados , Adenosina Trifosfato/metabolismo , Cationes Bivalentes/metabolismo , Línea Celular , ADN/metabolismo , Humanos , Magnesio/metabolismo , Timina/metabolismoRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS: Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/terapia , Terapia Neoadyuvante , Neoplasias Pancreáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/administración & dosificación , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/secundario , Quimioradioterapia Adyuvante/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Hospitales de Alto Volumen , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Neoplasia Residual , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Tomografía de Emisión de Positrones , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Tasa de Supervivencia , GemcitabinaRESUMEN
BACKGROUND: Despite evidence of limited benefit of antibiotics in acute bronchitis, most paediatric patients are prescribed them. OBJECTIVES: To assess the validity of the Bronchitis Severity Score (BSS) in assessing the clinical response to treatment of acute bronchitis, and determine whether clinical data and basic laboratory measurements can be used to guide antibiotic prescription. METHODS: We enrolled 200 patients (age range 6 months - 12 years) with clinically diagnosed acute bronchitis. They were divided into three groups according to age. All patients were evaluated three times during the bronchitis episode (days 0, 5 and 7). The primary outcome measurement was the change in the BSS from day 0 to day 7. RESULTS: On the initial visit, the mean (standard deviation (SD)) BSS was 8.36 (2.6), indicating moderate severity of bronchitis. The mean BSS decreased to 4.03 (2.3) on day 5 and to 2.36 (1.45) on day 7. Initial blood tests showed anaemia (80%), leucocytosis (6%), bandaemia (3%) and lymphocytosis (52%). Only four patients were positive for C-reactive protein, while the erythrocyte sedimentation rate was elevated in 98% of cases. There were significant correlations between bandaemia, fever grade (p<0.001) and white blood cell count with clinical variables such as the presence of secretions on chest auscultation (p<0.05) and toxic facies on general examination (p<0.05). CONCLUSIONS: Acute bronchitis in children is a self-limiting disease that does not require routine administration of antibiotics. The BSS is a simple and practical clinical scoring system that is useful in evaluating disease severity and monitoring disease resolution in acute bronchitis.
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Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4-dihydropyridine derivatives 1a-c and maleimides 2a-c using medium pressure Hg-arc lamp (λ > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These results indicate that compounds 1a-c undergoes intermolecular cycloaddition reaction through three biradical intermediates and behave photochemically different than those reported previously for the analogous 3,5-diacetyl and 3,5-dicarboxylic acid derivatives. The present work also offers simple access to novel tricyclic and tetracyclic nitrogen heterocyclic ring systems of potential biological and synthetic applications. The structure of the photoproducts was established spectroscopically and by single crystal X-ray crystallography.
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Dihidropiridinas/química , Procesos Fotoquímicos , Fotoquímica , Cristalografía por Rayos X , Reacción de Cicloadición , Dihidropiridinas/síntesis química , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Modelos Moleculares , Estructura Molecular , Nitrógeno/químicaRESUMEN
Irradiation of benzotriazoles 1a-e at λ = 254 nm in acetonitrile solution generated the corresponding 1,3-diradicals which underwent intermolecular cycloaddition with maleimides to afford the corresponding dihydropyrrolo[3,4-b]indoles and with acetylene derivatives to afford indoles as the major products. This offers an interesting and simple access to such ring systems of potential synthetic and biological interest. The structures of the photoproducts were established spectroscopically and by single crystal X-ray crystallography.
Asunto(s)
Indoles/síntesis química , Triazoles/química , Acetonitrilos/química , Cristalografía por Rayos X , Reacción de Cicloadición , Radicales Libres/química , Modelos Moleculares , Conformación Molecular , Fotólisis , Solventes/químicaRESUMEN
BACKGROUND: Complex anatomy of the forearm may impact on local control and survivals of soft tissue sarcoma. Little is known about characteristics and oncologic outcomes following surgical treatment. METHODS: Demographic and tumor data of 117 patients with forearm soft tissue sarcoma were collected and analyzed. Following limb salvage, survivals, and prognostic factors were studied. RESULTS: Seventy-three patients were males (62%) and 53 (45%) were referred after unplanned excision. Pleomorphic undifferentiated sarcoma was most frequent (45%). The average tumor size was 5.1 cm and grade III histology was mostly identified (53%). With radiotherapy, local recurrence occurs in 8 patients (7%) and 30 patients (24%) developed metastasis. Overall survival, disease free survival, local recurrence free survival, and metastasis free survival were 83%, 74%, 93%, and 74%, respectively. Better survival was found for grade I (80% vs. 60%) and small size (<5 cm) (72% vs. 47%). Large size tumor, extra-compartmental site, extramuscular, and virgin tumor were positive predictors of metastasis. CONCLUSION: Soft tissue sarcomas of the forearm are often referred after unplanned excision. Limb salvage was achieved for most and local recurrence remained low in context of radiotherapy. Metastatic progression remained frequent. Low grade and small size were predictors of survival.