RESUMO
Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.
RESUMO
The global rise of antibiotic resistance poses a substantial risk to mankind, underscoring the necessity for alternative antimicrobial options. Developing novel drugs has become challenging in matching the pace at which microbial resistance is evolving. Recently, nanotechnology, coupled with natural compounds, has emerged as a promising solution to combat multidrug-resistant bacteria. In the present study, silver nanoparticles were green-synthesized using aqueous extract of Phoenix dactylifera (variety Ajwa) fruits and characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) coupled with Energy dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and Thermogravimetric-differential thermal analysis (TGA-DTA). The in-vitro synergy of green synthesized P. dactylifera silver nanoparticle (PD-AgNPs) with selected antibiotics and bioactive extract of Punica granatum, i.e., ethyl acetate fraction (PGEF), was investigated using checkerboard assays. The most effective synergistic combination was evaluated against the QS-regulated virulence factors production and biofilm of Pseudomonas aeruginosa PAO1 by spectroscopic assays and electron microscopy. In-vivo anti-infective efficacy was examined in Caenorhabditis elegans N2 worms. PD-AgNPs were characterized as spherical in shape with an average diameter of 28.9 nm. FTIR analysis revealed the presence of functional groups responsible for the decrease and stabilization of PD-AgNPs. The signals produced by TGA-DTA analysis indicated the generation of thermally stable and pure crystallite AgNPs. Key phytocompounds detected in bioactive fractions include gulonic acid, dihydrocaffeic acid 3-O-glucuronide, and various fatty acids. The MIC of PD-AgNPs and PGEF ranged from 32 to 128 µg/mL and 250-500 µg/mL, respectively, against test bacterial strains. In-vitro, PD-AgNPs showed additive interaction with selected antibiotics (FICI 0.625-0.75) and synergy with PGEF (FICI 0.25-0.375). This combination inhibited virulence factors by up to 75 % and biofilm formation by 84.87 % in P. aeruginosa PAO1. Infected C. elegans worms with P. aeruginosa PAO1 had a 92.55 % survival rate when treated with PD-AgNPs and PGEF. The combination also reduced the reactive oxygen species (ROS) level in C. elegans N2 compared to the untreated control. Overall, these findings highlight that biosynthesized PD-AgNPs and bioactive P. granatum extract may be used as a potential therapeutic formulation against MDR bacteria.
Assuntos
Antibacterianos , Biofilmes , Sinergismo Farmacológico , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Phoeniceae , Extratos Vegetais , Punica granatum , Pseudomonas aeruginosa , Prata , Prata/farmacologia , Prata/química , Prata/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas Metálicas/química , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Phoeniceae/química , Virulência/efeitos dos fármacos , Punica granatum/química , Caenorhabditis elegans/efeitos dos fármacos , Química Verde , Difração de Raios X , Fatores de Virulência/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Frutas/química , Frutas/microbiologiaRESUMO
Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.
Assuntos
Hipofosfatasia , Adulto , Criança , Humanos , Adolescente , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Europa (Continente) , Prevalência , MutaçãoRESUMO
Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.
Assuntos
Hipofosfatasia , Lactente , Adulto , Recém-Nascido , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/epidemiologia , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Mutação , PrevalênciaRESUMO
BACKGROUND: This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features. METHODS: An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations. RESULTS: The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition. CONCLUSION: Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children.
Assuntos
Hipofosfatasia , Adulto , Criança , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Mutação , Estudos Retrospectivos , Fosfatase Alcalina/genética , Genótipo , FenótipoRESUMO
BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.
Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Hepacivirus , Hepatite C , Transplante de Pulmão , Complicações Pós-Operatórias , Viremia , Humanos , Transplante de Pulmão/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Hepatite C/cirurgia , Hepatite C/virologia , Hepacivirus/isolamento & purificação , Viremia/virologia , Viremia/etiologia , Taxa de Sobrevida , Rejeição de Enxerto/etiologia , Fatores de Risco , Doadores de Tecidos/provisão & distribuição , Adulto , Antivirais/uso terapêutico , TransplantadosRESUMO
PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.
Assuntos
Neoplasias da Mama , Terapia Cognitivo-Comportamental , Estudos de Viabilidade , Telemedicina , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Idoso , Adulto , Terapia Cognitivo-Comportamental/métodos , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/terapia , Inquéritos e Questionários , Qualidade do Sono , Medidas de Resultados Relatados pelo PacienteRESUMO
The polyuria and polydipsia state in diabetes insipidus (DI) can be challenging to manage for patients and clinicians with significant impact on the patients' well-being. A review of literature shows that nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide and potassium-sparing diuretics, along with low dietary solute and protein, and high water intake remain the standard medical therapy. Although these therapeutic approaches improve symptoms, the urine-concentrating defect is still considerable, posing a serious risk to patient's life from hypovolemia if high fluid intake is not maintained. Our case describes the challenges faced with the medical management of a patient with nephrogenic DI that was only partially responsive to standard medical therapy, resulting in debilitating effects on the patient's quality of life.
Assuntos
Diabetes Insípido Nefrogênico , Humanos , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/terapia , Diabetes Insípido Nefrogênico/complicações , Masculino , Diuréticos/uso terapêutico , Qualidade de Vida , FemininoRESUMO
Objective: The objective of this study was to determine the frequency of different congenital cardiac defects co-existing in karyotypically proved Down syndrome population. It also highlighted the association between gender and pattern of congenital cardiac defects and gender as a risk factor. Methods: A cross sectional comparative study was done in the Department of Genetics, Children Hospital Lahore in the year 2017. A total of 160 patients were subjected to karyotypic analysis through blood test for determining the type of Down Syndrome and Echocardiography of all established cases was performed for determining presence and types of congenital cardiac defects. Results were evaluated in terms of establishing co-existence of various cardiac phenotypes in Down Syndrome cases. Results: In karyotypically proven 160 cases of Down syndrome, 58.1% of Down Syndrome cases and 88.2% of Down Syndrome with Congenital Cardiac Defects presented in infancy. The odds ratio (OR) suggested that females are 1.72 times more likely to experience a cardiac effect compared to males. Female gender was potentially associated (p-value 0.07) with occurrence of Patent Ductus Arteriosus (47.8%), whereas VSD (Ventricular Septal Defects) was most prevalent (41.1%) in males. Patent Ductus Arteriosus + Atrial Septal Defects (44.4%) was the commonest cardiac defect in female cases. The combined data for pattern of cardiac anomalies showed no significant association with gender, as indicated by a p-value of 0.990. Conclusion: The study concluded that most of Down syndrome cases and Down syndrome with congenital cardiac defects present to the hospital in infancy. Female cases are more prone to develop cardiac defects as compared to males. The manifestation of PDA (Patent Ductus Arteriosus) was significantly associated as an isolated anomaly in females and VSD (Ventricular Septal Defects) as isolated anomaly in males. Patent Ductus Arteriosus tend to co-exist most with ASD (Atrial Septal Defects) in female cases. Gender was not established as a risk factor for affecting the pattern of cardiac defects.
RESUMO
Protein phosphatase 2A (PP2A) is a major phospho-Ser/Thr phosphatase and a key regulator of cellular signal transduction pathways. While PP2A dysfunction has been linked to human cancer and neurodegenerative disorders such as Alzheimer's disease (AD), PP2A regulation remains relatively poorly understood. It has been reported that the PP2A catalytic subunit (PP2Ac) is inactivated by a single phosphorylation at the Tyr307 residue by tyrosine kinases such as v-Src. However, multiple mass spectrometry studies have revealed the existence of other putative PP2Ac phosphorylation sites in response to activation of Src and Fyn, two major Src family kinases (SFKs). Here, using PP2Ac phosphomutants and novel phosphosite-specific PP2Ac antibodies, we show that cellular pools of PP2Ac are instead phosphorylated on both Tyr127 and Tyr284 upon Src activation, and on Tyr284 following Fyn activation. We found these phosphorylation events enhanced the interaction of PP2Ac with SFKs. In addition, we reveal SFK-mediated phosphorylation of PP2Ac at Y284 promotes dissociation of the regulatory Bα subunit, altering PP2A substrate specificity; the phosphodeficient Y127/284F and Y284F PP2Ac mutants prevented SFK-mediated phosphorylation of Tau at the CP13 (pSer202) epitope, a pathological hallmark of AD, and SFK-dependent activation of ERK, a major growth regulatory kinase upregulated in many cancers. Our findings demonstrate a novel PP2A regulatory mechanism that challenges the existing dogma on the inhibition of PP2A catalytic activity by Tyr307 phosphorylation. We propose dysregulation of SFK signaling in cancer and AD can lead to alterations in PP2A phosphorylation and subsequent deregulation of key PP2A substrates, including ERK and Tau.
Assuntos
Proteína Fosfatase 2 , Proteínas Proto-Oncogênicas c-fyn , Quinases da Família src , Doença de Alzheimer/metabolismo , Humanos , Fosfoproteínas Fosfatases , Fosforilação , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Tirosina/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Proteínas tau/metabolismoRESUMO
PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc), which confers significant morbidity and mortality. The current therapies and treatment strategies for SSc-associated PAH (SSc-PAH) are informed by those used to treat patients with idiopathic PAH (IPAH). There are, however, important differences between these two diseases that impact diagnosis, treatment, and outcomes. RECENT FINDINGS: Both SSc-PAH and IPAH are incompletely understood with ongoing research into the underlying cellular biology that characterize and differentiate the two diseases. Additional research seeks to improve identification among SSc patients in order to diagnose patients earlier in the course of their disease. Novel therapies specifically for SSc-PAH such as rituximab and dimethyl fumarate are under investigation. SUMMARY: Although patients with SSc-PAH and IPAH present with similar symptoms, there are significant differences between these two forms of PAH that warrant further investigation and characterization of optimal detection strategies, treatment algorithms, and outcomes assessment.
Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Escleroderma Sistêmico , Humanos , Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/etiologia , Escleroderma Sistêmico/complicaçõesRESUMO
Adherence to antiretroviral therapy (ART) is a major challenge for many youth living with HIV (YLWH). In this prospective proof-of-concept study, we assessed the feasibility and acceptability of conducting a study of video directly observed therapy (VDOT) as a method of improving medication adherence in YLWH who had a history of poor adherence to ART. The study had four phases; phase I - VDOT daily (4 months) using Facetime®; phase II - daily texting (2 months); phase III - weekly texting (3 months); phase IV - no intervention (3 months). Participants were seen in clinic on a monthly basis for assessment and laboratory evaluation. Five of eight eligible participants were enrolled. All achieved virologic suppression one month after enrollment. Three of five completed the study protocol and maintained virologic suppression through the 12-month period of study. Participant responses to the end-of-study questionnaire indicated satisfaction with the intervention and thought VDOT was helpful to them. Healthcare providers thought that the intervention was effective for some youth but was at times burdensome. This proof-of-concept study demonstrated that VDOT may be effective at improving medication adherence in previously poorly adherent YLWH and that larger studies of VDOT for such patients are both feasible and warranted.
Assuntos
Terapia Diretamente Observada , Infecções por HIV , Adolescente , Humanos , Terapia Antirretroviral de Alta Atividade , HIV , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Estudos Prospectivos , Estudo de Prova de ConceitoRESUMO
Background: Breastfeeding is not recommended for women living with HIV (WLWH) in Canada. We described the prevalence of breastfeeding and explored experiences of care, support, and stigma related to infant feeding. Setting: Quebec, Ontario, and British Columbia (Canada). Methods: Data were obtained from the HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) surveys, conducted between 2013 and 2018. Results: Breastfeeding was reported by 73.5% of the 786 women who delivered before HIV diagnosis and 7.3% of the 289 women who delivered after HIV diagnosis. Among them, earlier year of delivery, delivery outside of Canada, and African, Caribbean, Black ethnicity were independently associated with increased odds of breastfeeding. Among WLWH who had a live birth during the last year, 77% (40/52) felt that they had received support regarding infant feeding practices, and 77% (23/30) were concerned that not breastfeeding could lead to them being identified as WLWH. Among 71 women within one year postpartum at any one of the study waves, 89% reported having an undetectable viral load. Conclusion: Breastfeeding experiences were common among WLWH, most often prior to HIV diagnosis. Fear of unintentional HIV status disclosure when not breastfeeding and challenges to maintain an undetectable HIV viral load are important issues to address during postpartum care.
Assuntos
Infecções por HIV , Feminino , Lactente , Humanos , Estudos de Coortes , Infecções por HIV/epidemiologia , Canadá/epidemiologia , Saúde da Mulher , Ontário/epidemiologia , Aleitamento Materno , Período Pós-PartoRESUMO
OBJECTIVES: To describe children hospitalized with community-acquired pneumonia complicated by effusion (cCAP). DESIGN: Retrospective cohort study. SETTING: A Canadian children's hospital. PARTICIPANTS: Children without significant medical comorbidities aged < 18 years admitted from January 2015-December 2019 to either the Paediatric Medicine or Paediatric General Surgery services with any pneumonia discharge code who were documented to have an effusion/empyaema using ultrasound. OUTCOME MEASURES: Length of stay; admission to the paediatric intensive care unit; microbiologic diagnosis; antibiotic use. RESULTS: There were 109 children without significant medical comorbidities hospitalized for confirmed cCAP during the study period. Their median length of stay was 9 days (Q1-Q3 6-11 days) and 35/109 (32%) were admitted to the paediatric intensive care unit. Most (89/109, 74%) underwent procedural drainage. Length of stay was not associated with effusion size but was associated with time to drainage (0.60 days longer stay per day delay in drainage, 95%CI 0.19-1.0 days). Microbiologic diagnosis was more often made via molecular testing of pleural fluids (43/59, 73%) than via blood culture (12/109, 11%); the main aetiologic pathogens were S. pneumoniae (40/109, 37%), S. pyogenes (15/109, 14%), and S. aureus (7/109, 6%). Discharge on a narrow spectrum antibiotic (i.e. amoxicillin) was much more common when the cCAP pathogen was identified as compared to when it was not (68% vs. 24%, p < 0.001). CONCLUSIONS: Children with cCAP were commonly hospitalized for prolonged periods. Prompt procedural drainage was associated with shorter hospital stays. Pleural fluid testing often facilitated microbiologic diagnosis, which itself was associated with more appropriate antibiotic therapy.
Assuntos
Infecções Comunitárias Adquiridas , Derrame Pleural , Pneumonia , Criança , Humanos , Lactente , Estudos Retrospectivos , Staphylococcus aureus , Canadá , Pneumonia/complicações , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Streptococcus pneumoniae , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/diagnóstico , Streptococcus pyogenes , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural/terapiaRESUMO
For genetic counselors to effectively meet the needs of an ever-diversifying multicultural patient population, it is vital that their genetic counseling programs (GCPs) equip future genetic counselors to recognize the impact of a patient's ethnocultural background on clinical interactions (Towards a culturally competent system of care: A monograph on effective services for minority children who are severely emotionally disturbed (p. 28). CASSP Technical Assistance Center, Georgetown University Child Development Center, 1989). Concerns about genetic counseling cultural competency training (CCT) including content and delivery have been brought up by GCP students who identify as racial and ethnic minorities (Journal of Genetic Counseling, 29, 303-314). Though GCPs must meet the Accreditation Council of Genetic Counselors' (ACGC) accreditation criteria, there is a gap in knowledge regarding the focus, type, and methods of delivery that GCPs have chosen to incorporate into their CCT, as ACGC does not dictate the exact focus, delivery, or format of training curricula. This quantitative study aimed to (1) characterize the current focus, type, and delivery of ethnocultural competency training in GCPs as perceived by second-year genetic counseling students and recent graduates and (2) highlight their perception of its impact on their levels of preparedness and comfort when interacting with ethnoculturally diverse patients. One hundred and one survey responses were analyzed using descriptive statistics, chi-square analyses, two-sample Wilcoxon rank-sum, and Fisher's exact tests. The results reveal significant variability in the format, type, and delivery of CCT provided by GCPs. Participants perceive that CCT focusing on specific traditions, medical considerations, and systemic healthcare disparities (taught to 74%, 61%, and 94% of students, respectively) related to ethnoculturally diverse patients was more likely to increase their self-reported levels of preparedness and comfort for clinical interactions than training focused on racial or ethnic stereotypes and generalizations (taught to 88% of students). Although 94% of participants perceived their CCT as helpful, 61% reported they received an insufficient amount. In light of these results, we provide suggestions for the improvement of ethnocultural CCT and highlight future opportunities for more intentional and fruitful CCT in GCPs.
RESUMO
OBJECTIVES: Horizon scanning for health technology appraisal (HTA) in England involves topic notification to the National Institute for Health and Care Excellence (NICE) via technology briefings. This activity is undertaken by the Innovation Observatory with submission timelines designed to ensure that HTA decisions align with regulatory approval time. In this paper, we aimed to track and assess the progression and current status of the topics notified for HTA and provide a descriptive analysis of these topics. METHODS: Technology briefings were mapped from submission to NICE technology appraisal/highly specialized technologies recommendations from April 2017 until October 2021. This was done using a combination of searches on Google and NICE website, searching a downloadable spreadsheet containing NICE topic selection decisions, and querying NICE Topic Selection team. Analysis was undertaken regarding type of indications and interventions of submitted topics and published guidance. RESULTS: Six-hundred and ninety-three topics entered the NICE scoping process, of which 94 percent were prioritized. As of November 2021, approximately 39 percent of prioritized topics were in scoping/in progress, 31 percent were proposed/completed, 20 percent were suspended/terminated, and 4 percent were referred back to Innovation Observatory (IO) for further monitoring. CONCLUSIONS: Our work demonstrates that horizon scanning for HTA is a complex and time-intensive process. Timelines and progress through HTA is challenging due to the growing number of innovative medicines, significant uncertainties, and limited transparency in clinical development and regulatory pathways. A better understanding of clinical trials and regulatory requirements may help eliminate some of this uncertainty and improve timely HTA.
Assuntos
Tecnologia Biomédica , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício , Inglaterra , IncertezaRESUMO
OBJECTIVE: To determine the frequency of subtypes of Down syndrome by karyotyping, and to establish the frequency of congenital cardiac defects in this population. METHODS: The cross-sectional study was conducted at the Department of Genetics, Children Hospital, Lahore, Pakistan, from June 2016 to June 2017, and comprised of Down Syndrome patients aged <15 years. They were subjected to karyotypic analysis for determining the subtype of the syndrome, and echocardiography of all cases was done for the assessment of congenital cardiac defects. The two findings was subsequently used to establish a relation between the subtypes and congenital cardiac defects. Data collected, entered and analyzed by the SPSS version 20.0. RESULTS: Among the 160 cases, trisomy 21 was found in 154(96.2%), translocation 5(3.1%) and mosaicism 1(0.6%). Overall, 63(39.4%) children had cardiac defects. Among such patients, patent ductus arteriosus was most common 25(39.7%), followed by ventricular septal defects24(38.1%), atrial septal defects16(25.4%), complete atrioventricular septal defects 8(12.7%), and Tetralogy of Fallot3(4.8%), while 6(9.5%) children had other defects. Atrial septal defects was the most common double defect 9(56.2%) and had the highest coexistence with patent ductus arteriosus in Down syndrome cases with congenital cardiac defects. CONCLUSIONS: In Trisomy 21, the most common cardiac defect was patent ductus arteriosus, followed by ventricular septal defects in isolated defects, whereas in mixed defects, atrial septal defects and patent ductus arteriosus were the highest.
Assuntos
Síndrome de Down , Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Comunicação Interatrial , Criança , Humanos , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Estudos Transversais , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/epidemiologia , Comunicação Interatrial/genética , CariotipagemRESUMO
BACKGROUND: Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia. OBJECTIVE: Evaluate the physiologic response of patients with ME/CFS to a standardized OC. DESIGN: Respiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of ≥ 20 breaths per minute-either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2. PATIENTS: 63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29). MEASURES: Supine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension. RESULTS: The majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia. CONCLUSIONS: The 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.
Assuntos
Síndrome de Fadiga Crônica , Intolerância Ortostática , Pressão Sanguínea , Síndrome de Fadiga Crônica/diagnóstico , Frequência Cardíaca , Humanos , Intolerância Ortostática/diagnóstico , Qualidade de VidaRESUMO
PURPOSE: Sleep disturbance is common in patients with advanced interstitial lung disease (ILD) often complicated by pulmonary hypertension (PH) and may contribute to poor quality of life. The etiology of sleep disturbance and the relationship between PH and sleep architecture in patients with ILD remains unknown. METHODS: We performed a retrospective cohort study comparing sleep architecture on polysomnography in patients with ILD with and without PH, defined as mean pulmonary artery pressure on right heart catheterization ≥ 20 mmHg. We tested the hypothesis that patients with ILD and PH would have increased wake time after sleep onset (WASO) compared to patients with ILD without PH using univariate analysis and multivariable linear regression. RESULTS: In our cohort of patients with ILD who underwent polysomnography (N = 49), patients with PH had lower total diffusion capacity for carbon monoxide (DLCO) (9.28 vs. 12.87 ml/min/mmHg, P = 0.04) and percent DLCO (39% vs. 53%, P = 0.03). On polysomnography, patients with PH had increased percentage of total sleep time with saturation < 90% (T90) (17% vs. 6%, P = 0.03), decreased N2 sleep (181 vs. 233 min, P = 0.03), decreased %N2 sleep (59% vs. 66%, P = 0.04), increased %N1 sleep (22% vs. 14%, P = 0.02), decreased sleep efficiency (62% vs. 72%, P = 0.03), and increased WASO (133 vs. 84 min, P = 0.01). In multivariable analysis, PH was associated with a 43-min increase in WASO (95% CI 6.2-80.2, P = 0.02). CONCLUSION: Patients with ILD and PH have decreased total and %N2 sleep, increased %N1 sleep, decreased sleep efficiency, and increased WASO, likely indicating increased sleep fragmentation.
Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/complicações , Estudos Retrospectivos , Qualidade de Vida , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , SonoRESUMO
BACKGROUND: Gadofosveset is a gadolinium-based blood pool contrast agent that was approved by the United States Food and Drug Administration in 2008. Its unanticipated withdrawal from production in 2016 created a void in the blood pool agent inventory and highlighted the need for an alternative agent with comparable imaging properties. OBJECTIVE: The purpose of our study is to compare the diagnostic image quality, vascular contrast-to-noise ratio (CNR) and temporal signal characteristics of gadofosveset trisodium and ferumoxytol at similar molar doses for high-resolution, three-dimensional (3-D) magnetic resonance (MR) venography in children. MATERIALS AND METHODS: The medical records and imaging data sets of patients who underwent high-resolution 3-D gadofosveset-enhanced MR venography (GE-MRV) or ferumoxytol-enhanced MR venography (FE-MRV) were retrospectively reviewed. Two groups of 20 pediatric patients (age- and weight-matched with one patient common to both groups; age range: 2 days-15 years) who underwent high-resolution 3-D GE-MRV or FE-MRV at similar molar doses were identified and analyzed. Qualitative analysis of image quality and vessel definition was performed by two blinded pediatric radiologists. Interobserver agreement was assessed with the AC1 (first-order agreement coefficient) statistic. Signal-to-noise ratio (SNR) and CNR of the inferior vena cava and aorta were measured in the steady-state venous phase. Medical records were retrospectively reviewed for any adverse reactions associated with either contrast agent. RESULTS: Measured SNR and CNR of the inferior vena cava were higher for FE-MRV than GE-MRV (P = 0.034 and P < 0.001, respectively). The overall image quality score and individual vessel scores of FE-MRV were equal to or greater than GE-MRV (P = 0.084), with good interobserver agreement (AC1 = 0.657). The venous signal on FE-MRV was stable over the longest interval measured (1 h, 13 min and 46 s), whereas venous signal on GE-MRV showed more variability and earlier loss of signal. No adverse reactions were noted in any patient with either contrast agent. CONCLUSION: Ferumoxytol produces more uniform and stable enhancement throughout the entire venous circulation in children than gadofosveset, offering a wider time window for optimal image acquisition. FE-MRV offers a near-ideal approach to high-resolution venography in children at all levels of anatomical complexity.