RESUMEN
Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.
RESUMEN
INTRODUCTION: Recent expansion of cannabis legalization in multiple states calls for reexamination of the prevalence of cannabis use, cannabis use disorder (CUD), and the associations between CUD severity and substance use treatment. We used Andersen's behavioral model of healthcare use as the conceptual/analytic framework for examining treatment use. METHODS: We used data from the 2022 National Survey on Drug Use and Health (NSDUH; Nâ¯=â¯47,100, age 18+) to describe the prevalence of past-year cannabis use, CUD and CUD severity, other substance use disorders, and substance use treatment. We compared sociodemographic, mental health, healthcare use, and cannabis and other substance use characteristics by CUD severity. Finally, we used logistic regression models to examine the associations between CUD severity and substance use treatment. RESULTS: Of the U.S. adult population, 23.0â¯% used cannabis in the past year; 7.0â¯% had a CUD (3.9â¯% mild, 1.9â¯% moderate, and 1.2â¯% severe CUD); and 4.7â¯% received substance use treatment. Of past-year cannabis users, 30.3â¯% had CUD (16.9â¯% mild, 8.4â¯% moderate, and 5.0â¯% severe CUD), and 9.6â¯% received substance use treatment. Cannabis users had 3-4 times higher rates of other substance use disorders than nonusers. Of those with CUD, 38.4â¯% had moderate/severe mental illness, 52.4â¯% had other substance use disorders, and 16.5â¯% received substance use treatment. Among all cannabis users, moderate (aOR [adjusted odds ratios]â¯=â¯1.48, 95â¯% CIâ¯=â¯1.03-2.13) and severe (aORâ¯=â¯2.57, 95â¯% CIâ¯=â¯1.60-4.11) CUDs were associated with greater odds of substance use treatment. Among cannabis users without nicotine dependence and alcohol, opioid, tranquilizer/sedative, and stimulant use disorders, only severe CUD (aORâ¯=â¯6.03, 95â¯% CIâ¯=â¯3.37-10.78) was associated with greater odds of substance use treatment. CONCLUSIONS: This study shows increased prevalence of cannabis use and CUD among U.S. adults, and with or without other substance use disorders, CUD was associated with greater odds of substance use treatment. However, the overall low rate of treatment use among those with CUD is concerning. Healthcare providers need to provide education for both medical and recreational users on the development of tolerance and dependence. Harm reduction strategies to minimize the negative consequences of CUD are also needed.
RESUMEN
OBJECTIVES: Readability of patient-facing information of oral antibiotics detailed in the WHO all oral short (6 months, 9 months) has not been described to date. The aim of this study was therefore to examine (i) how readable patient-facing TB antibiotic information is compared to readability reference standards and (ii) if there are differences in readability between high-incidence countries versus low-incidence countries. METHODS: Ten antibiotics, including bedaquiline, clofazimine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, pretomanid, pyrazinamide, were investigated. TB antibiotic information sources were examined, consisting of 85 Patient Information Leaflets (PILs) and 40 antibiotic web resouces. Of these 85 PILs, 72 were taken from the National Medicines Regulator from six countries (3 TB high-incidence [Rwanda, Malaysia, South Africa] + 3 TB low-incidence [UK, Ireland, Malta] countries). Readability data was grouped into three categories, including (i) high TB-incidence countries (n = 33 information sources), (ii) low TB-incidence countries (n = 39 information sources) and (iii) web information (n = 53). Readability was calculated using Readable software, to obtain four readability scores [(i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index], as well as two text metrics [words/sentence, syllables/word]. RESULTS: Mean readability scores of patient-facing TB antibiotic information for FRE and FKGL, were 47.4 ± 12.6 (sd) (target ≥ 60) and 9.2 ± 2.0 (target ≤ 8.0), respectively. There was no significant difference in readability between low incidence countries and web resources, but there was significantly poorer readability associated with PILs from high incidence countries versus low incidence countries (FRE; p = 0.0056: FKGL; p = 0.0095). CONCLUSIONS: Readability of TB antibiotic PILs is poor. Improving readability of PILs should be an important objective when preparing patient-facing written materials, thereby improving patient health/treatment literacy.
RESUMEN
Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a Pseudomonas-dominant, Staphylococcus-dominant, and mixed dominance cluster. Shannon's diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. Pseudomonas spp. abundance was significantly reduced post-ETI, but eradication was not observed. Staphylococcus spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of Pseudomonas spp., Staphylococcus spp., and Serratia spp. in the sputum. Pseudomonas spp. and Staphylococcus spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of Pseudomonas spp. in the sinuses following ETI therapy. We also show that Staphylococcus spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant Staphylococcus aureus (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.
Asunto(s)
Aminofenoles , Benzodioxoles , Fibrosis Quística , Combinación de Medicamentos , Indoles , Microbiota , Quinolonas , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/complicaciones , Aminofenoles/uso terapéutico , Benzodioxoles/uso terapéutico , Quinolonas/uso terapéutico , Femenino , Adulto , Masculino , Indoles/uso terapéutico , Microbiota/efectos de los fármacos , Sistema Respiratorio/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Pirroles/uso terapéutico , Sinusitis/microbiología , Sinusitis/tratamiento farmacológico , Pirazoles/uso terapéutico , Adulto Joven , Piridinas/uso terapéutico , Pseudomonas/efectos de los fármacos , Pseudomonas/aislamiento & purificación , Pseudomonas/genética , Persona de Mediana Edad , PirrolidinasRESUMEN
OBJECTIVES: To estimate the carriage of Neisseira meningitidis (meningococci) in expectorated sputum from people with cystic fibrosis (CF) and to evaluate potential ramifications of such carriage for the health and (NM) wellbeing of physiotherapists performing airway clearance techniques. DESIGN: Descriptive observational study. MAIN OUTCOME MEASURES: Meningococcal carriage rate, CFTR mutation type and time to first meningococcal culture were determined. RESULTS: Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. NM was isolated from 6/100 (6%) adult CF patients who had F508del/F508del (homozygous), F508del/other (heterozygous) and other mutations. The median and mean time to first isolation of NM was 213 months and 230 months (standard deviation = 27.6 months), respectively, shortest time was 209 months, longest time 278 months. CONCLUSIONS: Physiotherapists should be aware of the risks to themselves of acquiring Neisseria meningtidis from CF patients' respiratory aerosols, whilst performing airway clearance techniques. Physiotherapists with underlying medical conditions or with specific concerns about meningococcal disease should discuss their circumstances with their occupational health team, to ensure optimal protection.
Asunto(s)
Portador Sano , Fibrosis Quística , Infecciones Meningocócicas , Neisseria meningitidis , Esputo , Humanos , Fibrosis Quística/microbiología , Neisseria meningitidis/aislamiento & purificación , Adulto , Masculino , Femenino , Esputo/microbiología , Adulto Joven , Adolescente , Niño , Fisioterapeutas , Preescolar , Salud Laboral , Persona de Mediana Edad , LactanteRESUMEN
Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive. Antibiotic susceptibility to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates (n = 11) from an adult cystic fibrosis patient, over a 63 month period. Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with Clinical and Laboratory Standards Institute methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole. Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II and III) preceding this complete resistotype. The bacterium continued to display further antibiotic susceptibility heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V-XI). The Relative Resistance Index of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such a requirement for large numbers of colony picks combined with antibiotic susceptibility-related methodological problems creates a conundrum in biomedical science practice, in providing a robust assay that will capture antibiotic susceptibility variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in antibiotic susceptibility testing with Burkholderia cenocepacia. Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their cystic fibrosis patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.
Asunto(s)
Antibacterianos , Infecciones por Burkholderia , Burkholderia cenocepacia , Fibrosis Quística , Pruebas de Sensibilidad Microbiana , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/complicaciones , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Burkholderia cenocepacia/efectos de los fármacos , Burkholderia cenocepacia/genética , Infecciones por Burkholderia/tratamiento farmacológico , Infecciones por Burkholderia/microbiología , Adulto , Farmacorresistencia BacterianaRESUMEN
The process of human parturition involves inflammation at the interface where fetal chorion trophoblast cells interact with maternal decidual stromal (DS) cells and maternal immune cells in the decidua (endometrium of pregnancy). This study tested the hypothesis that inflammation at the chorion-decidua interface (CDI) induces labor by negating the capacity for progesterone (P4) to block labor and that this is mediated by inactivation of P4 in DS cells by aldo-keto reductase family 1 member C1 (AKR1C1). In human, Rhesus macaque, and mouse CDI, AKR1C1 expression increased in association with term and preterm labor. In a human DS cell line and in explant cultures of term human fetal membranes containing the CDI, the prolabor inflammatory cytokine, interleukin-1ß (IL-1ß), and media conditioned by LPS-stimulated macrophages increased AKR1C1 expression and coordinately reduced nuclear P4 levels and P4 responsiveness. Loss of P4 responsiveness was overcome by inhibition of AKR1C1 activity, inhibition of AKR1C1 expression, and bypassing AKR1C1 activity with a P4 analog that is not metabolized by AKR1C1. Increased P4 activity in response to AKR1C1 inhibition was prevented by the P4 receptor antagonist RU486. Pharmacologic inhibition of AKR1C1 activity prevented parturition in a mouse model of inflammation-induced preterm parturition. The data suggest that inflammatory stimuli at the CDI drive labor by inducing AKR1C1-mediated P4 inactivation in DS cells and that inhibiting and/or bypassing of AKR1C1-mediated P4 inactivation is a plausible therapeutic strategy to mitigate the risk of inflammation-associated preterm birth.
Asunto(s)
20-Hidroxiesteroide Deshidrogenasas , Decidua , Inflamación , Macaca mulatta , Parto , Progesterona , Células del Estroma , Femenino , Animales , Progesterona/metabolismo , Progesterona/farmacología , Decidua/metabolismo , Humanos , Ratones , Células del Estroma/metabolismo , Embarazo , Inflamación/metabolismo , 20-Hidroxiesteroide Deshidrogenasas/metabolismo , 20-Hidroxiesteroide Deshidrogenasas/genética , Interleucina-1beta/metabolismo , Corion/metabolismoRESUMEN
BACKGROUND: Optimizing nutrition is essential for recovery after major surgery or severe illness. Feeding tubes (FT) can be placed in patients limited by oral enteral nutrition. Given the myriad of locations in which these procedures are performed (radiology, intensive care unit, and endoscopy suite), routine follow-up is challenging. The purpose of this study was to evaluate the impact of an FT clinic on nutrition. We hypothesized that enrollment in the FT clinic would result in improved nutritional outcomes. METHODS: Retrospective review of Veteran Affairs Medical Center patients with FTs placed from January 2010 to January 2020. Demographics and body mass index (BMI) were recorded. Serum albumin recorded within 1 month of tube placement was compared to within 1 month of tube removal, death, or at the end of the study period. FT clinic participation required at least 2 visits. Indications for FT placement and duration were recorded. Patients were excluded when both BMI and albumin values were incomplete, and if FTs were placed for decompression. RESULTS: Ninety-three patients underwent FT placement during the study period; 5 (5%) were excluded. The average age was 64.8±9.7 years, with the majority being male, 85 patients (97%). Eighteen (20%) patients were seen in the FT clinic (FTC) and 70 (80%) were managed outside of FTC (nFTC). There were no differences in age, gender, or indication for FT. Mean albumin increased 0.42±0.85 g/dL in the FTC group versus -0.07±0.72 g/dL in the nFTC group ( P =0.037). The FTC group BMI increased, 0.38 kg/m 2 vs. -1.48 kg/m 2 in nFTC patients, P =0.041. The FTC patients maintained their tubes longer (36.5 vs. 7.0 mo, P =0.0014). CONCLUSIONS: Patients managed in a dedicated FT clinic experienced an improvement in their serum albumin values and increases in their BMI. In addition, they also maintained their FTs longer. To optimize nutrition and reduce weight loss, patients who require FTs should be enrolled in a dedicated FT clinic.
Asunto(s)
Nutrición Enteral , Humanos , Masculino , Femenino , Nutrición Enteral/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Intubación Gastrointestinal , Estado Nutricional , Índice de Masa CorporalRESUMEN
BACKGROUND: Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. AIMS: To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. METHODS: Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. RESULTS: A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. CONCLUSION: In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.
RESUMEN
Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes. KEY TAKEAWAY/TAKE-HOME MESSAGES: HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.
RESUMEN
Four new studies inform on the multistep path to generate broadly active HIV-1 antibodies.
Asunto(s)
Vacunas contra el SIDA , Anticuerpos ampliamente neutralizantes , Anticuerpos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Vacunas contra el SIDA/inmunología , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Anticuerpos ampliamente neutralizantes/inmunologíaRESUMEN
BACKGROUND: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition. METHODS: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis. RESULTS: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.' CONCLUSIONS: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted.
Asunto(s)
Ejercicio Preoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Cuidados Preoperatorios/métodos , Terminología como AsuntoRESUMEN
OBJECTIVE: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT. METHODS: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis. RESULTS: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively. CONCLUSION: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time.
Asunto(s)
Esclerodermia Difusa , Trasplante Autólogo , Humanos , Femenino , Masculino , Persona de Mediana Edad , Esclerodermia Difusa/terapia , Australia , Adulto , Resultado del Tratamiento , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre , Selección de Paciente , Estudios de Cohortes , Supervivencia sin Progresión , Trasplante de Células Madre HematopoyéticasRESUMEN
Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic Pseudomonas aeruginosa populations are impacted by ETI. We found that pwCF remain infected throughout their upper and lower respiratory tract with their same strain of P. aeruginosa post-ETI, and these strains continue to evolve in response to the newly CFTR-corrected airway. Our work underscores the continued importance of CF airway microbiology in the new era of highly effective CFTR modulator therapy. IMPORTANCE: The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy Elexakaftor/Tezacaftor/Ivacaftor (ETI) has changed cystic fibrosis (CF) disease for many people with cystic fibrosis. While respiratory symptoms are improved by ETI, we found that people with CF remain infected with Pseudomonas aeruginosa. How these persistent and evolving bacterial populations will impact the clinical manifestations of CF in the coming years remains to be seen, but the role and potentially changing face of infection in CF should not be discounted in the era of highly effective modulator therapy.
Asunto(s)
Aminofenoles , Benzodioxoles , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Combinación de Medicamentos , Indoles , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Quinolonas , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/complicaciones , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Aminofenoles/uso terapéutico , Quinolonas/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Benzodioxoles/uso terapéutico , Indoles/uso terapéutico , Pirazoles/uso terapéutico , Pirroles/uso terapéutico , Piridinas/uso terapéutico , Tiofenos/uso terapéutico , Tiofenos/farmacología , Femenino , QuinolinasRESUMEN
BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.
Asunto(s)
Ejercicio Preoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Complicaciones Posoperatorias/prevención & control , Medición de Resultados Informados por el Paciente , Cuidados Preoperatorios/métodos , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Respiratory infection is a major cause of disease severity in people with cystic fibrosis (PwCF). This project aimed to establish the CF community's opinion regarding cross infection (CI), nebuliser hygiene, antimicrobial resistance, personal impact of microbiological findings and the role of the microbiology laboratory. METHODS: A questionnaire was completed anonymously (n = 280; PwCF (n = 128), parents (n = 123); friends/family/carers/charity personnel (n = 29)) from 13 countries. Readability scores (Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL)) were determined for CI/IP&C information from six national CF charities and 21 scientific abstracts. RESULTS: Respondents (72.5%) indicated knowledge of laboratory aspects of CF microbiology was important, however implications of microbiological findings on personal health/well-being were of higher importance (p < 0.0001). Cross infection/infection prevention & control (CI/IP&C) was of highest importance (95.6% respondents) with 27.3% indicating they were not given adequate information, particularly in older respondents (50 y+) (p = 0.006) versus young adults (16-29 y) and respondents from the Middle East versus N. America (p = 0.022) and Europe (p = 0.045). Responses highlighted how CI/IP&C health literacy could be enhanced. Respondents (77.3%), particularly females (p < 0.0001), indicated they would increase the frequency of nebuliser disinfection following guidance on infection risks/best practice, therefore an educational video was prepared. CI/IP&C readability scores (mean ± sd) from CF charities (FRE 52.5 ± 10.8; FKGL 9.7 ± 2.3) were more readable (p < 0.0001) than scientific abstracts (FRE 13.3 ± 11.1; FKGL 16.9 ± 2.3), however not meeting the targets (FRE≥60 and FKGL≤8). CONCLUSION: There is a requirement for further CI/IP&C evidence-based guidance, policies/guidelines, education awareness, best practice in the home environment and multi-modal communication, enabling the CF community to make informed choices on lifestyle behaviours.
RESUMEN
Global climate warming leads to ever-increasing glacier mass loss. Pine Island Glacier in Antarctica is one of the largest contributors to global sea level rise (SLR). One of the biggest uncertainties in the assessment of glacier contribution to SLR at present are subglacial hydrology processes which are less well known than other ice dynamical processes. We use the Glacier Drainage System (GlaDS) model which couples both distributed and channelized components to simulate the basal hydrology of Pine Island Glacier with basal sliding and meltwater production taken from a full-Stokes Elmer/Ice model fitting observed surface velocities. We find ≈100 km long Rothlisberger channels up to 26 m in diameter extending up glacier from the grounding line along the main trunk of Pine Island Glacier delivering 51 m3 s-1 of fresh water to the grounding line. Channelization occurs at high water pressure because of high basal melt rates (maximum of 1 m a-1) caused by high rates of shear heating in regions with fast ice flow (>1000 m a-1). We simulate a shallow "swamp" of 0.8 m water depth where flow transitions from a distributed system into the channels. We performed a set of 38 sensitivity experiments varying sheet and channel conductivity over 4 orders of magnitude. We find a threshold behavior in distributed sheet conductivity above which basal water pressures are unaffected by changing channel conductivities. Our findings suggest a strong need to better understand controls on basal water conductivity through the distributed system. This issue is critical to improve model-based predictive capability for the Pine Island Glacier and, more generally, the Antarctic Ice Sheet.
RESUMEN
INTRODUCTION: Rates of alcohol and illicit substance use are higher among persons with psychotic disorders relative to the general population. The adverse health and psychological effects of substance use behaviors disproportionately impact persons with psychotic disorders. Prior research has shown that persons with psychotic disorders experience increased difficulty in reducing substance use behaviors, and interventions targeting substance use behavior change among this population have demonstrated limited effectiveness. One reason for this is that little is known about the factors that influence substance use and behavior change among this population. To address these disparities, the present study investigated sociodemographic and treatment-related factors of substance use recurrence among persons with psychotic disorders who received substance use treatment services. METHODS: Data came from the 2015-2018 Treatment Episode Dataset-Discharges (TEDS-D). TEDS-D collects annual data on adolescent and adult discharges from state-certified substance use treatment centers in the United States. The study conducted all analyses with a subsample of 1956 adult discharges with a psychotic disorder who received services from an outpatient substance use treatment center for at least one month. χ2 tests of independence and multivariable logistic regression analyses were used to examine associations of sociodemographic and treatment-related characteristics with substance use recurrence while in treatment (α < 0.05 analyses). The study presents results from multivariable logistic regression models as adjusted odds ratios (AORs) with 95 % confidence intervals (CI). RESULTS: Those who were age 50 or older, were referred to treatment by the criminal justice system, and attended substance use self-help groups had lower odds of substance use recurrence while in treatment. Sex, educational attainment, employment status, living situation, type of substance use, and treatment history were not significantly associated with substance use recurrence. CONCLUSIONS: In designing treatment services, providers should consider whether focusing on sociodemographic, including cultural, factors can affect more positive substance use behavior change and other desired treatment outcomes among those with psychotic disorders and comorbid substance misuse. Further study is needed to identify these factors among specific subpopulations of those with psychotic disorders and substance misuse.
Asunto(s)
Trastornos Psicóticos , Trastornos Relacionados con Sustancias , Humanos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia , Trastornos Relacionados con Sustancias/psicología , Masculino , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/terapia , Femenino , Adulto , Adulto Joven , Adolescente , Persona de Mediana Edad , Estados Unidos/epidemiología , Recurrencia , Centros de Tratamiento de Abuso de Sustancias/estadística & datos numéricos , Comorbilidad , Factores Sociodemográficos , Alta del Paciente/estadística & datos numéricosRESUMEN
Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.