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Objective: Measures of the impact of vasomotor symptoms (VMS) have been used as outcomes in clinical trials but have not been compared. This study compares the Hot Flush Rating Scale (HFRS), the Hot Flash Related Daily Interference Scale (HFRDIS), and the shorter Hot Flash Interference (HFI) scale. Methods: Baseline data were taken from two studies including healthy women (menopause transition or postmenopause) and breast cancer patients experiencing VMS. Participants completed questionnaires on sociodemographics, the HFRS, the HFRDIS, the HFI, the Work and Social Adjustment Scale (WSAS), on depression (Generalized Anxiety Disorder 7), on anxiety (Patient Health Questionnaire 9), and on use of medical services. Results: A total of 169 women (129 with history of breast cancer and 40 without) aged 54.47 (standard deviation [SD] = 9.11) years took part. They had an average of 66 (SD = 40.94) VMS per week, with a mean HFRS problem-rating of 6.53 (SD = 1.99), HFRDIS score of 5.36 (SD = 2.22), and HFI score of 6.13 (SD = 2.30). The HFRS problem-rating, HFRDIS, and HFI were significantly associated (r = 0.61-0.85), had good internal reliability (α = 0.76-0.91), and had significant concurrent validity with mood, the WSAS, and use of medical services. VMS frequency was not associated with mood, the WSAS, or use of medical services. Conclusion: The HFRS problem-rating scale and the HFI are two brief, three-item measures that measure a similar concept of VMS interference/impact, with evidence of reliability and validity.
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Sofocos/diagnóstico , Menopausia , Índice de Severidad de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Anger and aggression among adults with intellectual disability (ID) are associated with a range of adverse consequences for their well-being and that of their family or staff carers. The aims were to evaluate the effectiveness of an anger management intervention for adults with mild to moderate ID and to evaluate the costs of the intervention and its impact on health and social care resource use. This paper is concerned with the latter aim. METHODS: A cluster-randomised controlled trial was conducted involving day services for adults with ID in Scotland, England and Wales. Incremental costs of delivering the intervention and its impact on subsequent total health and social care package costs were calculated. Full data comparing costs between baseline and follow-up 10 months later were collected for 67 participants in the intervention arm and 62 participants in the control arm. Cost differences between the groups at follow-up, adjusted for baseline levels, were calculated using non-parametric bootstrapping controlling for clustering. RESULTS: The mean hourly excess cost of intervention over treatment as usual was £12.34. A mean adjusted cost difference of £22.46 per person per week in favour of the intervention group was found but this was not statistically significant. CONCLUSIONS: The baseline-adjusted cost difference at follow-up would result in a fairly immediate compensation for the excess costs of intervention, provided the difference is not a statistical artefact. Further research is needed to clarify the extent to which it might represent a real saving in service support costs.
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Ira/fisiología , Terapia Cognitivo-Conductual/economía , Servicios de Salud/economía , Discapacidad Intelectual/economía , Discapacidad Intelectual/terapia , Adulto , Inglaterra , Femenino , Estudios de Seguimiento , Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Escocia , GalesRESUMEN
Based primarily on evidence from rodent models fasting is currently believed to improve metabolic health via activation of the AMPK-PGC-1α axis in skeletal muscle. However, it is unclear whether the skeletal muscle AMPK-PGC-1α axis is activated by fasting in humans. The current systematic review examined the fasting response in skeletal muscle from 34 selected studies (7 human, 21 mouse, and 6 rat). From these studies, we gathered 38 unique data points related to AMPK and 47 related to PGC-1α. In human studies, fasting mediated activation of the AMPK-PGC-1α axis is largely absent. Although evidence does support fasting-induced activation of the AMPK-PGC-1α axis in rodent skeletal muscle, the evidence is less robust than anticipated. Our findings question the ability of fasting to activate the AMPK-PGC-1α axis in human skeletal muscle and suggest that the metabolic benefits of fasting in humans are associated with caloric restriction rather than the induction of mitochondrial biogenesis. Registration: https://doi.org/10.17605/OSF.IO/KWNQY.
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Proteínas Quinasas Activadas por AMP , Factores de Transcripción , Humanos , Ratas , Ratones , Animales , Factores de Transcripción/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Roedores/metabolismo , Músculo Esquelético/metabolismo , Ayuno , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
BACKGROUND: TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. METHODS: We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden communities. Prevalent infection was defined as QuantiFERON™-TB Gold Plus (QFT-Plus) positivity as assessed at baseline. Subsequent conversion to QFT-Plus positivity was measured 3 years later among those QFT-Plus-negative at baseline. Multivariable logistic regression models examined factors associated with TB infection. RESULTS: QuantiFERON-positivity at baseline (prevalence: 22.6%, 95% CI 20.9-24.4), was independently associated with increasing age (aOR 1.24 per additional year, 95% CI 1.15-1.34) and household exposure to TB during the participant's lifetime (aOR 1.87, 95% CI 1.46-2.40). QFT-Plus conversion at year 3 (12.2%, 95% CI 10.5-14.0; annual infection rate: 3.95%) was associated with household exposure to an index TB case (aOR 2.74, 95% CI 1.05-7.18). CONCLUSION: Rates of QFT-diagnosed TB infection remain high in this population. The strong association with household TB exposure reinforces the importance of contact tracing, preventative treatment and early treatment of infectious disease to reduce community transmission.
CONTEXTE: La lutte contre la TB nécessite la compréhension et la perturbation de la transmission de la TB. Nous décrivons la prévalence, l'incidence et les facteurs de risque associés à l'infection tuberculeuse infantile au Cap, en Afrique du Sud. MÉTHODES: Nous rapportons des données transversales de référence et d'incidence prospective provenant d'un vaste essai mené auprès d'enfants d'écoles primaires vivant dans des communautés à forte charge de morbidité tuberculeuse. La prévalence de l'infection a été définie comme la positivité au QuantiFERON™-TB Gold Plus (QFT-Plus) telle qu'évaluée au départ. La conversion subséquente en QFT-Plus positif a été mesurée 3 ans plus tard chez les QFT-Plus négatifs au départ. Des modèles de régression logistique multivariée ont examiné les facteurs associés à l'infection tuberculeuse. RÉSULTATS: La positivité QuantiFERON-au départ (prévalence : 22,6%, IC à 95% 20,924,4), était indépendamment associée à l'augmentation de l'âge (aOR 1,24 par année supplémentaire, IC à 95% 1,151,34) et à l'exposition du ménage à la TB au cours de la vie du participant (aOR 1,87 ; IC à 95% 1,462,40). La conversion QFT-Plus à l'année 3 (12,2%, IC à 95% 10,514,0 ; taux d'infection annuel : 3,95%) était associée à l'exposition du ménage à un cas de tuberculose index (aOR 2,74 ; IC à 95% 1,057,18). CONCLUSION: Les taux d'infection tuberculeuse diagnostiquée par QFT restent élevés dans cette population. La forte association avec l'exposition à la TB dans les ménages renforce l'importance de la recherche des contacts, du traitement préventif et du traitement précoce des maladies infectieuses pour réduire la transmission communautaire.
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BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
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Tuberculosis Meníngea , Adolescente , Niño , Humanos , Tuberculosis Meníngea/tratamiento farmacológico , Nivel de Atención , Técnica Delphi , Guías de Práctica Clínica como AsuntoRESUMEN
European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.
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Antibacterianos/uso terapéutico , Tos/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedad Aguda , Adulto , Amoxicilina/uso terapéutico , Cefalosporinas/uso terapéutico , Ciprofloxacina/uso terapéutico , Farmacorresistencia Bacteriana , Europa (Continente) , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Prospectivos , Tetraciclina/uso terapéuticoRESUMEN
We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.
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Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Esputo/efectos de los fármacos , Enfermedad Aguda , Adulto , Tos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud/métodos , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.
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Anticestodos/administración & dosificación , Encefalopatías/diagnóstico , COVID-19 , Equinococosis/diagnóstico , Albendazol/administración & dosificación , Encefalopatías/tratamiento farmacológico , Encefalopatías/parasitología , Niño , Diagnóstico Tardío , Equinococosis/tratamiento farmacológico , Femenino , Humanos , Hipertensión Intracraneal/parasitología , Praziquantel/administración & dosificación , Convulsiones/parasitología , Sudáfrica , Tomografía Computarizada por Rayos XRESUMEN
Little is known about actual clinical practice regarding management of smokers compared with ex-smokers and nonsmokers presenting with acute cough in primary care, and whether a lower threshold for prescribing antibiotics benefits smokers. This was a multicentre 13-country European prospective observational study of primary care clinician management of acute cough in consecutive immunocompetent adults presenting with an acute cough of Asunto(s)
Antibacterianos/uso terapéutico
, Pautas de la Práctica en Medicina/estadística & datos numéricos
, Atención Primaria de Salud/estadística & datos numéricos
, Infecciones del Sistema Respiratorio/tratamiento farmacológico
, Infecciones del Sistema Respiratorio/epidemiología
, Fumar/epidemiología
, Enfermedad Aguda
, Adulto
, Anciano
, Actitud del Personal de Salud
, Tos/tratamiento farmacológico
, Tos/epidemiología
, Prescripciones de Medicamentos/estadística & datos numéricos
, Femenino
, Humanos
, Modelos Logísticos
, Masculino
, Persona de Mediana Edad
, Índice de Severidad de la Enfermedad
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The stimulatory effect of elevated [CO2 ] (e[CO2 ]) on crop production in future climates is likely to be cancelled out by predicted increases in average temperatures. This effect may become stronger through more frequent and severe heat waves, which are predicted to increase in most climate change scenarios. Whilst the growth and yield response of some legumes grown under the interactive effect of e[CO2 ] and heat waves has been studied, little is known about how N2 fixation and overall N metabolism is affected by this combination. To address these knowledge gaps, two lentil genotypes were grown under ambient [CO2 ] (a[CO2 ], ~400 µmol·mol-1 ) and e[CO2 ] (~550 µmol·mol-1 ) in the Australian Grains Free Air CO2 Enrichment facility and exposed to a simulated heat wave (3-day periods of high temperatures ~40 °C) at flat pod stage. Nodulation and concentrations of water-soluble carbohydrates (WSC), total free amino acids, N and N2 fixation were assessed following the imposition of the heat wave until crop maturity. Elevated [CO2 ] stimulated N2 fixation so that total N2 fixation in e[CO2 ]-grown plants was always higher than in a[CO2 ], non-stressed control plants. Heat wave triggered a significant decrease in active nodules and WSC concentrations, but e[CO2 ] had the opposite effect. Leaf N remobilization and grain N improved under interaction of e[CO2 ] and heat wave. These results suggested that larger WSC pools and nodulation under e[CO2 ] can support post-heat wave recovery of N2 fixation. Elevated [CO2 ]-induced accelerated leaf N remobilisation might contribute to restore grain N concentration following a heat wave.
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Dióxido de Carbono , Calor , Lens (Planta) , Fijación del Nitrógeno , Nitrógeno , Australia , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacología , Ambiente , Lens (Planta)/efectos de los fármacos , Lens (Planta)/crecimiento & desarrollo , Lens (Planta)/metabolismo , Nitrógeno/metabolismoRESUMEN
Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Pirimidinas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Fármacos Anti-VIH/toxicidad , Células Cultivadas , Cuello del Útero/virología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Luciferasas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/virología , Técnicas de Cultivo de Órganos , Pirimidinas/toxicidad , Inhibidores de la Transcriptasa Inversa/toxicidad , Linfocitos T/efectos de los fármacos , Linfocitos T/virologíaRESUMEN
OBJECTIVE: To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged Asunto(s)
Seropositividad para VIH
, Tuberculosis Bovina/epidemiología
, Animales
, Vacuna BCG/efectos adversos
, Bovinos
, Comorbilidad
, Humanos
, Lactante
, Transmisión Vertical de Enfermedad Infecciosa
, Mycobacterium bovis
, Vigilancia de la Población
, Estudios Prospectivos
, Sudáfrica/epidemiología
, Tuberculosis Bovina/transmisión
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PURPOSE OF REVIEW: To provide an update on the patterns of HIV drug resistance in children, including pretreatment drug resistance (PDR) and acquired drug resistance (ADR), focusing on children in low- and middle-income countries (LMICs) for whom empiric first-line (FL) and second-line (SL) antiretroviral regimens are usually recommended. RECENT FINDINGS: High levels of PDR, particularly to non-nucleoside reverse transcriptase inhibitors (NNRTIs), and poor treatment outcomes on NNRTI-based FL antiretroviral therapy (ART) have been widely reported among infants and young children. There is a paucity of recent data on the use of protease inhibitor (PI)-based FL and SL regimens in children, but studies have reported poor tolerability, adherence problems and the development of PI resistance. Limited access to virological monitoring and HIV drug resistance testing contributes to delays in identifying treatment failure due to ADR and delays in switching to SL regimens in children. Implementation of FL ART regimens that have a higher barrier to developing resistance and are safe and well tolerated is required in order to attain global treatment targets. Although PI-based regimens may be effective as FL or SL treatment in children, lack of appropriate formulations leading to poor tolerability, drug-drug interactions, and cost considerations have negatively impacted their use among children in LMICs. There is hope that dolutegravir-based regimens recommended for children by the World Health Organization will be widely implemented once child-friendly formulations are available, and dosing and safety studies currently underway are completed, and that this will significantly improve treatment outcomes.
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BACKGROUND: There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. OBJECTIVE: To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens. METHODS: This was a retrospective review of treatment-experienced children receiving a DRV/r-, RAL- or ETR-containing regimen as recommended by a paediatric expert review committee, based on HIV drug resistance testing. RESULTS: Thirty-five children of median age 8.8 years (interquartile range (IQR) 5.5 - 11) who had received ART for a median of 6.9 years (IQR 5 - 9.9) and started a DRV/r-, RAL- or ETR-containing regimen were included. Before starting such a regimen, the median CD4+ lymphocyte count and HIV-1 RNA level were 405.5 cells/µL (IQR 251.5 - 541) and 28 314 copies/mL (IQR 5 595.5 - 120 186.5) (log 4.5 (IQR 3.7 - 5)), respectively, in 24 subjects with available results. After a median of 2 years (IQR 1.3 - 4) on treatment, 29/30 (96.7%) and 23/30 (76.7%) subjects with available results had HIV-1 RNA levels of <400 and <50 copies/mL, respectively. CONCLUSIONS: This study found DRV/r-, RAL- and ETR-containing regimens to be effective in a group of treatment-experienced children and adolescents with multidrug-resistant HIV. Although the treatment regimens in this study were individualised based on HIV genotyping results, further research evaluating the safety and efficacy of standardised third-line treatment regimens in children of all ages is needed.
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Fissure sealant (FS) and fluoride varnish (FV) are effective in preventing dental caries when compared with a no-treatment control. However, the relative clinical effectiveness of these interventions is uncertain. The objective of the study was to compare the clinical effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- to 7-y-olds. The study design was a randomized clinical trial, with 2 parallel arms. The setting was a targeted-population program that used mobile dental clinics in schools located within areas of high social and economic deprivation in South Wales. A total of 1,016 children were randomized 1:1 to receive either FS or FV. Resin-based FS was applied to caries-free FPMs and maintained at 6-mo intervals. FV was applied at baseline and at 6-mo intervals for 3 y. The main outcome measures were the proportion of children developing caries into dentine (D4-6MFT) on any 1 of up to 4 treated FPMs after 36 mo. At 36 mo, 835 (82%) children remained: 417 in the FS arm and 418 in the FV arm. A smaller proportion of children who received FV ( n = 73, 17.5%) versus FS ( n = 82, 19.6%) developed caries into dentine on at least 1 FPM (odds ratio [OR] = 0.84; 95% CI, 0.59 to 1.21; P = 0.35), a nonstatistically significant difference between FS and FV treatments. The results were similar when the number of newly decayed teeth (OR = 0.86; 95% CI, 0.60 to 1.22) and tooth surfaces (OR = 0.85; 95% CI, 0.59 to 1.21) were examined. In a community oral health program, semiannual application of FV resulted in caries prevention that was not significantly different from that obtained by applying and maintaining FS after 36 mo (EudraCT: 2010-023476-23; ISRCTN: ISRCTN17029222).
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Cariostáticos/uso terapéutico , Atención Dental para Niños/organización & administración , Caries Dental/prevención & control , Fluoruros Tópicos/uso terapéutico , Selladores de Fosas y Fisuras/uso terapéutico , Niño , Femenino , Promoción de la Salud , Humanos , Masculino , Resultado del Tratamiento , GalesRESUMEN
OBJECTIVES: The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial. MATERIALS AND METHODS: The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus. RESULTS: Full or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained. CONCLUSIONS: There is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection.Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O'Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347-352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1.
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Concern and general awareness about the impacts of climate change in all sectors of the social-ecological-economic system is growing as a result of improved climate science products and information, as well as increased media coverage of the apparent manifestations of the phenomenon in our society. However, scales of climate variability and change, in space and time, are often confused and so attribution of impacts on various sectors, including the health sector, can be misunderstood and misrepresented. In this review, we assess the mechanistic links between climate and infectious diseases in particular, and consider how this relationship varies, and may vary according to different time scales, especially for aetiologically climate-linked diseases. While climate varies in the medium (inter-annual) time frame, this variability itself may be oscillating and/or trending on cyclical and long-term (climate change) scales because of regional and global scale climate phenomena such as the El-Nino southern oscillation coupled with global-warming drivers of climate change. As several studies have shown, quantifying and modelling these linkages and associations at appropriate time and space scales is both necessary and increasingly feasible with improved climate science products and better epidemiological data. The application of this approach is considered for South Africa, and the need for a more concerted effort in this regard is supported.
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Amino acids derived from ingested protein are potential substrates for gluconeogenesis. However, several laboratories have reported that protein ingestion does not result in an increase in the circulating glucose concentration in people with or without type 2 diabetes. The reason for this has remained unclear. In people without diabetes it seems to be due to less glucose being produced and entering the circulation than the calculated theoretical amount. Therefore, we were interested in determining whether this also was the case in people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes were given, in random sequence, 50 g protein in the form of very lean beef or only water at 0800 h and studied over the subsequent 8 h. Protein ingestion resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids; and a modest increase in respiratory quotient. The total amount of protein deaminated and the amino groups incorporated into urea was calculated to be approximately 20-23 g. The net amount of glucose estimated to be produced, based on the quantity of amino acids deaminated, was approximately 11-13 g. However, the amount of glucose appearing in the circulation was only approximately 2 g. The peripheral plasma glucose concentration decreased by approximately 1 mM after ingestion of either protein or water, confirming that ingested protein does not result in a net increase in glucose concentration, and results in only a modest increase in the rate of glucose disappearance.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Proteínas en la Dieta/administración & dosificación , Adulto , Anciano , Animales , Péptido C/sangre , Bovinos , Ritmo Circadiano , Ingestión de Líquidos , Ácidos Grasos no Esterificados/sangre , Glucagón/sangre , Humanos , Insulina/sangre , Masculino , Carne , Persona de Mediana Edad , Triglicéridos/sangre , Ácido Úrico/sangreRESUMEN
A range of skeletal abnormalities are evident in mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) including short stature and dysostosis multiplex, resulting from a deficiency in the lysosomal hydrolase N-acetylgalactosamine-4-sulphatase (4S). In this article, bone pathology was assessed in a feline model of MPS VI to evaluate the efficacy of enzyme replacement therapy (ERT) as a treatment modality for this genetic disorder. Osteopenia is clearly evident in MPS VI animals, with bone mineral volume (BV/TV) falling well below that of normal animals (4.39% vs. 20.11%, respectively). Trabecular bone architecture was also affected in MPS VI with fewer, thinner, and more widely spaced trabeculae apparent. Bone formation rate (BFR/BS) was also lower in MPS VI animals than controls (0.0011 mm3/mm2 per day vs. 0.008 mm3/mm2 per day, respectively). Vertebral and tibial bone length in MPS VI animals progressively fell behind normal values with increasing age, as did cortical bone thickness. Vertebral body shape was also altered. ERT with recombinant human 4S (rh4S) resulted in a vertebral BV/TV of 8.23% in animals treated with an intravenous enzyme dose of 1 mg/kg and a BV/TV of 14.33% in animals treated with a dose of 5 mg/kg. BFR/BS also increased to 0.0034 mm3/mm2 per day in animals treated with enzyme doses of either 1.0 or 5.0 mg/kg rh4S. All other affected histomorphometric parameters also improved with ERT to a level intermediate between MPS VI untreated animals and normals. However, individual animals treated with 0.2 mg/kg rh4S intravenously or 1.0 mg/kg rh4S administered subcutaneously did not exhibit an improvement over untreated MPS VI animals. Vertebral and tibial bone lengths, tibial cortical bone thickness, and vertebral body shape also responded to ERT, with a trend away from the untreated group. Thus, ERT had a positive effect on bone development in MPS VI animals that was dependent upon the dose of enzyme administered and the route of administration.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Condro-4-Sulfatasa/uso terapéutico , Mucopolisacaridosis VI/tratamiento farmacológico , Animales , Densidad Ósea/fisiología , Desarrollo Óseo/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/fisiopatología , Gatos , Modelos Animales de Enfermedad , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/patología , Microscopía Electrónica , Mucopolisacaridosis VI/fisiopatología , Osteoblastos/efectos de los fármacos , Osteoblastos/ultraestructura , Osteocitos/efectos de los fármacos , Osteocitos/ultraestructura , Proteínas Recombinantes/farmacologíaRESUMEN
BACKGROUND: Anger is a frequent problem for many people with intellectual disabilities, and is often expressed as verbal and/or physical aggression. Cognitive-behaviour therapy (CBT) is the treatment of choice for common mental health problems, but CBT has only recently been adapted for people with intellectual disabilities. Anger is the main psychological presentation in which controlled trials have been used to evaluate CBT interventions for people with intellectual disabilities but these do not include rigorous randomised studies. OBJECTIVES: To evaluate (1) the impact of a staff-delivered manualised CBT anger management intervention on (a) reported anger among people with mild to moderate intellectual disabilities, and (b) anger coping skills, aggression, mental health, quality of life and costs of health and social care; (2) factors that influence outcome; and (3) the experience of service users, lay therapists and service managers. DESIGN: A cluster randomised controlled trial based on 30 day centres (15 intervention and 15 control). Intention-to-treat comparisons of outcomes used a two-level linear regression model to allow for clustering within centres with baseline outcome levels as a covariate. Comparison of cost data used non-parametric bootstrapping. Qualitative analysis used interpretative phenomenological analysis and thematic analysis. SETTING: Recruited day centres had four-plus service users with problem anger who were prepared to participate, two-plus staff willing to be lay therapists, a supportive manager and facilities for group work, and no current anger interventions. PARTICIPANTS: A total of 212 service users with problem anger were recruited. Thirty-three were deemed ineligible (30 could not complete assessments and three withdrew before randomisation). Retention at follow-up was 81%, with 17 withdrawals in each arm. Two to four staff per centre were recruited as lay therapists. Eleven service users, nine lay therapists and eight managers were interviewed. INTERVENTIONS: The manualised intervention comprised 12 weekly 2-hour group sessions supplemented by 'homework'. Lay therapists received training and ongoing supervision from a clinical psychologist. Treatment fidelity, group attendance and resources used in intervention delivery were monitored. MAIN OUTCOME MEASURES: The primary outcome was the service user-rated Provocation Index (PI), a measure of response to hypothetical situations that may provoke anger. Secondary trial outcomes were the key worker-rated PI; the service user- and key worker-rated Profile of Anger Coping Skills (PACS); the service user-rated PACS imaginal provocation test (PACS-IPT), a measure of response to actual situations known to provoke anger; aggression; mental health; self-esteem; quality of life; and health and social care resource use. Assessments were administered before randomisation and at 16 weeks and 10 months after randomisation. RESULTS: Fourteen treatment groups were delivered, each with 12 sessions lasting an average of 114 minutes, with a mean of 4.9 service users and 2.0 lay therapists. The mean hourly cost per service user was £ 25.26. The mean hourly excess cost over treatment as usual was £ 12.34. There was no effect of intervention on the primary outcome - self-rated PI. There was a significant impact on the following secondary outcomes at the 10-month follow-up: key worker-rated PI, self-rated PACS-IPT and self- and key worker-rated PACS. Key workers and home carers reported significantly lower aggression at 16 weeks, but not at 10 months. There was no impact on mental health, self-esteem, quality of life or total cost of health and social care. Service users, key workers and service managers were uniformly positive. CONCLUSIONS: The intervention was effective at changing anger coping skills and staff-rated anger. Impact on self-rated anger was equivocal. With hindsight there are reasons, from an analysis of factors influencing outcomes, to think that self-rated PI was not a well-chosen primary outcome. Widespread implementation of manualised lay therapist-led but psychologist-supervised anger management CBT for people with mild to moderate intellectual disabilities is recommended.