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Bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators have demonstrated utility in nuclear medicine. In particular, the 64Cu2+ complexes have been extensively developed for hypoxia imaging and molecular imaging of peptide and protein markers of disease. However, the chemistry and application of bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators in combination with 99mTc, the most widely used radionuclide in nuclear medicine, is underexplored. Herein, a series of bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators were radiolabeled with nitrido-technetium-99m in an optimized one-pot synthesis from [99mTc]TcO4-. Optimization of the radiochemical syntheses allowed for production of the complexes in >90% radiochemical conversion with apparent molar activities of 3.3-5 GBq/µmol. Competition experiments demonstrated the excellent stability of the complexes. The nitrido-technetium-99 complexes were synthesized, and the chemical identities were investigated using mass spectrometry, spectroscopy, and density functional theory calculations. Complexation of nitrido-rhenium(V) was achieved with the N4-dialkylated bis(thiosemicarbazones). Planar imaging and ex vivo biodistribution studies of the five 99mTc complexes were conducted on healthy BALB/c mice to determine in vivo behavior. The lipophilic nature of the complexes resulted in uptake of 1.6-5.7% ID g-1 in the brain at 2 min postinjection and retention of 0.4-1.7% ID g-1 at 15 min postinjection. The stability of the complexes and the biodistribution data demonstrate that these chelators are ideal platforms for future production of radiopharmaceutical candidates.
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Tecnecio , Tiosemicarbazonas , Ratones , Animales , Tecnecio/química , Tiosemicarbazonas/química , Distribución Tisular , Radioisótopos , Radiofármacos/química , Quelantes/químicaRESUMEN
INTRODUCTION: The purpose of this study was to quantitatively evaluate the ramus bone parameters (ramus thickness and ramus depth) for miniscrew placement. An additional aim was to compare and contrast the ramus bone parameters in growing and nongrowing male and female subjects with hyperdivergent, normodivergent, hypodivergent facial types. METHODS: Cone-beam computed tomography scans of 690 subjects were evaluated. They were classified in terms of growth status, gender, and facial type. Ramus thickness was measured as the distance from the outer (buccal) to the inner (lingual) aspects of the mandibular ramus. Ramus depth was measured as the distance from the anterior border of the ramus to the inferior alveolar nerve canal. The measurements for ramus thickness and ramus depth were performed at 3 different levels bilaterally: (1) occlusal plane (OP), (2) 5 mm above the occlusal plane (5OP), and (3) 10 mm above the occlusal plane (10OP). RESULTS: Males showed a significantly higher ramus thickness than females (P <0.05). Ramus thickness decreased significantly (P <0.05) as we moved superior from the level of OP to 5OP and 10OP in all 3 facial types in both females (growing and nongrowing) and males (growing and nongrowing). Growing females and growing males had significantly higher ramus thickness than nongrowing females and nongrowing males, respectively. Ramus depth increased as we moved higher from the OP to 10OP. Hyperdivergent facial type showed a significantly reduced ramus depth compared with hypodivergent and normodivergent facial type in growing and nongrowing males and females at all 3 locations, namely OP, 5OP, and 10OP (P <0.05). CONCLUSIONS: Because of adequate ramus depth and ramus thickness, 5OP was considered the optimal insertion site for the placement of miniscrews. Patients with a hyperdivergent facial type showed significantly reduced ramus depth than hypodivergent and normodivergent facial types. Ramus thickness in males was significantly higher than in females in all facial types.
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Tomografía Computarizada de Haz Cónico , Mandíbula , Tomografía Computarizada de Haz Cónico/métodos , Femenino , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Nervio MandibularRESUMEN
BACKGROUND: Patients from ethnic minority backgrounds are underrepresented in clinical settings. Factors like cost of treatment, poor knowledge of the health system, geographic availability of services, lack of mental health literacy, differences in health beliefs, and social barriers have been identified as reasons for these inequalities. The aim of this study was to identify and compare barriers that parents from different ethnic groups face when accessing specialist services for obsessive-compulsive disorder (OCD) for their children. METHOD: Ten parents from White backgrounds and 10 from ethnic minority backgrounds were recruited from the National and Specialist OCD, BDD, and Related Disorders Clinic for Young People, London, United Kingdom. They were interviewed about their opinions and experiences when accessing treatment. RESULTS: Using thematic analysis, several common barriers for both groups were identified. These included a lack of knowledge of OCD, lack of resources within the health system, previous negative experiences, lack of trust in the mental health system, lack of time and financial issues, no support out of hours, bullying, and inconvenient location of services. In addition, there were several barriers that were endorsed by ethnic minority groups but not by the parents from White backgrounds, namely stigma and discrimination from within their communities, shame and denial, a general lack of trust in the health system by their cultural group, different beliefs about mental health issues, and discrimination from within the system. CONCLUSIONS: Policy-makers and clinicians should be aware of the additional barriers minority patients may face in accessing treatment and should support interventions designed to overcome them.
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PURPOSE: Despite similar prevalence rates across ethnicities, ethnic minorities with obsessive-compulsive disorder (OCD) are under-represented in research and clinical settings. The reasons for this disproportion have been sparsely studied. We explored potential differences in illness perception, help-seeking attitudes, illness knowledge, and causal attributions that could help explain the lower uptake of treatment for OCD amongst ethnic minorities. METHODS: Two-hundred and ninety-three parents (139 White British, 61 Black African, 46 Black Caribbean, and 47 Indian) were recruited from the general population in South-East London, UK. Using a text vignette methodology, participants completed a survey including questions on illness perception, help-seeking attitudes, OCD knowledge, and causal attributions. RESULTS: The groups did not differ in socio-demographic characteristics and family history of OCD. White British parents perceived that the OCD difficulties would have more negative impact on their children and that treatment would be more helpful, compared to the ethnic minorities; the largest differences were observed between White British and Indian parents. Ethnic minorities were more prone to say that would seek help from their religious communities. Black African parents were more in favor of not seeking help for the described difficulties and, in general, perceived more treatment barriers. White British parents seemed to be better informed about OCD than ethnic minority parents. CONCLUSIONS: The results offer some plausible explanations for the large inequalities in access to services amongst ethnic minorities with OCD. Clinicians and policy-makers need to be aware of these socio-cultural factors when designing strategies to encourage help-seeking behaviors in these populations.
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Población Negra/psicología , Conocimientos, Actitudes y Práctica en Salud/etnología , Grupos Minoritarios/psicología , Trastorno Obsesivo Compulsivo/etnología , Población Blanca/psicología , Adulto , Población Negra/estadística & datos numéricos , Región del Caribe/etnología , Femenino , Humanos , Londres , Masculino , Persona de Mediana Edad , Grupos Minoritarios/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Encuestas y Cuestionarios , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVE: We sought to evaluate if the placental alpha-microglobulin (PAMG)-1 test vs the combined traditional diagnostic test (CTDT) of pooling, nitrazine, and ferning would be a cost-beneficial screening strategy in the setting of potential preterm premature rupture of membranes. STUDY DESIGN: A decision analysis model was used to estimate the economic impact of PAMG-1 test vs the CTDT on preterm delivery costs from a societal perspective. Our primary outcome was the annual net cost-benefit per person tested. Baseline probabilities and costs assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2013 US dollars. RESULTS: Annual net benefit from PAMG-1 was $20,014 per person tested, while CTDT had a net benefit of $15,757 per person tested. If the probability of rupture is <38%, PAMG-1 will be cost-beneficial with an annual net benefit of $16,000-37,000 per person tested, while CTDT will have an annual net benefit of $16,000-19,500 per person tested. If the probability of rupture is >38%, CTDT is more cost-beneficial. Monte Carlo simulations of 1 million trials selected PAMG-1 as the optimal strategy with a frequency of 89%, while CTDT was only selected as the optimal strategy with a frequency of 11%. Sensitivity analyses were robust. CONCLUSION: Our cost-benefit analysis provides the economic evidence for the adoption of PAMG-1 in diagnosing preterm premature rupture of membranes in uncertain presentations and when CTDT is equivocal at 34 to <37 weeks' gestation.
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alfa-Globulinas/análisis , Rotura Prematura de Membranas Fetales/diagnóstico , Placenta/química , Análisis Costo-Beneficio , Árboles de Decisión , Técnicas de Diagnóstico Obstétrico y Ginecológico/economía , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: The purpose of this study was to assess the odds of all-cause mortality in individuals with diabetic foot ulceration (DFU) compared with those with diabetes and no history of DFU. In addition, we sought to determine the strength of association of DFU with cardiovascular and nonvascular mortality. METHODS: We obtained data for a cohort of patients who attended a secondary care diabetic foot clinic or a general diabetes clinic between 2009 and 2010. A clinic cohort of patients with diabetes and no history of DFU provided a control group. Cause-specific mortality was recorded during a median follow-up duration of 3.6 years (interquartile range, 3.3-4.2 years). The association between DFU and all-cause mortality was evaluated by Cox regression. The association between DFU and cardiovascular mortality was determined by competing risk modeling. RESULTS: We recorded 145 events of all-cause mortality and 27 events of cardiovascular mortality among 869 patients with diabetes. After adjustment for potential confounders, DFU was associated with both cardiovascular disease (hazard ratio, 2.53; 95% confidence interval, 0.98-6.49; P = .05) and all-cause mortality (hazard ratio, 3.98; 95% confidence interval, 2.55-6.21; P < .001). The proportion of deaths attributable to cardiovascular disease was similar between the groups (18% with diabetes only and 19% with DFU; P = .91). CONCLUSIONS: DFU is associated with premature death from vascular and nonvascular causes.
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Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus/epidemiología , Úlcera del Pie/mortalidad , Medición de Riesgo/métodos , Anciano , Enfermedades Cardiovasculares/complicaciones , Causas de Muerte/tendencias , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Úlcera del Pie/complicaciones , Humanos , Incidencia , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The use of benzodiazepines has been advised against in older people, but prevalence rates remain high. AIMS: To review the evidence for interventions aimed at reducing benzodiazepine use in older people. METHOD: We conducted a systematic review, assessment of risk of bias and meta-analyses of randomised controlled trials of benzodiazepine withdrawal and prescribing interventions. RESULTS: Ten withdrawal and eight prescribing studies met the inclusion criteria. At post-intervention, significantly higher odds of not using benzodiazepines were found with supervised withdrawal with psychotherapy (odds ratio (OR) = 5.06, 95% CI 2.68-9.57, P<0.00001) and withdrawal with prescribing interventions (OR = 1.43, 95% CI 1.02-2.02, P = 0.04) in comparison with the control interventions treatment as usual (TAU), education placebo, withdrawal with or without drug placebo, or psychotherapy alone. Significantly higher odds of not using benzodiazepines were also found for multifaceted prescribing interventions (OR = 1.37, 95% CI 1.10-1.72, P = 0.006) in comparison with control interventions (TAU and prescribing placebo). CONCLUSIONS: Supervised benzodiazepine withdrawal augmented with psychotherapy should be considered in older people, although pragmatic reasons may necessitate consideration of other strategies such as medication review.
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Ansiolíticos/administración & dosificación , Benzodiazepinas/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Abstinencia a Sustancias/prevención & control , Factores de Edad , Anciano , Ansiolíticos/efectos adversos , Benzodiazepinas/efectos adversos , Sesgo , Terapia Combinada/métodos , Esquema de Medicación , Humanos , Oportunidad Relativa , Placebos , Psicoterapia , Análisis de RegresiónRESUMEN
Persistent homicidal ideation (HI), while not common among psychiatric disorders, can occur within multiple diagnoses in the Diagnostic and Statistical Manual of Mental Disorders. There is a growing global and national concern for homicide and homicide-related deaths. In this case report, we discuss refractory homicidal ideation in an 18-year-old male with the diagnoses of autism spectrum disorder (ASD) and schizophrenia and a history of Tourette's syndrome and highlight the interplay of comorbidities and challenges in effective management and treatment.
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Natural killer (NK) cells can kill cancer cells via antibody-dependent cell-mediated cytotoxicity (ADCC): a tumor-associated IgG antibody binds to the Fcγ receptor CD16 on NK cells via the antibody Fc region and activates the cytotoxic functions of the NK cell. Here, we used PET imaging to assess NK cell migration to human epidermal growth factor receptor 2 (HER2)-positive HCC1954 breast tumors, examining the influence of HER2-targeted trastuzumab antibody treatment on NK cell tumor accumulation. Methods: Human NK cells from healthy donors were expanded ex vivo and labeled with [89Zr]Zr-oxine. In vitro experiments compared the phenotypic markers, viability, proliferation, migration, degranulation, and ADCC behaviors of both labeled (89Zr-NK) and unlabeled NK cells. Female mice bearing orthotopic human breast HCC1954 tumors were administered 89Zr-NK cells alongside trastuzumab treatment or a sham treatment and then scanned using PET/CT imaging over 7 d. Flow cytometry and γ-counting were used to analyze the presence of 89Zr-NK cells in liver and spleen tissues. Results: 89Zr cell radiolabeling yields measured 42.2% ± 8.0%. At an average specific activity of 16.7 ± 4.7 kBq/106 cells, 89Zr-NK cells retained phenotypic and functional characteristics including CD56 and CD16 expression, viability, migration, degranulation, and ADCC capabilities. In vivo PET/CT studies indicated predominant accumulation of 89Zr-NK cells in the liver and spleen. Ex vivo analyses of liver and spleen tissues indicated that the administered human 89Zr-NK cells retained their radioactivity in vivo and that 89Zr did not transfer to cells of murine soft tissues, thus validating this 89Zr PET method for NK cell tracking. Notably, 89Zr-NK cells migrated to HER2-positive tumors, both with and without trastuzumab treatment. Trastuzumab treatment was associated with an increased 89Zr-NK cell signal at days 1 and 3 after injection. Conclusion: In vitro, 89Zr-NK cells maintained key cellular and cytotoxic functions. In vivo, 89Zr-NK cells trafficked to HER2-postive tumors, with trastuzumab treatment correlating with enhanced 89Zr-NK infiltration. This study demonstrates the feasibility of using PET to image 89Zr-NK cell infiltration into solid tumors.
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Células Asesinas Naturales , Radioisótopos , Trastuzumab , Circonio , Células Asesinas Naturales/inmunología , Circonio/química , Animales , Ratones , Humanos , Femenino , Línea Celular Tumoral , Trastuzumab/farmacología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptor ErbB-2/metabolismo , Tomografía de Emisión de Positrones , Marcaje Isotópico , Movimiento Celular/efectos de los fármacos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapiaRESUMEN
INTRODUCTION: Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long-acting (LA) regimen recommended for maintaining HIV-1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation-effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months. METHODS: Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm-S) or enhanced arm (Arm-E). Arm-S included video injection training and provider/patient toolkits. Additionally, Arm-E included skilled wrap-around team meetings, face-to-face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi-structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1-5 Likert scale ranging from 1 = "completely disagree" to 5 = "completely agree"). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed. RESULTS: Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation- and intervention-based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections. CONCLUSIONS: CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible. GOV NUMBER: NCT04399551.
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Fármacos Anti-VIH , Infecciones por VIH , Piridonas , Rilpivirina , Humanos , Rilpivirina/uso terapéutico , Rilpivirina/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Europa (Continente) , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Piridonas/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , DicetopiperazinasRESUMEN
Burkholderia pseudomallei is the etiological agent of human melioidosis, a disease with a broad spectrum of clinical manifestations ranging from fatal septicemia to chronic localized infection or asymptomatic latent infection. Most clinical and immunological studies to date have focused on the acute disease process; however, little is known about pathology and immune response in chronic melioidosis. Here, we have developed a murine model of chronic disease by challenging C57BL/6 mice intranasally with a low dose of B. pseudomallei and monitoring them up to 100 days postinfection. Bacterial burdens were heterogeneous in different animals at all time points, consistent with the spectrum of clinical severity observed in humans. Proinflammatory cytokines such as gamma interferon (IFN-γ), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were induced during chronic infection, and histopathological analysis showed features in common with human melioidosis. Interestingly, many of these features were similar to those induced by Mycobacterium tuberculosis in humans, such as development of a collagen cord that encapsulates the lesions, the presence of multinucleated giant cells, and granulomas with a caseous necrotic center, which may explain why chronic melioidosis is often misdiagnosed as tuberculosis. Our model now provides a relevant and practical tool to define the immunological features of chronic melioidosis and aid in the development of more effective treatment of this disease in humans.
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Burkholderia pseudomallei/patogenicidad , Modelos Animales de Enfermedad , Melioidosis/etiología , Melioidosis/patología , Administración Intranasal , Animales , Quimiocina CCL2/metabolismo , Quimiocinas/metabolismo , Enfermedad Crónica , Colágeno/metabolismo , Citocinas/metabolismo , Femenino , Células Gigantes/patología , Granuloma/etiología , Granuloma/patología , Humanos , Técnicas para Inmunoenzimas , Interferón gamma/metabolismo , Interleucina-6/metabolismo , Melioidosis/metabolismo , Ratones , Ratones Endogámicos C57BL , NecrosisRESUMEN
The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of Southeast Asia and a potential bioterrorism threat. We have used susceptible BALB/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. Intranasal vaccination with live attenuated B. pseudomallei increased survival and induced interferon-γ-secreting T cells in the lung. Intranasal delivery of CpG oligodeoxynucleotides also provided significant protection; however, combining preexposure vaccination with CpG treatment at the time of infection or up to 18 hours after infection, provided significantly greater protection than either treatment alone. This combination prolonged survival, decreased bacterial loads by >1000-fold, and delayed the onset of sepsis. This novel approach may be applicable to other potential biodefense agents for which existing countermeasures are not fully effective.
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Adyuvantes Inmunológicos/farmacología , Vacunas Bacterianas/inmunología , Armas Biológicas , Melioidosis/prevención & control , Oligodesoxirribonucleótidos/farmacología , Animales , Burkholderia pseudomallei , Islas de CpG/inmunología , Femenino , Pulmón/microbiología , Melioidosis/tratamiento farmacológico , Melioidosis/microbiología , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/inmunología , Linfocitos T/fisiologíaRESUMEN
Regular chronic kidney disease (CKD) screening can facilitate earlier diagnosis of CKD and preventative action to reduce the risk of CKD progression. People with type 2 diabetes are at a higher risk of developing CKD; hence, it is recommended that they undergo annual screening. However, resources may be limited, particularly in lower-to-middle income countries, and those at the highest risk of having an abnormal CKD screening result should be prioritised for screening. We have developed models to determine which patients are at a high risk of renal impairment. We have shown that, for people with type 2 diabetes and no previous diagnosis of CKD stage 3-5, it is possible to use age, gender, body mass index, duration of type 2 diabetes and blood pressure information to detect those at a higher risk of a reduced glomerular filtration rate. When blood measurements are available, triglyceride and cholesterol measurements can be used to improve the estimate of the risk. Even though risk factors were associated with an increased urine albumin:creatinine ratio, we found no clinical benefit of using the model over a screen-all approach.
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The care of the individual with diabetic foot disease (DFD) represents a significant challenge. In addition to the primary foot pathology, individuals with DFD are frequently compromised by multiple co-existent medical complications. Successful management of DFD, therefore requires simultaneous addressal of these issues alongside high-quality foot care. We explore the pharmacological treatments in DFD with an emphasis on the emerging putative technologies centred on addressing the pathobiology of wound healing but also discuss developments in infection control, Charcot neuroarthropathy, cardiovascular and diabetes care. Many of these will have a significant impact on future treatment paradigms and how we amalgamate these novel technologies may help shape the standard of care in DFD hereafter. However, there is a need for better quality of evidence and cost-effectiveness data prior to widespread adoption into routine care is considered.
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Diabetes Mellitus , Pie Diabético , Pie Diabético/tratamiento farmacológico , Humanos , Cicatrización de HeridasRESUMEN
BACKGROUND: This economic evaluation and literature review was conducted with the primary aim to compare the cost-effectiveness of laparoscopic assisted supracervical hysterectomy (LASH) with NICE's gold-standard treatment of Levonorgestrel-releasing intrauterine system (LNG-IUS) for menorrhagia. MATERIALS AND METHODS: A cost-utility analysis was conducted from an NHS perspective, using data from two European studies to compare the treatments. Individual costs and benefits were assessed within one year of having the intervention. An Incremental Cost-Effectiveness Ratio (ICER) was calculated, followed by sensitivity analysis. Expected Quality Adjusted Life Years (QALYS) and costs to the NHS were calculated alongside health net benefits (HNB) and monetary net benefits (MNB). RESULTS: A QALY gain of 0.069 was seen in use of LNG-IUS compared to LASH. This yielded a MNB between -£44.99 and -£734.99, alongside a HNB between -0.0705 QALYs and -0.106 QALYS. Using a £20,000-£30,000/QALY limit outlined by NICE,this showed the LNG-IUS to be more cost-effective than LASH, with LASH exceeding the upper bound of the £30,000/QALY limit. Sensitivity analysis lowered the ICER below the given threshold. CONCLUSIONS: The ICER demonstrates it would not be cost-effective to replace the current gold-standard LNG-IUS with LASH, when treating menorrhagia in the UK. The ICER's proximity to the threshold and its high sensitivity alludes to the necessity for further research to generate a more reliable cost-effectiveness estimate. However, LASH could be considered as a first line treatment option in women with no desire to have children.
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Histerectomía/economía , Dispositivos Intrauterinos/economía , Levonorgestrel/normas , Menorragia/cirugía , Análisis Costo-Beneficio/métodos , Análisis Costo-Beneficio/estadística & datos numéricos , Femenino , Humanos , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Dispositivos Intrauterinos/estadística & datos numéricos , Laparoscopía/economía , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Levonorgestrel/economía , Levonorgestrel/farmacología , Menorragia/economía , Calidad de Vida/psicología , Años de Vida Ajustados por Calidad de Vida , Medicina Estatal/organización & administración , Medicina Estatal/estadística & datos numéricosRESUMEN
PURPOSE: The distribution and vaccination of COVID-19 vaccines to billions of people worldwide will likely be one of the biggest public health undertakings in history. There has been a large focus on identifying processes to safely, efficiently, and effectively vaccinate large populations. We aimed to describe the development and operationalization of a drive-in COVID-19 vaccine site in a parking garage adjacent to outpatient clinics at University of Florida (UF) Health Physicians and how it was informed by the roll-out of SARS-CoV-2 testing and administration of respiratory vaccinations. DESIGN/METHODOLOGY/APPROACH: A technical description and analysis of a drive-in COVID-19 vaccine site. FINDINGS: We incrementally increased the number of vaccines performed per day from 300 in the first 2 weeks to 700 an additional 2 weeks later. By the end of January, we completed nearly 14 000 vaccinations. At this capacity, we estimate the site could performed 5000 vaccinations per week. PRACTICAL IMPLICATIONS: This manuscript provides step-by-step guidance how to develop, operationalize, and implement a sustainable drive-in COVID-19 vaccination site. ORIGINALITY/VALUE: To our knowledge, this is the first description of a drive-in approach to COVID-19 vaccination. Our findings can help inform other health entities as they develop or expand vaccination efforts that may serve as a template for other sites to adapt.
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Condiloma Acuminado/epidemiología , Errores Diagnósticos , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Vacunas contra Papillomavirus/inmunología , Vacunación/estadística & datos numéricos , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/prevención & control , Humanos , Vacunas contra Papillomavirus/administración & dosificación , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Treatment-resistant schizophrenia (TRS) is a major cause of disability. Clozapine is currently the only antipsychotic medication licensed for its treatment. However, the rate of treatment resistance among outpatients with schizophrenia or other psychoses, and the rate of use of clozapine among them, is not known. AIMS: The aims of this study are (a) to determine the point prevalence of treatment-resistant psychosis in a community sample, and (b) to determine the number of patients with TRS who have never had a clozapine trial. METHOD: Clinico-demographic data were extracted from the case notes for 202 patients from two community mental-health teams. RESULTS: We found that 56% (99/176) had a diagnosis of TRS, and 52% (51/99) of these patients had never been treated with clozapine. Patients of non-white ethnicity were less likely to have had a clozapine trial (p=0.009). The point prevalence of treatment resistance within the bipolar affective disorder sample was 19% (5/26). CONCLUSION: These findings suggest that TRS is common in the community mental-health team, and a large proportion of these patients have not received clozapine. These findings indicate that identifying and treating treatment resistance should be a focus of community services for schizophrenia.
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Antipsicóticos/uso terapéutico , Trastorno Bipolar , Clozapina/uso terapéutico , Trastornos Psicóticos , Esquizofrenia , Adulto , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Femenino , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/epidemiología , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiologíaRESUMEN
In this study, we show that invisible flicker adaptation reduces the perceived duration of a subsequently viewed stimulus in control subjects, but not in dyslexics. Dyslexics, like controls, show apparent duration compression after 20Hz flicker and show normal shifts in apparent temporal frequency after adaptation. However a subgroup of the test group, scoring low on both a test of phonological skill (spoonerisms) and a test of literacy (NART), show an apparent temporal expansion after 5Hz flicker adaptation, a finding not previously seen in controls. Recent studies have linked genes conferring susceptibility to a cluster of language and sensory deficits to anomalous neural migration, providing a tentative biological basis for dyslexia. However it has proved difficult to establish a clear link between sensory deficits and impaired reading. The results presented here point to an abnormal adaptation response within the early precortical stages of the magnocellular pathway, occurring in tandem with a deficit in word-level cognitive processing, providing psychophysical evidence for anomalous cortico-thalamic circuits in dyslexia.