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IMPORTANCE: Fungal endophthalmitis is an uncommon and serious intraocular infection, often with poor outcomes. This study examines the trend in this disease over 20 years, to inform clinician decision-making and optimize patient outcomes. BACKGROUND: Due to infrequent presentation of fungal endophthalmitis, there is limited understanding to formulate a standardized approach to management. DESIGN: A prospective case series over the period January 1, 1999 to December 31, 2018. PARTICIPANTS: Patients with clinically diagnosed fungal endophthalmitis managed at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. METHODS: Review of the Victorian Endophthalmitis Registry for endophthalmitis episode of each patient. MAIN OUTCOME MEASURES: Patient demographics, co-morbidities, visual acuity (VA) at presentation, aetiology, treatment, microbiology results and final VA outcome. RESULTS: Eighty-four cases of fungal endophthalmitis were identified over the study period with a median age of 43.5 years [IQR 30.8-63.0]. Then, 65.5% (n = 55) of patients were male; 81.0% (n = 68) of these cases were secondary to endogenous causes, of which 55.9% were associated with intravenous drug use (IVDU). Among the exogenous causes, penetrating eye injury (56.3%) was the most common aetiological factor. Thirty-nine patients (46.4%) grew Candida species from ocular fluid specimens, all of which were sensitive to fluconazole. CONCLUSION AND RELEVANCE: Our case series provides important insights into fungal endophthalmitis-a high degree of suspicion for fungal endophthalmitis in patients with history of IVDU, and relatively good outlook for vision when Candida is the causative organism. This should allow institutions to implement a standardized management strategy based on evidence.
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Endoftalmitis , Infecciones Fúngicas del Ojo , Adulto , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/epidemiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria , Agudeza Visual , VitrectomíaRESUMEN
IMPORTANCE: This is the largest Gram-negative endophthalmitis specific series and provides important evidence to guide management. BACKGROUND: Endophthalmitis is a sight-threatening emergency. Gram-negative infections are associated with poorer visual outcomes; however, there is limited literature pertaining to this uncommon condition. DESIGN: Prospective case series. PARTICIPANTS: All patients presenting with endophthalmitis to a tertiary institution over a 20-year period. METHODS: Data were collected prospectively and entered into a registry. Patients with microbiological evidence of Gram-negative infection were included in the analysis. MAIN OUTCOMES MEASURES: Final visual acuity (VA), precipitating events, causative organisms, antibiotic sensitivity profiles and risk factors for poor visual outcomes were reported. RESULTS: One hundred Gram-negative organisms were isolated in 97 eyes. Final VA was worse than 6/60 in 65 (67.0%) eyes at follow-up and 29 (29.9%) eyes were eviscerated or enucleated. Microbial keratitis (26.8%, n = 26) and Pseudomonas aeruginosa (34.0%, n = 34) were the most common precipitating event and causative organism, respectively. Eight (8.0%) isolates were third-generation cephalosporin resistant; of which, 7 (88.0%) were sensitive to ciprofloxacin. Preceding microbial keratitis (OR = 13.16, P = .015) or P. aeruginosa infections (OR = 3.40, P = .045) were strongly associated with poorer visual outcomes (worse than 6/60). CONCLUSIONS AND RELEVANCE: Visual outcomes following Gram-negative endophthalmitis are extremely poor, with almost 30% of patients being eviscerated or enucleated. A majority of ceftazidime resistant organisms are sensitive to ciprofloxacin, providing evidence to support the empirical use of quinolones. Clinicians should be mindful that infections secondary to P. aeruginosa or microbial keratitis carry a particularly poor prognosis.
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Endoftalmitis , Infecciones Bacterianas del Ojo , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/epidemiología , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: In Nepal, hypothermia is a major risk factor for newborn survival, but the country's public health care sector has insufficient capacity to improve newborn survival given the burden imposed by distance to health facilities and cost. Low-cost technology to provide newborn thermal care in resource-limited environments exists, but lacks effective distribution channels. This study aims to develop a private sector distribution model for dedicated newborn thermal care technology to ensure equitable access to thermal protection and ultimately improve newborn health in Nepal. METHODS: We conducted a document analysis of newborn health policy in Nepal and a scoping literature review of approaches to newborn hypothermia in the region, followed by qualitative interviews with key stakeholders of newborn health in Nepal. RESULTS: Current solutions addressing newborn hypothermia range from high-technology, high-cost incubators to low-cost behavioral interventions such as skin-to-skin care. However, none of these interventions are currently implemented at scale. A distribution model that provides incentives for community health volunteers and existing public health services in Nepal can deliver existing low-cost infant warmers to disadvantaged mothers where and when needed. Newborn technology can serve as an adjunct to skin-to-skin care and potentially create demand for newborn care practices. CONCLUSION: Harnessing market forces could promote public health by raising awareness of newborn challenges, such as newborn hypothermia, and triggering demand for appropriate health technology and related health promotion behaviors. Market approaches to promoting public health have been somewhat neglected, especially in economically disadvantaged and vulnerable populations, and deserve greater attention in Nepal and other settings with limited public health service delivery capacity.
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Atención a la Salud/organización & administración , Hipotermia/prevención & control , Cuidado del Lactante/instrumentación , Equipo Infantil/provisión & distribución , Sector Privado , Comercio , Política de Salud , Humanos , Recién Nacido , Método Madre-Canguro , Modelos Teóricos , Nepal , Organizaciones , Pobreza , Población RuralAsunto(s)
Desprendimiento de Retina/cirugía , Curvatura de la Esclerótica/métodos , Agudeza Visual , Vitrectomía/métodos , Vitreorretinopatía Proliferativa/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/complicaciones , Vitreorretinopatía Proliferativa/etiología , Adulto JovenRESUMEN
Purpose: Stickler Syndromes are multisystem collagenopathies affecting 1 in 7500-9000 individuals and are associated with craniofacial, ocular, auditory, and musculoskeletal complications. Prophylactic retinopexy treatment reduces the risk of retinal detachment, emphasising the need for early detection and multidisciplinary referral. This study evaluated knowledge and awareness of Stickler Syndromes among allied health professionals and their perceived needs for targeted education to improve multidisciplinary care. Methods: A cross-sectional survey was undertaken among audiologists, speech pathologists, optometrists, orthoptists, and physiotherapists in Australia. Survey questions included practitioner demographics, awareness and knowledge of Stickler Syndromes, confidence managing Stickler Syndromes, and perception of multidisciplinary care needs for Stickler Syndromes. Results: Of 180 healthcare professions who participated (79% female; 78% aged between 25 and 44 years), 55% indicated that they had heard of Stickler Syndrome, and 14% had directly worked with patients known to have Stickler Syndromes. Practitioners who had were either optometrists, orthoptists, or audiologists. The most recognised clinical sign of Stickler Syndromes was retinal detachment (selected by 66% of optometrists and orthoptists and 16% of other professions), but only 41% of optometrists and orthoptists (27% all respondents) selected cryopexy as a potential management strategy. Vitreous anomaly was recognised as a clinical feature by 20% of all respondents. Overall, 69% of allied health professionals did not feel confident managing Stickler Syndromes, and a similar number of practitioners (69%) indicated that they were willing to attend professional development courses for complex conditions such as Stickler Syndromes. Conclusion: This study provides meaningful insights on awareness and knowledge of Stickler Syndromes among allied healthcare professionals. Targeted clinician education, enhanced communication between healthcare entities, and multidisciplinary care programs can significantly improve the integrated care of Stickler Syndromes leading to better patient outcomes.
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Endophthalmitis is an ophthalmological emergency requiring timely and appropriate diagnosis and treatment. Microbiological methods of microscopy (Gram's staining) and culture are the current gold standard for organism identification. However, a significant proportion of endophthalmitis remains culture-negative-perhaps the inflammation is non-infectious in origin, results from a novel organism are unidentifiable or because the causative organism is non-culturable often due to pre-treatment with antibiotics. This review outlines the microbiological profile of endophthalmitis, current clinically used methods for organism identification, and the newer molecular techniques of polymerase chain reaction (PCR) and next-generation sequencing (NGS) technology as diagnostic tools for endophthalmitis. They offer the potential to improve organism identification rates and clinical outcomes in infectious diseases, representing an exciting future direction for organism identification in endophthalmitis. Based on the largest ophthalmic hospital in Australia, we highlight the key practical challenges faced by Australian diagnostic laboratories for their use in a clinical setting.
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Endoftalmitis , Infecciones Bacterianas del Ojo , Humanos , Bacterias/genética , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/etiología , Técnicas Bacteriológicas/métodos , ADN Bacteriano/análisis , Australia , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/complicacionesRESUMEN
Background: Endophthalmitis is an infection of ocular tissues, often with devastating outcomes for vision. Immunomodulation is an emerging avenue for therapeutic intervention in endophthalmitis, with the expression of cytokines central to potential mechanisms. This literature review with a systematic approach characterizes the cytokine expression in both animal and human staphylococcal and streptococcal endophthalmitis. Method and Results: Four online databases were searched for studies profiling cytokine levels in animal models or human populations with staphylococcal and/or streptococcal endophthalmitis. Of the 1,060 articles identified, 14 studies were included in this review comprising eight animal models and six human populations. Mouse, rat, and rabbit models of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae endophthalmitis had elevated levels of IL-1ß, IL-6, IFN-γ, TNF-α, and IL-8, with earlier peaks observed in S. epidermidis infection. Human endophthalmitis demonstrated significantly increased mediator levels compared to controls for a range of pro-inflammatory and anti-inflammatory cytokines, chemokines, and growth factors. Several associations were established between cytokine concentrations and both initial visual acuity and visual prognosis, with no consistent correlations across trials. Conclusions: It may be that virulence factors and the combinations of toll-like receptors activated influence the pathogen-specific visual outcomes observed in endophthalmitis. Furthermore, disease severity and potential therapeutic targets may be dependent on synergistic and compensatory cytokine pathways and the expression of anti-inflammatory mediators. Future research should aim to better characterize the roles of inflammatory mediators and solidify associations between pathogens, inflammation, and endophthalmitis outcomes. This has exciting implications for the prevention and treatment of endophthalmitis in clinical settings.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Endoftalmitis/prevención & control , Oftalmología/estadística & datos numéricos , Complicaciones Posoperatorias/prevención & control , Pautas de la Práctica en Medicina/estadística & datos numéricos , Degeneración Macular Húmeda/tratamiento farmacológico , Endoftalmitis/etiología , Encuestas Epidemiológicas , Humanos , Inyecciones Intravítreas , Ranibizumab , Factores de Riesgo , Encuestas y Cuestionarios , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , VictoriaRESUMEN
Guidelines for the surgical treatment of cutaneous primary malignant melanoma are well established; however, the approach to the treatment of the regional lymph nodes remains more controversial. In many centres, sentinel lymph node biopsy has been adopted as routine in the treatment of malignant melanoma for prognostic purposes, as it is not of proven therapeutic benefit. The Multicentre Selective Lymphadenectomy Trial II aims to determine the comparative benefits of subsequent completion lymphadenectomy versus observation in those found to have a positive sentinel node biopsy. Until results are available, the risks of the procedure must be weighed against the value of prognostic information gained from performing a sentinel node biopsy. In this retrospective analysis of sentinel lymph node biopsies at our institution, we show that in general, short-term morbidity associated with this procedure is low, but that morbidity is higher in a subgroup of people with higher weight or body mass index, and in those whose biopsy is located in the groin.
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Melanoma/patología , Melanoma/cirugía , Biopsia del Ganglio Linfático Centinela/efectos adversos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Anciano , Índice de Masa Corporal , Ensayos Clínicos Fase II como Asunto , Femenino , Ingle/patología , Ingle/cirugía , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidadAsunto(s)
Antibacterianos/administración & dosificación , Extracción de Catarata , Cefazolina/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Endoftalmitis/prevención & control , Complicaciones Posoperatorias/prevención & control , Cámara Anterior/efectos de los fármacos , Australia , Encuestas Epidemiológicas , Humanos , Soluciones Oftálmicas , Oftalmología/estadística & datos numéricos , Encuestas y CuestionariosAsunto(s)
Aerosoles/análisis , COVID-19/epidemiología , SARS-CoV-2 , Vitrectomía , Aire/análisis , Animales , COVID-19/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Fluoresceína/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Humanos , Modelos Animales , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Fotograbar , OvinosRESUMEN
BACKGROUND: Once considered an affliction of people in high-income countries, diabetes mellitus is increasingly seen as a global epidemic. However, for many countries very little is known about the prevalence of diabetes and its complications. This study aims to estimate the prevalence of diabetes, and diabetic retinopathy, in adults in Timor-Leste. METHODS: From March 2013 to May 2014, adult patients being assessed for cataract surgery at the Sentru Matan Nasional (National Eye Centre) in Dili, Timor-Leste had a point-of-care HbA1c measurement performed on the DCA Vantage device (Siemens Ltd) under a quality framework. A diagnostic cut-off of 6.5% (48 mmol/mol) HbA1c was used for diagnosis of diabetes. Ocular examination, blood pressure, demographic and general health data were also collected. Diabetic retinopathy assessment was carried out by ophthalmologists. RESULTS: A total of 283 people [mean age 63.6 years (range 20-90 years)] were tested and examined during the study period. Forty-three people (15.2%) were found to have diabetes, with a mean HbA1c of 9.5% (77 mmol/mol). Of these, 27 (62.9%) were newly diagnosed, with a mean HbA1c of 9.7% (83 mmol/mol) and a range of 6.6-14% (49-130 mmol/mol). Nearly half (48.1%) of people newly diagnosed with diabetes had an HbA1c over 10.0% (86 mmol/mol). Of those with known diabetes, only 68.8% were receiving any treatment. Mean HbA1c for treated patients was 9.9% (85 mmol/mol). Diabetic retinopathy was identified in 18.6% of people with diabetes, of whom half had no previous diagnosis of diabetes. CONCLUSIONS: This study estimates the prevalence of diabetes at 15% in adults in Timor-Leste, a substantial proportion of whom have evidence of diabetic retinopathy. This is consistent with regional estimates. With the majority of patients undiagnosed, and management of people known to have diabetes largely inadequate, point-of-care testing is a valuable tool to assist with diabetes case detection and management. Whilst only a preliminary estimate, our data provides important impetus for further investigation of the prevalence and impact of diabetes in Timor-Leste. It provides guidance that further investment is required in expanding testing, as well as in prevention and treatment.
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Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Diabetes Mellitus/sangre , Retinopatía Diabética/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Prevalencia , Factores de Riesgo , Timor Oriental/epidemiologíaRESUMEN
Cholinergic efferent fibers modify hair cell responses to mechanical stimulation. It is hypothesized that calcium entering the hair cell through a nicotinic receptor activates a small-conductance (SK), calcium-activated potassium channel to hyperpolarize the hair cell. The calcium signal may be amplified by calcium-induced calcium release from the synaptic cisternae. Pharmacological tests of these ideas in the intact cochlea have been technically difficult because of the complex and fragile structure of the mammalian inner ear. We turned to the Xenopus laevis lateral line organ, whose simplicity and accessibility make it a model for understanding hair cell organ function in a relatively intact system. Drugs were applied to the inner surface of the skin while monitoring the effects of efferent stimulation on afferent fiber discharge rate. Efferent effects were blocked by antagonists of SK channels including apamin (EC50 = 0.5 microM) and dequalinium (EC50 = 12 microM). The effect of apamin was not enhanced by co-administration of phenylmethylsulfonyl fluoride, a proteolysis inhibitor. Efferent effects were attenuated by ryanodine, an agent that can interfere with calcium-induced calcium release, although relatively high (mM) concentrations of ryanodine were required. Fluorescent cationic styryl dyes, 4-di-2-asp and fm 1-43, blocked efferent effects, although it was not possible to observe specific entry of the dye into the base of hair cells. These pharmacological findings in the Xenopus lateral line organ support the hypothesis that effects of efferent stimulation are mediated by calcium entry through the nicotinic receptor via activation of SK channels and suggest the generality of this mechanism in meditating cholinergic efferent effects.
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Acetilcolina/farmacología , Células Ciliadas Auditivas/efectos de los fármacos , Neuronas Eferentes/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Animales , Antiinfecciosos Locales/farmacología , Apamina/farmacología , Atropina/farmacología , Calcio/metabolismo , Calcio/farmacología , Decualinio/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Colorantes Fluorescentes/farmacología , Células Ciliadas Auditivas/fisiología , Técnicas In Vitro , Antagonistas Muscarínicos/farmacología , Neuronas Eferentes/fisiología , Fluoruro de Fenilmetilsulfonilo/farmacología , Inhibidores de Proteasas/farmacología , Compuestos de Piridinio/farmacología , Compuestos de Amonio Cuaternario/farmacología , Rianodina/farmacología , Transmisión Sináptica/fisiología , Factores de Tiempo , Xenopus laevisRESUMEN
One feature of neuronal discharge proposed to play a role in coding temporal information is the relative refractory period that follows each action potential. In neurons innervating hair cells, there is an extended refractory period that can last =100 ms. We have taken a pharmacological approach to examine the extended refractory period in the Xenopus lateral line organ. We show that each action potential in the afferent fiber, whether generated spontaneously or through an antidromic electrical pulse, decreases the probability of subsequent afferent discharge for a period of =100 ms. We show that the extended refractory period can be modulated with drugs that alter glutamatergic transmission between the hair cell and the afferent fiber. The extended refractory period can be enhanced by perfusion with agents that reduce synaptic activity. These agents include blockers of voltage-dependent transmitter release, such as cobalt, as well as glutamate receptor antagonists, such as CNQX and kynurenic acid. Conversely, perfusion with agents that increase synaptic activity through activation of the glutamate receptors, such as AMPA or kainate, reduces the magnitude of suppression during the extended refractory period. The extended refractory period is greatly reduced by iberiotoxin and tetraethylammonium (TEA), indicating it may be mediated in large part by a calcium-dependent potassium channel. The ability to modulate the extended refractory period with changes in synaptic input suggests a simple, dynamic mechanism by which strong input (i.e., large or frequent excitatory postsynaptic potentials) can be strengthened and weak inputs weakened.