A 12-year follow up survey of childhood blindness at schools for the blind in Cambodia.

BACKGROUND: Cambodia is a low-income country in South East Asia with a population of 15.5 million people of whom 4.9 million (38%) are under the age of 16. The causes of childhood blindness in Cambodia have not been investigated since the first survey of schools for the blind done in 2009 by our group. Given the large demographic and economic shifts in Cambodia since 2009 it is important to determine if these causes have changed in order to ensure intervention programmes are appropriately targeted. The purpose of the present study is to investigate the prevalence of causes of childhood blindness at schools for the blind in Cambodia. METHODS: Students between the ages of 5 and 16 years who were attending schools for the blind in Cambodia were examined by a consultant paediatric ophthalmologist and had clinical photographs taken. Distance visual acuity was measured using a logMAR tumbling E chart and the WHO definitions of blindness and severe visual impairment were used. The examining ophthalmologist recorded the anatomical site and aetiology of vision loss using the WHO Prevention of Blindness eye examination record for children. Collected data were compared to a previous survey from 2009. RESULTS: Data from 73 students were included for analysis. The most common anatomical location of abnormality causing vision loss was the cornea (n = 20, 33.9%) followed by the lens and retina (n = 11, 18.64% each). Hereditary factors (n = 29, 49.15%) and childhood diseases (n = 27, 45.76%) were the most common aetiological causes of childhood blindness. The majority (71.19%) of childhood blindness was avoidable. The present study did not demonstrate 0a significant difference in the causes of childhood blindness compared to 2009. CONCLUSIONS: Corneal pathologies continue to represent the most common cause of vision loss amongst the surveyed population and the majority of causes of childhood blindness continue to be avoidable. These findings will facilitate the development of evidence-based targeted interventional programmes in Cambodia.

Cryptococcal endophthalmitis complicated by immune reconstitution inflammatory syndrome in a renal transplant recipient: A case report and review of the literature.

A 59 year old male renal transplant recipient developed endogenous cryptococcal endophthalmitis which was complicated by immune reconstitution inflammatory syndrome (IRIS). Herein we report a novel diagnostic test using lateral flow assay, the management of cryptococcal endophthalmitis and the novel complication of intraocular IRIS in a solid organ transplant recipient.

Salvageable waste associated with intravitreal injections: A local medical waste management approach.

BACKGROUND: Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single-use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age-related macular degeneration and diabetic macular oedema. METHODS: A prospective controlled cohort study was performed over 5 weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real-time sorting of waste occurred. The number of injections given and waste amounts were recorded. RESULTS: 116 and 286 injections were given at Sites A and B, respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared with 175.1 g at our intervention site. This represents a 62.8% reduction (p < 0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8 kg (67.5%) was salvageable. CONCLUSIONS: This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy among other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real-world methodology.

Does selective evaluation of gastric aspirates in preterm infants influence time to full enteral feeding?

The use of routine gastric aspiration in the assessment of feeding intolerance is widespread in neonatal practice. Our article seeks to answer the clinical question, 'In premature infants receiving feeds via nasogastric or orogastric tube [P], does routine evaluation of gastric aspirates [I] compared with selective evaluation of gastric aspirates [C] reduce the time taken to establish full feeds without complications [O]?' Articles were identified through MEDLINE and reference lists from the sources found were reviewed for additional publications. Three papers were critically appraised and National Health and Medical Research Centre grades of level of evidence have been assigned to each. We found limited evidence to either support or reject the practice of routine gastric aspiration in preterm infants. There were no increases in the rates of significant complications in studies underpowered for this outcome. The decision to perform routine or selective gastric aspiration should be determined by individual centres. A large scale randomised controlled trial would be of significant benefit in determining the value of routine gastric aspiration in preterm infants.

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis.

Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N = 7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.

Fast-track surgery for acute appendicitis in children: a systematic review of protocol-based care.

BACKGROUND: 'Fast-track' surgery protocols aim to standardize and rationalize post-operative care, with evidence of safety and efficacy in both uncomplicated and complicated childhood appendicitis. Generalization for broader adoption has been limited by variation in protocol design, including specific antibiotic choice, discharge criteria, post-operative monitoring and patient selection. METHODS: A systematic review of the literature was performed to evaluate the current evidence underpinning fast-track protocols for childhood appendicitis and identify areas of consensus and controversy. RESULTS: About 33 studies met the inclusion criteria, including four prospective observational studies, 20 case-control studies, seven cohort studies and two randomized controlled trials studying uncomplicated (n = 9), complicated (n = 18) and mixed cohorts (n = 6). Reduction in length of hospital stay was almost universally reported, with equivalent or improved complication rates. Key themes of protocols included antibiotic choice and duration, discharge criteria and post-operative laboratory and radiographic testing. Rationalized analgesia is an underexplored aspect of protocol design, and a standardized definition of complicated appendicitis remains elusive. CONCLUSION: Standardized care of childhood appendicitis has been shown to be safe and effective in several local and international centres. Next steps include investigation of a complicated appendicitis protocol that integrates rationalized analgesia in appendicectomy recovery, and development of a consistent classification scheme for complicated disease to aid in identification of amenable cohorts.

Molecular and Cellular Mechanisms for Trapping and Activating Emotional Memories.

Recent findings suggest that memory allocation to specific neurons (i.e., neuronal allocation) in the amygdala is not random, but rather the transcription factor cAMP-response element binding protein (CREB) modulates this process, perhaps by regulating the transcription of channels that control neuronal excitability. Here, optogenetic studies in the mouse lateral amygdala (LA) were used to demonstrate that CREB and neuronal excitability regulate which neurons encode an emotional memory. To test the role of CREB in memory allocation, we overexpressed CREB in the lateral amygdala to recruit the encoding of an auditory-fear conditioning (AFC) memory to a subset of neurons. Then, post-training activation of these neurons with Channelrhodopsin-2 was sufficient to trigger recall of the memory for AFC, suggesting that CREB regulates memory allocation. To test the role of neuronal excitability in memory allocation, we used a step function opsin (SFO) to transiently increase neuronal excitability in a subset of LA neurons during AFC. Post-training activation of these neurons with Volvox Channelrhodopsin-1 was able to trigger recall of that memory. Importantly, our studies show that activation of the SFO did not affect AFC by either increasing anxiety or by strengthening the unconditioned stimulus. Our findings strongly support the hypothesis that CREB regulates memory allocation by modulating neuronal excitability.

Large-Scale Fluorescence Calcium-Imaging Methods for Studies of Long-Term Memory in Behaving Mammals.

During long-term memory formation, cellular and molecular processes reshape how individual neurons respond to specific patterns of synaptic input. It remains poorly understood how such changes impact information processing across networks of mammalian neurons. To observe how networks encode, store, and retrieve information, neuroscientists must track the dynamics of large ensembles of individual cells in behaving animals, over timescales commensurate with long-term memory. Fluorescence Ca(2+)-imaging techniques can monitor hundreds of neurons in behaving mice, opening exciting avenues for studies of learning and memory at the network level. Genetically encoded Ca(2+) indicators allow neurons to be targeted by genetic type or connectivity. Chronic animal preparations permit repeated imaging of neural Ca(2+) dynamics over multiple weeks. Together, these capabilities should enable unprecedented analyses of how ensemble neural codes evolve throughout memory processing and provide new insights into how memories are organized in the brain.

Efficient strategies to find diagnostic test accuracy studies in kidney journals.

AIM: Nephrologists looking for quick answers to diagnostic clinical questions in MEDLINE can use a range of published search strategies or Clinical Query limits to improve the precision of their searches. We aimed to evaluate existing search strategies for finding diagnostic test accuracy studies in nephrology journals. METHODS: We assessed the accuracy of 14 search strategies for retrieving diagnostic test accuracy studies from three nephrology journals indexed in MEDLINE. Two investigators hand searched the same journals to create a reference set of diagnostic test accuracy studies to compare search strategy results against. RESULTS: We identified 103 diagnostic test accuracy studies, accounting for 2.1% of all studies published. The most specific search strategy was the Narrow Clinical Queries limit (sensitivity: 0.20, 95% CI 0.13-0.29; specificity: 0.99, 95% CI 0.99-0.99). Using the Narrow Clinical Queries limit, a searcher would need to screen three (95% CI 2-6) articles to find one diagnostic study. The most sensitive search strategy was van der Weijden 1999 Extended (sensitivity: 0.95; 95% CI 0.89-0.98; specificity 0.55, 95% CI 0.53-0.56) but required a searcher to screen 24 (95% CI 23-26) articles to find one diagnostic study. Bachmann 2002 was the best balanced search strategy, which was sensitive (0.88, 95% CI 0.81-0.94), but also specific (0.74, 95% CI 0.73-0.75), with a number needed to screen of 15 (95% CI 14-17). CONCLUSION: Diagnostic studies are infrequently published in nephrology journals. The addition of a strategy for diagnostic studies to a subject search strategy in MEDLINE may reduce the records needed to screen while preserving adequate search sensitivity for routine clinical use.

Encoding and storage of spatial information in the retrosplenial cortex.

The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information.

Synaptic tagging during memory allocation.

There is now compelling evidence that the allocation of memory to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random and that instead specific mechanisms, such as increases in neuronal excitability and synaptic tagging and capture, determine the exact sites where memories are stored. We propose an integrated view of these processes, such that neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity reflect related aspects of memory allocation mechanisms. Importantly, the properties of these mechanisms suggest a set of rules that profoundly affect how memories are stored and recalled.

Systematic reviews of surgical procedures in children: quantity, coverage and quality.

AIM: Systematic reviews have the potential to map those areas where children are under-represented in surgical research. We aimed to describe and evaluate the quantity, coverage and the quality of conduct and reporting of systematic reviews of surgical procedures in children. METHODS: We searched four biomedical databases, a systematic review register, reference lists and conducted hand searching to identify relevant reviews. Two reviewers worked independently to critically appraise included studies and abstract data. We assessed reporting quality using the preferred reporting items for systematic reviews and meta-analysis statement and methodological quality using the Assessment of Multiple SysTemAtic Reviews tool. RESULTS: Fifteen systematic reviews were identified, representing 0.01% of all paediatric surgical citations in MEDLINE and Embase. Thirteen of the reviews were Cochrane reviews, and most reviews (12/15) addressed subspecialty interests such as otorhinolaryngology. The median number of included trials per systematic review was four (interquartile range 1 to 9.5), the median number of primary outcomes was 5.5 (interquartile range 3.5 to 7.5). In general, reporting and methodological quality was good although there were several omissions, particularly around completeness of reporting of statistical methods used, and utilisation of quality assessments in analyses. Outcomes were often not clearly defined and descriptions of procedures lacked sufficient detail to determine the similarities and differences among surgical procedures within the contributing trials. CONCLUSION: Systematic reviews of surgical procedures in children are rarely published. To improve the evidence base and guide research agendas, more systematic reviews should be conducted, using standard guidelines for conduct and reporting.

Tests for latent tuberculosis in people with ESRD: a systematic review.

BACKGROUND: The relative diagnostic accuracy of interferon γ release assays (IGRAs; based on ELISA [enzyme-linked immunosorbent assay] or ELISPOT [enzyme-linked immunosorbent spot], ie, the QuantiFERON and T-SPOT.TB tests, respectively) and the tuberculin skin test (TST) for latent tuberculosis (TB) infection in people with end-stage kidney disease is uncertain and national guidelines for their use are inconsistent. STUDY DESIGN: Systematic review. SELECTION CRITERIA FOR STUDIES: Evaluated performance of tests for latent TB with clinical risk-factor assessment. SETTING & POPULATION: People with end-stage kidney disease (chronic kidney disease stage 5 [eGFR <15] or kidney transplant recipients). No limits on setting. INDEX TESTS: ELISA- or ELISPOT-based IGRAs, TST, assays to detect antimycobacterial antibodies, and flow cytometry-based tests. OUTCOMES: Odds of test positivity with clinical risk factor for latent TB, expressed as ORs and relative ORs (RORs). RESULTS: 47 studies (6,828 participants) were included, but only 30 studies (4,546 participants) contained sufficient data to contribute to meta-analysis. Studies were predominately in the dialysis population (23/30; 3,700 participants) in countries with low to moderate TB prevalence (0.0-50.0 cases/10(5) persons). BCG vaccination rate was variable (2.7%-100.0%). 9 studies compared IGRAs with the TST directly, 17 studies evaluated the TST only, and the other 4 studies evaluated other tests. Compared to a positive TST result, a positive ELISA-based IGRA result was associated more strongly with radiologic evidence of past TB (ROR, 4.29; 95% CI, 1.83-10.3; P = 0.001) and contact with active TB (ROR, 3.36; 95% CI, 1.61-7.01; P = 0.001). Compared to a negative TST result, a negative ELISA-based IGRA result was associated more strongly with BCG vaccination (ROR, 0.30; 95% CI, 0.14-0.63; P = 0.002). There were insufficient data to compare performance of the ELISPOT-based IGRA with the TST or ELISA-based IGRA. LIMITATIONS: 17 of 47 included studies (36.2%) did not contain sufficient data to contribute to meta-analysis. CONCLUSIONS: Compared to the TST, the ELISA-based IGRA was associated more strongly with risk factors for latent TB in end-stage kidney disease.

Medical device regulation in Australia: safe and effective?

OBJECTIVE: To describe the frequency, characteristics and outcomes of reports of possible harms related to medical devices submitted to the Australian Therapeutic Goods Administration (TGA) using data made publicly available on the TGA website. DESIGN AND SETTING: A retrospective analysis, conducted in January 2012, of data made publicly available on the TGA website from January 2000 to December 2011. MAIN OUTCOME MEASURES: The number and nature of reports of medical device incidents, recalls and alerts. RESULTS: Up to December 2011, 6812 incidents involving medical devices were reported to the TGA, although there were several periods where data were unavailable. Incidents were reported more frequently in later years, most often by device sponsors, and were often attributed to mechanical problems. 295 deaths and 2357 serious injuries have been related to incidents, with serious injury (597) highest in 2009. Most incidents involving medical devices were not investigated (47.5%), or, after investigation, no further action was taken (25.0%). During the same time period, there were 35 medical device recalls and 34 medical device alerts issued by the TGA, with no consistent increase over time. CONCLUSIONS: Despite TGA reform proposals, greater transparency is still needed. Issues that have not been addressed include patchy and conflicting data in the public domain and lack of explanations for the large proportion of uninvestigated reports. To maintain public confidence in the national regulatory system these problems need to be resolved.

Molecular and cellular approaches to memory allocation in neural circuits.

Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention. Recent findings suggest that memory allocation is not random, but rather specific mechanisms regulate where information is stored within a neural circuit. New methods that allow tagging, imaging, activation, and inactivation of neurons in behaving animals promise to revolutionize studies of brain circuits, including memory allocation. Results from these studies are likely to have a considerable impact on computer science, as well as on the understanding of memory and its disorders.