A Contribution to the Study of Phlyctenular Ophthalmia.

n/

Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration:A whole cell recording study in situ

Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart–brainstem preparation to make whole cell patch clamp recordings from T3–4 SPNs (n = 98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVC(like), 39%) from cutaneous vasoconstrictor-like (CVC(like), 28%) SPNs. The MVC(like) SPNs have higher baseline firing frequencies (2.52 ± 0.33 Hz vs. CVC(like) 1.34 ± 0.17 Hz, P = 0.007). The CVC(like) have longer after-hyperpolarisations (314 ± 36 ms vs. MVC(like) 191 ± 13 ms, P < 0.001) and lower input resistance (346 ± 49  MΩ vs. MVC(like) 496 ± 41 MΩ, P < 0.05). MVC(like) firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVC(like) SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs

Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting

Are specific initiatives required to enhance prescribing of generic atypical antipsychotics in Scotland? International implications

Background National and regional authorities in Scotland have introduced multiple measures to appreciably enhance prescribing efficiency for the proton pump inhibitors (PPIs), statins and renin-angiotensin inhibitor drugs. Generic oral risperidone recently became available in Scotland; however, schizophrenia is a complex disease with advice from respected authorities suggesting that treatment should be individualised. Aims To assess (i) changes in atypical antipsychotic drug (AAP) utilisation and expenditure following the availability of oral generic risperidone in Scotland; (ii) to determine (a) current INN prescribing rates for risperidone following generic availability and (b) decrease in expenditure/DDD for generic risperidone; (iii) to suggest additional measures that could possibly be introduced in Scotland to further enhance prescribing of generic AAPs; and (iv) to provide guidance to NHS Scotland as well as other European authorities on the implications. Methods Retrospective observational study and an interrupted time series design. Results No appreciable change in the utilisation patterns of risperidone pre- and postgeneric availability. Appreciable INN prescribing averaged 93-98% of total oral risperidone. Generic risperidone was 84% below prepatent loss prices by study end, reducing annual expenditure for oral risperidone in 2010 by GB£3.19mn compared with prepatent loss situation. However, overall expenditure on AAPs increased by 42% from 2005 to 2010. Discussion As expected, there was no change in utilisation patterns for risperidone, although potential to influence prescribing patterns. Continued high INN prescribing suggests no problems with generic risperidone in practice. Costs will start to decrease as more AAPs lose their patents (olanzapine and quetiapine). There is the possibility to accelerate this reduction through educational activities. Conclusion There is potential to realise some savings with generic AAPs. However, this is limited by the complexity of the disease area. Any measures introduced must aim at increasing the prescribing of generic AAPs first line in suitable patients. © 2013 Blackwell Publishing Ltd

The economic impacts of foot and mouth disease – What are they, how big are they and where do they occur?

AbstractAlthough a disease of low mortality, the global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animals affected. This impact can be separated into two components: (1) direct losses due to reduced production and changes in herd structure; and (2) indirect losses caused by costs of FMD control, poor access to markets and limited use of improved production technologies. This paper estimates that annual impact of FMD in terms of visible production losses and vaccination in endemic regions alone amount to between US$6.5 and 21 billion. In addition, outbreaks in FMD free countries and zones cause losses of >US$1.5 billion a year.FMD impacts are not the same throughout the world:1.FMD production losses have a big impact on the world's poorest where more people are directly dependent on livestock. FMD reduces herd fertility leading to less efficient herd structures and discourages the use of FMD susceptible, high productivity breeds. Overall the direct losses limit livestock productivity affecting food security.2.In countries with ongoing control programmes, FMD control and management creates large costs. These control programmes are often difficult to discontinue due to risks of new FMD incursion.3.The presence, or even threat, of FMD prevents access to lucrative international markets.4.In FMD free countries outbreaks occur periodically and the costs involved in regaining free status have been enormous.FMD is highly contagious and the actions of one farmer affect the risk of FMD occurring on other holdings; thus sizeable externalities are generated. Control therefore requires coordination within and between countries. These externalities imply that FMD control produces a significant amount of public goods, justifying the need for national and international public investment.Equipping poor countries with the tools needed to control FMD will involve the long term development of state veterinary services that in turn will deliver wider benefits to a nation including the control of other livestock diseases

Hypothermia in a surgical intensive care unit

BACKGROUND: Inadvertent hypothermia is not uncommon in the immediate postoperative period and it is associated with impairment and abnormalities in various organs and systems that can lead to adverse outcomes. The aim of this study was to estimate the prevalence, the predictive factors and outcome of core hypothermia on admission to a surgical ICU. METHODS: All consecutive 185 adult patients who underwent scheduled or emergency noncardiac surgery admitted to a surgical ICU between April and July 2004 were admitted to the study. Tympanic membrane core temperature (Tc) was measured before surgery, on arrival at ICU and every two hours until 6 hours after admission. The following variables were also recorded: age, sex, body weight and height, ASA physical status, type of surgery, magnitude of surgical procedure, anesthesia technique, amount of intravenous fluids administered during anesthesia, use of temperature monitoring and warming techniques, duration of the anesthesia, ICU length of stay, hospital length of stay and SAPS II score. Patients were classified as either hypothermic (Tc ≤ 35°C) or normothermic (Tc> 35°C). Univariate analysis and multiple regression binary logistic with an odds ratio (OR) and its 95% Confidence Interval (95%CI) were used to compare the two groups of patients and assess the relationship between each clinical predictor and hypothermia. Outcome measured as ICU length of stay and mortality was also assessed. RESULTS: Prevalence of hypothermia on ICU admission was 57.8%. In univariate analysis temperature monitoring, use of warming techniques and higher previous body temperature were significant protective factors against core hypothermia. In this analysis independent predictors of hypothermia on admission to ICU were: magnitude of surgery, use of general anesthesia or combined epidural and general anesthesia, total intravenous crystalloids administrated and total packed erythrocytes administrated, anesthesia longer than 3 hours and SAPS II scores. In multiple logistic regression analysis significant predictors of hypothermia on admission to the ICU were magnitude of surgery (OR 3.9, 95% CI, 1.4–10.6, p = 0.008 for major surgery; OR 3.6, 95% CI, 1.5–9.0, p = 0.005 for medium surgery), intravenous administration of crystalloids (in litres) (OR 1.4, 95% CI, 1.1–1.7, p = 0.012) and SAPS score (OR 1.0, 95% CI 1.0–1.7, p = 0.014); higher previous temperature in ward was a significant protective factor (OR 0.3, 95% CI 0.1–0.7, p = 0.003). Hypothermia was neither a risk factor for hospital mortality nor a predictive factor for staying longer in ICU. CONCLUSION: The prevalence of patient hypothermia on ICU arrival was high. Hypothermia at time of admission to the ICU was not an independent factor for mortality or for staying longer in ICU

Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700