Community consultation in emergency neurotrauma research: results from a pre-protocol survey.

BACKGROUND: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of an acute subdural haematoma (ASDH). In 2011, a collaborative group of neurosurgeons, neuro-intensive care physicians and trial methodologists was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of DC, in comparison to simple craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multi-centre, pragmatic, parallel group randomised trial of DC versus simple craniotomy for adult head-injured patients with an ASDH. Clinical trials in the emergency setting face the problem that potential participants may be incapacitated and their next of kin initially unavailable. As a result, consent and enrolment of participants can often be difficult. METHOD: In the current study, we aimed to assess public opinion regarding participation in the RESCUE-ASDH trial and acceptability of surrogate consent by conducting a pre-protocol community consultation survey. RESULTS: One hundred and seventy-one subjects completed the survey. Eighty-four percent of participants responded positively when asked if they would participate in the proposed trial. Ninety-six percent and 91 % answered positively when asked if they found surrogate consent by their next of kin and an independent doctor acceptable, respectively. None of the characteristics of the study population were found to affect the decision to participate or the acceptability of surrogate consent by the next of kin. Being religious showed a trend towards higher acceptability of surrogate consent by a doctor. Conversely, an education to degree level and above showed a trend towards reduced acceptability of surrogate consent by a doctor. CONCLUSIONS: Our community consultation survey shows that the proposed trial is acceptable to the public. In addition, the results suggest high levels of acceptability of surrogate consent by next of kin or independent doctor amongst our community.

Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

Comparison between pulse waveform analysis and thermodilution cardiac output determination in patients with severe pre-eclampsia.

BACKGROUND: This study compared cardiac output (CO) measurements derived from pulse waveform analysis with values obtained by thermodilution (TD), in patients with post-partum complications of severe pre-eclampsia. METHODS: Eighteen patients were recruited, 24-96 h post-delivery. After central venous calibration of the pulse waveform analysis monitor (LiDCOplus), CO readings were compared with those obtained by the TD method and repeated twice at 15 min intervals. The comparison was repeated after peripheral venous calibration. Further comparisons were made in eight patients at 120 and 240 min after peripheral venous calibration. RESULTS: Data were pooled for measurements at 0, 15, and 30 min after calibration. For the comparison between TD and LiDCOplus using central venous calibration, TD exhibited a significant positive bias of 0.58 litre min⁻¹ [95% confidence interval (CI): 0.77 to 0.39]. After peripheral venous calibration, there was no significant bias [0.16 litre min⁻¹ (95% CI: -0.37 to 0.06)]. The estimated limits of agreement for central and peripheral venous calibrations were -2.12 to 0.96 and -1.50 to 1.20 litre min⁻¹, respectively. When comparing LiDCOplus and TD, there was no time-based effect at 120 or 240 min post-peripheral calibration. CONCLUSIONS: Central and peripheral venous calibrations of the LiDCOplus monitor were associated with clinically insignificant bias when compared with TD. Limits of agreement were within the recommendation of 30% for acceptance of a new CO technique when compared with current reference methods. This form of minimally invasive CO monitoring may have a valuable role in obstetric critical care.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

The Critical Care Society of Southern Africa guidelines on the allocation of scarce critical care resources during the COVID-19 public health emergency in South Africa.

Letter by Gopalan et al. on article by Singh and Moodley (Singh JA, Moodley K. Critical care triaging in the shadow of COVID-19: Ethics considerations. S Afr Med J 2020;110(5):355-359. https://doi.org/10.7196/SAMJ.2020.v110i5.14778); and response by Singh and Moodley.

Evidence for validity of a national physician and patient-reported, cross-sectional survey in China and UK: the Disease Specific Programme.

OBJECTIVE: Diabetes represents a significant challenge for Chinese healthcare providers. Healthcare decision-making is generally based on many data sources, including randomised controlled and real-world studies; however, good-quality data from Chinese diabetes patients are scarce. We performed an initial validation to assess the representativeness of one source of real-world data-the Diabetes Adelphi Disease Specific Programme (DSP) in China. SETTING: China, UK. PARTICIPANTS: The Chinese DSP included 2060 patients with previously diagnosed type 2 diabetes mellitus (T2DM) sampled by 200 physicians. The reference Chinese population comprised 238 639 patients with previously diagnosed T2DM. The UK DSP contained 1481 patients with T2DM sampled by 125 physicians; the reference UK population comprised 289 patients with diabetes. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was comparison of unweighted China DSP and reference data for sex, body mass index (BMI), blood pressure (BP), patients achieving glycosylated haemoglobin (HbA1c)<7%, total cholesterol, coronary heart disease and dyslipidaemia. The secondary outcome was comparison of weighted UK DSP and reference data for BMI, BP, mean HbA1c, total cholesterol, smoking and insulin status. RESULTS: Comparison of unweighted China DSP and reference data revealed statistical equivalence for BMI, systolic BP, proportion of patients achieving HbA1c <7%, total cholesterol, coronary heart disease and dyslipidaemia. Sex, age, diabetes duration, diastolic BP and mean HbA1c level were not equivalent, although differences were generally small. Weighting of data did not substantially affect the results. A similar pattern was observed for UK data. CONCLUSIONS: This study provides evidence that the methodology used for the China and UK parts of the Diabetes DSP produces representative samples that are comparable with other independent sources of patient treatment outcomes data, which may ultimately inform public health decision-making. Although this method could be used in other countries, the current validation applies to UK and China. Further research is required for other countries.

Luteinizing hormone secretion and corticotropin-releasing factor gene expression in the paraventricular nucleus of rhesus monkeys following cortisol synthesis inhibition.

Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulating LH secretion in primates. This was accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7) following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls while increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axis. In a second experiment, metyrapone was infused for 10 h before collecting serial blood samples every 15 min for 6 h. Although this protocol produced a sustained increase in ACTH, no apparent effect on pulsatile LH secretion compared with saline controls was observed. Mean LH (+/- SEM) levels calculated for consecutive 2-h increments were 87.6 +/- 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8 (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/- 5.8, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA levels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy between CRF and cortisol, the LH response to insulin-induced hypoglycemia was contrasted in saline and metyrapone pretreated monkeys. LH concentrations were reduced to approximately 40% of basal levels following insulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH secretion in rhesus monkeys, presumably due in part to increased neuroendocrine CRF secretion, LH secretion was not inhibited during either the acute or more chronic phase of corticotroph activation. Absence of LH inhibition was not due to low cortisol concentrations resulting from metyrapone because metyrapone did not prevent hypoglycemia-induced suppression of LH secretion. We conclude that increased neuroendocrine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discussed.

Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients.

Antihypertensive drugs slow the progressive decline in renal function seen in patients with insulin-dependent diabetes and nephropathy. In a recent study, the ACE inhibitor captopril protected against this deterioration in renal function. We developed an economic model to analyse the cost impact of ACE inhibitor treatment on progression to endstage renal failure (ESRF) in diabetic patients over 4 years. Two scenarios were compared: one describing the progression of a cohort of 1000 patients receiving 25 mg captopril three times daily, and the other for an equivalent cohort without such prophylactic treatment. Previously published data were used to estimate the transition rates for each stage from the onset of renal failure until death. All direct costs were discounted by an annual rate of 6%, and were subjected to sensitivity analysis. The discounted cost saving of ACE inhibitor treatment for a cohort of 1000 patients was estimated as 0.95 million pounds over 4 years. Under sensitivity analysis, these results were very robust to variations in the costs of ESRF treatment. Prophylactic treatment with ACE inhibitors was predicted to provide substantial increases in life expectancy and reduction in the incidence of ESRF, while also providing significant economic savings.

An economic analysis of the Survival and Ventricular Enlargement (SAVE) Study. Application to the United Kingdom.

Recent studies have shown that ACE inhibitors reduce morbidity and mortality after myocardial infarction (MI). While these trials have obvious clinical implications, the widespread introduction of a new treatment for a condition as common as MI also has clear cost implications. The results of the post-MI studies with ACE inhibitors suggest that restricted use of treatment-in high-risk patients-is likely to be most cost effective, whereas treatment of all MI survivors, many of whom are at low risk, will be least cost effective. An approach somewhere in between may maximise clinical benefit at an acceptable cost. Economic analysis may help in deciding how these drugs might be best used after MI. We have conducted a cost-effectiveness and cost-utility analysis of the Survival and Ventricular Enlargement (SAVE) study, which reported the benefit of ACE inhibitors in intermediate-risk patients. Assuming all MI survivors require measurement of left ventricular function before selection for treatment (the approach used in the SAVE study), the incremental cost per life-year gained (LYG), over 4 years, using prophylactic captopril is approximately 10000 pounds sterling (Pounds) [1994 to 1995 values]. The cost per quality-adjusted life-year (QALY) is similar. These incremental cost per LYG and cost per QALY ratios compare favourably with other commonly used symptomatic and prophylactic treatments, and argue for extending post-MI use of ACE inhibitors to intermediate-as well as high-risk patients.

Physiological noise and its influence on vibrotactile perception thresholds.

Vibration of physiological origin (physiological noise) was studied when a small diameter probe, attached to a vibrator and accelerometer for the determination of vibrotactile perception thresholds, was held in contact with a fingertip. The acceleration spectrum consisted of a broad plateau between 0.1 and 10 Hz, where the power spectral density was about -20 dB re 1 (m/s2)2/Hz, and it fell rapidly with increasing frequency above 10 Hz. Substantial contributions from respiration (0.2-1 Hz), blood circulation (1-5 Hz), and hand tremor (6-8 Hz) could be identified. The physiological noise was largely independent of subject, contact force, and probe diameter, and it was approximately equal in amplitude to the threshold of the vibrotactile perception. Current knowledge of the masking and adaptation of vibrotactile signals indicates that vibrotactile thresholds in the frequency range 2-250 Hz may be influenced by the magnitude of this physiological noise under some conditions of flesh stimulation.

Assessing the severity of the neurological component of the hand-arm vibration syndrome.

In view of the observation in epidemiologic studies that the neurological component of the hand-arm vibration syndrome develops first, a conservative measure of the presence and progression of the syndrome may be obtained from the degree of numbness and loss of fine touch. Degraded tactile spatial resolution, as measured by step and gap detection with an esthesiometer, has been found, on the average, in stages 2 and 3 of the Taylor-Pelmear classification for vibration-induced white finger (VWF). Present evidence suggests that this occurrence is due to the degeneration of slowly adapting (type I) and, possibly, fast adapting (type I) mechanoreceptors, and/or their nerve fibers. The apparatus commonly employed for measuring vibrotactile perception thresholds in clinical studies records the sensitivity of fast adapting type II mechanoreceptors (pacinian corpuscles), which play no role in step or gap detection. They may, however, provide early evidence of neurological changes occurring in the syndrome, as a significant degradation in the threshold of fast adapting type II receptors appears to develop, on the average, before stage 2 of VWF.

Assessment of impaired tactile sensation. A pilot study.

Three methods are compared for assessing impaired tactile sensation in vibration-exposed workers: a medical examination including traditional neurological tests and refined measures of vibrotactile perception and gap detection. Of 18 subjects only 12 were judged free of confounding factors--five forestry workers exposed to chain-saw vibration, aged 28 (SD 5) years, and seven laboratory workers not exposed to vibration, aged 36 (SD 7) years. Each method identified the same subject as suffering the most from tactile impairment, but they differed in their ranking of the severity of sensory changes. The ranking by gap detection and vibrotactile perception at low frequencies was the most consistent [Spearman rank correlation coefficient (r) = 0.90]. The clinical results, when staged according to the neurological component of vibration-induced white finger, ranked the thresholds for gap detection and low-frequency vibrotactile perception equally well (r = 0.70). In contrast, the Taylor-Pelmear staging of the clinical results poorly represented the ranking of tactile thresholds recorded for these workers (r = 0.00 and -0.20, respectively). It also appeared that improved techniques for measuring vibrotactile and gap perception thresholds can detect sensory changes in the fingers not consistently found by conventional clinical tests.

Nosocomial respiratory syncytial virus infection in neonatal units in the United Kingdom.

Nosocomial Respiratory Syncytial Virus infections are frequently reported and tend to be more severe, because of comorbidity, such reports, however, are frequently from a single centre. The incidence and outcomes of nosocomial Respiratory Syncytial Virus infection in UK neonatal units over a five year period were estimated by interrogating the Capse Health Care Knowledge Systems database, which contains anonymised details of 55% of UK hospital admissions. A total of 79,642 admissions commenced on the infants' date of birth and contained an ICD-10 code for low birth weight or immaturity. Thirty-seven of the 79,642 admissions also contained a Respiratory Syncytial Virus code. Two (5.4%) with Respiratory Syncytial Virus and 2,736 (3.4%) without Respiratory Syncytial Virus died. Survivors with Respiratory Syncytial Virus codes experienced significantly increased length of stay. In the extreme immaturity sub-group the length of stay was 117.5 days with Respiratory Syncytial Virus and 51.3 days without Respiratory Syncytial Virus (p = 0.0002). In the low birth weight or other preterm sub-group the length of stay with Respiratory Syncytial Virus was 69.2 and without Respiratory Syncytial Virus 14.7 days (p < 0.0001). The observed low rate for nosocomial Respiratory Syncytial Virus (0.46/1000 admissions) should be regarded as a minimum. The increased length of stay in infants with Respiratory Syncytial Virus infection emphasises that units should have guidelines to prevent and deal with Respiratory Syncytial Virus outbreaks.