A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Artificial light at night (ALAN) disrupts behavioural patterns of reef corals.

Increasing levels of Artificial Light At Night (ALAN) alter the natural diel cycles of organisms at global scale. ALAN constitutes a potential threat to the light-dependent functioning of symbiotic scleractinian corals, the habit-founders of warm, shallow water reefs. Here, we show that ALAN disrupts the natural diel tentacle expansion and contraction behaviour, a key mechanism for prey capture and nutrient acquisition in corals. We exposed four symbiotic scleractinian coral species to different ALAN treatments (0.4-2.5 µmol quanta m-2 s-1). Exposure to ALAN levels of 1.2 µmol quanta m-2 s-1 and above altered the normal tentacle expansion response in diurnal species (Stylophora pistillata and Duncanopsammia axifuga). The tentacle expansion pattern of nocturnal species (Montastraea cavernosa and Lobophyllia hemprichii) was less affected, which may indicate a greater capacity to tolerate ALAN exposure. The results of this work suggest that ALAN has the potential to affect nutrient acquisition mechanisms of symbiotic corals which may in turn result in changes in the coral community structure in shallow water reefs in ALAN-exposed areas.

Systemic biomarkers currently implicated in the formation of abdominal wall hernia: A systematic review of the literature.

BACKGROUND: Surgery to the abdominal wall is ubiquitous worldwide and hernia treatment is challenging and expensive, posing a critical need to tailor treatment to individual patient risk-factors. In this systematic review, we consider specific systemic factors with potential as biomarkers of hernia formation. METHODS: A healthcare database-assisted search, following PRISMA guidelines, identified journal articles for inclusion and analysis. RESULTS: 14 biomarker studies were selected, comparing hernia patients and hernia-free controls, focusing on markers of extracellular matrix (ECM) remodelling and collagen turnover. Matrix metalloproteinase-2 was increased in patients with inguinal hernia. Markers of type IV collagen synthesis were increased in patients with abdominal wall hernia; while markers of fibrillar collagen synthesis were reduced. Additional other ECM signalling proteins differ significantly within published studies. CONCLUSION: We identify a lack of high-quality evidence of systemic biomarkers in tailoring treatment strategies relative to patient-specific risks, but recognise the potential held within biomarker-based diagnostic studies to improve management of hernia pathogeneses.

Risk factors for undescended testis.

The hypothesis that undescended testis is caused by an excess of maternal oestrogen in pregnancy has been tested indirectly in a case-control study comparing mothers of boys with undescended testis (83) and mothers of normal boys (129) born on the same day. The study concentrated on the gestation of the boys, but also investigated the mother's previous obstetric history and postnatal events in the boys. The hypothesis predicted that there should be an excess of nausea, vomiting and hypertension in mothers of cases, but in fact the pregnancies of the case and control mothers were similar in all respects except one. The exception was the increased liability of the mothers of cases to threatened abortion. Mothers of cases also had an increased tendency to miscarry in previous conceptions, a reduced number of deliberate terminations and evidence of decreased fertility. An alternative hypothesis is suggested which would explain these findings. This is that placental function is impaired in the gestation of affected boys and the secretion of human chorionic gonadotrophin is reduced. This leads to changes in fetal testicular function and possible maldescent. Those born with undescended testis were more likely to present to a general practitioner with illness in the first three years after birth and this difference was mainly due to asthma, eczema, jaundice and feeding difficulties.

Detection of depression and facilitation of quantal electromyographic responses in man.

Quantal EMG responses in human muscles and methods of evoking and recording them are described briefly. Techniques and statistical tests for the analysis of quantal H-reflexes are derived from probit analysis: to give a precise estimate of reflex threshold; to characterize the responding motoneurones; to assess threshold shift. With these techniques, the precision of the threshold estimate is usually better than +/- 2%. A probability profile and its associated cumulative sum chart are constructed from quantal response data to assess the latency and time course of conditioned changes in response probability. The application of these techniques is illustrated using recordings from recent experiments in man.

Intermittent transmission in the reciprocal inhibitory pathway from flexor muscle Ia afferents to extensor motoneurons in man.

Variations in soleus reflex EMG following single conditioning stimuli to tibialis anterior Ia afferents were quantified in man by means of a simple index of inhibition. Probability of test reflex depression was greatly increased at conditioning-testing intervals of 1-4 ms, although the magnitude of depression was small. These findings are consistent with the existence of intermittent but functionally effective Ia reciprocal inhibitory transmission onto soleus motoneurons.

Definition of human reflex excitability by statistical analysis of quantal EMG responses.

A precise method has been devised to estimate soleus motoneurone pool excitability by probit analysis of quantal (all-or-none) reflex EMG responses to critical electrical stimulation. The technique is shown to be sensitive to changes induced by weak excitatory or inhibitory inputs and is likely to be useful in the study of monosynaptic proprioceptive reflexes.

Determination of excitability in human proprioceptive reflexes: analysis and characteristics of EMG thresholds of postural muscle.

In order to derive indirect indices of reflex excitability, human soleus (Sol) H reflex and direct M response threshold intensities (HT, MT) were determined by probit analysis of quantal responses elicited in the surface electromyogram (EMG). Within sessions, HT and MT co-varied with respect to time along a logarithmic time-course, both attaining effectively stable levels after 40-60 min of recording. The pattern of this co-variation was imposed by non-reflex factors, primarily the electrode system employed. Sampling distributions of stable thresholds were positively skewed (median values: HT, 5.20 mA, MT, 6.83 mA), and concurrently determined values were strongly correlated (r = 0.965). The Sol threshold ratio (HT/MT) was largely unaffected by non-reflex factors and was therefore stable within subjects, both within sessions (with respect to time) and between sessions. This ratio was normally distributed (mean = 0.753 +/- 0.079 S.D.). Criteria of indirect indices of reflex excitability are proposed: HT satisfies the criteria applicable to a relative index. However, the characteristics of the threshold ratio permit its use as a powerful absolute index of proprioceptive reflex excitability.

Reciprocal inhibition of proprioceptive reflexes in man revealed by a threshold shift technique.

Variations in soleus H-reflex threshold following single conditioning stimuli to tibialis anterior afferents were studied in man by probit analysis of quantal electromyographic responses. The H-reflex threshold was elevated in 6 out of 7 subjects (conditioning-test interval, 2 ms) when conditioning strengths were greater than about 0.70 X tibialis anterior motor threshold: the degree of elevation was exponentially related to conditioning strength. Analysis of response variability indicated that in some cases weaker conditioning was also effective. These findings are consistent with the view that reciprocal inhibition effectively modulates the threshold, rather than the amplitude, of proprioceptive reflex discharge.

Undescended testis and hormone levels in early pregnancy.

A case-control study was carried out on mothers of boys with undescended testis to investigate the hypotheses that raised maternal levels of oestrogen or reduced levels of human chorionic gonadotrophin in early pregnancy might be factors in the environment of the fetus associated with this condition. No significant difference in the levels of either of these hormones was found, though, if anything, levels of oestrogen may have been lower in cases than in controls, and not higher as previously postulated.

Deaths from ischaemic heart disease and infant mortality in England and Wales.

Death rates from ischaemic heart disease (IHD) in English and Welsh counties are correlated, in both men and women, with the infant mortality rates of those counties when the individuals whose deaths are considered were young, thus confirming previous findings in Norway. In England and Wales, however, there is an equally good correlation between deaths from IHD and infant mortality patterns up to and including that for the same time period as the IHD deaths. The British data provide no grounds for concluding from these relationships that living conditions during early life per se bear a causal relationship to deaths from IHD.

Maternal and other factors of cryptorchidism--a case-control study in Japan.

A case-control study of cryptorchidism was undertaken in Japan. A hundred and eight mothers of children with cryptorchidism and mothers of their matched controls were surveyed. After 4 pairs which consisted of one of twin siblings either in the cases or the controls were excluded, 104 paired data of singletons were analyzed. As a result, a significantly smaller proportion of the case mothers had suffered from vomiting during the index pregnancy than that of the control mothers (odds ratio, or OR = 0.50, 95% confidence interval, or CI 0.28-0.89). A significantly larger proportion of the case mothers had delivered the index child by vacuum or breech extraction, or Caesarean section than that of the control mothers (OR = 2.09, 95% CI 1.01-3.98). A significantly larger proportion of the case mothers had never breast-fed the index child than that of the control mothers (OR = 3.50, 95% CI 1.20-10.21). Significantly larger proportions of the cases had inguinal hernia (OR = 9.00, 95% CI 1.29-62.97), or congenital cardiac diseases (OR = 8/0, p < 0.05) than those of the controls. It was inferred that endogenous hormonal milieu of a mother, rather than exogenous hormones, might be associated with the occurrence of cryptorchidism.

Schistosoma mansoni: the structure and elemental composition of pre-acetabular penetration gland cell secretion in pre-emergent cercariae.

The structure and elemental composition of the secretory products of the pre-acetabular penetration gland cells of pre-emergent cercariae of Schistosoma mansoni have been investigated at an ultrastructural level using X-ray probe microanalysis. The secretion contains 2 types of bodies, one homogeneous and one heterogeneous with electron-lucent areas. Using a variety of fixation and sectioning techniques it has been shown that the apparent electron density of the homogeneous bodies (Type B) is the result of interaction with osmium tetroxide and stain. The small electron-lucent areas of the other type of secretory body (Type A) represent regions where granules have been leached out by processing media. X-ray analysis of cercariae still within sporocysts has indicated that these granules are very rich in calcium, and it is suggested that the calcium is absorbed by the developing cercariae through the sporocyst wall from the molluscan haemolymph.

Travel and ischaemic heart disease.

The hypothesis that travel precipitates acute ischaemic heart disease (IHD) was tested in a case-control study of holidaymakers admitted to hospital in Great Yarmouth. The distance that patients with IHD had travelled to reach Great Yarmouth was on average greater than that travelled by patients with other diseases. I conclude that the greater distances travelled by patients with IHD may have helped to precipitate the attack.

Resting length of the human soleus muscle.

The quantitative relationship between soleus muscle length and the angle of the ankle joint was studied in human cadaver lower limbs of various lengths. The ratio of soleus length to fibula length (lsol/lfib) was linearly related to ankle angle phi A. An expression for soleus resting length lr was derived from the parameters of this relationship and lr was estimated to be 0.998 lfib (S.E. of estimate = 0.004, P less than 0.0001). This gave a mean (+/- S.D.) value of lr of 361.4 (+/- 16.9) mm. The fractional change of lsol produced by rotation of the ankle joint was 0.004 lr.deg-1. The results of these analyses are used to predict lsol changes in intact subjects under varying experimental conditions.

The dissolution rate of zinc pyrithione.

Synopsis A method of measuring and correlating the rate at which zinc pyrithione dissolves during a shampoo is described. The rise in zinc concentration of a solution in a stirred vessel following the introduction of a dose of zine pyrithione suspension was measured as a function of time using atomic absorption spectrophotometry. An analysis of the mass transfer processes occurring during the dissolution of a suspended solid in a stirred vessel was used to correlate the concentration-time measurements. The analysis allows a calculation of the characteristic solution time, the mass transfer coefficient and the diffusion coefficient for the system. In this way the effect of changing shampoo formulation can be systematically studied.