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.

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.

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.

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.

Diet and basal cell skin cancer: results from the EPIC-Norfolk cohort.

BACKGROUND: The incidence of non-melanoma skin cancer (NMSC) in Britain has been increasing over the past 50 years. This has been attributed to increased sunlight exposure, but the increased exposure has not been quantified, and in any case, much of the increase in incidence has occurred in those parts of the body, mainly the head and neck, that have always been exposed to sunlight. There is evidence that increased dietary fat intake has increased the sensitivity of the skin to the carcinogenic potential of sunlight, particularly in causing squamous cell tumours. OBJECTIVES: To test the hypothesis that increased dietary fat is a risk factor for NMSC. METHODS: The hypothesis was tested in a nested case-control study. The cohort was that recruited for the EPIC-Norfolk study, the cases (n = 123) were subjects with NMSC diagnosed since recruitment, and the controls (n = 247) were randomly selected from the same cohort. The effect of diet on the incidence of NMSC was assessed using conditional logistic regression. RESULTS: As there were so few cases (14) with squamous cell tumours they were excluded from the statistical analyses. Fat intake was not found to be a risk factor: the unadjusted odds ratio (OR) of basal cell cases vs. controls was estimated as 0.860/(25.5 g total fat daily) with 95% confidence interval (CI) (0.663, 1.116), P = 0.25. Exploratory analyses of diet components and food groups found a protective effect of increased vitamin E consumption: unadjusted OR of basal cell cases vs. controls was 0.731/(3.06 mg vitamin E daily), 95% CI (0.564, 0.948), P = 0.015. Adjusted analyses gave broadly similar results. CONCLUSIONS: The potentiating factor remains unknown: if dietary fat has any effect on NMSC, it is not apparent when basal cell tumours are considered. There was no evidence of a generalized healthy eating effect. A substantial protective effect was found in exploratory analyses for the fat soluble antioxidant vitamin E.

Early recurrence of benign meningioma correlates with expression of mini-chromosome maintenance-2 protein.

We have investigated the potential utility of monoclonal antibodies against mini-chromosome maintenance-2 protein (Mcm2) in predicting meningioma recurrence. MCM proteins are members of the DNA-binding prereplicative complex and are essential for eukaryotic DNA replication. They are present throughout the cell cycle, but are down-regulated in quiescence and cell differentiation, making them specific markers of proliferating cells. We analysed 10 benign meningiomas that subsequently recurred within a 5-year period, together with 20 matched non-recurrent benign meningiomas. There was no significant correlation between histological subtype, mitotic count or Ki-67 labelling index and tumour recurrence. We observed that whilst the average Mcm2 labelling index (LI) of the tumour section as a whole (LI(Ave)) is not significantly different between recurrent and nonrecurrent meningiomas, the Mcm2 labelling index in the area of highest proliferative activity within the tumour section (LI(Max)) is significantly higher in recurrent meningiomas (p < 0.0001). Seven out of the 10 recurrent meningiomas displayed a Mcm2 LI((Max) greater than 30%, compared to 0 out of 20 for non-recurrent tumours. In conclusion, these results suggest that analysis of Mcm2 expression may facilitate identification of patients with a high risk of meningioma recurrence, for whom adjuvant radiotherapy may be of benefit.

Striking increase in incidence of prostate cancer in men aged < 60 years without improvement in prognosis.

Increased awareness and improved diagnostic techniques have led to earlier diagnosis of prostate cancer and increased detection of subclinical cases, resulting in improved prognosis. We postulated that the considerable increase in incidence under age 60 is not attributable only to increased detection. To test this hypothesis, we studied incidence, mortality and relative survival among middle-aged patients diagnosed in south-east Netherlands and East Anglia (UK) between 1971 and 1994. Prostate-specific antigen (PSA) testing did not occur before 1990. Between 1971 and 1989, the age-standardized incidence at ages 40-59 increased from 8.8 to 12.5 per 10(5) in The Netherlands and from 7.0 to 11.6 per 10(5) in East Anglia. Five-year relative survival did not improve in East Anglia and even declined in southeast Netherlands from 65% [95% confidence interval (CI) 47-83) in 1975-79 to 48% (CI 34-62) in 1985-89. Mortality due to prostate cancer among men aged 45-64 years increased by 50% in south-east Netherlands and by 61% in East Anglia between 1971 and 1989, but decreased slightly in the 1990s. Because other factors adversely influencing the prognosis are unlikely, our results indicate an increase in the incidence of fatal prostate cancer among younger men in the era preceding PSA testing.

Adolescent milk, dairy product and fruit consumption and testicular cancer.

There is an association between dairy product consumption and the incidence of testicular cancer in different countries. To test the hypothesis that milk and dairy products are risk factors, a case-control study was performed in East Anglia, UK. All the cases were men with testicular cancer and for each of the 200 cases there were four controls, two cancer controls and two population controls. The response rate of those eligible subjects who received a questionnaire was: cases 73%, cancer controls 65% and population controls 57%. All responding subjects completed a dietary questionnaire including questions on current and adolescent milk, dairy product and fruit and vegetable consumption. The answers were corroborated when possible by the subjects' mothers using a separate questionnaire. Cases consumed significantly more milk in adolescence than population controls, but this difference did not apply to other dairy products or fruit. The consumption of milk by cancer controls was intermediate between cases and population controls. Cancer controls with non-epithelial cancers had a milk consumption similar to cases, whereas subjects with epithelial cancers had a consumption similar to population controls. In a multivariate analysis the odds ratio between cases and population controls for the association of undescended testis and testicular cancer was 7.19 (95% CI 2.36-21.9) and for each extra quarter pint of milk consumed it was 1.39 (95% CI 1.19-1.63).

Oesophageal cancer mortality in Europe: paradoxical time trend in relation to smoking and drinking.

The main risk factors for oesophageal cancer previously identified in western Europe are tobacco smoking and alcohol drinking. However, a study of the time trend from 1951 to 1985 of the mortality from oesophageal cancer in 17 European countries shows that, except among the younger age groups in men, oesophageal cancer had either decreased or increased only slightly in most countries. This trend differed from that of lung cancer, cirrhosis and alcohol consumption which had in general increased substantially during the period. The results strongly suggest that population-wide changes in certain undetermined risk/protective factor(s), one possibility of which is the consumption of fruit, had overridden the effect of tobacco and alcohol and resulted in a reduction of oesophageal cancer risk. Apart from further efforts to reduce smoking and drinking, studies to identify the factor(s) will be of great public health importance to the prevention of oesophageal cancer.

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.

Maternal factors of testicular cancer: a case-control study in Japan.

A case-control study was undertaken in Japan to clarify maternal or prenatal factors associated with testicular cancer. Information was obtained from 37 mothers of testicular cancer patients, recruited from the discharge records of nine hospitals in Hokkaido, the northern island of Japan. Thirty-seven mothers forming a control group were then surveyed at five public health centers. Each control was selected by individually matching the sex and birth year to a testicular cancer case. Univariate analysis revealed that there were no statistically significant differences in the variables surveyed. Multivariate logistic regression analysis, however, showed that case mothers had significantly fewer live-births than control mothers when the following four variables were adjusted (adjusted relative risk per live-birth = 0.43, P = 0.025): age at indexed birth, duration of breast-feeding for indexed child, birth order, experience of induced abortion.

PIP: Researchers compared data provided by mothers of 37 testicular cancer patients 46 years old (1986) at 9 hospitals on the northern island of Hokkaido in Japan with those from 37 mothers of matched controls (1987) to examine the significance of maternal or prenatal factors associated with testicular cancer in Japan. The univariate analysis did not indicate any statistically significant differences in the variables. Yet when data were controlled for age at indexed birth, duration of breast-feeding the indexed child, birth order, and experience of an induced abortion, the researchers found that mothers of testicular cancer patients were more likely to have fewer live births than the mothers of the controls (relative risk=0.43; p=.025). No other significant differences existed. The researchers suggested several possible explanations and proposed that a common third factor may have played a role. For example, studies in Europe showed that the significant factor may be higher social class, since higher social class mothers have fewer live births, and testicular cancer is more prevalent in higher social class men. This also may be due to a different diet or sedentary life style in these men. The hormonal state of an infertile mother may be related to a higher incidence of testicular cancer in her son. Two possible bias sources in this study included a low incidence of testicular cancer in Japan which yielded a small sample size and a low response rate (60% for case mothers and 70% for control mothers). The researchers concluded that additional research is needed to clarify the association between testicular cancer and maternal subfertility.

Body size and cancer of the testis.

In the search for possible causes for the enormous increase in testicular cancer incidence in Denmark, we tested the hypothesis that a high fat or calorie intake in adolescence and consequently relative obesity is a promotional factor for testicular cancer. A total of 438 cases and three controls for each case were included in the study. Data originated from health examination of men liable for military service. Data were analysed by logistic regression analysis. No systematic statistically significant differences in body measurements [height, weight and body-mass index (weight/height2)] could be shown. Rather than being obese a slight trend was observed towards the future victims of testicular cancer being lighter, smaller and thinner than unaffected controls.

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.

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.

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.