Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) for diagnosis and management of bladder outlet obstruction in men: study protocol for a randomised controlled trial.

BACKGROUND: Lower urinary tract symptoms (LUTS) comprise storage symptoms, voiding symptoms and post-voiding symptoms. Prevalence and severity of LUTS increase with age and the progressive increase in the aged population group has emphasised the importance to our society of appropriate and effective management of male LUTS. Identification of causal mechanisms is needed to optimise treatment and uroflowmetry is the simplest non-invasive test of voiding function. Invasive urodynamics can evaluate storage function and voiding function; however, there is currently insufficient evidence to support urodynamics becoming part of routine practice in the clinical evaluation of male LUTS. DESIGN: A 2-arm trial, set in urology departments of at least 26 National Health Service (NHS) hospitals in the United Kingdom (UK), randomising men with bothersome LUTS for whom surgeons would consider offering surgery, between a care pathway based on urodynamic tests with invasive multichannel cystometry and a care pathway based on non-invasive routine tests. The aim of the trial is to determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome than one in which it is included, at 18 months after randomisation. This primary clinical outcome will be measured with the International Prostate Symptom Score (IPSS). We will also establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery as a main secondary outcome. DISCUSSION: The general population has an increased life-expectancy and, as men get older, their prostates enlarge and potentially cause benign prostatic obstruction (BPO) which often requires surgery. Furthermore, voiding symptoms become increasingly prevalent, some of which may not be due to BPO. Therefore, as the population ages, more operations will be considered to relieve BPO, some of which may not actually be appropriate. Hence, there is sustained interest in the diagnostic pathway and this trial could improve the chances of an accurate diagnosis and reduce overall numbers of surgical interventions for BPO in the NHS. The morbidity, and therapy costs, of testing must be weighed against the cost saving of surgery reduction. TRIAL REGISTRATION: Controlled-trials.com - ISRCTN56164274 (confirmed registration: 8 April 2014).

Protocol for a randomised controlled trial for Reducing Arthritis Fatigue by clinical Teams (RAFT) using cognitive-behavioural approaches.

INTRODUCTION: Rheumatoid arthritis (RA) fatigue is distressing, leading to unmanageable physical and cognitive exhaustion impacting on health, leisure and work. Group cognitive-behavioural (CB) therapy delivered by a clinical psychologist demonstrated large improvements in fatigue impact. However, few rheumatology teams include a clinical psychologist, therefore, this study aims to examine whether conventional rheumatology teams can reproduce similar results, potentially widening intervention availability. METHODS AND ANALYSIS: This is a multicentre, randomised, controlled trial of a group CB intervention for RA fatigue self-management, delivered by local rheumatology clinical teams. 7 centres will each recruit 4 consecutive cohorts of 10-16 patients with RA (fatigue severity ≥ 6/10). After consenting, patients will have baseline assessments, then usual care (fatigue self-management booklet, discussed for 5-6 min), then be randomised into control (no action) or intervention arms. The intervention, Reducing Arthritis Fatigue by clinical Teams (RAFT) will be cofacilitated by two local rheumatology clinicians (eg, nurse/occupational therapist), who will have had brief training in CB approaches, a RAFT manual and materials, and delivered an observed practice course. Groups of 5-8 patients will attend 6 × 2 h sessions (weeks 1-6) and a 1 hr consolidation session (week 14) addressing different self-management topics and behaviours. The primary outcome is fatigue impact (26 weeks); secondary outcomes are fatigue severity, coping and multidimensional impact, quality of life, clinical and mood status (to week 104). Statistical and health economic analyses will follow a predetermined plan to establish whether the intervention is clinically and cost-effective. Effects of teaching CB skills to clinicians will be evaluated qualitatively. ETHICS AND DISSEMINATION: Approval was given by an NHS Research Ethics Committee, and participants will provide written informed consent. The copyrighted RAFT package will be freely available. Findings will be submitted to the National Institute for Health and Care Excellence, Clinical Commissioning Groups and all UK rheumatology departments. ISRCTN: 52709998; Protocol v3 09.02.2015.

Head covering - a major modifiable risk factor for sudden infant death syndrome: a systematic review.

BACKGROUND: Some victims of sudden infant death syndrome (SIDS) are found with their heads covered with bedclothes, but the significance of this is uncertain. The aim of this review is to describe the prevalence of head covering, the magnitude of the risk and how far the suggested causal mechanisms agree with current epidemiological evidence. METHODS: Systematic review of population-based age-matched controlled studies. RESULTS: Controlled observations of head covering for the final sleep were found in 10 studies. The pooled prevalence in SIDS victims was 24.6% (95% CI 22.3% to 27.1%) compared to 3.2% (95% CI 2.7% to 3.8%) among controls. The pooled univariate odds ratio (OR) was 9.6 (95% CI 7.9 to 11.7) and the pooled adjusted OR from studies mainly conducted after the fall in SIDS rate was 16.9 (95% CI 12.6 to 22.7). The risk varied in strength but was significant across all studies. In a quarter of cases and controls head covering had occurred at least once previously (pooled adjusted OR = 1.1; 95% CI 0.9 to 1.4). The population attributable risk (27.1%; 95% CI 24.7% to 29.4%) suggests avoiding head covering might reduce SIDS deaths by more than a quarter. CONCLUSIONS: The epidemiological evidence does not fully support postulated causal mechanisms such as hypoxia, hypercapnoea and thermal stress, but neither does it support the idea that head covering is part of some terminal struggle. Head covering is a major modifiable risk factor associated with SIDS deaths and parental advice to avoid this situation should be emphasised.

Sudden Infant Death Syndrome and the time of death: factors associated with night-time and day-time deaths.

OBJECTIVE: To investigate the diurnal occurrence of Sudden Infant Death Syndrome (SIDS) and interaction with established risk factors in the infant sleeping environment. METHODS: A 3 year population-based case-control study, in five English Health Regions. Parentally defined day-time or night-time deaths of 325 SIDS infants and reference sleep of 1300 age-matched controls. RESULTS: The majority of SIDS deaths (83%) occurred during night-time sleep, although this was often after midnight and at least four SIDS deaths occurred during every hour of the day. The length of time from last observed alive until the discovery of death ranged from

Should pacifiers be recommended to prevent sudden infant death syndrome?

OBJECTIVES: Our aim was to review the evidence for a reduction in the risk of sudden infant death syndrome (SIDS) with pacifier ("dummy" or "soother") use, to discuss possible mechanisms for the reduction in SIDS risk, and to review other possible health effects of pacifiers. RESULTS: There is a remarkably consistent reduction of SIDS with pacifier use. The mechanism by which pacifiers might reduce the risk of SIDS is unknown, but several mechanisms have been postulated. Pacifiers might reduce breastfeeding duration, but the studies are conflicting. CONCLUSIONS: It seems appropriate to stop discouraging the use of pacifiers. Whether it is appropriate to recommend pacifier use in infants is open to debate.

Sudden infant death syndrome and sleeping position in pre-term and low birth weight infants: an opportunity for targeted intervention.

AIMS: To determine the combined effects of sudden infant death syndrome (SIDS) risk factors in the sleeping environment for infants who were "small at birth" (pre-term (<37 weeks), low birth weight (<2500 g), or both). METHODS: A three year population based, case-control study in five former health regions in England (population 17.7 million) with 325 cases and 1300 controls. Parental interviews were carried out after each death and reference sleep of age matched controls. RESULTS: Of the SIDS infants, 26% were "small at birth" compared to 8% of the controls. The most common sleeping position was supine, for both controls (69%) and those SIDS infants (48%) born at term or > or =2500 g, but for "small at birth" SIDS infants the commonest sleeping position was side (48%). The combined effect of the risk associated with being "small at birth" and factors in the infant sleeping environment remained multiplicative despite controlling for possible confounding in the multivariate model. This effect was more than multiplicative for those infants placed to sleep on their side or who shared the bed with parents who habitually smoked, while for those "small at birth" SIDS who slept in a room separate from the parents, the large combined effect showed evidence of a significant interaction. No excess risk was identified from bed sharing with non-smoking parents for infants born at term or birth weight > or =2500 g. CONCLUSION: The combined effects of SIDS risk factors in the sleeping environment and being pre-term or low birth weight generate high risks for these infants. Their longer postnatal stay allows an opportunity to target parents and staff with risk reduction messages.

The prevalence and characteristics associated with parent-infant bed-sharing in England.

AIMS: To investigate the characteristics of parent-infant bed-sharing prevalence in England. METHODS: Data on night-time sleeping practices from a two year, local, longitudinal study and a three-year, national, cross-sectional study were obtained. A total of 261 infants in North Tees were followed up at 1 and 3 months of age, as were 1095 infants aged 1 week to 1 year from five English health regions. RESULTS: Data from both studies found that almost half of all neonates bed-shared at some time with their parents (local = 47%, 95% CI 41 to 54; national = 46%, 95% CI 34 to 58), and on any one night in the first month over a quarter of parents slept with their baby (local = 27%, 95% CI 22 to 33; national = 30%, 95% CI 20 to 42). Bed-sharing was not related to younger mothers, single mothers, or larger families, and was not more common in the colder months, at weekends, or among the more socially deprived families; in fact bed-sharing was more common among the least deprived in the first months of life. Breast feeding was strongly associated with bed-sharing, both at birth and at 3 months. Bed-sharing prevalence was uniform with infant age from 3 to 12 months; on any one night over a fifth of parents (national = 21%, 95% CI 18 to 24) slept with their infants. CONCLUSION: Bed-sharing is a relatively common practice in England, not specific to class, but strongly related to breast feeding.

Family, socioeconomic and prenatal factors associated with failure to thrive in the Avon Longitudinal Study of Parents and Children (ALSPAC).

BACKGROUND: The epidemiological profile of infants failing to thrive is unclear. The aim of this study is to investigate the prenatal and socioeconomic factors associated with these infants using standardized weight gain conditional on previous weight. METHODS: In a large UK population cohort study, 11 718 infants born at term in 1991-1992 with no major congenital abnormalities were identified. Using a weight gain criterion conditional on initial weight from birth to 6-8 weeks, 6-8 weeks to 9 months, and birth to 9 months, the slowest gaining 5% were identified. RESULTS: None of the prenatal factors was associated with failure to thrive in the multivariable analysis nor were traditional markers of socioeconomic deprivation such as poor parental education or low occupational status. Parental height was significantly correlated with slow infant weight gain in both separate periods and from birth to 9 months (Pearson's r = +0.20, P < 0.001). Eight times as many infants born to shorter parents (8.7%, 95% CI: 6.6, 11.3) showed slow weight gain as infants born to taller parents (1.1%, 95% CI: 0.5, 2.5). Higher parity was also related to slow infant weight gain; infants born in the fourth or subsequent pregnancy were twice as likely to fail to thrive from birth to 9 months (8.3%, 95% CI: 6.4, 10.6) as first-born infants (3.4%, 95% CI: 2.9, 10.6). CONCLUSIONS: Future studies need to take account of parental height when calculating growth standards and look at why failure to thrive is more common, not in poorer families but in larger families.

Sudden unexplained infant death in 20 regions in Europe: case control study.

BACKGROUND: After striking changes in rates of sudden unexplained infant death (SIDS) around 1990, four large case-control studies were set up to re-examine the epidemiology of this syndrome. The European Concerted Action on SIDS (ECAS) investigation was planned to bring together data from these and new studies to give an overview of risk factors for the syndrome in Europe. METHODS: We undertook case-control studies in 20 regions. Data for more than 60 variables were extracted from anonymised records of 745 SIDS cases and 2411 live controls. Logistic regression was used to calculate odds ratios (ORs) for every factor in isolation, and to construct multivariate models. FINDINGS: Principal risk factors were largely independent. Multivariately significant ORs showed little evidence of intercentre heterogeneity apart from four outliers, which were eliminated. Highly significant risks were associated with prone sleeping (OR 13.1 [95% CI 8.51-20.2]) and with turning from the side to the prone position (45.4 [23.4-87.9]). About 48% of cases were attributable to sleeping in the side or prone position. If the mother smoked, significant risks were associated with bed-sharing, especially during the first weeks of life (at 2 weeks 27.0 [13.3-54.9]). This OR was partly attributable to mother's consumption of alcohol. Mother's alcohol consumption was significant only when baby bed-shared all night (OR increased by 1.66 [1.16-2.38] per drink). For mothers who did not smoke during pregnancy, OR for bed-sharing was very small (at 2 weeks 2.4 [1.2-4.6]) and only significant during the first 8 weeks of life. About 16% of cases were attributable to bed-sharing and roughly 36% to the baby sleeping in a separate room. INTERPRETATION: Avoidable risk factors such as those associated with inappropriate infants' sleeping position, type of bedding used, and sleeping arrangements strongly suggest a basis for further substantial reductions in SIDS incidence rates.

The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study.

OBJECTIVES: To investigate whether the accelerated immunisation programme in the United Kingdom is associated, after adjustment for potential confounding, with the sudden infant death syndrome. DESIGN: Population based case-control study, February 1993 to March 1996. Parental interviews were conducted for each death and for four controls matched for age, locality, and time of sleep. Immunisation status was taken from records held by the parents. SETTING: Five regions in England with a combined population of over 17 million. SUBJECTS: Immunisation details were available for 93% (303/325) of infants whose deaths were attributed to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained sudden deaths; and 95% (1515/1588) of controls. RESULTS: After all potential confounding factors were controlled for, immunisation uptake was strongly associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval 0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43)) after further adjustment for other factors specific to the infant's sleeping environment. Similar proportions of SIDS deaths and reference sleeps (corresponding to the time of day during which the index baby had died) among the controls occurred within 48 hours of the last vaccination (5% (7/149) v 5% (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term temporal association with immunisation was found (P=0.78). Of the SIDS infants who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of illness that suggested that medical contact was required, compared with 26% (16/61) of the non-immunised SIDS infants of similar age. The findings for the infants who died suddenly and unexpectedly but of explained causes mirrored those for SIDS infants. CONCLUSIONS: Immunisation does not lead to sudden unexpected death in infancy, and the direction of the relation is towards protection rather than risk.

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk.

AIMS: To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS). DESIGN: Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference. SETTING: Five regions in England (population greater than 17 million, more than 470 000 live births over three years). SUBJECTS: 247 SIDS cases and 1110 controls. RESULTS: The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (deltazw) = -0.38 (SD 1.40) v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1. 48-2.07, p < 0.0001) than for those with lower birth weight (OR = 1. 09, 95% CI 0.61-1.95, p = 0.76). There was no evidence of increased growth retardation before death. CONCLUSIONS: Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment.

A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal? CESDI SUDI Research Group. Confidential Inquiry into Stillbirths and Deaths in Infancy study.

OBJECTIVES: To compare the clinical characteristics associated with sudden infant death syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population, > 17 million; live births, > 470,000). SUBJECTS: SIDS: 325 infants; explained SUDI: 72 infants; controls: 1,588 infants. RESULTS: In the univariate analysis, all the clinical features and health markers at birth, after discharge from hospital, during life, and shortly before death, significant among the infants with SIDS were in the same direction among the infants who died of explained SUDI. In the multivariate analysis, at least one apparent life threatening event had been experienced by more of the infants who died than in controls (SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81; 95% CI, 2.52 to 112.30). Using a retrospective illness scoring system based on "Baby Check", both index groups showed significant markers of illness in the last 24 hours (SIDS: 22% v 8% controls; OR = 4.17; 95% CI, 1.88 to 9.24; explained SUDI: 49% v 8% controls; OR = 31.20; 95% CI, 6.93 to 140.5). CONCLUSIONS: The clinical characteristics of SIDS and explained SUDI are similar. Baby Check might help identify seriously ill babies at risk of sudden death, particularly in high risk infants.

Babies sleeping with parents: case-control study of factors influencing the risk of the sudden infant death syndrome. CESDI SUDI research group.

OBJECTIVE: To investigate the risks of the sudden infant death syndrome and factors that may contribute to unsafe sleeping environments. DESIGN: Three year, population based case-control study. Parental interviews were conducted for each sudden infant death and for four controls matched for age, locality, and time of sleep. SETTING: Five regions in England with a total population of over 17 million people. SUBJECTS: 325 babies who died and 1300 control infants. RESULTS: In the multivariate analysis infants who shared their parents' bed and were then put back in their own cot had no increased risk (odds ratio 0.67; 95% confidence interval 0.22 to 2.00). There was an increased risk for infants who shared the bed for the whole sleep or were taken to and found in the parental bed (9.78; 4.02 to 23.83), infants who slept in a separate room from their parents (10.49; 4.26 to 25.81), and infants who shared a sofa (48.99; 5.04 to 475.60). The risk associated with being found in the parental bed was not significant for older infants (>14 weeks) or for infants of parents who did not smoke and became non-significant after adjustment for recent maternal alcohol consumption (>2 units), use of duvets (>4 togs), parental tiredness (infant slept 2 people per room of the house). CONCLUSIONS: There are certain circumstances when bed sharing should be avoided, particularly for infants under four months old. Parents sleeping on a sofa with infants should always be avoided. There is no evidence that bed sharing is hazardous for infants of parents who do not smoke.

Epidemiology of SIDS and explained sudden infant deaths. CESDI SUDI Research Group.

OBJECTIVES: To establish whether epidemiologic characteristics for sudden infant death syndrome (SIDS) have changed since the decrease in death rate after the "Back to Sleep" campaign in 1991, and to compare these characteristics with sudden and unexpected deaths in infancy (SUDI) from explained causes. DESIGN: Three-year, population-based, case-control study. Parental interviews were conducted soon after the death and for 4 controls matched for age and date of interview. All sudden unexpected deaths were included in the study and the cause of death was established by a multidisciplinary panel of the relevant health care professionals taking into account past medical and social history of the mother and infant, the circumstances of death, and a full pediatric postmortem examination. Contributory factors and the final classification of death were made using the Avon clinicopathologic system. SETTING: Five regions in England, with a total population of >17 million people, took part in the study. The number of live births within these regions during the particular time each region was involved in the study was 473 000. STUDY PARTICIPANTS: Three hundred twenty-five SIDS infants (91.3% of those available), 72 explained SUDI infants (86.7% of those available), and 1588 matched control infants (100% of total for cases included). RESULTS: Many of the epidemiologic features that characterize SIDS infants and families have remained the same, despite the recent decrease in SIDS incidence in the United Kingdom. These include the same characteristic age distribution, few deaths in the first few weeks of life or after 6 months, with a peak between 4 and 16 weeks, a higher incidence in males, lower birth weight, shorter gestation, and more neonatal problems at delivery. As in previous studies there was a strong correlation with young maternal age and higher parity and the risk increased for infants of single mothers and for multiple births. A small but significant proportion of index mothers had also experienced a previous stillbirth or infant death. The majority of the SIDS deaths (83%) occurred during the night sleep and there was no particular day of the week on which a significantly higher proportion of deaths occurred. Major epidemiologic features to change since the decrease in SIDS rate include a reduction in the previous high winter peaks of death and a shift of SIDS families to the more deprived social grouping. Just more than one quarter of the SIDS deaths (27%) occurred in the 3 winter months (December through February) in the 3 years of this study. In half of the SIDS families (49%), the lone parent or both parents were unemployed compared with less than a fifth of control families (18%). This difference was not explained by an excess of single mothers in the index group. Many of the significant factors relating to the SIDS infants and families that distinguish them from the normal population did not distinguish between SIDS and explained SUDI. In the univariate analysis many of the epidemiologic characteristics significant among the SIDS group were also identified and in the same direction among the infants dying as SUDI attributable to known causes. The explained deaths were similarly characterized by the same infant, maternal, and social factors, 48% of these families received no waged income. Using logistic regression to make a direct comparison between the two index groups there were only three significant differences between the two groups of deaths: 1) a different age distribution, the age distribution of the explained deaths peaked in the first 2 months and was more uniform thereafter; 2) more congenital anomalies were noted at birth (odds ratio [OR] = 3.14; 95% confidence intervals [CI]: 1.52-6. (ABSTRACT TRUNCATED)

Pacifier use and sudden infant death syndrome: results from the CESDI/SUDI case control study. CESDI SUDI Research Team.

OBJECTIVES: To investigate the relation between pacifier use and sudden infant death syndrome (SIDS). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population > 17 million). SUBJECTS: 325 infants who had died from SIDS and 1300 control infants. RESULTS: Significantly fewer SIDS infants (40%) than controls (51%) used a pacifier for the last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence interval (CI), 0.46 to 0.83) and the difference increased when controlled for other factors (multivariate OR, 0.41; 95% CI, 0. 22 to 0.77). However, the proportion of infants who had ever used a pacifier for day (66% SIDS v 66% controls) or night sleeps (61% SIDS v 61% controls) was identical. The association of a risk for SIDS infants who routinely used a pacifier but did not do so for the last sleep became non-significant when controlled for socioeconomic status (bivariate OR, 1.39 (0.93 to 2.07)). CONCLUSIONS: Further epidemiological evidence and physiological studies are needed before pacifier use can be recommended as a measure to reduce the risk of SIDS.

Altered mitochondrial function in canine ceroid-lipofuscinosis.

The neuronal ceroid-lipofuscinoses (NCL) are a group of autosomal recessively inherited neurodegenerative disorders characterized by progressive dementia, neuronal atrophy, and premature death. The late infantile and juvenile types of NCL show massive accumulation of mitochondrial ATP synthase subunit c protein in both mitochondria and lysosomes. The specific accumulation of this mitochondrial protein suggests that mitochondrial function may be impaired in the NCL diseases. Therefore, a study was conducted to determine whether oxidative phosphorylation is altered in liver mitochondria from English setters with NCL, an animal model in which there is also massive accumulation of the subunit c protein. The ADP/O ratios were significantly depressed in affected and carrier dogs, suggesting that the disease mutation led to a partial uncoupling of oxidative phosphorylation. On the other hand, ADP-stimulated respiration rates were higher than normal in both carriers and affected dogs. The increased respiration rates were highest in the carriers, and may reflect a compensatory response to the reduced efficiency of oxidative phosphorylation. Accompanying the increased respiration rates were elevations in mitochondrial ADP content with the elevation being greater in the carriers than in the affected dogs. This suggests that the increased respiration rates may be due, at least in part, to enhanced ADP uptake by the mitochondria. In the carriers, the enhanced respiration rate may be sufficient to offset the reduced efficiency of oxidative phosphorylation. In the affected animals, which had lower respiration rates than the carriers, the enhanced respiration rates may not be sufficient to offset the reduced efficiency of oxidative phosphorylation. Impaired mitochondrial function may therefore contribute to the disease pathology.