Change from transrectal to transperineal ultrasound-guided prostate biopsy under local anaesthetic eliminates sepsis as a complication.

Transrectal ultrasound-guided (TRUS) biopsy of the prostate is associated with increased risk of post-procedural sepsis with associated morbidity, mortality, re-admission to hospital, and increased healthcare costs. In the study institution, active surveillance of post-procedural infection complications is performed by clinical nurse specialists for prostate cancer under the guidance of the infection prevention and control team. To protect hospital services for acute medical admissions related to the coronavirus disease 2019 (COVID-19) pandemic, TRUS biopsy services were reduced nationally, with exceptions only for those patients at high risk of prostate cancer. In the study institution, this change prompted a complete move to transperineal (TP) prostate biopsy performed in outpatients under local anaesthetic. TP biopsies eliminated the risk of post-procedural sepsis and, consequently, sepsis-related admission while maintaining a service for prostate cancer diagnosis during the COVID-19 pandemic.

Pedestrian deaths in children--potential for prevention.

The National Paediatric Mortality Database was reviewed for the six year period 1st January 2006 to 31st December 2011 and all pedestrian deaths extracted, after review of available data the deaths were categorized as either traffic or non-traffic related. There were 45 child pedestrian fatalities in the period examined. Traffic related deaths accounted for 26 (58%) vs. 19 (42%) non-traffic related. Analysis of the deaths showed there was a male preponderance 28 (62%), weekend trend 22 (49%) with an evening 16 (35%) and summer peak 20 (44%). The highest proportion of deaths occurred in the 1-4 year age group 24 (53%), with 13 (28%) due to low speed vehicle rollovers, mainly occurring in residential driveways 8 (61%). Child pedestrian fatalities are highly preventable through the modification of risk factors including behavioural, social and environmental. Preventative action needs to be addressed, particularly in relation to non-traffic related deaths i.e, low speed vehicle rollovers.

Sudden unexplained death in childhood. An audit of the quality of autopsy reporting.

Cases of sudden unexplained death in childhood (SUDC) in Ireland in children aged > 1 year and < 5 years were examined in order to assess the quality of autopsy reporting. All SUDC cases are notified to and documented by the National Sudden Infant Death Register (NSIDR) in Ireland along with all cases of sudden infant death syndrome (SIDS) referring to sudden infant deaths less than one year of age. The database of the NSIDR in Ireland was interrogated and cases of SIDS and SUDC were compared over a fifteen-year period (1995-2009). SIDS cases whose autopsies were conducted in the same hospital in the same year as the index SUDC case were used for comparison. The autopsy report for each case was examined and modified Rushton (MR) score(s1) calculated. MR scores were compared along with the number of paediatric pathology prosectors and the year of autopsy examination between the two groups. 45 cases were registered as SUDC (age 52 - 152 weeks) between 1995-2009. Autopsy reports were available for 43/45 (95%) of these. 43 SIDS cases from the same year and site of autopsy were used for comparison. Overall MR scores were higher in the SIDS cases, with 29/43 (67%) cases obtaining the minimum arbitrary score (MAS) of > 300 compared to 25/43 (58%) of SUDC cases. Paediatric pathologists in specialist centres carried out similar numbers of SIDS autopsies and SUDC autopsies (46% SIDS, 44% SUDC). Autopsies carried out by paediatric pathologists in specialist centres met the MAS in 19/21 (90%) SIDS cases and 18/19 (95%) SUDC cases. Based on our findings we recommend referral of all SUDC cases to specialist centres for optimal autopsy examination and investigation, and that cases of sudden unexpected death in children over 1 year of age are investigated according to the same guidelines as are used for unexpected death under one year of age.

Maternal smoking and alcohol consumption during pregnancy as risk factors for sudden infant death.

A population based case control study was conducted to examine alcohol consumption and maternal smoking during pregnancy and the risk of SIDS in an Irish population. Each SIDS case (n = 287) was compared with control infants (n = 832) matched for date and place of birth for infants born from 1994 to 2001. Conditional logistic regression was used to investigate differences between Cases and Controls establishing Odds Ratio's (OR) and 95% Confidence Intervals (CI). Mothers who smoked were 3 times more likely to have a SIDS Case, and a dose response effect was apparent, with mothers smoking 1-10 cigarettes/day OR 2.93 (CI 1.50-5.71), and those smoking > 10 cigarettes/day OR 4.36 (CI 2.50-7.61). More Case mothers consumed alcohol during pregnancy than Control mothers and, within drinkers, the amount of alcohol consumed was also greater (p < 0.05). A dose response with frequency of drinking was apparent. The adjusted odds ratio for those consuming alcohol in all three trimesters was 3.59 (CI:1.40-9.20). Both of these risk factors are modifiable and need to be incorporated into antenatal education from a SIDS point of view.

Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis.

OBJECTIVE: To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis. METHODS: Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses. RESULTS: A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P < or = 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically. CONCLUSIONS: Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.

An 8 year study of risk factors for SIDS: bed-sharing versus non-bed-sharing.

BACKGROUND: It is unclear if it is safe for babies to bed share with adults. In Ireland 49% of sudden infant death syndrome (SIDS) cases occur when the infant is bed-sharing with an adult. OBJECTIVE: To evaluate the effect of bed-sharing during the last sleep period on risk factors for SIDS in Irish infants. DESIGN: An 8 year (1994-2001) population based case control study of 287 SIDS cases and 831 controls matched for date, place of birth, and sleep period. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression. RESULTS: The risk associated with bed-sharing was three times greater for infants with low birth weight for gestation (UOR 16.28 v 4.90) and increased fourfold if the combined tog value of clothing and bedding was > or =10 (UOR 9.68 v 2.34). The unadjusted odds ratio for bed-sharing was 13.87 (95% CI 9.58 to 20.09) for infants whose mothers smoked and 2.09 (95% CI 0.98 to 4.39) for non-smokers. Age of death for bed-sharing and sofa-sharing infants (12.8 and 8.3 weeks, respectively) was less than for infants not sharing a sleep surface (21.0 weeks, p<0.001) and fewer bed-sharing cases were found prone (5% v 32%; p = 0.001). CONCLUSION: Risk factors for SIDS vary according to the infant's sleeping environment. The increased risk associated with maternal smoking, high tog value of clothing and bedding, and low z scores of weight for gestation at birth is augmented further by bed-sharing. These factors should be taken into account when considering sleeping arrangements for young infants.

How reliable are SIDS rates?

There is increasing concern with using SIDS as a diagnosis, especially where the postmortem examination reveals additional findings that may be contributory to the death exclusion. This report shows how varying the criteria for a diagnosis of SIDS significantly alters the SIDS rate in Ireland.

A multivariate "time based" analysis of SIDS risk factors.

AIMS: To investigate the influence of analytical design on the variability of published results in studies of sudden infant death syndrome (SIDS). METHODS: The results of a prospective case-control study, of 203 cases of SIDS, and 622 control infants are presented. All variables significant on univariate analysis were included in a multivariate model analysed in nine stages, starting with sociodemographic variables, then sequentially and cumulatively adding variables relating to pregnancy history, current pregnancy, birth, the interval from birth to the week prior to death, the last week, the last 48 hours, and the last sleep period. A ninth stage was created by adding placed to sleep prone for the last sleep period. RESULTS: As additional variables are added, previously published SIDS risk factors emerged such as social deprivation, young maternal age, > or =3 previous live births, maternal smoking and drinking, urinary tract infection in pregnancy, reduced birth weight, and the infant having an illness, regurgitation, being sweaty, or a history of crying/colic in the interval from birth to the week before death, with co-sleeping and the lack of regular soother use important in the last sleep period. As the model progressed through stages 1-9, many significant variables became non-significant (social deprivation, young maternal age, maternal smoking and drinking) and in stage 9 the addition of placed to sleep prone for the last sleep period caused > or =3 previous live births and a reduced birth weight to become significant. CONCLUSION: The variables found to be significant in a case-control study, depend on what is included in a multivariate model.

Factors relating to the infant's last sleep environment in sudden infant death syndrome in the Republic of Ireland.

AIM: To identify risk factors for sudden infant death syndrome (SIDS) in the sleeping environment of Irish infants. METHODS: A five year population based case-control study with parental interviews conducted for each case and three controls matched for age, place of birth, and last sleep period. A total of 203 SIDS cases and 622 control infants born 1994-98 were studied. RESULTS: In a multivariate analysis, co-sleeping significantly increased the risk of SIDS both as a usual practice (adjusted OR 4.31; 95% CI 1.07 to 17.37) and during the last sleep period (adjusted OR 16.47; 95% CI 3.73 to 72.75). The associated risk was dependent on maternal smoking (OR 21.84; 95% CI 2.27 to 209.89), and was not significant for infants who were > or =20 weeks of age (OR 2.63; 95% CI 0.49 to 70.10) or placed back in their own cot/bed to sleep (OR 1.07; 95% CI 0.21 to 5.41). The use of pillows, duvets, and bedding with tog value > or =10 were not significant risk factors when adjusted for the effects of confounding variables, including maternal smoking and social disadvantage. However, the prone sleeping position remains a significant SIDS risk factor, and among infants using soothers, the absence of soother use during the last sleep period also significantly increased the SIDS risk (OR 5.83; CI 2.37 to 14.36). CONCLUSION: Co-sleeping should be avoided in infants who are <20 weeks of age, or whose mothers smoked during pregnancy. The prone position remains a factor in some SIDS deaths, and the relation between soother use and SIDS is a complex variable requiring further study.

Development and validation of the Glasgow Epilepsy Outcome Scale (GEOS): a new instrument for measuring concerns about epilepsy in people with mental retardation.

PURPOSE: To develop a measure for use with adults with epilepsy and mental retardation, capable of assessing both clinical and care concerns and of quantifying treatment outcomes. METHODS: Extensive validational and other psychometric evaluation was undertaken, comprising initial scale development work with 48 carers and 46 health practitioners, followed by formal field testing on a sample of 186 patients, using 384 respondents (160 clinicians, 141 staff, 83 family). Recognised qualitative methods were applied to identify central themes, and psychometric procedures generated data on validity, reliability, and component structure. RESULTS: A total of 1,007 items of concern was generated, which was reduced systematically to a representative set of 90 items. The GEOS-90 comprises four subscales: concerns about "seizures," "treatment," "caring," and "social impact," each explaining approximately 70% of variance. Subscales and factor scales had strong internal consistency (alpha > or = 0.82). Stepwise linear regression was applied to derive a short-form version with similar structure. Thirty-five items were retained (GEOS-35; alpha > or = 0.89). Both scales discriminated moderately on clinical variables (number of seizure types, mono- vs. polytherapy, seizure frequency; all values of p < 0.05) and demonstrated concurrent validity with interview ratings from the ELDQOL (p < 0.05). CONCLUSIONS: The GEOS scales appear valid and reliable for use with clinical populations of people with mental retardation.

Phytoestrogens and gonadotropin-releasing hormone pulse generator activity and pituitary luteinizing hormone release in the rat.

Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans. The aims of this study were 2-fold: 1) to determine in vivo whether genistein and coumestrol act on the GnRH pulse generator to suppress hypothalamic multiunit electrical activity volleys and associated LH pulses and/or on the pituitary to suppress the LH response to GnRH; and 2) to examine the effect of these phytoestrogens on GnRH-induced pituitary LH release in vitro and to determine whether estrogen receptors are involved. Wistar rats were ovariectomized and chronically implanted with recording electrodes and/or indwelling cardiac catheters, and blood samples were taken every 5 min for 7--11 h. Intravenous infusion of coumestrol (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) resulted in a profound inhibition of pulsatile LH secretion, a 50% reduction in the frequency of hypothalamic multiunit electrical activity volleys, and a complete suppression of the LH response to exogenous GnRH. In contrast, both genistein (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) and vehicle were without effect on pulsatile LH secretion. Coumestrol (10(-5) M; over 2 or 4 h) suppressed GnRH-induced pituitary LH release in vitro, an effect blocked by the antiestrogen ICI 182,780. It is concluded that coumestrol acts centrally to reduce the frequency of the hypothalamic GnRH pulse generator. In addition, the inhibitory effects of coumestrol on LH pulses occur at the level of the pituitary by reducing responsiveness to GnRH via an estrogen receptor-mediated process.

Mitochondrial and mitochondrial-related nuclear genetic function in rabbit urinary bladder following reversal of outlet obstruction.

Partial outlet obstruction of the rabbit urinary bladder causes increased tissue hypertrophy and decreased contractility of that organ; we showed that, in an experimental rabbit model, both correlate closely with alterations in the status and expression of mitochondrial (mt), and mt-related nuclear, genetic parameters in bladder smooth muscle. Here we investigate the rate and overall level of recovery of mt and nuclear genetic function following reversal of outlet obstruction in the same animal model. Release from outlet obstruction at 28 days resulted in improvement in both level of hypertrophy and contractile function in all bladders studied. However, bladders fell into two groups based on whether relative copy mt genome number per cell was above or below that of unobstructed controls. Bladders with high mt DNA content adjusted organellar genome copy number toward normal post-reversal but did not properly adjust mt transcript levels; mt-related nuclear transcripts in these samples showed recovery. Bladders with low mt DNA content showed no adjustment of those levels toward normal post-reversal but did show some adjustment in other mt and nuclear genetic parameters. Thus, a limiting factor for return of normal bladder function following reversal of outlet obstruction may be recovery of normal mt genetic performance.

Mitochondrial involvement in bladder function and dysfunction.

Benign bladder pathology resulting from prostatic hypertrophy or other causes is a significant problem associated with ageing in humans. This condition is characterized by increased bladder mass, decreased urinary flow rate, decreased compliance, and these and other changes in bladder function often subject patients to increased risk of urinary tract infection. While the physiologic attributes of benign bladder pathology have been extensively described in humans and in various animal model systems, the biochemical and molecular genetic bases for that pathology have only recently been investigated in detail. Studies demonstrate that mitochondrial energy production and utilization are severely impaired in bladder smooth muscle during benign bladder disease, and to a large extent this realization has provided a rational basis for understanding the characteristic alterations in urinary flow and compliance in bladder tissue. Recent investigations targeting the detailed molecular basis for impaired mitochondrial function in the disease have shown that performance of the organellar genetic system, and to a large extent that of relevant portions of the nuclear genetic system as well, is severely aberrant in bladder tissue. In this article, we discuss the physiologic aspects of benign bladder disease, summarize biochemical evidence for the altered mitochondrial energy metabolism that appears to underlie bladder pathology, review the structure and function of the mitochondrial genetic system, and discuss molecular genetic studies of that system which have begun to provide a mechanistic explanation for the biochemical and physiological abnormalities that characterize the disease. We also discuss areas for further research which will be critically important in increasing our understanding of the detailed causes of benign bladder pathology.

A pilot study: use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures.

OBJECTIVE: To study the effects of the adenine analog, fludarabine, on patients with refractory dermatomyositis and polymyositis, and to assess variables used in following myositis patients during medical intervention. METHODS: Patients whose myositis was not controlled by prednisone and at least one other immunosuppressive medication were entered into a pilot study during which they received 6 monthly cycles of intravenous fludarabine. Patients were assessed at baseline, every other month, and at month 7 for primary outcome measures of strength and function. Other measurements including peripheral blood cell subsets, muscle enzymes, and various assessments of disease activity were followed monthly during the fludarabine infusion period and for up to 6 months post therapy. RESULTS: Of 16 patients who entered the study, 4 patients were classified as improved, and 7 patients were classified as unchanged. Five patients who withdrew before month 7 were classified as treatment failures. Fludarabine caused a significant and prolonged lymphopenia without an increase in infectious complications over that seen with other immunosuppressive agents used for myositis. A sudden death of one patient at the end of the study was not thought to be drug related. Variables followed during the study emphasized the distinction between patient functional improvement and disease remission. CONCLUSION: A subset of patients with refractory myositis may benefit from fludarabine therapy and controlled trials are indicated. Refinement and validation of variables useful for following myositis patients await larger studies.

The Epilepsy Outcome Scale: the development of a measure for use with carers of people with epilepsy plus intellectual disability.

This paper describes the development of a new scale for the assessment of epilepsy in people with learning disabilities. The scale was developed and validated in consultation with principal carers, and reflects their concerns about seizures, their impact and their treatment. Further testing of the scale revealed high internal consistency, testretest reliability and a robust factor structure. The scale can be completed in 5-10 min and may be useful as an outcome measure both in clinical practice and in research trials.

Transcription of mitochondrial and mitochondria-related nuclear genes in rabbit bladder following partial outlet obstruction.

Using the rabbit model, we showed that partial outlet obstruction of the urinary bladder causes significant changes in the status and expression of the mitochondrial (mt) genetic system in bladder smooth muscle immediately after obstruction is initiated. Here we investigate quantitatively the severity of the mt genetic response to partial outlet obstruction in both short- and long-term obstructed rabbits. Based on previous functional studies, bladders with mass < 6 fold greater than control were considered compensated; bladders with mass > 6 fold that of control were considered decompensated. Analyses of DNA from compensated rabbit bladders showed that relative mt genome copy number decreased to 30% of control values. Transcript analyses for these samples showed that mt RNA levels increased 3 fold to compensate for lower template copy number. Analysis of decompensated bladders demonstrated that mt genome copy number increased to approximately 90% of control levels; mt transcripts progressively decreased in these samples by as much as 30 fold. In contrast, transcription of a mt-related nuclear gene decreased 3-9 fold in compensated bladders but increased 10-30 fold in decompensated bladders. Activity for the cytochrome oxidase complex, and for the mt enzyme citrate synthase, decreased steadily with increasing bladder hypertrophy. These data suggest that bladder dysfunction following partial outlet obstruction is mediated partly by a significant loss in mt and mt-related nuclear gene coordination.