Improving the Quality of Paediatric ECG Interpretation.

Aims Our aim was to complete an audit loop and identify whether implementing a paediatric ECG checklist improved the documentation and therefore the quality of paediatric ECG interpretation. We designed a paediatric ECG and education proforma in a Paediatric Emergency Department and incorporated it into daily practice. Methods We audited the medical records of children presenting with clinical indications for ECG. We included 40 records before and 40 records after the introduction of a paediatric ECG interpretation checklist. Results We assessed 10 items of documentation of which 8 related to the wave-form. Recording of these ranged from 0-65% before and from 95-100% after the checklist. Conclusion An intervention to introduce a paediatric ECG checklist, including education proforma, demonstrated significant improvement in the interpretation and documentation of a paediatric ECG. We recommend the use of this checklist in primary care and hospital settings.

Paediatric Head Injury and Traumatic Brain Injury.

Aim To determine prevalence of head injury presenting to paediatric emergency departments (PEDs) and characterise by demographics, triage category, disposition neuroimaging or re-attendance. Methods Presentations in 2014 and 2015, with diagnoses of head injury, intracranial bleed, skull fracture including single or re-attendances within 28 days post head injury to all national PEDs, were analysed. Demographics, triage score, imaging rate, admission, mechanisms and representation rate were recorded. Results Head injury was diagnosed in 13,392 of 224,860 (5.9%), median (IQR) age 3.9 (1.4 - 8.3) years. Regionally 3% of children <5 years attend each year. The total admitted/transferred was 10.8% (n=1460). Neuroimaging rate was 4.3% (n= 570). Falls predominated. Sport accounted for 12.2%. Conclusion One in twenty children PED presentations are head injury, over half in preschool children. A sizeable number were symptomatic reflected by admission, transfer, imaging or re-attendance. Observational management was favoured over imaging reflected in the higher admission versus imaging rate.

Strengthening Animal-Human Relationships as a Doorway to Indigenous Holistic Wellness.

One of the most devastating effects of colonization has been fragmented relations among humans and their more-than-human counterparts. Traditionally, Indigenous peoples positioned animals as equitable partners in interconnected human and more-than human networks, animated with spirit and the ability to act and communicate. Many Indigenous peoples continue to regard animals as sacred and utilize the gifts that they bestow in traditional healing settings. Indigenous understandings of interwoven and reciprocal social networks of human and more-than-human relations must be restored and supported in contemporary health settings in order to "do no further harm" and facilitate Indigenous peoples' healing journeys. Reconciliation across Western and Indigenous contexts requires learning to work together with the more-than-human world and developing ethical spaces for health research in which holistic wellness is appreciated and understood in the context of all our relations. In order to help (re)connect and strengthen human relations with the more-than-human world, a culturally adapted and locally refined animal-human relationship workshop was delivered in a rural Saskatchewan First Nation community where traditional Elders, adults, and youth participants shared stories about the role of animals for their healing and holistic wellness trajectories. The results revealed that animal-human relationships are physical and spiritual in nature, with both domestic and wild animals playing various important person roles in the lives of community members; these person roles are not metaphorical but rather assume all the sentience and agency that the term person implies. The findings have clear practical and policy implications for health services, education, environmental sustainability, and bioresource management.

Atresia Hymenalis with Haematometrocolpos: A Benefit of Teaching a Case Series and Review of the Literature.

We present four cases of atresia hymenalis with resultant haematometrocolpos diagnosed in quick succession in the emergency department with a literature review.

Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease.

Mutations in glucosidase, beta, acid (GBA) are associated with cognitive impairment in Parkinson disease (PD) as well as dementia with Lewy bodies. For both of these diseases, dementia and hallucinations are typically treated with cholinesterase inhibitors and antipsychotics. However, in some lysosomal storage disorders certain antipsychotic medications are poorly tolerated. This study examined cholinesterase inhibitor and antipsychotic use in monoallelic GBA-related PD to explore potential pharmacogenetic relationships. Monoallelic GBA mutation carriers with PD (GBA-PD) with at least two clinic visits (n = 34) were matched for age-of-onset and gender to GBA and leucine-rich repeat kinase 2 (LRRK2) mutation negative idiopathic PD subjects (IPD) (n = 60). Information regarding cholinesterase inhibitor and antipsychotic use as well as impaired cognition (UPDRS Mentation >1) and hallucinations (UPDRS Thought Disorder >1) were obtained. GBA-PD more frequently reported hallucinations (HR = 5.0; p = 0.01) and they were more likely to have cognitive impairment but this was not statistically significant (HR 2.2, p = 0.07). Antipsychotic use was not significantly different between GBA-PD and IPD (HR = 1.9; p = 0.28), but GBA-PD were more likely to have sustained cholinesterase inhibitor use (HR = 3.1; p = 0.008), even after adjustment for cognition and hallucinations. Consistent with reports of worse cognition, GBA-PD patients are more likely to use cholinesterase inhibitors compared to IPD. While there was no difference in antipsychotic use between IPD and GBA-PD, persistent use of quetiapine in GBA-PD suggests that it is tolerated and that a significant interaction is unlikely. Further prospective study in larger samples with more extensive cognitive assessment is warranted to better understand pharmacogenetic relationships in GBA-PD.

The national incidence and outcomes of gastroschisis repairs.

The birth prevalence of gastroschisis worldwide has increased over the past decades. We aim to determine the Irish national incidence of gastroschisis repairs (NIGR) over a 5 year period (2007- 2011) and clinical outcomes by a retrospective cohort review of cases admitted to all Irish paediatric surgical units. Seventy patients were identified. The NIGR per 10,000 live births was 1.96 (SD 0.51) per year. Fifty eight (82%) were antenatally detected. Twenty eight (40%) had primary repair day 1 with the remaining repaired in a median of 3(2-5.75) days. Thirty three (47%) experienced a central catheter related infection. Duration of stay was significantly correlated with decreasing gestational age (p = 0.016), decreasing birthweight (p = 0.005), increasing numbers of blood transfusions (p < 0.001) and co-morbidity or complication (p < 0.001). This study provides individual centres with patient outcomes and national data that can be provided to parents and clinical staff regarding the clinical course of gastroschisis.

Greater risk of parkinsonism associated with non-N370S GBA1 mutations.

Mutations in ß-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkinsonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR = 22.5; p = 0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations.

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease.

BACKGROUND: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. METHODS: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [(18)F]-fluorodeoxyglucose or [(18)F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. RESULTS: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [(18)F]-fluorodeoxyglucose (n = 3) and [(18)F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. CONCLUSIONS: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.

Gender differences in the risk of familial parkinsonism: beyond LRRK2?

G2019S mutations in the LRRK2 gene are responsible for up to 18% of PD in individuals of Jewish descent. While a male preponderance of Parkinson disease (PD) has been consistently reported, this gender difference is not noted in LRRK2 G2019S mutation carriers. In order to test whether there is an increased genetic component in women of Jewish background in general, we examined family history of parkinsonism in 175 Jewish PD patients (82 female and 93 male) and assessed whether parkinsonism was more frequent in family members of women with PD in comparison with family members of men with PD, adjusting for LRRK2 G2019S mutations in the proband. Using Cox proportional hazard models to evaluate the risk of parkinsonism among family members of PD subjects, having a daughter with PD compared with a son was associated with increased risk of parkinsonism in the parent (HR 2.59, p=0.014) as was having a child with a LRRK2 G2019S mutation (HR 3.19, p=0.003). The increased risk among parents of women with PD persisted when adjusting for LRRK2 status (HR 2.19, p=0.023). Among individuals of Jewish descent, there is a relatively greater genetic load in women with PD, and this is not fully accounted for by the G2019S mutation. Further study that evaluates family information bias and assesses the role of glucocerebrosidase mutations is indicated.

Inhibition of a dual chamber pacemaker by oversensing of far-field atrial depolarisation in a patient after His-bundle ablation.

After His-bundle ablation, a 54-year-old pacemaker-dependent patient suffered from severe presyncopal attacks one year after pacemaker replacement. The attacks were caused by ventricular inhibition due to atrial far-field sensing during paroxysmal atrial flutter.

Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers.

The authors examined prospectively whether dietary folate and other factors known to influence methyl-group availability were associated with the development of exocrine pancreatic cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Of the 27,101 healthy male smokers aged 50--69 years who completed a self-administered dietary questionnaire at baseline, 157 developed pancreatic cancer during up to 13 years of follow-up from 1985 to 1997. Cox proportional hazards models were used to estimate the hazards ratios and 95% confidence intervals. The adjusted hazards ratio comparing the highest with the lowest quintile of dietary folate intake was 0.52 (95% confidence interval: 0.31, 0.87; p-trend = 0.05). Dietary methionine, alcohol intake, and smoking history did not modify this relation. No significant associations were observed between dietary methionine, vitamins B(6) and B(12), or alcohol intake and pancreatic cancer risk. Consistent with prior studies, this study shows that cigarette smoking was associated with an increased risk (highest compared with lowest quintile, cigarettes per day: hazards ratio = 1.82; 95% confidence interval: 1.10, 3.03; p-trend = 0.05). These results support the hypothesis that dietary folate intake is inversely associated with the risk of pancreatic cancer and confirm the risk associated with greater cigarette smoking.

Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men.

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B(6), vitamin B(12)) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B(12), or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B(6) levels. Compared with men with the lowest vitamin B(6) concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B(6) in lung cancer.

Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk.

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.

Effects of long-term alpha-tocopherol supplementation on serum hormones in older men.

BACKGROUND: alpha-tocopherol supplementation significantly reduced risk of prostate cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. Sex hormones are thought to be involved in the etiology of prostate cancer. We examined whether long-term supplementation with alpha-tocopherol modified serum hormone levels. METHODS: Men who were cancer-free consumed > or = 90% of the study capsules, and who had both baseline and follow-up blood available, were eligible for the study. One hundred men who received alpha-tocopherol were matched on age, study center, and length of time between blood draws to 100 men who received a placebo. Multivariate linear regression models which allowed for a separate intercept for each matched pair were used to evaluate the effect of alpha-tocopherol supplementation on follow-up hormone concentrations. RESULTS: Compared to men who received a placebo, we found significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentrations among men who received alpha-tocopherol, after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking, and fasting time. Geometric mean (95% confidence interval; CI) androstenedione concentration among men who received alpha-tocopherol was 145 ng/dl (CI, 137-153) after adjusting for covariates, compared to 158 ng/dl (CI, 148-167) among men who received a placebo. Mean testosterone concentrations for men who received alpha-tocopherol and placebo were 539 (CI, 517-562) and 573 (CI, 549-598) ng/dl, respectively. CONCLUSIONS: These results suggest that long-term alpha-tocopherol supplementation decreases serum androgen concentrations, and could have been one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha-tocopherol treatment group of the ATBC Study.

Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk.

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.

Serum carotenoids are associated with increased lung cancer risk among alcohol drinkers, but not among non-drinkers in a cohort of tin miners.

To examine the association between pre-diagnostic serum carotenoid levels and lung cancer risk and the effects of alcohol intake on the carotenoid-lung cancer relationship, we conducted a case-control study in an occupational cohort from the Yunnan Tin Corporation in China. During 6 years of follow-up, 339 cases of confirmed lung cancer were diagnosed. Among these cases, those who donated pre-diagnostic blood (n = 108) were eligible for this study. For each case, two individuals alive and free of cancer at the time of case diagnosis, matched on age, sex, and date of blood collection, were selected as controls. Serum beta-carotene (odds ratios (ORs) for tertiles: 1, 1.3, 2.0) and beta-cryptoxanthin (ORs for tertiles: 1, 1.8, 2.9) levels were positively associated with lung cancer risk after adjustment for tobacco use and radon exposure. Among alcohol drinkers, higher serum carotenoid levels were significantly associated with increased lung cancer risk (alpha-carotene OR 2.2, 95% confidence interval (CI) 1.1-4.4, beta-carotene OR 7.6, 95% CI 3.1-18.6, lutein/zeaxanthin OR 2.3, 95% CI 1.2-6.6 and beta-cryptoxanthin OR 7.6, 95% CI 2.7-21.5). Conversely, risk estimates among non-drinkers suggest a possible protective association for higher carotenoid levels.

Prolonged episodes of persistent asthma: A distinct clinical pattern with characteristic clinical features.

STUDY OBJECTIVES: To investigate a clinical pattern of unexplained persistent asthma that is episodic in nature and lasts for months to years. This pattern of prolonged episodes of unexplained, persistent asthma was not defined previously. DESIGNS: Investigating the clinical features using a retrospective cohort design. SETTING AND PATIENTS: Eighteen subjects (ages, 13 to 64 years) from an allergy practice in a large prepaid health maintenance organization who had two or more prolonged episodes of unexplained persistent asthma lasting >/= 2 months during a 12-year period. RESULTS: These subjects accounted for 39 asthmatic episodes lasting from 2 to 74 months (median, 7 months). The duration of the episodes positively correlates with the severity of asthma (p = 0.02) at the initial part of the episodes. All episodes demonstrated a similar pattern, with symptom severity greatest at the onset and gradually diminishing until recovery. The relatively symptom-free intervals between the episodes ranged from 1.5 to 63 months (median, 13 months). Fifty-six percent of the episodes (95% confidence interval [CI], 40% to 72%) were associated with symptoms very suggestive or suggestive of an infection of the upper respiratory tract at the onset of the episodes; 33% of the episodes (95% CI, 19% to 50%) had possible symptoms suggestive of an infection; whereas only 10% of the episodes (95% CI, 3% to 24%) had questionable or no symptoms suggestive of an infection of the upper respiratory tract. Thirty-four episodes had the onset between September and March, whereas only 5 episodes occurred between April and August (p < 0. 001). CONCLUSIONS: These observations indicate that prolonged episodes of unexplained, persistent asthma lasting for months to years constitute a distinct clinical pattern of asthma with characteristic clinical features.

Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.