Sam Sheps

Early risk factors for miscarriage: a prospective cohort study in pregnant women.

Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage.

Stress and reproductive failure: past notions, present insights and future directions

ProblemMaternal stress perception is frequently alleged as a cause of infertility, miscarriages, late pregnancy complications or impaired fetal development. The purpose of the present review is to critically assess the biological and epidemiological evidence that considers the plausibility of a stress link to human reproductive failure.MethodsAll epidemiological studies published between 1980 and 2007 that tested the link between stress exposure and impaired reproductive success in humans were identified. Study outcomes were evaluated on the basis of how associations were predicted, tested and integrated with theories of etiology arising from recent scientific developments in the basic sciences. Further, published evidence arising from basic science research has been assessed in order to provide a mechanistic concept and biological evidence for the link between stress perception and reproductive success.ResultsBiological evidence points to an immune–endocrine disequilibrium in response to stress and describes a hierarchy of biological mediators involved in a stress trigger to reproductive failure. Epidemiological evidence presents positive correlations between various pregnancy failure outcomes with pre-conception negative life events and elevated daily urinary cortisol. Strikingly, a relatively new conceptual approach integrating the two strands of evidence suggests the programming of stress susceptibility in mother and fetus via a so-called pregnancy stress syndrome.ConclusionsAn increasing specificity of knowledge is available about the types and impact of biological and social pathways involved in maternal stress responses. The present evidence is sufficient to warrant a reconsideration of conventional views on the etiology of reproductive failure. Physicians and patients will benefit from the adaptation of this integrated evidence to daily clinical practice.

Epidemiology of bicycle injury, head injury, and helmet use among children in British Columbia: a five year descriptive study

Objectives and methods—Data on 1462 injured bicyclists aged 1–19, obtained over a period of five years from the British Columbia Childrens Hospital as part of a national emergency room based program in Canada, were analyzed to describe the epidemiology of injuries, helmet use, and the occurrence of head injuries before the enactment of a new mandatory helmet law. The odds ratio (OR) and 95% confidence interval (CI) were calculated for non-users compared with helmet users. Results—Bicycle injuries comprised 4% of all injuries seen in the five year study period. The proportion of admissions was 12.7% among bicyclists, significantly higher than the 7.9% admissions of all 35 323 non-bicyclist children who were seen during the study period (OR = 1.96, CI = 1.44 to 1.99). Boys were injured more often than girls. The proportion of admissions for boys was 13.8% compared with 10.2% among girls (OR = 1.41, CI = 0.97 to 2.05). More than 70% of injured bicyclists reported no helmet use. The proportion of admissions of injured bicyclists who did not use helmets was always higher than the proportion of admissions of those who used helmets (OR = 2.23, CI = 1.39 to 3.62). Head and face injuries occurred more often among those who did not use helmets (OR = 1.55, CI= 1.18 to 2.04 ). However, there was no excess of minor head injuries among non-users (OR = 1.10, CI = 0.60 to 2.06). Of the 62 concussions, 57 occurred to non-helmet users (OR = 4.04, CI = 1.55 to 11.47). Most injuries occurred in the upper (46.4%) or lower extremities (32.4%). Dental injuries occurred slightly more often among helmet users compared with non-users but this excess was not statistically significant (OR = 1.29, CI = 0.76 to 2.20). Conclusion—The data indicate the need to control injuries by using helmets. A decrease in the number of head injuries and their severity is expected when bicycle helmet use becomes law in British Columbia.

Age-Related Changes in Humoral and Cell- Mediated Immunity in Down Syndrome Children Living at Home

ABSTRACT. Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 μg/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.

The Effect of Maternal Age on Adverse Birth Outcomes: Does Parity Matter?

OBJECTIVES To examine the effect of parity on the association between older maternal age and adverse birth outcomes, specifically stillbirth, neonatal death, preterm birth, small for gestational age, and neonatal intensive care unit admission. METHODS We conducted a retrospective cohort study of singleton births in British Columbia between 1999 and 2004. In the cohort, 69 023 women were aged 20 to 29, 25 058 were aged 35 to 39, and 4816 were aged 40 and over. Perinatal risk factors, obstetric history, and birth outcomes were abstracted from the British Columbia Perinatal Database Registry. Logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals for adverse outcomes in the two older age groups compared with the young control subjects. RESULTS Compared with younger control subjects, women aged 35 to 39 years had an aOR of stillbirth of 1.5 (95% CI 1.2 to 1.9) and women aged >or= 40 years also had an aOR of 1.5 (95% CI 1.0 to 2.4). The aOR for NICU admission was 1.2 (95% CI 1.0 to 1.3) in women aged 35 to 39 years and 1.4 (95% CI 1.1 to 17) in women aged >or= 40 years compared with younger control subjects. The risk of preterm birth and SGA differed by parity. The aOR for preterm birth compared with younger primiparas was 1.5 (95% CI 1.4 to 1.7) for women aged 35 to 39 years and 1.6 (95% CI 1.3 to 2.0) for women aged >or= 40 years. In multiparas the aOR for preterm birth was 1.1 (95% CI 1.1 to 1.2) in women aged 35 to 39 and 1.3 (95% CI 1.1 to 1.5) in women >or= 40 years. The aOR for SGA in primiparas was 1.2 (95% CI 1.1 to 1.4) for women aged 35 to 39 and 1.4 (95% CI 1.1 to 1.7) for women aged >or= 40 years. The risk of neonatal death was not significantly different between groups. CONCLUSION Older women were at elevated risk of stillbirth, preterm birth, and NICU admission regardless of parity. Parity modified the effect of maternal age on preterm birth and SGA. Older primiparas were at elevated risk for SGA, but no association between age and SGA was found in multiparas. Older primiparas were at higher risk of preterm birth than older multiparas compared with younger women.

Childhood, adolescent, and young adult cancer survivors research program of British Columbia: Objectives, study design, and cohort characteristics†

The Childhood, Adolescent, and Young Adult Cancer Survivors Research Program (CAYACS) has been established in the province of British Columbia (BC), Canada, to carry out research into late effects and survivor care in multiple domains, and to inform policy and practice.

Infection and immunity in Down syndrome: A trial of long-term low oral doses of zinc†

To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

Determinants of hospitalization for a cutaneous injection-related infection among injection drug users: a cohort study

AstractBackgroundCutaneous injection-related infections (CIRI) are a primary reason individuals who inject drugs (IDU) are hospitalized. The objective of this study was to investigate determinants of hospitalization for a CIRI or related infectious complication among a cohort of supervised injection facility (SIF) users.MethodsFrom 1 January 1 2004 until 31 January 2008, using Cox proportional hazard regression, we examined determinants of hospitalization for a CIRI or related infectious complication (based on ICD 10 codes) among 1083 IDU recruited from within the SIF. Length of stay in hospital and cost estimates, based on a fully-allocated costing model, was also evaluated.ResultsAmong hospital admissions, 49% were due to a CIRI or related infectious complication. The incidence density for hospitalization for a CIRI or related infectious complication was 6.07 per 100 person-years (95% confidence intervals [CI]: 4.96 - 7.36). In the adjusted Cox proportional hazard model, being HIV positive (adjusted hazard ratio [AHR] = 1.79 [95% CI: 1.17 - 2.76]) and being referred to the hospital by a nurse at the SIF (AHR = 5.49 [95% CI: 3.48 - 8.67]) were associated with increased hospitalization. Length of stay in hospital was significantly shorter among participants referred to the hospital by a nurse at the SIF when compared to those who were not referred (4 days [interquartile range {IQR}: 2-7] versus 12 days [IQR: 5-33]) even after adjustment for confounders (p = 0.001).ConclusionsA strong predictor of hospitalization for a CIRI or related infectious complication was being referred to the hospital by a nurse from the SIF. This finding indicates that nurses not only facilitate hospital utilization but may provide early intervention that prevents lengthy and expensive hospital visits for a CIRI or related infectious complication.

Reflections on safety and interprofessional care: Some conceptual approaches

A cornerstone of the emerging ideas about safety in health care is an emphasis on the development of learning organizations (whether hospitals, operating rooms [ORs], intensive care units [ICUs], home care programs, emergency departments [EDs], etc.). Senge (1990), in The Fifth Discipline, notes that one of the five dimensions he considers critical to safety is team learning, the others being personal mastery (or competencies as we would call them now), mental models, building a shared vision and system thinking. System thinking is the Fifth Discipline of the title, which he considers as integrating all the others. While this may be true at the macro level, at the micro level the concept of team learning should lead directly to both a shared vision and the development of mental models, cognitive processes that are clearly linked and critical for good team performance. Moreover, team building and performance are, among other things, critical to the development of resilience as a key adverse event mitigating strategy, as most recently discussed at length by experts in the field in the book edited by Hollnagel, Woods and Leveson (2006), Resilience engineering: Concepts and precepts. Moreover, these authors, as well as Rasmussen (1986), Dekker (2002) and Reason (1990), among others, have constructed a very strong case for the influence of systems within which professionals work. Systems, whether in health care or other domains, are complex and dynamic and thus inherently give rise to situations in which safety inadvertently but inherently is compromised, whether arising from the specific tools and tasks used in patient care, or higher level management decisions shaping the macro level features of the system. Within such a dynamic and highly inter-active system environment, team development is what inter-disciplinary care is all about, although until recently inter-disciplinarity was more implicit than explicit, rather superficial and not founded on the fundamental importance of the role shared mental models or shared vision play in creating high reliability teams, the exception being the clinical domains of operating rooms and anesthesia (Sexton et al., 1998a, 1998b). In addition, recent work by Weick et al. (1999), Rochlin (1999), and

Hospitalisations 1998-2000 in a British Columbia population-based cohort of young cancer survivors: report of the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Research Program.

BACKGROUND AND OBJECTIVES Because of late effects among survivors of cancer in young people, increased hospitalisations would be expected. This study determined the occurrence, frequency and days in hospital (DIH) of hospital admissions among 5-year survivors of childhood and adolescent cancer diagnosed in British Columbia (BC), compared hospitalisation risk with the general population and examined the impact of sociodemographic, health care system and clinical factors. DESIGN This population-based study frequency matched 1157 survivors of cancer diagnosed before 20 years of age from 1970 to 1992 from the BC Cancer Registry with 11,570 randomly selected individuals from BCs health insurance plan Client Registry. Administrative hospitalisation records from 1998 to 2000 were linked to study cohorts, and regression and trend analyses were carried out. RESULTS From 1998 to 2000, 240 (21%) of survivors and 614 (5.3%) of the population sample were admitted to hospital at least once [adjusted OR=4.36 (95% CI 3.68-5.16)]. Hospitalised survivors had a higher average number of admissions (2.0 versus 1.5 admissions, respectively) and longer mean DIH (10.9 versus 7.8d, respectively) than hospitalised population controls. Female gender and older age increased the risk of hospitalisation, as did the presence of a relapse or second cancer by 5 years post-diagnosis. CONCLUSION Our cohort of child and adolescent cancer survivors had higher odds of hospitalisation, more admissions among those hospitalised and longer stay in hospital compared to the population sample. This has implications for health care system resources and appropriate management of late effects of survivors.