Investigating the assumptions of the self‐controlled case series method

We describe some simple techniques for investigating 2 key assumptions of the self‐controlled case series (SCCS) method, namely, that events do not influence subsequent exposures and that events do not influence the length of observation periods. For each assumption, we propose some simple tests based on the standard SCCS model, along with associated graphical displays. The methods also enable the user to investigate the robustness of the results obtained using the standard SCCS model to failure of assumptions. The proposed methods are investigated by simulations and applied to data on measles, mumps and rubella vaccine, and antipsychotics.     

Prevalence of Orthohantavirus-Reactive Antibodies in Humans and Peri-Domestic Rodents in Northern Ethiopia

In 2012, Tigray orthohantavirus was discovered in Ethiopia, but its seasonal infection in small mammals, and whether it poses a risk to humans was unknown. The occurrence of small mammals, rodents and shrews, in human inhabitations in northern Ethiopia is affected by season and presence of stone bunds. We sampled small mammals in two seasons from low- and high-density stone bund fields adjacent to houses and community-protected semi-natural habitats in Atsbi and Hagere Selam, where Tigray orthohantavirus was first discovered. We collected blood samples from both small mammals and residents using filter paper. The presence of orthohantavirus-reactive antibodies in blood was then analyzed using immunofluorescence assay (human samples) and enzyme linked immunosorbent assays (small mammal samples) with Puumala orthohantavirus as antigen. Viral RNA was detected by RT-PCR using small mammal blood samples. Total orthohantavirus prevalence (antibodies or virus RNA) in the small mammals was 3.37%. The positive animals were three Stenocephalemys albipes rats (prevalence in this species = 13.04%). The low prevalence made it impossible to determine whether season and stone bunds were associated with orthohantavirus prevalence in the small mammals. In humans, we report the first detection of orthohantavirus-reactive IgG antibodies in Ethiopia (seroprevalence = 5.26%). S. albipes lives in close proximity to humans, likely increasing the risk of zoonotic transmission.     

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m² with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m² (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.     

Soil-Transmitted Helminthic Infections and Geophagia among Pregnant Women in Jimma Town Health Institutions,Southwest Ethiopia

BackgroundPregnancy is a key step for human''s reproduction and continuity of generation. Pregnant women are among at risk groups for the infection of soil-transmitted helminths (STHs). STHs are highly prevalent in low- and middle-income countries due to the deprived environmental sanitation and personal hygiene. Eating soil (geophagia) is also commonly practiced by pregnant women, particularly in developing countries. The aim of this study was to determine the prevalence of STHs and geophagia, and to assess associated factors among pregnant women in Jimma, Southwest Ethiopia.MethodsA cross sectional study was conducted among 407 pregnant women attending antenatal care (ANC) at different health facilities located in Jimma Town. Data related to sociodemographic and geophagia practice was collected using a structured questionnaire and STH infections status was determined by using McMaster technique.ResultsA total of 407 pregnant women were included in this study. The overall prevalence of any STHs was 19.7% (80/407). Ascaris lumbricoides was the most prevalent 45(56.2%), followed by Trichuris trichiura 19(23.8%) and hookworms 12(15%). There were 4(5%) of double infection with A. lumbricoides and T. trichiura. Overall, 71 (17.4%) of the pregnant women responded to practice geophagia. STHs infection was significantly higher among geophagic pregnant women (p<0.01) and pregnant women who practiced geophagia were 3 times more likely (OR 2.9, 95% CI 1.3–4.2) to have the STHs compared to non-geophagic. Out of those who claimed soil eating habits, 59.1% preferred reddish soil type. Geophagia practice was significantly higher during the third trimester as compared to first and second (p<0.05).ConclusionGeophagia is a risky behavior and this study showed a significant association of geophagia practice with STH infections, although the causal relation could not be established.     

Bedside monitoring of CBF with xenon-CT and a mobile scanner: a novel method in neurointensive care

Combining previously independently established techniques our objective was to develop and evaluate a method for bedside qualitative assessment of cerebral blood flow in neurointensive care (NICU) patients. The CT-protocol was optimized using phantoms and comparing a mobile CT-scanner (Tomoscan-M, Philips) with two stationary CT scanners. Thirty-two per cent xenon was delivered with standard equipment (Enhancer 3000). Mean cortical flow in volunteers was 48 ml/min/100 g, with the mean vascular territorial flow varying between 45 and 66 ml/min/100 g. The potential clinical usefulness was illustrated in three patients with vasospasm following subarachnoid haemorrhage. Our conclusion is that quantitative bedside measurements of CBF can be repeatedly performed in an easy and safe way in a standard NICU-setting, using xenon-inhalation and a mobile CT-scanner. The method is useful for the decision-making, and is a good example of how the quality of multi-modality monitoring in the NICU can be developed and further diversified.     

Urban youth violence: Do definitions and reasons for violence vary by gender?

This study explored how young boys and girls living in low income urban neighborhoods defined and described reasons associated with youth violence. Five focus groups were conducted with 29 youth between the ages of 8 and 12 recruited from four selected study neighborhoods. Participants were asked to describe youth violence. Appropriate probes were used to explore similarities and differences by gender with regard to the reasons for violence. Definitions of youth violence were consistent across participants and included verbal threats, physical contact, and often the use of a weapon. Several common reasons for violence were found among both boys and girls; romantic relationships, respect, idle time, gangs.cliques, and witnessing violence. Reasons for violence unique to boys include fighting about issues related to money and illicit drugs. Gossip was identified as a reason specific to why girls engage in violence. Youth violence was perceived as a common problem impacting the lives of the boys and girls in this study. Although many of the reasons identified for violence are similar among boys and girls, select gender differences do exist. Future research and prevention efforts to address youth violence should engage young people in efforts to understand and address this important public health topic.     

Identification and quantification of the hydroxyeicosatetraenoic acids, 20-HETE and 12-HETE, in the cerebrospinal fluid after subarachnoid hemorrhage

PURPOSE: The monohydroxylated metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), is a potent vasoconstrictor of cerebral microvessels. 20-HETE formation is substantially elevated in the cerebral spinal fluid (CSF) in the rat subarachnoid hemorrhage (SAH) model. The presence of 20-HETE in human CSF has not been demonstrated. Therefore, it was the purpose of this study to determine if HETE metabolites are present in human CSF after SAH. METHODS: CSF samples were collected daily from four SAH patients over 15 days. HETE metabolites were separated by HPLC with identification by ion-trap MS/MS and quantification via single quadrupole MS operating in negative single ion monitoring mode. RESULTS: Two major metabolites were identified as 12-HETE and 20-HETE. 20-HETE maximal concentrations were 2.9 and 0.7 ng/ml at approximately 70 h in the two patients with symptomatic cerebral vasospasm (SV) after SAH. Concentrations of 12-HETE in these patients peaked at 21.9 ng/ml and 2.8 ng/ml. Concentrations of 20-HETE and 12-HETE were non-detectible in the majority of the samples obtained from two matched SAH patients without SV. CONCLUSIONS: This study is the first to demonstrate that 20-HETE and 12-HETE are present in the CSF of SAH patients at physiologically relevant concentrations. Based on this information future prospective studies will allow for the delineation of the role of these metabolites in the pathogenesis of SAH.     

The effects of admission alcohol level on cerebral blood flow and outcomes after severe traumatic brain injury

This study examined the relationship between admission serum alcohol level (ETOH) and cerebral blood flow (CBF) and outcomes in the adult traumatic brain injured (TBI) population. We hypothesized that individuals with ETOH > 100 mg/dL will have decreased blood flow on admission and poorer outcomes. Eighty subjects, age 16-65, with severe TBI (Glasgow Coma Score [GCS] 100 mg/dL at the time of admission after a TBI were associated with a decrease in global CBF. Elevated serum ETOH level at time of injury did not, however, impact outcomes.