Association between childhood infection, serum inflammatory markers and intelligence: findings from a population-based prospective birth cohort study.

A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood - a critical period of development for the immune and nervous systems - and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the relationship between inflammatory markers and IQ. Very high infection burden (90+ percentile) was associated with higher CRP levels, but this relationship was explained by body mass index (adjusted odds ratio (OR) 1·19; 95% confidence interval (CI) 0·95-1·50), maternal occupation (adjusted OR 1·23; 95% CI 0·98-1·55) and atopic disorders (adjusted OR 1·24; 95% CI 0·98-1·55). Higher CRP levels were associated with lower IQ; adjusted ß = -0·79 (95% CI -1·31 to -0·27); P = 0·003. There was no strong evidence for an association between infection and IQ. The findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function.

A microwave resonator integrated on a polymer microfluidic chip.

We describe a novel stacked split-ring type microwave (MW) resonator that is integrated into a 10mm by 10mm sized microfluidic chip. A straightforward and scalable batch fabrication process renders the chip suitable for single-use applications. The resonator volume can be conveniently loaded with liquid sample via microfluidic channels patterned into the mid layer of the chip. The proposed MW resonator offers an alternative solution for compact in-field measurements, such as low-field magnetic resonance (MR) experiments requiring convenient sample exchange. A microstrip line was used to inductively couple MWs into the resonator. We characterised the proposed resonator topology by electromagnetic (EM) field simulations, a field perturbation method, as well as by return loss measurements. Electron paramagnetic resonance (EPR) spectra at X-band frequencies were recorded, revealing an electron-spin sensitivity of 3.7·10(11)spins·Hz(-1/2)G(-1) for a single EPR transition. Preliminary time-resolved EPR experiments on light-induced triplet states in pentacene were performed to estimate the MW conversion efficiency of the resonator.

Adverse events related to medications identified by a Canadian poison centre.

BACKGROUND: Poison centres are an underutilized source of information on adverse events related to medications, including therapeutic errors and adverse drug reactions. OBJECTIVE: To demonstrate the feasibility of using a poison centres' electronic data to identify and describe adverse events related to medications. METHODS: This one-year, retrospective cross-sectional pilot study was conducted at one Canadian Poison Centre. All records from the IWK Regional Poison Centre database in Nova Scotia between November 1, 2007 and October 31, 2008 for unintentional exposures were abstracted for a descriptive data analysis. RESULTS: An issue related to use of a medication was the main reason for 1,525 (32.5%) of 4,697 eligible calls. Of the 1,525 calls, 970 (63.6%) were coded as 'unintentional-general.' There were 470 (30.8%) calls for unintentional therapeutic errors and 61 (4.0%) for adverse drug reactions. The majority of calls involving medications were judged to have resulted in minimal or no toxic effect (78.4%). However, 3.3% of calls involving adverse drug reactions resulted in admission to a critical care unit (n=2). Approximately 1% of calls involving unintentional therapeutic errors resulted in admission to hospital (n=6). CONCLUSIONS: Calls to poison centres provide a potentially valuable source of information on adverse events related to medications that are likely not reported elsewhere. Establishment of a mechanism to routinely share information from all Canadian poison centres with relevant national drug safety programs (e.g., MedEffect™ Canada) will provide a supplementary source of information and contribute to building capacity for detection of sentinel events and pharmacosurveillance.

The association between a prolonged stay in the emergency department and adverse events in older patients admitted to hospital: a retrospective cohort study.

OBJECTIVE: Patient safety studies have identified older adults as a high-risk group for adverse events (AEs). As frequent users of the emergency department (ED), they are vulnerable to the negative consequences of ED crowding. The study objective was to determine whether a prolonged ED stay is associated with an increased risk for the occurrence of AEs for older patients admitted to hospital. METHODS: This retrospective cohort study was conducted at the largest adult tertiary care facility in Atlantic Canada (1 July 2005-31 March 2006). All community-dwelling persons 65 years and older admitted to an acute inpatient unit from the ED were eligible. The exposure of interest was total length of stay (LOS) in the ED. The primary outcome was the occurrence of an AE in-hospital. AEs were identified from administrative diagnostic data using previously validated screening criteria. RESULTS: The average age of 982 eligible participants was 77.8 years (SD 7.8). The majority (75.0%) experienced a prolonged ED LOS as defined by national guidelines. There was evidence of at least one AE in 140 (14.3%) records. After adjustment, for every hour spent in the ED, the odds of experiencing an AE in-hospital increased 3% (OR 1.03, 95% CI 1.004 to 1.05). Those with an AE had twice the hospital LOS (20.2 vs 9.8 days, p < 0.00001). INTERPRETATION: A prolonged ED stay for older admitted patients is associated with an increased risk of an in-hospital AE. The longer hospital LOS associated with AEs further reduces the availability of acute care beds, thus exacerbating ED crowding.

Long-term complications of bone-anchored hearing aids: a 14-year experience.

OBJECTIVES: To report cases of long-term surgical complications, implant failure and revision surgery, within a large bone-anchored hearing aid programme. STUDY DESIGN: Retrospective, case-cohort study. SETTING: Tertiary referral centre. PATIENTS: One hundred and sixty-five adults and children who had undergone a total of 177 bone-anchored hearing aid implantations. INTERVENTION: Diagnosis and explanation of adverse events and device failure. MAIN OUTCOME MEASURES: Operative complications and survival analysis, surgical challenges related to revisions, and causes of failure. RESULTS: Twenty-one per cent of patients (3.4 per cent of those observed) suffered from skin reactions; this rate did not increase over time. Seventeen per cent had loss of osseointegration at a median interval of 6.3 months. Loss of osseointegration was observed more frequently in patients with a 3 mm compared with a 4 mm fixture (p < 0.001). Intra-operatively, the only complication was bleeding, occurring in 3 per cent of patients. Post-operative complications included: primary bleeding (2 per cent); severe skin reactions requiring intravenous antibiotics, cautery or grafting (8 per cent); thickening or overgrowth of skin requiring excision (8 per cent); failure of osseointegration requiring a new fixture (18 per cent); and graft necrosis requiring revision (1 per cent). In two patients, it was necessary to explore the area to remove overgrowth of bone. In 16 patients (10 per cent), the bone-anchored hearing aid had to be abandoned due to failure of osseointegration (n = 4), dissatisfaction with the aid (n = 6), intolerable pain (n = 4), hair growth around the abutment (n = 1) or recurrent infections (n = 1). In 12 of these patients, the bone-anchored hearing aid was removed surgically. Overall, 57 patients (34 per cent) underwent revision surgery. CONCLUSION: Awareness of complications is becoming increasingly important in bone-anchored hearing aid programme. A substantial workload of device maintenance should be anticipated, and patients should be appropriately counselled beforehand. Ninety per cent of our patients chose to persevere with this form of hearing rehabilitation.

Opinions on provider profiling: telephone survey of stakeholders.

The views of producers, purchasers, and users of provider profiling concerning this practice were studied. A snowball sample of individuals representing seven groups with a stake in retrospective provider profiling were interviewed by telephone over a 12-week period in 1997. Participants were asked what they believed were the most important uses for profiles, who should receive copies of profiles, and what the limitations of profiles are. A semi-structured format was used to ensure that each interview was comparable and complete. The responses were aggregated, and qualitative research approaches were used to analyze them. A total of 40 people were interviewed. A majority of the respondents cited physician education, changing physician behavior, and monitoring and improving the quality of care as valid uses of provider profiles. A majority believed that the recipients of profile data should include the individual providers being profiled, medical administrative staff, people directly involved in the profiling program, pharmacists, and health plan administrators. The respondents acknowledged many limitations of profiles, with the top concern being inherent problems in the use of billing and administrative databases for profiling. Interviews with stakeholders in provider profiling yielded insights into the strengths and weaknesses of profiling, as well as echoing findings reported elsewhere. Health system administrators and health care professionals need to be aware of these issues as they use and modify profiling.

New method for detection of heart allograft rejection: validation of sensitivity and reliability in a rat heterotopic allograft model.

BACKGROUND: Patients with inflammatory heart muscle diseases would benefit from a safe, convenient, rapidly performed diagnostic technique with real-time results not involving tissue removal. We have performed a detailed evaluation of detection of heart allograft rejection by autofluorescence in a heterotopic abdominal rat heart allograft model ex vivo. METHODS AND RESULTS: Recipient rats with allograft (Lewis to Fisher 344; n=71) and isograft (Lewis to Lewis; n=33) hearts, treated with cyclosporine or untreated, were killed at days 2, 4, 7, 14, 21, 28, and 56 after transplant. Nontransplant controls with (n=24) or without (n=24) immunosuppressive therapy were also studied. When the rats were killed, autofluorescence spectra were acquired under blue-light excitation from midtransverse ventricular sections of native and transplanted hearts. Corresponding sections were then evaluated pathologically by a modified International Society for Heart and Lung Transplantation (ISHLT) grading schema. The spectral differences between rejecting and nonrejecting hearts were quantified by linear discriminant functions, producing scores that decreased progressively with increasing severity of tissue rejection. Mean+/-SD discriminant function scores were 2.9+/-1.6, 1.8+/-2.2, -0.1+/-2.8, -1.2+/-2.3, and -2.3+/-3.0 for isografts and allograft ISHLT grades 0, I, II, and III, respectively (Spearman rank-order correlation -0.6; P<0.001, test for trend). Cyclosporine had no detectable effect on the spectra. CONCLUSIONS: The correlation between changes in autofluorescence spectra and ISHLT rejection grade strongly supports the possibility of catheter-based, fluorescence-guided surveillance of rejection.

Disease management program for asthma: baseline assessment of resource use.

Resource use by asthma patients was assessed as a step in the development of a disease management program by a university teaching hospital, a health maintenance organization (HMO), and a national pharmacy benefit management company (PBM). Medication profiles and medical records were reviewed for all HMO patients who had a diagnosis of asthma and a pharmacy claim for an asthma-related drug in 1993; patients with chronic obstructive pulmonary disease were excluded. These 656 patients' use of health care resources (outpatient clinic visits, emergency room and urgent care visits, hospital admissions, and, the associated costs were determined, as were variances from the PBM's clinical guidelines for asthma. Members 0-4 years of age had the most outpatient and emergency/urgent care visits and the most hospital admissions. Forty-four of the patients received high-dose beta-agonist therapy, and 20 of these patients did not receive either an inhaled anti-inflammatory drug or a short course of corticosteroids. The 44 patients had more outpatient clinic and emergency room/urgent care visits, more admissions, and greater total health care costs than the other patients with asthma. The asthma patients' mean health care cost in 1993 was $203, compared with $110 for all enrollees in the HMO. For patients with high use of beta-agonists, the mean cost was nearly three times that for the other asthma patients. The baseline review of resource use identified aspects of medication use that were at variance with treatment guidelines for asthma patients.

Blue microchip laser fabricated from Nd:YAG and KNbO(3).

A Nd:YAG/KNbO(3) composite-material microchip laser has generated blue radiation at 473 nm with output powers of 1 mW when diode laser pumped and 9 mW when Ti:sapphire laser pumped. The fundamental radiation generated by the quasi-three-level (4)F(3/2)-(4)I(9/2) transition in Nd:YAG at 946 nm was frequency doubled in KNbO(3) angle cut to be type I critically phase matched at 45 degrees C. Despite the normally isotropic nature of Nd:YAG, the fundamental is emitted linearly polarized and orthogonal to the linearly polarized blue radiation.

Basal forebrain innervation of rodent neocortex: studies using acetylcholinesterase histochemistry, Golgi and lesion strategies.

Acetylcholinesterase (AChE)-rich projections from basal forebrain to neocortex cerebri were characterized in the present study. The purpose was to investigate 3 aspects of these projections in rats and mice that have been incompletely described in previous work: intracortical organization of the fibers, subcortical pathways and axonal branching patterns of individual basal forebrain neurons. AChE histochemistry, lesions and Golgi impregnations were the principal strategies employed in this light microscopic study. The moderately dense, AChE-stained innervation of neocortex can be altered by intracortical lesions. The results depended on the region involved and the orientation of the lesion. Sagittal knife cuts had barely detectable effects, regardless of sites. Coronal knife cut lesions in medial cortex resulted in substantial loss of staining in cingulate and medial occipital fields. In contrast, coronal lesions of lateral or anterior cortex produce only small zonal reductions in staining. The interpretation of the latter findings that we favor is that AChE-rich basal forebrain fibers enter lateral/anterior cortex and branch densely there, but in tangentially limited and overlapping terminal domains. Observations on the topography and targets of AChE-rich basal forebrain cortical afferents revealed that the fibers could be grouped based on certain characteristics. Three sets of fibers were distinguishable: anterior pathway innervating cortex of the frontal pole. These fibers were traceable to the region of the substantia innominata/nucleus basalis. They crossed the neostriatum and external capsule in the sagittal plane, forming in 3 dimensions an orderly sheet-like array of fibers bridging the anteroventral surface of the neostriatum with nearby polar cortex medial pathway innervating cingulate and medial occipital cortex. Emerging predominantly from the region of the diagonal band, the fibers run caudally as a triangular bundle in deep layer VI of cingulate cortex. lateral pathway innervating most of remaining lateral neocortex. The fibers radiate out from substantia innominata/nucleus basalis with a complex 3-dimensional organization. In all pathways, fibers enter and initially run within layer VI before ascending pialward, although the intracortical course in layer VI differs between pathways. These fibers primarily terminate in layer V with a secondary concentration in layer I. However, the latter appears to receive substantial AChE-stained inputs from other sources, possibly intracortical, as well. The pathways overlap at their respective boundary zones. This system is comparably organized in rats and mice.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison of the composition and catabolism in vitro of porcine very low density lipoprotein subfractions prepared by gel exclusion and heparin-affinity chromatography.

A comparison of the subfractions prepared from porcine plasma very low density lipoproteins by gel exclusion and heparin-Sepharose affinity chromatography revealed that the smallest and largest particles had the highest affinity for the glycosaminoglycan and had the highest ratio of apolipoprotein E to apolipoprotein CII. When the rates of triglyceride hydrolysis catalysed by lipoprotein lipase were compared for the subfractions the results were consistent with the view that apolipoprotein E may play a role in facilitating the catabolism of very low density lipoprotein triglyceride in the presence of glycosaminoglycan.