Taller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis.

Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30-40% for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. SUMMARY: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case-control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11-1.46), 1.34 (95% CI 1.04-1.73) and 1.45 (95% CI 1.04-2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.

A pilot study to examine the feasibility of insulin glargine in subjects with impaired fasting glucose, impaired glucose tolerance or new-onset type 2 diabetes.

OBJECTIVE: People with early type 2 diabetes and pre-diabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) are at risk of hyperglycaemia-related complications, including cardiovascular disease. Insulin, traditionally reserved as late treatment in type 2 diabetes, may also be a useful therapy in this population. We examined the short-term efficacy and tolerability of insulin glargine (glargine) in individuals with early or pre-type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicentre, double-blind, placebo-controlled, randomized, parallel group, 12-day study, subjects with IGT/IFG (n=9), newly diagnosed type 2 diabetes (n=9) or normal glucose tolerance (n=3) (confined to a clinical research unit taking a prescribed diet) were randomized to once-daily glargine (n=16) or placebo (saline; n=5) at bedtime. Dose was titrated to achieve target fasting blood glucose (FBG) 80-95 mg/dL. RESULTS: Over the treatment period, mean FBG decreased in glargine-treated subjects (from 100.0+/-18.8 to 85.6+/-18.4 mg/dL), but was unchanged in placebo-treated subjects (from 112.5+/-10.6 to 111.3+/-17.5 mg/dL). Mean eight-point blood glucose value decreased by 9.7 mg/dL in the glargine group, but increased by 8.1 mg/dL in the placebo group. Mean post-exercise blood glucose was similar before and after glargine treatment, but increased after placebo treatment. Five subjects receiving glargine experienced 16 mild symptomatic hypoglycaemia episodes; however, no hypoglycaemia occurred during exercise. Mean body weight decreased in both the glargine (-0.44 kg) and placebo (-0.25 kg) groups, in line with dietary restrictions. CONCLUSIONS: The results of this pilot study suggest that glargine can be used by people with IFG, IGT or new-onset type 2 diabetes for management of hyperglycaemia with low risk of hypoglycaemia. However titration of insulin in people on dietary restrictions should be more cautious as they may be more prone to hypoglycaemia. Further studies are warranted to determine the clinical benefits of this approach.

An elementary introduction to Bayesian computing using WinBUGS.

Bayesian statistics provides effective techniques for analyzing data and translating the results to inform decision making. This paper provides an elementary tutorial overview of the WinBUGS software for performing Bayesian statistical analysis. Background information on the computational methods used by the software is provided. Two examples drawn from the field of medical decision making are presented to illustrate the features and functionality of the software.

Computing population-based estimates of health-adjusted life expectancy.

Observed health-adjusted life expectancy (HALE) is an indicator of population health. There are a number of ways to compute HALE for a community. The authors surveyed several methods and demonstrate resulting variation in the estimates of HALE. Quality of well-being (QWB) measures from 1,430 participants in the Beaver Dam Health Outcomes Study are taken as weights. Actuarial life-table methods using community mortality data, State of Wisconsin census data from two time frames, and U.S. census data are used with the QWB to estimate HALE. Measurement of community population health using HALE computations can be completed with national, regional, or local data. Community-level estimates may not be well approximated using large-scale mortality experience. A Bayesian method is developed combining the local data with regional data. The Bayesian method creates a smooth set of rates, retains the local flavor of the community, and gives a measure of variability of the estimated HALE.

A management tool for controlling the rate of non-acceptable inpatient hospital claims.

This paper demonstrates a tool for substantially improved monitoring of the validity of health insurance claims. Using a Bayesian regression model, we predict the probability of a non-acceptable claim (NAC) for each claim record and the expected number of NACs for any set of claims. When applied to a large set of hospital discharge claims, the tool shows a substantial improvement in the ability to estimate the actual number of NACs in the set. The tool permits ongoing monitoring of claims, more precise control, and a substantial reduction in audit cost in claims administration. It is conceptually applicable to other ongoing quality control systems, where inexpensively obtained information can be used to predict events that are costly to measure directly.

Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air.

BACKGROUND: Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of 5-lipoxygenase activating protein, BAYx 1005, on the bronchospastic response to cold dry air hyperventilation was investigated in asthmatic patients. METHODS: After a screening cold dry air hyperventilation challenge to document cold air responsiveness, 16 asthmatic subjects (baseline forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a randomised, double blind, crossover design. Leukotriene synthesis inhibition was estimated by measuring the concentration of leukotriene B4 in whole blood stimulated with calcium ionophore A21387. RESULTS: Treatment with BAYx 1005 produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production, while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02). CONCLUSIONS: Treatment with BAYx 1005, a novel inhibitor of leukotriene synthesis, produced a significant blunting of cold dry air responsiveness consistent with the hypothesis that leukotrienes mediate part of the bronchoconstriction induced by hyperventilation of cold dry air.

Direct evidence for a role of the mast cell in the nasal response to aspirin in aspirin-sensitive asthma.

BACKGROUND: A subset of patients with asthma experience adverse nasoocular reactions after ingestion of aspirin or agents that inhibit cyclooxygenase. Recent evidence has implicated the leukotrienes in the nasoocular reaction, but the cellular sources and mechanism of activation are unknown. We used nasal lavage with and without a 5-lipoxygenase inhibitor, zileuton, to define the role of leukotrienes and to profile nasal cellular activation during this reaction. METHODS: A group of eight patients with asthma shown to have adverse reactions to aspirin documented by a 15% or greater decrease in forced expiratory volume in 1 second, accompanied by an elevation in urinary leukotriene E4 after ingestion of aspirin, received aspirin or placebo in a study with a crossover design. Nasal symptoms and nasal tryptase, histamine, leukotriene, and eosinophil cationic protein levels were evaluated. Serum tryptase and urinary histamine levels were also assessed. Subjects were then randomized to receive a week of treatment with zileuton or placebo, according to a double-blind, crossover design followed by aspirin challenge and measurement of the same mediators. RESULTS: Aspirin ingestion produced a marked increase in nasal symptoms from a baseline symptom score of 2.1 +/- 0.7 to a maximum of 8.4 +/- 1.2 (p < 0.0007). Aspirin ingestion produced a mean maximal increase in nasal tryptase of 3.5 +/- 2.6 ng/ml, whereas placebo ingestion produced a mean maximal increase of 0.1 +/- 0.2 ng/ml (p < 0.05, aspirin vs placebo). Mean maximal nasal histamine increased 1.73 +/- 1.16 ng/ml versus 0.08 +/- 0.08 ng/ml from baseline (p < 0.05, aspirin vs placebo). Aspirin produced a mean maximal increase in nasal leukotriene value of 152 pg/ml versus a 16 pg/ml decrease after placebo ingestion (p < 0.05). Zileuton treatment blocked the increase in nasal symptoms after aspirin ingestion (maximum nasal symptom score of 1.6 +/- 0.6 with zileuton vs 5.5 +/- 0.9 with placebo [p < 0.0053]). It also blocked the rise in nasal tryptase (p = 0.011) and nasal leukotriene (p < 0.05) levels after aspirin ingestion. Zileuton treatment had no significant effect on the recovery of nasal histamine. CONCLUSION: The increase in nasal symptoms in aspirin-sensitive patients with asthma after aspirin ingestion is associated with increases in nasal tryptase, histamine, and cysteinyl leukotriene levels. This mediator profile is consistent with mast cell activation during the nasal response to aspirin and suggests that 5-lipoxygenase products are essential for the nasal response to aspirin.

The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin.

A subset of persons with asthma develop bronchospasm, naso-ocular, gastrointestinal, and/or dermal reactions after ingesting aspirin (ASA) or agents with the capacity to inhibit cyclooxygenase. The bronchopulmonary reactions have been associated with a rise in urinary LTE4. We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known sensitivity to ASA accompanied by LTE4 hyperexcretion. We first confirmed ASA sensitivity and an increase in urinary LTE4 after ASA ingestion in these patients using a placebo-controlled ASA challenge. Subjects were then randomized to a double-blind, crossover trial to examine the effects of zileuton versus placebo on the response to ASA. Zileuton treatment decreased baseline urinary LTE4 excretion from a mean of 469 +/- 141 pg/mg creatinine to 137 +/- 69 pg/mg creatinine (p < 0.02) and blunted the maximum increase in urinary LTE4 after ingestion of ASA (3,539 +/- 826 pg/mg creatinine versus 1,120 +/- 316 pg/mg creatinine [p < 0.01]). The pre-ASA challenge FEV1 was unchanged by zileuton (3.41 +/- 0.15 L versus 3.35 +/- 0.17 L, zileuton versus placebo). Zileuton prevented the fall in FEV1 in response to ingestion of ASA; post-ASA ingestion the mean of the minimal FEV1 fell to 2.72 +/- 0.18 L on the placebo day while there was no significant fall on the zileuton day (3.26 +/- 0.17 L; p < 0.014). Zileuton also prevented the development of the nasal, gastrointestinal (p < 0.006 and p < 0.025, respectively), and dermal symptoms which developed after ASA ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical imaging rounds: hypertension in a postpartum patient.

The authors report a case of a 26-year-old female with gestational headaches, hypertension, weight loss, and tachycardia. Symptoms continued postpartum and a hypertensive workup revealed an adrenal mass and elevated catecholamines.

Blind spot enlargement as a manifestation of multifocal choroiditis.

Enlargement of the blind spot without optic disc edema has been reported in patients with no other ocular findings (acute idiopathic blind spot enlargement) and in patients with multiple evanescent white dot syndrome. We describe three patients with multifocal choroiditis who developed acute symptomatic enlargement of the blind spot. All three patients were young women in excellent health. During the course of the blind spot enlargement, the appearance of the optic nerve remained normal. We demonstrate that acute enlargement of the blind spot without disc edema occurs in patients with multifocal choroiditis. This enlargement is likely due to peripapillary retinal dysfunction. We speculate on the association of multifocal choroiditis with acute idiopathic blind spot enlargement and multiple evanescent white dot syndrome.

Groin Strain and Other Possible Causes of Groin Pain.

In brief: Groin strains (and injuries assumed to be groin strains) have been treated with a simple, straightforward approach. However, complications too often arise from inadequate diagnosis or improper management of these injuries. A pelvic stress fracture, an avulsion injury, and even a tumor can be confused with a groin strain. This article discusses the importance of differential diagnosis, which can help prevent serious complications. The authors also present a case report of a football player who was diagnosed with myositis following a groin strain he had sustained a year earlier.

Neodymium:YAG laser cutting of intraocular lens haptics in vitro and in vivo.

Various complications following intraocular lens (IOL) surgery result in explantation of the lenses. Haptic fibrosis may necessitate cutting the IOL haptics prior to removal. In this study we used the neodymium: YAG (Nd:YAG) laser to cut polypropylene and poly(methyl methacrylate) (PMMA) haptics in vitro and in rabbit eyes. In vitro we were able to cut 100% of both haptic types successfully (28 PMMA and 30 polypropylene haptics). In rabbit eyes we were able to cut 50% of the PMMA haptics and 43% of the polypropylene haptics. Poly(methyl methacrylate) haptics were easier to cut in vitro and in vivo than polypropylene haptics, requiring fewer shots for transection. Complications of Nd:YAG laser use frequently interfered with haptic transections in rabbit eyes. Haptic transection may be more easily accomplished in human eyes.

An instrument to aid intracapsular cataract extraction of dislocated lenses.

Techniques for surgical removal of a dislocated lens have evolved considerably in the past 30 years. There has been a change in preference from open-sky techniques to the use of automated vitrectomy instruments. We introduce an instrument which may be useful in selected patients with dislocated lenses. This instrument is placed through the pars plana to entrap the lens anteriorly without trauma to the retina or ciliary body. Cryoextraction of the lens through a limbal incision is then performed. We feel this instrument will be most useful in the management of a dislocated nucleosclerotic lens.

A clinical analysis of pseudopapilledema. I. Population, laterality, acuity, refractive error, ophthalmoscopic characteristics, and coincident disease.

To clarify clinical features of pseudopapilledema, 142 cases (250 eyes) were analyzed regarding sex, age, race, bilaterality, acuity, refractive error, fundus characteristics, and coincident disease. Ninety-eight cases of identifiable hyaline bodies ([HB] group 1) were compared with 44 cases of pseudopapilledema without HB (group 2). The following results were notable: marked predominance of whites; one third in group 1 were unilateral, and 14% of all pseudopapilledema was unilateral; in only one eye did HB apparently account for diminished acuity; refractive error distribution paralleled that in the general population; anomalous vascular patterns occurred in 20% of group 1 and in 31% of group 2; pigment epithelial changes were found in 33% of group 1 and in 20% of group 2; and a statistically significant association was found with retinitis pigmentosa only. Analysis of field defects is the subject of a companion report.

A clinical analysis of pseudopapilledema. II. Visual field defects.

Goldmann perimetry was performed on patients with pseudopapilledema. The cases were subdivided into those with ophthalmoscopically visible hyaline bodies (HB), (group 1) and those without (group 2). In group 1, 37 of 52 eyes (71%) demonstrated field abnormalities, including enlargement of the blind spot (68%) and various nerve fiber bundle defects (70%); inferior nasal defects were the single most frequent defect. In group 2, ten of 47 eyes (21%) showed only enlarged blind spots and two fields were generally constricted. No nerve fiber generally constricted. No nerve fiber bundle defects were found in this group. It is noted that field defects related to other ocular or intracranial diseases may be found in patients with intrapapillary HBs.

Ultrasonic characteristics of chronic atrophic pyelonephritis.

Six cases of chronic atrophic pyelonephritis were studied with gray scale ultrasound. The findings are analogous to those seen pathologically, namely a focal or multifocal process with loss of renal parenchyma, retraction of one or more calyces, decrease in renal size, and increased echoes from fibrosis. In the proper clinical setting, the diagnosis of chronic atrophic pyelonephritis can be made using ultrasound technique.

An economical operant space interface for the PDP-8 computer.

An inexpensive input/output transfer system between a PDP-8/1 Digital Equipment Corporation computer and two operant stations is described. An interrupt facility is included. Slight modification of this interface will also permit it to work with the newer PDP-8 series computers.