Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Multiple imputation using linked proxy outcome data resulted in important bias reduction and efficiency gains: a simulation study.

BACKGROUND: When an outcome variable is missing not at random (MNAR: probability of missingness depends on outcome values), estimates of the effect of an exposure on this outcome are often biased. We investigated the extent of this bias and examined whether the bias can be reduced through incorporating proxy outcomes obtained through linkage to administrative data as auxiliary variables in multiple imputation (MI). METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we estimated the association between breastfeeding and IQ (continuous outcome), incorporating linked attainment data (proxies for IQ) as auxiliary variables in MI models. Simulation studies explored the impact of varying the proportion of missing data (from 20 to 80%), the correlation between the outcome and its proxy (0.1-0.9), the strength of the missing data mechanism, and having a proxy variable that was incomplete. RESULTS: Incorporating a linked proxy for the missing outcome as an auxiliary variable reduced bias and increased efficiency in all scenarios, even when 80% of the outcome was missing. Using an incomplete proxy was similarly beneficial. High correlations (> 0.5) between the outcome and its proxy substantially reduced the missing information. Consistent with this, ALSPAC analysis showed inclusion of a proxy reduced bias and improved efficiency. Gains with additional proxies were modest. CONCLUSIONS: In longitudinal studies with loss to follow-up, incorporating proxies for this study outcome obtained via linkage to external sources of data as auxiliary variables in MI models can give practically important bias reduction and efficiency gains when the study outcome is MNAR.

Prediction of violent crime on discharge from secure psychiatric hospitals: A clinical prediction rule (FoVOx).

BACKGROUND: Current approaches to assess violence risk in secure hospitals are resource intensive, limited by accuracy and authorship bias and may have reached a performance ceiling. This study seeks to develop scalable predictive models for violent offending following discharge from secure psychiatric hospitals. METHODS: We identified all patients discharged from secure hospitals in Sweden between January 1, 1992 and December 31, 2013. Using multiple Cox regression, pre-specified criminal, sociodemographic, and clinical risk factors were included in a model that was tested for discrimination and calibration in the prediction of violent crime at 12 and 24 months post-discharge. Risk cut-offs were pre-specified at 5% (low vs. medium) and 20% (medium vs. high). RESULTS: We identified 2248 patients with 2933 discharges into community settings. We developed a 12-item model with good measures of calibration and discrimination (area under the curve=0.77 at 12 and 24 months). At 24 months post-discharge, using the 5% cut-off, sensitivity was 96% and specificity was 21%. Positive and negative predictive values were 19% and 97%, respectively. Using the 20% cut-off, sensitivity was 55%, specificity 83% and the positive and negative predictive values were 37% and 91%, respectively. The model was used to develop a free online tool (FoVOx). INTERPRETATION: We have developed a prediction score in a Swedish cohort of patients discharged from secure hospitals that can assist in clinical decision-making. Scalable predictive models for violence risk are possible in specific patient groups and can free up clinical time for treatment and management. Further evaluation in other countries is needed. FUNDING: Wellcome Trust (202836/Z/16/Z) and the Swedish Research Council. The funding sources had no involvement in writing of the manuscript or decision to submit or in data collection, analysis or interpretation or any aspect pertinent to the study.

Intestinal-transit and lactose intolerance in chronic alcoholics.

Intestinal transit time of lactulose and malabsorption of lactose were measured by hydrogen excretion in breath following ingestion of 20 g lactulose or 25 g lactose. Patients were 20 recently drinking, adequately nourished, chronic, male alcoholics. Many (65%) complained of diarrhea while drinking actively. Small bowel transit was significantly shorter in alcoholics with diarrhea (62 +/- 8.6 min) than in normal controls (93 +/- 10.4 min, p less than 0.05). It increased significantly after 8-10 days abstinence, to a value of 101.5 +/- 11 min, not significantly different from normal controls. Following lactulose 75% of alcoholics developed diarrhea after 1-2 days compared with only 15% after 8-10 days of abstinence; 40% had diarrhea after lactose in the initial study, whereas no subjects had diarrhea from the same dose after a period of sobriety. These data suggest that drinking alcoholics have an increased sensitivity to osmotic loads, which is associated with diarrhea, shortened transit time, and lactose intolerance. Abnormalities disappeared 8-10 days following cessation of drinking and normal diet.

A study of phosphoenolpyruvate carboxykinase from Moniliformis dubius (Acanthocephala).

Procedures have been developed for the extraction and subsequent purification of the enzyme phosphoenolpyruvate carboxykinase (GTP) (PEPCK) from Moniliformis dubius (Acanthocephala), a parasite of the rat small intestine. This is believed to be the first purification of PEPCK from an invertebrate animal. The enzyme, when purified to homogeneity as indicated by electrophoretic criteria, has a molecular weight of 73 700. Kinetic studies indicated that the enzyme had a pH optimum of 5.5 and required Mn2+ as the divalent cation. The apparent Km values determined for the substrates of the carboxylation reaction were low compared with the published values for purified PEPCK from vertebrate sources. Several competitive inhibitors were found and their Ki values determined. The possible regulation of PEPCK activity in M. dubius is discussed with reference to the observed kinetic parameters.

Topography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury.

STUDY DESIGN: Axonal injury was examined in 18 human cases of acute spinal cord compression using amyloid precursor protein as a marker of AI. OBJECTIVES: To topographically map and semiquantitate axonal injury in spinal cord compression of sufficient severity to produce para- or quadriplegia. SUMMARY OF BACKGROUND DATA: Amyloid precursor protein is carried along the axon by fast axoplasmic transport and has been extensively used as a marker of traumatic axonal injury. METHODS: The study group comprised 18 cases of spinal cord compression (17 due to fracture dislocation of the vertebral column and 1 iatrogenic compression from Harrington rods) and two normal control. All the cords were examined according to a standard protocol, and at least 10 segmental levels were immunostained using a monoclonal antibody to amyloid precursor protein and immunopositive AI was semiquantitated using a grading system to provide the axonal injury severity score (AISS). The focal injury at the site of cord compression (haemorrhage, haemorrhagic necrosis, ischaemic necrosis) was also semiquantitated to provide the focal injury area score (FIAS). AI occurring around the site of focal compression (focal axonal injury severity score or FAISS) was distinguished from AI distant to the focal injury (nonfocal axonal injury severity score or NFAISS). RESULTS: All 18 cases showed widespread amyloid precursor protein immunoreactive axonal injury and the AISS ranged from 28 to 60%. In all cases, the FAISS was greater than the NFAISS and there was a statistically significant relationship between the AISS and the FIAS. CONCLUSION: Acute spinal cord compression of sufficient severity to produce permanent paralysis causes widespread axonal damage that is maximal at the site of compression but also present throughout the length of the cord in segments far distant from the site of the focal injury.

Purification and properties of phosphoenolpyruvate carboxykinase from Hymenolepis diminuta (Cestoda).

A method is described for the purification of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) from the cestode Hymenolepis diminuta. When purified to electrophoretic homogeneity, the enzyme had a molecular weight of 70,600 and an isoelectric point of 7.5. Kinetic studies indicated that the pH 5.6 was optimal for the carboxylation reaction and that Mn++ was the preferred divalent cation; there was no activity of the enzyme in the presence of Mg++. Apparent Km values for the carboxylation reaction were determined; those for GDP (20.6 muM) and PEP (38.9 muM) were lower than the values previously reported. GTP, GMP, ITP, IMP, fumarate, succinate and alpha-ketoglutarate were found to be competitive inhibitors and their Ki values determined.

Mebendazole concentrations in sheep plasma.

Formulated mebendazole was administered to sheep by intraruminal injection at dose rates of 12.5, 25, 50 or 100 mg/kg bodyweight. The concentrations of mebendazole and two major metabolites were measured by high-performance liquid chromatography in plasma taken at intervals up to 48 hours after treatment. At 12.5 mg/kg the peak plasma concentration was 0.22 +/- 0.03 microM mebendazole, rising to 0.76 +/- 0.04 microM at 100 mg/kg. Peak plasma concentrations occurred between nine and 24 hours for all dose rates and declined rapidly. Two major metabolites were detected; their concentrations exceeded that of mebendazole at all dose rates.

Patterns of immunocytochemical staining for ferritin and transferrin in the human spinal cord following traumatic injury.

Normally Fe(2+) is strictly controlled within the central nervous system (CNS) because of its potential to react with oxygen and form free radicals.(1,2) Traumatic spinal cord injury (TSCI) leads to cell damage and haemorrhage, both of which may increase the pool of free iron.(3) The aim of this study was to examine the response to TSCI of the iron storage protein ferritin (Ft) and the iron transport protein transferrin (Tf). The study found a significant increase in Ft positive cells compared to controls and a significant correlation between the number of Ft positive cells and the severity of injury. Significantly fewer Tf positive cells were seen in the trauma cases compared to the control and there was no relation with the severity of injury. These observations suggest a disturbance in normal iron metabolism within the spinal cord following injury, with possible implications for free radical mediated secondary damage.

Calculation of the number of cancer deaths prevented by the Uranium Mill Tailings Remedial Action Project.

The Uranium Mill Tailings Remedial Action Project has completed remedial action at 22 uranium mill tailings sites and about 5,000 properties ("vicinity properties") where tailings were used in construction, at a total cost of $1.45 billion. This paper uses existing data from Environmental Impact Statements and Environmental Assessments, and vicinity property calculations, to determine the total number of cancer deaths averted by the Uranium Mill Tailings Remedial Action Project. The cost-effectiveness of remediating each site, the vicinity properties, and the entire project is calculated. The cost per cancer death averted was four orders of magnitude higher at the least cost-effective site than at the most cost-effective site.

Do thinner rigid gas permeable contact lenses provide superior initial comfort?

To test the hypothesis that thinner rigid gas permeable (RGP) contact lenses provide superior initial comfort, RGP lenses of 3 center thicknesses, 0.08, 0.12, and 0.16 mm, in otherwise matched parameters, were worn for 30 min by 17 unadapted subjects in a controlled, double masked, randomized study. Comfort ratings (0 to 100) after 30 min of wear were 42 +/- 30, 55 +/- 27, and 57 +/- 28 for the 0.08-, 0.12-, and 0.16-mm thick lenses, respectively (p = 0.04, multiple analysis of variance (MANOVA)), and 93 +/- 13 for the hydrogel control lens. The thinnest RGP lens was significantly less comfortable than its thicker counterparts (p = 0.03, Univariate F-test). There were no differences among the test lenses in edge shape, front surface wettability, or static lens fittings, and small differences in movement, vertical decentration, and front surface geometry were not significantly related to comfort. We hypothesize that the greater flexibility of the thinnest lens resulted in greater deformation of the lens during a blink cycle, causing transient peripheral lens lifting and interaction with the upper eyelid, thereby reducing comfort. In conclusion we found that thinner RGP lenses do not provide an initial comfort advantage and that very thin and, as a corollary, very flexible, RGP lenses can actually be less comfortable initially than stiffer, but otherwise matched, designs.

Prediction of chronicity in acute low back pain.

Forty-eight patients seeking treatment for low back pain were assessed in the acute stage to see if they exhibited characteristics that would predict response to medical treatment. It was hoped that, if there were personality and demographic differences between patients who did and those who did not respond to standard medical treatment, potential chronic pain patients could be identified and targeted for special treatment. Stepwise discriminant analysis yielded a prediction equation that correctly identified 41 of the 48 cases (85.4%). Acute patients who became chronic complained of pain over a wider area of the body; had deeper, more central pain; were highly anxious; and had a lower activity level. Although cross-validation studies are needed, identification of potentially chronic pain patients may be feasible, making appropriate early intervention possible.

Patient-controlled epidural analgesia after thoracotomy: a comparison of meperidine with and without bupivacaine.

The purpose of this study was to compare meperidine to meperidine with bupivacaine when used for patient-controlled epidural analgesia (PCEA) after thoracotomy. For 3 days after thoracotomy patients received thoracic PCEA with meperidine 0.1% plain or with added bupivacaine 0.1% or 0.01%. No background infusion was used. All patients received indomethacin postoperatively for the duration of the study. Patients were assessed with respect to meperidine consumption, analgesia, and side effects. Sixty-six patients participated. Patients in all three groups obtained effective analgesia with median meperidine consumption of 5-6 mg/h. There were no significant differences between groups in meperidine consumption or pain scores at rest or with coughing. The addition of bupivacaine 0.1% reduced the incidence of pruritus (P = 0.036), but 5 of 23 patients in this group were with-drawn from the study because of significant hypotension, oliguria, and/or motor or sensory block (P = 0.006). We conclude that the addition of bupivacaine 0.1% or 0.01% to thoracic PCEA meperidine 0.1% does not affect meperidine requirements or analgesia after thoracotomy. The addition of bupivacaine 0.1% may reduce pruritus, but is associated with signs of excessive sensory, motor, or autonomic blockade in a significant number of patients.