Development and validation of the Cambridge Multimorbidity Score

BACKGROUND: Health services have failed to respond to the pressures of multimorbidity. Improved measures of multimorbidity are needed for conducting research, planning services and allocating resources. METHODS: We modelled the association between 37 morbidities and 3 key outcomes (primary care consultations, unplanned hospital admission, death) at 1 and 5 years. We extracted development (n = 300 000) and validation (n = 150 000) samples from the UK Clinical Practice Research Datalink. We constructed a general-outcome multimorbidity score by averaging the standardized weights of the separate outcome scores. We compared performance with the Charlson Comorbidity Index. RESULTS: Models that included all 37 conditions were acceptable predictors of general practitioner consultations (C-index 0.732, 95% confidence interval [CI] 0.731-0.734), unplanned hospital admission (C-index 0.742, 95% CI 0.737-0.747) and death at 1 year (C-index 0.912, 95% CI 0.905-0.918). Models reduced to the 20 conditions with the greatest combined prevalence/weight showed similar predictive ability (C-indices 0.727, 95% CI 0.725-0.728; 0.738, 95% CI 0.732-0.743; and 0.910, 95% CI 0.904-0.917, respectively). They also predicted 5-year outcomes similarly for consultations and death (C-indices 0.735, 95% CI 0.734-0.736, and 0.889, 95% CI 0.885-0.892, respectively) but performed less well for admissions (C-index 0.708, 95% CI 0.705-0.712). The performance of the general-outcome score was similar to that of the outcome-specific models. These models performed significantly better than those based on the Charlson Comorbidity Index for consultations (C-index 0.691, 95% CI 0.690-0.693) and admissions (C-index 0.703, 95% CI 0.697-0.709) and similarly for mortality (C-index 0.907, 95% CI 0.900-0.914). INTERPRETATION: The Cambridge Multimorbidity Score is robust and can be either tailored or not tailored to specific health outcomes. It will be valuable to those planning clinical services, policymakers allocating resources and researchers seeking to account for the effect of multimorbidity

Developmental transitions in body color in chacma baboon infants: Implications to estimate age and developmental pace

OBJECTIVES: In many primates, one of the most noticeable morphological developmental traits is the transition from natal fur and skin color to adult coloration. Studying the chronology and average age at such color transitions can be an easy and noninvasive method to (a) estimate the age of infants whose dates of birth were not observed, and (b) detect interindividual differences in the pace of development for infants with known birth dates. MATERIALS AND METHODS: Using a combination of photographs and field observations from 73 infant chacma baboons (Papio ursinus) of known ages, we (a) scored the skin color of six different body parts from pink to gray, as well as the color of the fur from black to gray; (b) validated our method of age estimation using photographic and field observations on an independent subset of 22 infants with known date of birth; and (c) investigated ecological, social, and individual determinants of age-related variation in skin and fur color. RESULTS: Our results show that transitions in skin color can be used to age infant chacma baboons less than 7 months old with accuracy (median number of days between actual and estimated age = 10, range = 0-86). We also reveal that food availability during the mother's pregnancy, but not during lactation, affects infant color-for-age and therefore acts as a predictor of developmental pace. DISCUSSION: This study highlights the potential of monitoring within- and between-infant variation in color to estimate age when age is unknown, and developmental pace when age is known

Does physical activity counselling enhance the effects of a pedometer-based intervention over the long-term : 12-month findings from the Walking for Wellbeing in the West study

Peer reviewedPublisher PD

Quantification of methylmercury and geochemistry of mercury in sediments from a contaminated area of Descoberto (MG), Brazil.

In 2002, metallic Hg was found buried in a rural area of Descoberto city, Brazil. The origin of the Hg was a gold mining explotation plant established nearly one century ago. Although a number of studies have been conducted in order to assess the contamination of the area, none of them investigated the presence of methylated Hg in the hydric system. In this work methylmercury (CH3Hg?) was determined using gas chromatography-pyrolysis-atomic fluorescence detection (CG-pyro-AFS) in material from rain sedimentation boxes and stream sediments near the contaminated area. Total Hg concentration (HgT) along with the chemical speciation by thermo-desorption were performed. HgT in material from the sedimentation boxes was found to be very high, up to 41,580 mg kg 1, even in the rainy season, when in general HgT were much lower than in dry season. The samples from the Grama and Rico streams show a range of HgT from 5.8 to 266 mg kg 1. The thermo-desorption analysis showed predominance of Hg2?, possibly linked to organic sulfur, suggested by a good positive correlation between Hg2?, HgT, organic mater (OM) and total S. The CH3Hg? concentration in stream sediment samples ranged from <0.07 to 1.87 mg kg 1 and in the samples of sedimentation boxes the concentrations were 1.33 and 8.0 mg kg 1 during dry season. The sample with the highest percentage of HgT as Hg2? (98%) presented also the highest percentage of CH3Hg? (0.7%). These are high values, showing that care should be taken to avoid the transport of this material to the hydrological system. Further studies on the transfer through the food chain would be very important

Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.

OBJECTIVE: Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. STUDY DESIGN: To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. RESULTS: After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. CONCLUSIONS: It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included

Presynaptic actions of 4-Aminopyridine and γ-aminobutyric acid on rat sympathetic ganglia in vitro

Responses to bath-applications of 4-aminopyridine (4-AP) and -aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1–1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B-and C-fibre potentials were prolonged. In 4-AP solution (0.1–0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked bursts of spikes and EPSPs in addition to a neuronal depolarization. These bursts, which were not elicited by glycine, glutamate, taurine or (±)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane

Dimensions of Children's Health Beliefs

Health beliefs interviews were conducted with 250 children aged 6-17 years. A factor analysis of the items resulted in six correlated fac tors which were interpreted as 1) specific health concerns, 2)general health concerns, 3) perceived parental concern, 4) perceived general susceptibility, 5) perceived susceptibility to specific conditions, and 6) perceived seriousness of and susceptibility to disease. Factor scores were computed and two-way analyses of variance (by age and sex of child) were conducted on six sets of factor scores. No significant sex differences or sex by age in teraction effects were noted. Younger children scored significantly higher on "specific health concerns"and "perceived general susceptibility,"while older children scored significantly higher on "perceived parental concern. " Tests of differences among variances showed a tendency for the variability to be greater among younger children. The results are interpreted as pro viding partial support for a model of children's health beliefs and as a basis for further operationalization of concepts which are central to an understand ing of motivated health behavior. Implications for practice are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66657/2/10.1177_109019818000700304.pd

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Cell cycle times of short-term cultures of brain cancers as predictors of survival

Tumour cytokinetics estimated in vivo as potential doubling times (Tpot values) have been found to range in a variety of human cancers from 2 days to several weeks and are often related to clinical outcome. We have previously developed a method to estimate culture cycle times of short-term cultures of surgical material for several tumour types and found, surprisingly, that their range was similar to that reported for Tpot values. As Tpot is recognised as important prognostic variable in cancer, we wished to determine whether culture cycle times had clinical significance. Brain tumour material obtained at surgery from 70 patients with glioblastoma, medulloblastoma, astrocytoma, oligodendroglioma and metastatic melanoma was cultured for 7 days on 96-well plates, coated with agarose to prevent proliferation of fibroblasts. Culture cycle times were estimated from relative 3H-thymidine incorporation in the presence and absence of cell division. Patients were divided into two groups on the basis of culture cycle times of ⩽10 days and >10 days and patient survival was compared. For patients with brain cancers of all types, median survival for the ⩽10-day and >10-day groups were 5.1 and 12.5 months, respectively (P=0.0009). For 42 patients with glioblastoma, the corresponding values were 6.5 and 9.0 months, respectively (P=0.03). Lower grade gliomas had longer median culture cycle times (16 days) than those of medulloblastomas (9.9 days), glioblastomas (9.8 days) or melanomas (6.7 days). We conclude that culture cycle times determined using short-term cultures of surgical material from brain tumours correlate with patient survival. Tumour cells thus appear to preserve important cytokinetic characteristics when transferred to culture