Patient centred assessment of quality of life for patients with four common conditions.

OBJECTIVES: To assess the reliability, validity, and responsiveness of a new quality of life measure, the patient generated index (PGI) of quality of life, in patients with four common clinical conditions. DESIGN: Prospective one year follow up study. SETTING: Outpatient departments and four general practices in Grampian, Scotland. SUBJECTS: 1746 patients consulting a general practitioner in one of four practices, or referred to outpatients from all Grampian practices over a four month period, with low back pain, menorrhagia, suspected peptic ulcer, and varicose veins. MAIN OUTCOME MEASURES: Postal questionnaire including the PGI, SF-36 health survey, and clinically derived condition specific measures of disease severity. RESULTS: Test-retest reliability was satisfactory for group comparisons (intraclass correlation coefficient 0.65). Validity was confirmed by the observed association of the PGI with the SF-36, condition specific instruments, and sociodemographic variables. For low back pain, the PGI and the SF-36 pain scale were found to be most responsive to clinical change. For patients with menorrhagia and suspected peptic ulcer, only the condition specific instruments detected larger changes than the PGI. CONCLUSIONS: It is possible to develop a patient generated index of quality of life that not only assesses the extent to which patients' expectations are matched by reality but also satisfies criteria of reliability and responsiveness to change. Further work is required to make the PGI more acceptable and meaningful to patients, but it is believed that it offers an exciting new approach to the evaluation of medical care.     

Prediction of perinatal mortality at an early stage of pregnancy

AIM: To define the probability of foetal and neonatal death (PFND) in Lithuania by means of the Medical Birth registry. METHODS: The Medical Birth registry for the year 2002 (29,619 pregnancies resulting in delivery) was used, covering social, environmental, health behaviour factors, obstetric history, health status of pregnant women, and delivery. RESULTS: A statistically significant model has been obtained in which 12 out of 45 analysed factors were significant for the risk of perinatal mortality (PM). In the case of previous neonatal pathology, e.g. damage to CNS, the risk of PM (OR 5.2; 95% CI = 2.1-13.3) was similar to the reported manual work or harmful working conditions during pregnancy (OR 4.8; 95% CI = 1.9-12.1 and OR 4.5; 95% CI = 1.3-15.2, respectively). The influence of father's alcohol abuse (OR 2.6; 95% CI = 1.4-4.7) was comparable to that of the stillborns or premature deliveries. The combination of several factors increased PFND significantly: maternal smoking during pregnancy and paternal smoking and alcohol abuse raised PFND to 0.03 (OR 6.8), mother's hard manual work in combination with harmful conditions during pregnancy increased OR more than 10 times (PFND 0.32) as compared with the situation when only one of those factors was present. CONCLUSIONS: The influence of social, environmental, and behavioural factors on the risk of PM was comparable to that of some of the complications during a previous pregnancy. The combination of risk factors significantly increased PFND. Using modelling, the individual prognosis may be presented to every pregnant woman at an early stage of pregnancy to potentially decrease the impact of unfavourable risk factors on PM.     

Myosteatosis at diagnosis is adversely associated with 2-year survival in women with estrogen receptor-negative metastatic breast cancer

Breast Cancer Research and Treatment - To examine the relationship between skeletal muscle (SM) and cancer-specific outcomes for women with estrogen receptor-negative (ER?) metastatic breast...     

Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C_max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC_0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 to P < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC_0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.     

Effect of cortisone treatment on the active transport of calcium by the small intestine

It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis.The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D(2) or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of (3)H-vitamin D(3), did not provide evidence in favor of a harmone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D.The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the effects of vitamin D, but seems to be independent of any direct interaction with the parent vitamin or its metabolites. If a disorder in vitamin D metabolism is at all involved, it is at a step subsequent to 25-hydroxylation.     

The relevance of somatosensory auras in refractory temporal lobe epilepsies

The purpose of this study is to look at the prevalence, characteristics, and prognostic value of somatosensory auras (SSAs) in patients who have undergone temporal lobe epilepsy (TLE) surgery to treat drug‐resistant focal epilepsy. We retrospectively reviewed all patients with drug‐resistant epilepsy who underwent TLE surgery at Cleveland Clinic between 2005 and 2010 (n = 333) to study the prevalence, characteristics, and prognostic implications of SSA in the context of TLE surgery. Analyses were performed using two seizure outcome definitions: complete seizure freedom and Engel classification. Of the 333 patients, 26 (7.8%) had SSA. Almost half (12 patients) had unilateral sensory symptoms, whereas the rest had bilateral symptoms. Tingling and numbness were the most frequently reported sensations. Compared to their non‐SSA counterparts, patients with SSA had the same clinical and imaging characteristics, but had a higher rate of breakthrough seizures (p = 0.03), although most (54%) were still able to achieve Engel class of I (p = 0.02). Based on our results we would encourage detailed presurgical testing, which may include an invasive evaluation to analyze the extent of the epileptogenic zone in patients with SSA and suspected TLE.     

Increasing incidence of HIV‐ associated tuberculosis in Romanian injecting drug users

Background

A high prevalence of tuberculosis (TB) among HIV‐positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and characteristics of TB in HIV‐infected IDUs referred to a national centre.

Methods

Prospective observational cohort study of all newly‐diagnosed HIV‐positive IDUs admitted to Victor Babes Hospital, Bucharest, between January 2009 and December 2014. Socio‐demographics, clinical characteristics and outcomes of HIV/TB co‐infected IDUs were compared to HIV‐positive IDUs without TB.

Results

170/598 (28.5%) HIV‐infected IDUs were diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014 (P < 0.001). HIV/TB co‐infected individuals had lower median CD4 cell counts 75 (vs. 450/mm³, P < 0.0001) and higher median HIV viral loads 5.6 log₁₀ (vs. 4.9 log₁₀, P < 0.0001) when presenting to healthcare services. 103/170 (60.6%) HIV/TB co‐infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi‐Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co‐infection (P < 0.0001), extra‐pulmonary TB (P = 0.0026) and extensively drug resistant TB (P = 0.024).

Conclusions

Tuberculosis (TB) is an increasing problem in HIV‐infected IDUs in Romania. Presentation is often with advanced HIV, significant TB drug resistance and consequent outcomes are poor.