[Is family history dispensable?]. / Ist die Familienanamnese verzichtbar?

As an element of risk assessment in applications for life insurance, family medical history has a particular significance since given impairments can occur more frequently within families. Family history is not only genetic in nature. Depending on the impairment, it is also explained by external factors. There has been little literature on this topic so far, although the spectrum of family history-related impairments is very large, and their effect is highly dependent on the type of product. This paper presents a new method for assessing the effects of information contained in family history on claims, based on typical age patterns for German life insurance products (life, disability and long term care insurance), using the example of breast cancer and schizophrenia. This method helps life insurers to better understand what impact questions on family history during the stage of application have on the risk. Thus, the study contributes to the often discussed question on how essential questions on family history are.

Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment.

Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

The purpose of this study was to determine whether the baseline metabolic profile (that is, metabotype) of a patient with major depressive disorder (MDD) would define how an individual will respond to treatment. Outpatients with MDD were randomly assigned to sertraline (up to 150 mg per day) (N=43) or placebo (N=46) in a double-blind 4-week trial. Baseline serum samples were profiled using the liquid chromatography electrochemical array; the output was digitized to create a 'digital map' of the entire measurable response for a particular sample. Response was defined as ≥50% reduction baseline to week 4 in the 17-item Hamilton Rating Scale for Depression total score. Models were built using the one-out method for cross-validation. Multivariate analyses showed that metabolic profiles partially separated responders and non-responders to sertraline or to placebo. For the sertraline models, the overall correct classification rate was 81% whereas it was 72% for the placebo models. Several pathways were implicated in separation of responders and non-responders on sertraline and on placebo including phenylalanine, tryptophan, purine and tocopherol. Dihydroxyphenylacetic acid, tocopherols and serotonin were common metabolites in separating responders and non-responders to both drug and placebo. Pretreatment metabotypes may predict which depressed patients will respond to acute treatment (4 weeks) with sertraline or placebo. Some pathways were informative for both treatments whereas other pathways were unique in predicting response to either sertraline or placebo. Metabolomics may inform the biochemical basis for the early efficacy of sertraline.

Genome-wide association study identifies multiple novel loci associated with disease progression in subjects with mild cognitive impairment.

Alzheimer's disease (AD) is the leading cause of dementia among the elderly population; however, knowledge about genetic risk factors involved in disease progression is limited. We conducted a genome-wide association study (GWAS) using clinical decline as measured by changes in the Clinical Dementia Rating-sum of boxes as a quantitative trait to test for single-nucleotide polymorphisms (SNPs) that were associated with the rate of progression in 822 Caucasian subjects of amnestic mild cognitive impairment (MCI). There was no significant association with disease progress for any of the recently identified disease susceptibility variants in CLU, CR1, PICALM, BIN1, EPHA1, MS4A6A, MS4A4E or CD33 following multiple testing correction. We did, however, identify multiple novel loci that reached genome-wide significance at the 0.01 level. These top variants (rs7840202 at chr8 in UBR5: P=4.27 × 10(-14); rs11637611 with a cluster of SNPs at chr15q23 close to the Tay-Sachs disease locus: P=1.07 × 10(-15); and rs12752888 at chr1: P=3.08 × 10(-11)) were also associated with a significant decline in cognition as well as the conversion of subjects with MCI to a diagnosis of AD. Taken together, these variants define approximately 16.6% of the MCI sub-population with a faster rate of decline independent of the other known disease risk factors. In addition to providing new insights into protein pathways that may be involved with the progress to AD in MCI subjects, these variants if further validated may enable the identification of a more homogeneous population of subjects at an earlier stage of disease for testing novel hypotheses and/or therapies in the clinical setting.

Association between concentrations of urinary type II collagen neoepitope (uTIINE) and joint space narrowing in patients with knee osteoarthritis.

OBJECTIVE: To examine whether urine concentrations of type II collagen neoepitope (uTIINE) distinguish subjects with progressive radiographic and/or symptomatic knee osteoarthritis (OA) from those with stable disease. METHODS: Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month randomized-controlled trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Urine samples were obtained every 6 months for determination of the creatinine (Cr)-adjusted uTIINE concentration. RESULTS: Baseline uTIINE levels were unrelated to JSN in the placebo group. However, among subjects in the active treatment group, a 1-standard deviation increment in baseline uTIINE (68 ng/mM Cr) was associated with a marginally significant, two-fold increase in the odds of progression of JSN (odds ratio 2.04, 95% confidence interval 0.98-4.28). The within-subject mean of uTIINE values at baseline, 6 months and 12 months was associated with concurrent JSN measured at 16 months (0.10mm of JSN per 69 ng/mM Cr, P=0.008). Similar results were seen in the interval between months 16 and 30 and in analyses using the maximum of intercurrent uTIINE levels. CONCLUSION: Baseline uTIINE was not a consistent predictor of JSN in subjects with knee OA. However, serial measurements of uTIINE reflect concurrent JSN.

Anaesthetic management of labour and caesarean delivery of a patient with hyperkalaemic periodic paralysis.

We describe a parturient with hyperkalaemic periodic paralysis who presented for induction of labour and subsequently, caesarean section. Epidural analgesia and anaesthesia were used successfully in a multidisciplinary plan aimed at avoiding a peripartum attack and providing safe delivery. Management of this rare condition is discussed along with a review of the available literature.

Assessment of the radioanatomic positioning of the osteoarthritic knee in serial radiographs: comparison of three acquisition techniques.

OBJECTIVE: Recent studies using various standardized radiographic acquisition techniques have demonstrated the necessity of reproducible radioanatomic alignment of the knee to assure precise measurements of medial tibiofemoral joint space width (JSW). The objective of the present study was to characterize the longitudinal performance of several acquisition techniques with respect to long-term reproducibility of positioning of the knee, and the impact of changes in positioning on the rate and variability of joint space narrowing (JSN). METHODS: Eighty subjects were randomly selected from each of three cohorts followed in recent studies of the radiographic progression of knee osteoarthritis (OA): the Health ABC study (paired fixed-flexion [FF] radiographs taken at a 36-month interval); the Glucosamine Arthritis Intervention Trial (GAIT) (paired metatarsophalangeal [MTP] radiographs obtained at a 12-month interval), and a randomized clinical trial of doxycycline (fluoroscopically assisted semiflexed anteroposterior (AP) radiographs taken at a 16-month interval). Manual measurements were obtained from each radiograph to represent markers of radioanatomic positioning of the knee (alignment of the medial tibial plateau and X-ray beam, knee rotation, femorotibial angle) and to evaluate minimum JSW (mJSW) in the medial tibiofemoral compartment. The effects on the mean annualized rate of JSN and on the variability of that rate of highly reproduced vs variable positioning of the knee in serial radiographs were evaluated. RESULTS: Parallel or near-parallel alignment was achieved significantly more frequently with the fluoroscopically guided positioning used in the semiflexed AP protocol than with either the non-fluoroscopic FF or MTP protocol (68% vs 14% for both FF and MTP protocols when measured at the midpoint of the medial compartment; 75% vs 26% and 34% for the FF and MTP protocols, respectively, when measured at the site of mJSW; P<0.001 for each). Knee rotation was reproduced more frequently in semiflexed AP radiographs than in FF radiographs (66% vs 45%, P<0.01). In contrast, the FF technique yielded a greater proportion of paired radiographs in which the femorotibial angle was accurately reproduced than the semiflexed AP or MTP protocol (78% vs 59% and 56%, respectively, P<0.01 for each). Notably, only paired radiographs with parallel or near-parallel alignment exhibited a mean rate of JSN (+/-SD) in the OA knee that was more rapid and less variable than that measured in all knees (0.186+/-0.274 mm/year, standardized response to mean [SRM]=0.68 vs 0.128+/-0.291 mm/year, SRM=0.44). CONCLUSION: This study confirms the importance of parallel radioanatomic alignment of the anterior and posterior margins of the medial tibial plateau in detecting JSN in subjects with knee OA. The use of radiographic methods that assure parallel alignment during serial X-ray examinations will permit the design of more efficient studies of biomarkers of OA progression and of structure modification in knee OA.

Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients.

OBJECTIVE: To evaluate the prevalence of synovitis in painful medial tibiofemoral knee osteoarthritis (OA) and to evaluate correlation between synovitis and the structural severity and progression of tibiofemoral cartilage damage. STUDY: Multicenter, longitudinal, 1-year duration. PATIENTS: Primary painful knee OA (ACR criteria) of the medial tibiofemoral compartment, with pain of the signal knee on at least 30 days in the past 2 months, medial joint space width > or = 2mm, at least 10% of one cartilage surface of the medial compartment affected by superficial fibrillation or worse at baseline arthroscopy. ARTHROSCOPIC PARAMETERS: Knee arthroscopy under local anesthesia was performed and videorecorded at entry and after 1 year. Medial chondropathy was scored by using Societe Francaise d'Arthroscopie (SFA) score (0-100) and reader's overall assessment (VAS score, 100 mm). Progression of medial chondropathy was defined by a change in SFA and VAS scores over 4.5 and 8.0 mm after 1 year, respectively. Medial perimeniscal synovium was scored as normal (few translucent and slender villi, fine vascular network), reactive (proliferation of opaque villi), or inflammatory (hypervascularization and/or proliferation of hypertrophic and hyperemic villi). Medial chondropathy and synovitis were scored by a single reader blind to chronology of paired videotapes. RESULTS: Four hundred and twenty-two patients were enrolled (mean age: 61 years, females: 59%, body mass index: 31, mean disease duration: 4 years) and completed the 1-year study. Synovial abnormalities were present in 50% of the patients with reactive and inflammatory aspects in 29% and 21% of the patients, respectively. Patients with a reactive or inflammatory medial synovium had a more severe medial chondropathy. The worsening in medial chondropathy after 1 year was statistically more severe in the group of patients with an inflammatory perimeniscal synovial membrane at baseline compared to patients with normal and reactive aspects, with no difference between these two latter groups. The odds ratio for progression in VAS score after 1 year was 3.11 (95% CI [1.07, 5.69]) for patients with inflammatory synovium at baseline compared to patients with normal synovium. CONCLUSIONS: This study suggests that abnormalities of the medial perimeniscal synovium are a common feature of painful medial knee OA, associated with more severe medial chondropathy. It also suggests that an inflammatory aspect of the medial perimeniscal synovium could be considered as a predictive factor of subsequent increased degradation of medial chondropathy.

Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule.

A large family with dominantly inherited rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia, resulting in brachydactyly was linked to COL2A1, the gene encoding proalpha1(II) collagen. Mutational analysis of the gene by exon sequencing identified a novel mutation in the C-propeptide region of the molecule. The glycine to aspartic acid change occurred in a region that is highly conserved in all fibrillar collagen molecules. The resulting phenotype does not fit easily into pre-existing subgroups of the type II collagenopathies, which includes spondyloepiphyseal dysplasia, and the Kniest, Strudwick, and Stickler dysplasias.

Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Morality and bureaucracy in health and social policy.

The outgoing Director General set aside the usual biennial report approach of reviewing IHF's activities over the previous 2 years. Instead Dr. Pickering reviewed the developments in health care over the last decade, the period he has held office. He decried the emasculating role of bureaucracy in health care and the lack of morality in decision-making in social and health policy. The article is a cri de coeur' for a fundamental ethical review of the basis for health care changes.

Group purchasing--an international future? Health Industry Group Purchasing Association Expo Conference, October 9-11, 1996, Orlando, Florida, USA.

As Providers and suppliers in the U.S. health care market place have adopted a mindset more attuned to today's economic realities, they've made cost cutting a top priority-and to help them achieve that, they have turned to GPOs and the prospects they offer for control of supply costs through bulk buying. Will the purchasing world cross international boundaries and get even smaller? What benefits can be expected from group purchasing organisations developing an international network? Can the International Hospital Federation play a role?

Quality hospital care--global trends and future challenges.

This paper provides an international overview of trends and elements of quality services provision in hospitals. The factors reviewed are hospital accreditation, government quality intervention, resource review, clinical procedure standardisation, patient education, high technology, financial mechanisms, risk management and evidence based medicine as relates to quality.

Evaluating the benefits and limitations of an accreditation system.

While accreditation programmes are not a quality assurance panacea, long experience has shown their benefits to substantially outweigh real or perceived negative impacts. It is argued that such systems are an essential basis for more sophisticated quality assurance programmes. Accreditation programmes also have unexpected benefits in the general management of hospitals.

Radial ray defects, renal ectopia, duodenal atresia and hydrocephalus: the extended spectrum for Fanconi anaemia.

We present two families with a striking concordance of multiple anomalies. These include duodenal and other bowel atresia, radial ray defects especially absent or vestigial thumb, renal ectopia and hydrocephalus. The presence of diagnostically raised sensitivity to mitomycin C in the first family has confirmed Fanconi anaemia. This has further increased the spectrum of abnormalities in Fanconi anaemia and highlights the importance of mitomycin C analysis if elements of this spectrum are encountered.

Utilizing cardiovascular data bases to guide the balance of cost and quality.

Cardiovascular administrators are being asked to focus on quality, cost-efficient operations of their service lines, to market that service, to secure business through managed-care contracting and to increase direct referral volume.

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)