No Prognostic Importance of Resistance to Activated Protein C in Unstable Coronary Artery Disease Despite Signs of Thrombin Activation

Resistance to activated protein C (APC resistance) is the single most important hemostatic defect associated with venous thromboembolic disease. However, little is known about this defect in arterial disease. The aim of this study was thus to investigate the frequency and prognostic importance of APC resistance and its influence on the coagulation system in one type of arterial thrombosis. In this study, 323 patients admitted to hospital because of unstable coronary artery disease, that is, unstable angina pectoris or non-Q-wave myocardial infarction, were investigated and compared with a reference group of apparently healthy individuals. The patients participated in a prospective, multicenter, randomized, and placebo-controlled investigation evaluating the protective value of low molecular weight heparin (dalteparin) in unstable coronary artery disease. The APC ratio was assayed using a modified activated partial thromboplastin time reaction method to measure the response to activated protein C. APC resistance was defined as an APC ratio 2.2. Signs of thrombin activation were measured by prothrombin fragment 1+2 levels. The 7.2% (23/318) occurrence of APC resistance found in patients did not differ from the 5.8% (4/69) level in the reference population (P = 0.16). A significant elevation of the prothrombin fragment 1+2 median level of 2.5 nM (interquartile range, 1.9-3.2 nM) was found in the patients with APC resistance compared with 1.7 nM (interquartile range, 1.2-2.4 nM) in the group with a normal APC ratio (P < 0.01). During the 150-day follow-up period, there was no increased risk of cardiac events in patients with APC resistance. Although accompanied by signs of increased thrombin formation, APC resistance does not seem to be an important risk factor for the development of instability in coronary artery disease.     

Increased hip-fracture incidence in the county of Osterg?tland, Sweden, 1940-1986, with forecasts up to the year 2000: an epidemiological study.

The incidence of hip fractures in the county of Osterg?tland in Sweden has increased dramatically from 1940 to 1986, mainly due to an increase in age-specific incidence of trochanteric fractures. The increase is most pronounced in people over 80 but is present even in age groups down to 50 years. If the age-specific incidence rates continue to increase, and the population of the elderly grows in accordance with the forecast, there will be 70% more hip fractures in the year 2000 than in 1985.     

Delayed hypersensitivity response and vitamin D deficiency

The relationship between delayed hypersensitivity and serum levels of 25-hydroxyvitamin D were examined in sixty-three elderly people. After intracutaneous injection of five recall antigens (Candida, mumps, PPD, tricophyton and varidase) nineteen subjects showed no response (anergy), seven showed only a weak reaction (relative anergy), and thirty-seven a normal reaction. In the anergic group mean serum level of 25-hydroxyvitamin D was significantly lower than in the group with normal immunoreactivity. Five subjects with anergy and serum 25-hydroxyvitamin D below 20 nmol/l were treated with oral vitamin D or UV irradiation for two to three months, after which both the serum 25-hydroxyvitamin D levels and the delayed hypersensitivity were normalized. In a non-treated group anergy persisted in seven out of nine patients in a second skin test. We conclude that anergy in the delayed hypersensitivity skin test in humans may in some cases be due to vitamin D deficiency.     

Acceptability and Adherence in a Chemoprevention Trial among Women at Increased Risk for Breast Cancer Attending the Modena Familial Breast and Ovarian Cancer Center (Italy)

Chemoprevention for women at risk for breast cancer has been shown to be effective, but in actual practice, women's uptake of chemoprevention has been poor. We explored factors that influence acceptability, adherence, and dropout in the International Breast (Prevention) Intervention Study during our first 3 years of activity at the Modena Familial Breast and Ovarian Cancer Center. We evaluated socio‐demographic characteristics, health status, adherence, and side effect intensity. Semi‐structured interviews analyzed reasons for accepting/refusing/stopping the trial. A total of 471 postmenopausal women were invited to participate, of which 319 declined to participate (68%), 137 accepted to participate (29%), and 15 participants did not make a final decision (3%). Breast cancer‐related worries and trust in our preventive and surveillance programs were the most frequent reasons for accepting. Side effect‐related worry was the most frequent reason for refusing. General practitioners' and family members' opinions played an important role in the decision‐making process. Adherence significantly decreased after a 12‐month follow‐up, but it remained unchanged after 24‐ and 36‐month follow‐ups. Mild/moderate side effects reported by women did not change after 12 months of treatment. Forty percent of women withdrew from the study due to complaints of side effects. We concluded that chemoprevention trials are difficult medical experiments and that the process of deciding about whether or not to participate is based mainly on beliefs and values. This study has important clinical implications. During counselling with prospective participants, it is important to emphasize the potential benefits and to promote an informed choice. How participants make decisions, their belief systems, and their perception of risk are all factors that should be investigated in future research.     

The 9+ screening test score does not predict injuries in elite floorball players

We aimed to examine whether the 9+ screening test score could predict injuries in elite floorball players. Eighty-four elite floorball players participated in the study. At baseline, two physiotherapists assessed the participants using the 9+ screening test. The test score reflects strength, stability, mobility, and functional movement pattern with an emphasis on the lower body and core. Injuries that occurred the following season (2013/2014) were recorded by medical staff, coaches, and/or self-reported by the players. Overall, there was no relationship between the 9+ screening test score and injury risk (OR = 0.96 per SD lower test score, P = .84). We, therefore, conclude that the 9+ screening test is not suited for overall injury risk prediction in elite floorball players. Whether the test may be used to predict risk of certain injury types more strongly related to inadequate mobility and strength (eg, muscle ruptures or strains) warrants further investigation.     

Prevalence of protein-energy malnutrition in a large population of elderly people at home

The prevalence of protein-energy malnutrition (PEM) was examined in 1206 randomly selected elderly people aged 65 to 80 years living in their own homes. Nutritional assessment was based on weight loss, weight index, triceps skin fold, arm muscle circumference, serum albumin and prealbumin, and delayed cutaneous hypersensitivity (DCH) reaction. The prevalence of PEM was 5 per cent. If people with signs of inflammation were excluded, the prevalence of PEM was 3.5 per cent. When other nutritional indices, used by other authors among hospitalized patients, were applied to our sample prevalence values from 2.6 to 4.1 per cent were obtained. the prevalence was not related to sex or age. DCH increased the sensitivity of the screening method but causes of anergy other than PEM must be taken into account. It is concluded that PEM, in a degree shown to impair the prognosis at hospital, does occur among elderly people at home in an industrialized country.     

Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study

BACKGROUND: Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss. METHODS: We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21-79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss. RESULTS: A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=-0.14 to -0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=-0.23 to -0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%). CONCLUSIONS: These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.     

Breast ultrasonography (BU) in the screening protocol for women at hereditary-familial risk of breast cancer: has the time come to rethink the role of BU according to different risk categories?

This article evaluates the breast cancer (BC) screening efficacy of biannual ultrasound (US) in three different risk categories. In a single-center, prospective, nonrandomized comparison study, BRCA mutation carriers and women with high risk (HR) or intermediate risk (IR) received mammography (MMG), ultrasound, (US) and Magnetic Resonance Imaging (MRI), scheduled according to the risk categories. Single and combined sensitivity were evaluated in specific groups of risk and the US performance at six-monthly interval was notably considered. Among 2,313 asymptomatic women at different risk (136 mutation carriers, 1,749 at HR and 428 at IR) 211 developed a BC, of which 193 (91.5%) were screen detected BC (SDBC) and 18 (8.5%) were interval BC (IBC). The SDBC detection rate (DR) was 11.2 per 1.000 person-years (37.9, 8.5 and 16.1 for BRCA, HR and IR, respectively); 116 BC were detected by MMG (DR = 6.6 × 1,000 persons-years), 62 by US (DR = 3.6 × 1,000 persons-years) and 15 by MRI, that was applied only in 60 BRCA women (DR = 37 × 1,000 persons-years). At the six-monthly US, 52 BC were detected (DR = 3.0 × 1,000 persons/years), of which 8 were BRCA-related. The most sensitive technique was MRI (93.7%) followed by MMG (55%) and US (29.4%). Combined sensitivity for MMG plus US was 100% in HR and 80.4% for IR women (p < 0.01). In BRCA mutated patients, MRI alone with annual US performed after six months, could be offered. In HR patients, MMG plus biannual US provide the most sensitive diagnosis and for IR group an annual MMG could be sufficient.