Policy and Economic Considerations for Frailty Screening in the Canadian Healthcare System.

Canada faces significant policy and economic challenges related to healthcare for frail older adults. Annual per capita healthcare costs for people over age 65 are five times those for people under 65. Flat economic growth and an aging workforce decrease tax revenue, which funds 70% of health spending. Governments are shifting policy to enhance person-centered care and shifting spending from hospitals to primary and community care. Recognizing that frailty and evidence-based frailty screening can contribute directly to reform initiatives, what are the policy and economic considerations, both nationally and internationally, around frailty screening that will benefit patients, families and/or the wider health system? Based on key informant interviews, we present recommendations for approaching policy and economic challenges in frailty through the following healthcare policy instruments: financing, funding, legislation, regulation, technology, interdisciplinary care, person-centered service and health promotion.

[Repeat thrombolysis in acute myocardial infarction]. / Ismételt thrombolysis acut myocardialis reinfarctusban.

During two years period (Jul. 97-Aug. 99) data of patients suffering from recurrent acute myocardial infarct within 6 days were compared by retrospective analysis. In this interval authors treated 58 patients with recurrent myocardial infarct. 22 patients were transmitted to a catheterisation lab, data of the other 36 patients were compared. There were two treatment groups: 18 patients received repeated thrombolysis (IT group), and 18 patients got conventional therapy (HT group). In the thrombolytic group 15 patients received streptokinase infusion again, and urokinase infusion was administred in 3 patients at second time. The patients were not transferred to a cath lab, because of their older ages (10 patients), or capacity problems (13 patients), or in absence of their signed consent (13 patients). Comparisons were made on the basis of non invasive diagnostic procedures (reperfusion signs suggested by ECGs and enzymatic changes, and left ventricular ejection fraction at discharge), bleeding rate, and frequency of recurring angina at the 3 months visit, and on the basis of mortality. Ejection fractions and reperfusion signs were better in the repeated thrombolytic group (time of maximal level ST elevation: IT 19.70 +/- 6.00 min, HT 23.17 +/- 5.15 min, p = 0.26 NS; T wave inversion time within six hours: IT 168 +/- 45.17 min, HT 170 +/- 58.99 min, p = 0.94; reperfusion arrhythmia: IT 7, HT 3, p = 0.15; CK peak time: IT 16.89 +/- 6.94 hour, HT 20.00 +/- 6.72 hour, p = 0.18 NS; CK-MB peak time: IT 12.22 +/- 7.19 hour, HT 16.67 +/- 6.17, hour, p = 0.55; > 3 x CK peak time: IT 14.18 +/- 6.03 hour, HT 20.00 +/- 7.37 hour, p = 0.06, > 3 x CK-MB peak time: IT 8.80 +/- 4.54 hour, HT 15.20 +/- 6.19 hour, p = 0.02, ECHO EF: IT 48.53 +/- 6.81%, HT 43.14 +/- 4.90%, p = 0.02, Isotope ventriculography EF: IT 50.87 +/- 5.45%, HT 44.57 +/- 4.89%, p = 0.003), however the bleeding rate was moderately higher (minor bleeding: IT 7, HT 3, p = 0.15, major bleeding: IT 3, HT 1). The frequency of ischemic episodes at 3-month visit, and 3-month mortality were similar in the two groups (episodes of angina: IT 2.00 +/- 1.57, HT 2.42 +/- 1.88, p = 0.55; mortality: IT 4, HT 6, p = 0.46). Repeated thrombolysis is an effective therapeutical tool in centres without cath lab--according to the risk-benefit ratio too--in the case of early repeated myocardial infarct.

Expression and localisation of synaptotagmin isoforms in endocrine beta-cells: their function in insulin exocytosis.

Exocytosis of insulin containing Large Dense Core Vesicles (LDCVs) from pancreatic beta-cells and derived cell lines is mainly controlled by Ca(2+). Several lines of evidence have demonstrated a role of the Ca(2+)- and phospholipid-binding protein synaptotagmin (syt) in this event. Synaptotagmins form a large protein family with distinct affinities for Ca(2+) determined by their two C(2) domains (C(2)A/B). Except for the well-characterized isoforms I and II, their role is still unclear. We have used here insulin-secreting cells as a model system for LDCV exocytosis to gain insight into the function of synaptotagmins. Immunocytochemical analysis revealed that of the candidate Ca(2+) sensors in LDCV exocytosis, syt III was not expressed in primary beta-cells, whereas syt IV was only found adjacent to the TGN. However, syt V-VIII isoforms were expressed at different levels in various insulin-secreting cells and in pancreatic islet preparations. In streptolysin-O permeabilized primary beta-cells the introduction of recombinant peptides (100 nM) corresponding to the C(2) domains of syt V, VII and VIII, but not of syt III, IV or VI, inhibited Ca(2+)-evoked insulin exocytosis by 30% without altering GTP gamma S-induced release. Our observations demonstrate that syt III and IV are not involved in the exocytosis of LDCVs from primary beta-cells whereas V, VII and VIII may mediate Ca(2+)-regulation of exocytosis.

Hemidesmosomal molecular changes in dermatitis herpetiformis; decreased expression of BP230 and plectin/HD1 in uninvolved skin.

Recent BP230-knockout experiments with subsequent blistering and recently identified plectin/HD1 mutations in epidermolysis bullosa simplex patients suggest that defective expression of BP230 and plectin/HD1 may predispose to blister formation in human skin. We have studied the expression of the epithelial adhesion complex as well as the basement membrane and anchoring fibril antigens in uninvolved dermatitis herpetiformis skin to find out if alterations can be detected in these structures predisposing to the blister formation typical of the disease. Ten uninvolved dermatitis herpetiformis skin specimens, which all showed clear granular deposits of IgA under the basement membrane in direct immunofluorescence and five normal skin specimens, were studied by indirect immunofluorescence technique. Six uninvolved dermatitis herpetiformis skin specimens showed distinctly decreased immunoreaction for BP230 and four uninvolved dermatitis herpetiformis skin specimens showed distinctly decreased immunoreaction for plectin/HD1. All five skin controls showed strong immunoreactions for BP230 and plectin/HD1. Other hemidesmosomal proteins including BP180 and integrin alpha6beta4, as well as basement membrane proteins laminin-5, laminin-1, nidogen and type IV collagen, and the anchoring fibril protein type VII collagen showed a normal strong expression. Our results suggest that alterations in BP230 and plectin/HD1 may contribute or predispose to blister formation in dermatitis herpetiformis skin.

Clinical application of the nitroglycerin lingual spray.

The effect of sublingually administered nitrate spray was investigated with noninvasive methods. During 3 months, 82 patients were entered into the study: 40 with angina pectoris, 15 with acute myocardial infarction, 18 with hypertensive crisis, and 9 with left ventricular failure or acute pulmonary edema. The hemodynamic effects of two jets of nitroglycerin spray (0.8 mg Nitrolingual spray; Pohl-Boskamp, Hohenlocksted, Germany) was measured on heart rate, blood pressure, and flow velocity at baseline and 1, 5, and 10 minutes after drug administration. Flow velocities were measured through the left ventricular outflow tract and the mitral valve (early diastolic wave and atrial wave) with bedside Doppler echocardiography. The time to improvement and occurrence of adverse events was analyzed. Heart rate was constant after the therapy (75 +/- 8, 75 +/- 10, 75 +/- 10, and 75 +/- 9 beats per min; not significant), and systolic blood pressure decreased significantly 1 minute after administration and remained decreased throughout the examination (135 +/- 27, 124 +/- 21, 125 +/- 19, and 124 +/- 22 mm Hg, respectively; p < 0.001). The diastolic blood pressure was also significantly decreased (82 +/- 17, 79 +/- 14, 78 +/- 12, 78 +/- 14 mm Hg; p < 0.001). A significant increase in flow velocities in the left ventricular outflow tract was detected (90 +/- 8, 101 +/- 10, and 114 +/- 13 cm/s; p < 0.001) concomitantly with a significant increase in the early diastolic flow (46 +/- 4, 65 +/- 6, and 76 +/- 8 cm/s; p < 0.001) and the atrial wave (101 +/- 9, 110 +/- 10, and 118 +/- 9 cm/s; p < 0.001). This increase of flow velocity was less pronounced through the mitral valve than through the left ventricular outflow tract.

Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits.

The exocytotic release of potent hormones is a tightly controlled process. Its direct regulation without the involvement of second messengers would ensure rapid signal processing. In streptolysin O-permeabilized insulin-secreting cells, a preparation allowing dialysis of cytosolic macromolecules, activation of alpha 2-adrenergic receptors caused pertussis toxin-sensitive inhibition of calcium-induced exocytosis. This inhibition was mimicked very efficiently by the use of specific receptor-mimetic peptides, indicating the involvement of Gi and, to a lesser extent, of G(o). The regulation was exerted beyond the ATP-dependent step of exocytosis. In addition, low nanomolar amounts of pre-activated Gi/G(o) directly inhibited exocytosis. As transient overexpression of constitutively active mutants of G alpha i1, G alpha i2, G alpha i3 and G alpha o2 but not of G alpha o1 reproduced this regulation, the G alpha subunit alone is sufficient to induce inhibition. These results define exocytosis as an effector for heterotrimeric G-proteins and delineate the properties of the transduction pathway.

The blink reflex in migraine.

The blink reflex is an objective and useful method to study the trigeminal system. It was recorded in 43 migraine patients and the findings compared with those of 31 healthy controls. The latencies of the R1 component were in the normal range in both groups. The R2 latencies ranged between 30 and 32 ms in the control group. In contrast, more than half of the patients with migraine had R2 latencies between 32 and 35 ms in the migraine group. Some migraine patients had latencies above 35 ms. The R2 latency was statistically significantly different between controls and migraineurs (p < 0.0001). Our findings indicate that trigeminal afferents and/or polysynaptic pathway in brainstem may be altered in migraine.

Androgenic-anabolic steroid effects on serum and skin surface lipids, on red cells, and on liver enzymes.

The effects of large doses of testosterone and anabolic steroids on the serum lipids and skin surface lipids were studied during a 12-week strength training period. Decreased serum high-density lipoprotein cholesterol (HDLC) (P less than 0.001) and elevated serum triglyceride (P less than 0.05) levels were found at the same time with an elevated skin surface lipid cholesterol level. The erythropoiesis and function of the liver were only slightly stimulated. These abnormalities were assumed to be a direct effect of the testosterone and anabolic steroids.

The effect of testosterone and anabolic steroids on the skin surface lipids and the population of Propionibacteria acnes in young postpubertal men.

The effect of testosterone and anabolic steroids on skin surface lipids and the population of Propionibacteria acnes (P. acnes) was studied in power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 12-week strength training period. After 8 weeks' use of hormones the amount of dissolved skin surface lipids (SSL), and the Colony Forming Units/cm2 (CFU/cm2) of P. acnes had increased (p less than 0.01). The percentage values of dissolved SSL constituents changed. The cholesterol (CHO) and also the relative values of free fatty acids (FFA) increased. SSL constituents obtained by collection on absorbent paper likewise changed the dissolved constituents. It was concluded that high doses of testosterone and anabolic steroids may increase the SSL, the P. acnes population, and the percentage of the CHO and FFA of the skin surface lipids in healthy young men.

Effect of testosterone and anabolic steroids on the size of sebaceous glands in power athletes.

The effect of testosterone and anabolic steroids on the size of sebaceous glands was studied by means of interactive morphometry in skin biopsies of power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 4-week strength training period. After 4 weeks' use of hormones, the area of sectioned sebaceous glands enlarged significantly by a factor of 89.2% (p less than 0.005). The number of cells in the so-called differentiating cell pool (DCP) and in the undifferentiated cell pool (UCP) also increased significantly (p less than 0.025, p less than 0.05, respectively). The size of the area occupied by UCP cells increased significantly (p less than 0.05). The study suggests that high doses of testosterone and anabolic steroids lead to an enlargement of sebaceous glands in male power athletes.

Effect of androgenic and anabolic steroids on the sebaceous gland in power athletes.

The effect of androgenic and anabolic steroids on sebaceous gland activity and the composition of sebum was studied in power athletes. The subject self-administered large doses of androgenic and anabolic hormones during a 12-week-period of strength training. After 4 weeks of administration of hormones the sebum excretion rate increased significantly (p = 0.002) and it remained high throughout the period of exogenous steroid use. The amounts of cholesterol were significantly increased during that period. There were no differences in the amounts of the following lipid groups; free fatty acids, squalen, triglycerides, wax esters, diglycerides and paraffins. It was concluded that large doses of androgenic and anabolic steroids lead to an increase in sebum output in healthy young adult males.

Comparative studies with somatostatin and cysteamine in different behavioral tests on rats.

In the present study the effects of somatostatin and cysteamine (a selective decreaser of the somatostatin level in the body) were compared in different behavioral tests on rats. Somatostatin inhibited the extinction of active avoidance behavior 8 hr and 24 hr after intracerebroventricular (ICV) treatment, while cysteamine facilitated it 4 hr and 8 hr after subcutaneous (SC) treatment. Somatostatin did not significantly influence the cysteamine-induced facilitation of the extinction. Somatostatin did not have a significant effect on T-maze spatial discrimination learning and reverse learning, whereas cysteamine markedly attenuated the performance 4 hr (1st day) after treatment. Somatostatin in a dose of 4 micrograms (ICV) increased the locomotor activity 10 min after treatment, while cysteamine markedly decreased all parameters of the open-field test. These effects of the drug had disappeared 24 hr after treatment. If different doses of somatostatin (4 micrograms or 10 micrograms ICV) were administered to cysteamine-pretreated rats, the peptide did not modify the drug-induced changes in the open-field test. The data suggest that the brain somatostatin might have a physiological role in the organization of certain types of behavior.