Comprehensive assessment of cryogenic storage risk and quality management concerns: best practice guidelines for ART labs.

Recent publicized events of cryogenic storage tank failures have created nationwide concern among infertility patients and patients storing embryos and gametes for future use. To assure patient confidence, quality management (QM) plans applied by in vitro fertilization (IVF) laboratories need to include a more comprehensive focus on the cryostorage of reproductive specimens. The purpose of this review is to provide best practice guidelines for the cryogenic storage of sperm, oocytes, embryos, and other reproductive tissues (e.g., testicular and ovarian tissue, cord blood cells, and stem cells) and recommend a strategy of thorough and appropriate quality and risk management procedures aimed to alleviate or minimize the consequences from catastrophic events.

Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

Implementing health promotion programmes in schools: a realist systematic review of research and experience in the United Kingdom.

BACKGROUND: Schools have long been viewed as a good setting in which to encourage healthy lifestyles amongst children, and schools in many countries aspire to more comprehensive, integrated approaches to health promotion. Recent reviews have identified evidence of the effects of school health promotion on children's and young people's health. However, understanding of how such programmes can be implemented in schools is more limited. METHODS: We conducted a realist review to identify the conditions and actions which lead to the successful implementation of health promotion programmes in schools. We used the international literature to develop programme theories which were then tested using evaluations of school health promotion programmes conducted in the United Kingdom (UK). Iterative searching and screening was conducted to identify sources and clear criteria applied for appraisal of included sources. A review advisory group comprising educational and public health practitioners, commissioners, and academics was established at the outset. RESULTS: In consultation with the review advisory group, we developed four programme theories (preparing for implementation, initial implementation, embedding into routine practice, adaptation and evolution); these were then refined using the UK evaluations in the review. This enabled us to identify transferable mechanisms and enabling and constraining contexts and investigate how the operation of mechanisms differed in different contexts. We also identified steps that should be taken at a senior level in relation to preparing for implementation (which revolved around negotiation about programme delivery) and initial implementation (which centred on facilitation, support, and reciprocity-the latter for both programme deliverers and pupils). However, the depth and rigour of evidence concerning embedding into routine practice and adaptation and evolution was limited. CONCLUSIONS: Our findings provide guidance for the design, implementation, and evaluation of health promotion in schools and identify the areas where further research is needed.

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes.

AIMS: To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2). RESULTS: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). CONCLUSIONS: Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.

Cardiovascular risk and thiazolidinediones--what do meta-analyses really tell us?

Meta-analyses of clinical trials suggest that the use of the thiazolidinedione (TZD), rosiglitazone, in patients with type 2 diabetes mellitus may increase the risk of myocardial ischaemic events by 30-40%. Although these controversial data must be interpreted with caution, in the absence of definitive prospective cardiovascular (CV) outcomes data, they represent a prominent source of evidence concerning the CV safety of rosiglitazone. The results of meta-analyses and a large randomized-controlled CV outcomes trial provide strong evidence that pioglitazone does not increase the risk of coronary events. This article clarifies the clinical significance of these meta-analytical findings alongside other sources of evidence and assesses their impact on evolving treatment guidelines and recommendations for the use of TZDs in patients with type 2 diabetes.

Recent discoveries in assessment of coronary heart disease: impact of vascular mechanisms on development of atherosclerosis.

Until recently, arterial stenosis and occlusion due to buildup of atherosclerotic plaque were recognized as the primary causes of coronary heart disease (CHD). Currently, CHD is viewed as a lifelong process of endothelial inflammation, thrombosis, and plaque instability and rupture. Lifestyle modification is an important first step in prevention of CHD, but even those patients who are the most committed to following a healthy diet and lifestyle frequently require the addition of drug therapy to further reduce risk. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce risk by lowering low-density lipoprotein cholesterol levels, as well as by stabilizing plaques, restoring endothelial function, and counteracting oxidative and inflammatory processes. Angiotensin-converting enzyme inhibitors also have antiatherogenic properties. Early, aggressive lipid intervention is the key to primary and secondary prevention of CHD.

Novel approach to rotational atherectomy results in low restenosis rates in long, calcified lesions: long-term results of the San Antonio Rotablator Study (SARS).

Ablation technique and adjunctive strategy may affect restenosis after rotational atherectomy. To minimize trauma to the vascular wall, we changed the technique of rotablation as follows: the RPM range was decreased to 140,000-160,000 RPM, the ablation was performed using a repetitive pecking motion, avoiding a decrease in the rotational speed of the burr greater than 3,000 RPM, long lesions were divided into segments and each segment was separately ablated, and the burr-to-artery ratio was intended to be approximately 0.75. To prevent coronary spasm, before and after each pass, 100-200 microg nitroglycerin and 100-200 microg verapamil i.c. boluses were administered. Adjunctive PTCA was performed using a closely sized 1.1:1 balloon-to-artery ratio with a noncompliant balloon at low pressures for 120 sec. The study incorporated 111 patients with a combined total of 146 calcified lesions. Results. A total of 31.5% of patients underwent a multivessel procedure. No deaths occurred. Q-wave MI and/or creatine kinase elevation greater than three times baseline levels occurred in 4.5% of patients. By quantitative coronary angiography (QCA), the reference vessel diameter was 3.13+/-0.59 mm, mean lesion length was 33.41+/-18.58 mm. Percent stenosis and mean luminal diameter were as follows: at baseline 75.7%+/-10.8%, or 0.76+/-0.41mm, Post-rotational atherectomy 41.5%+/-3.6%, or 1.83+/-0.43 mm, Post-PTCA 18.2%+/-11.9%, or 2.56+/-0.50 mm. Six-month angiographic follow-up was available in 64 (57.7%) pts. Net luminal gain was 1.15+/-0.76 mm, with a late luminal loss of 0.65+/-0.84 mm. The mean diameter stenosis at follow-up was 37.6%+/-28.5%, with MLD 1.91+/-1.21 mm. The binary restenosis rate was 28.1%. Therefore, modification of rotational atherectomy technique with adjunctive PTCA resulted in a favorable restenosis rate in long, calcified lesions. Cathet. Cardiovasc. Intervent. 48:48-53, 1999.

Predicting severe angiographic coronary artery disease using computerization of clinical and exercise test data.

Currently the standard exercise test is shifting from being a tool for the cardiologist to utilization by the nonspecialist. This change could be facilitated by computerization similar to the interpretation programs available for the resting ECG. Therefore, we sought to determine if computerization of both exercise ECG measurements and prediction equations can substitute for visual analysis performed by cardiologists to predict which patients have severe angiographic coronary artery disease. We performed a retrospective analysis of consecutive patients referred for evaluation of possible or known coronary artery disease who underwent both exercise testing with digital recording of their exercise ECGs and coronary angiography at two university-affiliated Veteran's Affairs medical centers and a Hungarian hospital. There were 2,385 consecutive male patients with complete data who had exercise tests between 1987 and 1997. Measurements included clinical and exercise test data, and visual interpretation of the ECG paper tracings and > 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized ECG measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were only able to correctly classify two or three more patients out of 100 tested than ECG measurements alone. beta-Blockers had no effect on test characteristics while ST depression on the resting ECG decreased specificity. By setting probability limits using the scores from the equations, the population was divided into high-, intermediate-, and low-probability groups. A strategy using further testing in the intermediate group resulted in 86% sensitivity and 85% specificity for identifying patients with severe coronary disease. We conclude that computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist and computerized scores only minimally improved the discriminatory power of the test. However, using these scores in a stratification algorithm allows the nonspecialist physician to improve the discriminatory characteristics of the standard exercise test even when resting ST depression is present. Computerization permitted accurate identification of patients with severe coronary disease who require referral.

Acute directional coronary atherectomy prior to stenting in complex coronary lesions: ADAPTS Study.

The purpose of this study was to determine the results of directional coronary atherectomy (DCA) combined with stenting in a high-risk patient population. The use of stenting or DCA alone for aorto-ostial lesions, total chronic occlusions, long lesions, and lesions containing thrombus is associated with lowered success and a relatively high restenosis rate. Between July 1993 and October 1996, we treated 89 lesions with the combined approach of DCA and stenting in 60 consecutive patients. Thirty-one (51.7%) patients were treated because of unstable angina, 11 (18.3%) for post-myocardial infarction (MI) angina, 3 (5.0%) for acute MI, and 15 (25.0%) patients for stable angina. A total of 43 (71.7%) patients had multivessel disease, 19 (31.7%) had undergone previous coronary artery bypass graft (CABG), and 17 (28.3%) patients had undergone multivessel revascularization. The procedure was successful in all patients; and no postprocedural deaths or emergent CABG occurred. Two patients (3.3%) had non-Q-wave MI after the procedure and 1 patient (1.7%) experienced Q-wave MI due to subacute stent closure 7 days after the procedure. During follow-up ranging from 6 months to 3 years, 2 (3.3%) patients died, 2 (3.3%) required CABG surgery, 1 (1.7%) patient had an MI, and 6 patients (10.0%) required target vessel revascularization. By the quantitative coronary angiography, the initial minimal luminal diameter (MLD) averaged 0.91+/-0.45 mm (74.7+/-11.8% stenosis) increasing to 3.80+/-0.44 mm (-6.7+/-12.1%) after the combined approach procedure. Thirty patients (50.0%) met criteria for late (> or =6 months) angiographic follow-up. Late MLD loss averaged 1.13+/-1.07 mm, for a mean net gain of 1.61+/-1.23 mm. Available angiographic follow-up evaluation showed a restenosis rate of 13.3%. A combined approach, defined as the use of both DCA and stenting, is safe and yields a low restenosis rate in high-risk patients who have lesions known to respond less favorably to stenting or DCA alone.

Can computerization of the exercise test replace the cardiologist?

BACKGROUND: The type of practitioners who use the standard exercise test is changing. Once a tool of the cardiologist, the standard exercise test is now being performed by internists and other noncardiologists. Because this change could be facilitated by computerization similar to the computerized interpretation programs available for the resting electrocardiograph (ECG), we performed this analysis. A secondary aim was to demonstrate the effects of medication status and resting ECG abnormalities on test diagnostic characteristics because these factors affect utility of the exercise test by the generalist. METHODS AND RESULTS: A retrospective analysis was performed of consecutive patients referred at 2 university-affiliated Veteran's Affairs Medical Centers and a Hungarian Hospital for evaluation of chest pain and possible ischemic heart disease. There were 1384 consecutive male patients without a prior myocardial infarction with complete data who had exercise tests and coronary angiography between 1987 and 1997. Measurements included clinical, exercise test data, and visual interpretation of the ECG recordings as well as more than 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were superior to single ECG measurements. Beta-blockers had no effect on test characteristics, whereas resting ST depression was associated with decreased specificity and increased sensitivity. CONCLUSIONS: Computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist; computerized scores that included clinical and exercise test results exhibited the greatest diagnostic power. Applying scores with a computer allows the practicing physician to improve the diagnostic characteristics of the standard exercise test. This approach is successful even when there is resting ST depression, thus lessening the need for more expensive nuclear or imaging studies.

Angioscopic evaluation of site-specific administration of ReoPro.

Systemic administration of newer antiplatelet agents such as the GP IIb/IIIa agent ReoPro (Centocor BV Leiden, The Netherlands) has been shown to decrease the early incidence of recurrent ischemia and recurrent myocardial infarction. The currently approved protocol for administration of ReoPro involves an initial weight adjusted bolus followed by a systemic infusion over the next 12 hr. The systemic administration is proposed as the only route of administration because it is stated that the drug must be exposed to circulating platelets. An alternative approach would be to deliver ReoPro locally and allow the platelets to disaggregate only when in contact with the local arterial wall. The optimal method of monitoring the efficacy of such a strategy is to visually assess the presence of platelet rich or red blood cell rich thrombus using angioscopy. We report our initial experience in 12 patients who received local administration of ReoPro using currently approved catheters for local administration of agents into coronary arteries who were evaluated before and after intervention using intracoronary angioscopy. None of the patients received a subsequent 12-hr infusion. There was successful resolution of thrombus in 11 of 12 patients. Recurrent ischemia occurred in one patient without myocardial infarction.