Recommendations for spinal rehabilitation professionals regarding sexual education needs and preferences of people with spinal cord dysfunction: a mixed-methods study.

STUDY DESIGN: Mixed-methods study using comprehensive survey and semi-structured interviews. OBJECTIVES: Compare the experiences of sexual education during rehabilitation for people with non-traumatic spinal cord dysfunction (SCDys) and traumatic spinal cord injury (SCI), determine preferences for the delivery of this information and provide recommendations for spinal rehabilitation professionals. SETTING: Community, Australia. METHODS: Adults completed survey (traumatic SCI n=115; SCDys=39) or were interviewed (SCDys: n=21). Survey included questions regarding sexual education during rehabilitation, participant satisfaction with this and preferred modes for receiving such information. These themes were also explored during interviews. RESULTS: No difference between SCI and SCDys regarding satisfaction or preferred modes of presentation (all P>0.05). People with SCDys were less likely to report receiving sexuality education during rehabilitation (SCDys n=11, 30%; SCI n=61, 53%; P=0.03). Interviews suggested that this may be gendered, as only two women recalled receiving sexual education, whereas men often received this as part of continence management. Overall, only 18% were satisfied or very satisfied with sexual education and information received, and 36% were dissatisfied or very dissatisfied. Preferred modes for receiving sexuality information included sexuality counsellor (n=97), recommended internet sites (n=77), peer support workers (n=76), staff discussion (n=67), written information (n=67) and DVD (n=58). These preferences were confirmed during interviews, although women expressed a strong preference for written information sheets. CONCLUSION: There was very low satisfaction with sexuality education during rehabilitation. Our findings highlight the scope and directions for improving the sexual education and information given to people with both SCDys and SCI during rehabilitation.

Hydrodynamic gene delivery to the pig liver via an isolated segment of the inferior vena cava.

Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the hepatic veins. Pigs (18-20 kg weight) were given the pGL3 plasmid via two programmable syringe pumps in parallel. Volumes corresponding to 2% of body weight (360-400 ml) were delivered at 100 ml s(-1) via a Y connector. The IVC segment pressure, portal venous pressure, arterial pressure, electrocardiogram (ECG) and pulse were monitored. Concurrent studies were performed in rats for interspecies comparisons. The hydrodynamic procedure generated intrahepatic vascular pressures of 101-126 mm Hg, which is approximately 4 times higher than in rodents, but levels of gene delivery were approximately 200-fold lower. Suprahepatic IVC clamping caused a fall in arterial pressure, with the development of ECG signs of myocardial ischaemia, but these abnormalities resolved rapidly. The IVC segment approach is a clinically acceptable approach to liver gene therapy. However, it is less effective in pigs than in rodents, possibly because of larger liver size or a less compliant connective tissue framework.

Cardiovascular function following acute volume overload for hydrodynamic gene delivery to the liver.

Hydrodynamic gene delivery to the liver is a valuable experimental tool and an attractive option for nonviral gene therapy of liver disease. However, little attention has been paid to the major obstacle to clinical application: acute volume overload of the cardiovascular system. We delivered volumes of DNA solution (pGL3 plasmid) corresponding to 1, 2, 4, 6 and 8% of the body weight at 100 ml/min to the inferior vena cava (IVC) of DA strain rats. Central venous pressure (CVP), arterial pressure, pulse and electrocardiogram (ECG) were continuously recorded for subsequent analysis. Each volume produced a characteristic response, but all (including the 1% volume) caused severe falls in blood pressure and pulse within 1-2 s of the infusion, with ectopic beats and widening of the QRS complex in the ECG. The response to volumes of 4% and higher suggested that the liver acted as a volume sink, mitigating the immediate effects of volume overload. The 6 and 8% volumes caused profound and protracted falls in blood pressure and pulse, with a multitude of severe electrical abnormalities in the heart, including electromechanical dissociation. Vagal blockade with atropine, and the use of Ringer's solution to prevent electrolyte disturbances, did not ameliorate this picture.

Ischaemic and non-ischaemic cardiomyopathies--cardiac MRI appearances with delayed enhancement.

Over the past few years, cardiovascular magnetic resonance (CMR) imaging has rapidly developed and is now a robust clinical tool capable of providing high-resolution images of the heart in any desired plane. Delayed contrast-enhanced CMR (DE-CMR) can be used for non-invasive tissue characterization, with differing patterns of hyperenhancement displayed by ischaemic and non-ischaemic cardiomyopathies. This review explains the theory behind delayed hyperenhancement, and demonstrates the potential of DE-CMR in the diagnosis of a wide range of different cardiac disease states.

Systematic review of studies of quality of clinical care in general practice in the UK, Australia and New Zealand.

OBJECTIVES: Little is known about the quality of clinical care provided outside the hospital sector, despite the increasingly important role of clinical generalists working in primary care. In this study we aimed to summarise published evaluations of the quality of clinical care provided in general practice in the UK, Australia, and New Zealand. DESIGN: A systematic review of published studies assessing the quality of clinical care in general practice for the period 1995-9. SETTING: General practice based care in the UK, Australia, and New Zealand. Main outcome measures-Study design, sampling strategy and size, clinical conditions studied, quality of care attained for each condition (compared with explicit or implicit standards for the process of care), and country of origin for each study. RESULTS: Ninety papers fulfilled the entry criteria for the review, 80 from the UK, six from Australia, and four from New Zealand. Two thirds of the studies assessed care in self-selected practices and 20% of the studies were based in single practices. The majority (85.5%) examined the quality of care provided for chronic conditions including cardiovascular disease (22%), hypertension (14%), diabetes (14%), and asthma (13%). A further 12% and 2% examined preventive care and acute conditions, respectively. In almost all studies the processes of care did not attain the standards set out in national guidelines or those set by the researchers themselves. For example, in the highest achieving practices 49% of diabetic patients had had their fundii examined in the previous year and 47% of eligible patients had been prescribed beta blockers after an acute myocardial infarction. CONCLUSIONS: This study adopts an overview of the magnitude and the nature of clinical quality problems in general practice in three countries. Most of the studies in the systematic review come from the UK and the small number of papers from Australia and New Zealand make it more difficult to draw conclusions about the quality of care in these two countries. The review helps to identify deficiencies in the research, clinical and policy agendas in a part of the health care system where quality of care has been largely ignored to date. Further work is required to evaluate the quality of clinical care in a representative sample of the population, to identify the reasons for substandard care, and to test strategies to improve the clinical care provided in general practice.

Quality of ambulatory care after myocardial infarction among Medicare patients by type of insurance and region.

PURPOSE: To evaluate use of effective cardiac medications and rehabilitation after myocardial infarction in the ambulatory setting in health maintenance organizations (HMOs) and fee-for-service care, and by region. SUBJECTS AND METHODS: We surveyed elderly Medicare patients during 1996 and 1997 in California (n = 516), Florida (n = 304), and the Northeast (n = 220; Massachusetts, New York, and Pennsylvania) approximately 18 months after myocardial infarction. We assessed use of cardiac medications and rehabilitation for HMO (n = 520) and fee-for-service (n = 520) patients matched by age, sex, month of infarct, and region. RESULTS: Across all regions, similar proportions of HMO and fee-for-service patients were using aspirin (72%, n = 374 vs. 74%, n = 387), beta-blockers (38%, n = 195 vs. 32%, n = 168), angiotensin-converting enzyme inhibitors (31%, n = 159 vs. 29%, n = 148), cholesterol-lowering agents (28%, n = 146 vs. 30%, n = 157), and calcium channel blockers (31%, n = 162 vs. 31%, n = 159; all P >0.07), except in California where more HMO patients received beta-blockers (36%, n = 93 vs. 26%, n = 66, P = 0.01). In adjusted analyses, use of these drugs did not differ significantly between HMO and fee-for-service patients. Substantial regional differences were evident in the use of beta-blockers (Northeast 46%, n = 102; Florida 34%, n = 102; California 31%, n = 159) and cholesterol-lowering agents (California 35%, n = 182; Florida 24%, n = 73; Northeast 22%, n = 48; each P <0.001). Fee-for-service patients were more likely than HMO patients to receive cardiac rehabilitation in unadjusted (32%, n = 167, vs. 22%, n = 141, P = 0.001) and adjusted analyses. CONCLUSIONS: Both HMO and fee-for-service patients would likely benefit from greater use of beta-blockers and cholesterol-lowering agents. Professional fees for cardiac rehabilitation may promote increased use among fee-for-service patients. Future studies should assess the quality of ambulatory cardiac care in different types of HMOs and the reasons for geographic variations in cardiac drug use.

Explanation for the decline in coronary heart disease mortality rates in Auckland, New Zealand, between 1982 and 1993.

BACKGROUND: We sought to determine how much of the recent, substantial fall in coronary heart disease (CHD) mortality rates in New Zealand can be attributed to "evidence-based" medical and surgical treatments and how much can be attributed to cardiovascular risk factor reductions. METHODS AND RESULTS: A cell-based mortality model was developed and refined. This model combined (1) the published effectiveness of cardiological treatments and risk factor reductions with (2) data on all medical and surgical treatments administered to all CHD patients and (3) trends in population cardiovascular risk factors (principally smoking, cholesterol, and hypertension) from 1982 to 1993 in Auckland, New Zealand (population 996 000). Between 1982 and 1993, CHD mortality rates fell by 23.6%, with 671 fewer CHD deaths than expected from baseline mortality rates in 1982. Forty-six percent of this fall was attributed to treatments (acute myocardial infarction 12%, secondary prevention 12%, hypertension 7%, heart failure 6%, and angina 9%), and 54% was attributed to risk factor reductions (smoking 30%, cholesterol 12%, population blood pressure 8%, and other, unidentified factors 4%). These proportions remained relatively consistent after a robust sensitivity analysis. CONCLUSIONS: Approximately half the CHD mortality rate fall in Auckland, New Zealand, was attributed to medical therapies, and approximately half was attributed to reductions in major risk factors. These findings emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments and actively promotes a prevention program, particularly for smoking, diet, and blood pressure reduction.

Waiting times and prioritization for coronary artery bypass surgery in New Zealand.

OBJECTIVES: To review the New Zealand coronary artery bypass priority score instituted in May 1996, and specifically to determine whether it prioritizes patients at high risk of cardiac events while waiting. The New Zealand score is compared with the Ontario urgency rating score, and waiting times for surgery are compared with the maximum times recommended by the Ontario consensus panel. DESIGN: Retrospective review of patients accepted for isolated coronary artery bypass surgery between 1 January 1993 and 31 January 1996. SETTING: Green Lane Hospital, Auckland, New Zealand. MAIN OUTCOME MEASURES: Waiting time, cardiac death, myocardial infarction, and cardiac readmission. RESULTS: The median waiting times were five days for hospital cases (n = 721) and 146 days for out of hospital cases (n = 701). Of the latter group, 28% waited more than a year, 33% had their surgery expedited because of worsening symptoms, and 19% failed to meet the cut off point set by the New Zealand score for acceptance onto the list. Twenty two patients died, 18 on the outpatient waiting list (waiting list mortality 2.6%, risk 0.28% per month of waiting), and 132 were readmitted, 12% with myocardial infarction and 76% with unstable angina. Risk factors for a composite end point of death or myocardial infarction and/or cardiac readmission were: previous coronary artery bypass surgery (p = 0. 001), class III or IV angina (p = 0.002), and hypertension (p = 0. 005). The New Zealand score did not identify those at risk. Excluding hospital cases, 32% had surgery within the time recommended by the Ontario consensus panel. CONCLUSIONS: Waiting times for coronary artery bypass surgery in New Zealand are considerably longer than those in Ontario, Canada. By using a numerical cut off point, implementation of the New Zealand priority scoring system has restricted access to coronary surgery on the basis of funding constraints rather than clinical appropriateness. The score does not add greatly to the clinicians' prioritization in predicting those patients who will suffer events while waiting.

High frequency of K-ras codon 12 mutations in bronchoalveolar lavage fluid of patients at high risk for second primary lung cancer.

A high frequency of K-ras mutations may indicate preneoplastic changes in the bronchial epithelium as a result of genotoxic injury. With the use of sensitive detection techniques, we report a higher prevalence of K-ras mutations in bronchoalveolar lavage than has been reported previously for lung cancer. A PCR/ligase chain reaction technique was used to determine K-ras codon 12 mutations in a group of 52 bronchoalveolar lavage specimens from patients at risk of a second lung cancer. Of the specimens examined, 84% contained at least one mutation in K-ras codon 12, corroborated by an allele-specific hybridization method. These results suggest that point mutations in K-ras codon 12 are widespread in the bronchial epithelium. Based on these preliminary findings, further evaluation of this efficient sensitive assay to monitor K-ras status should be conducted in larger clinical cohorts where clinical outcomes will ultimately be available. Such a trial will define the utility of K-ras codon 12 mutation status as a marker of lung cancer.

Detection of K-ras oncogene mutations by polymerase chain reaction-based ligase chain reaction.

To evaluate a rapid multiplexed assay to detect three common K-ras codon 12 mutations, primer pairs complementary to the wild-type and mutant loci were developed and tested with lung cancer cell lines with previously identified mutation status. The sensitivity of detection of mutations was determined to be at least 1% using spiked samples containing K-ras codon 12 mutations. This assay was then used to evaluate prospectively K-ras status in airways of individuals at high risk of lung cancer by analysis of bronchoalveolar lavage (BAL) specimens from patients who have been previously treated for lung cancer. DNA was extracted from BAL specimen cell pellets, and PCR-based ligase chain reaction was performed for mutations in the first position of codon 12 of K-ras, with positive and negative controls. Of 10 BAL samples, 4 contained 1 mutation (GGT --> TGT), 1 contained 2 mutations (GGT --> TGT and GGT --> AGT), and the rest were wild-type. The BAL mutations were validated by cloning and screening with mutant-specific probes followed by confirmation sequencing.

Practical and clinical nutritional concerns during spaceflight.

Experience with space exploration to date has raised more questions regarding nutritional requirements for astronauts than it has answered. As mission lengths continue to increase, nutrient imbalances due to alterations in intake, dietary requirements, bioavailability, or excretion, may become more important. Factors adversely affecting intake include those as straightforward as stress and as complex as space-adaptation syndrome. Metabolic alterations induced by shifts in fluid and electrolyte balance, neuroendocrine function, and changes in hepatic protein synthesis and skeletal muscle type that result in nutrient partitioning to different biochemical pathways may also affect dietary requirements. Food processing effects on nutrient stability and digestibility, which apply to limited quantities of our usual diet on Earth, may become more important for diets that contain little fresh food during extended-length missions. Whereas nutrient and water recycling through ecosystems is taken for granted on Earth, specific effects of trace contaminant accumulation will require greater attention for prolonged space flights. Human factors, esthetics, and user-friendly operations will be necessary to facilitate the psychological as well as physiological health of the astronauts.

Evaluation of liquid chromatography coupled with high-field 1H NMR spectroscopy for drug metabolite detection and characterization: the identification of paracetamol metabolites in urine and bile.

The applicability of coupled reversed-phase high performance liquid chromatography (HPLC)-NMR spectroscopy for the detection and identification of paracetamol (N-(4-hydroxyphenyl)acetamide) and its sulfate, glucuronide and N-acetylcysteinyl metabolites in the unprocessed biological fluids, human urine, rat urine and rat bile, is investigated. Analysis of these samples was performed by gradient HPLC elution and directly coupled 500 MHz 1H NMR spectroscopy detection using a combination of one- and two-dimensional NMR methods in stopped-flow mode. The stopped-flow approach is demonstrated to be an efficient technique for identification of drug metabolites which have, for example, a UV-chromophore. Stopped-flow HPLC analysis with NMR detection is a viable technique and halting the chromatographic process several times during a run has a negligible effect on the separation and NMR characterization. The post-acquisition data processing method of 'quantified maximum entropy' is shown to provide a means of improving the quality of spectra for minor components, thus aiding NMR resonance assignments.