How Should Harm Reduction Strategies Differ for Adolescents and Adults?

Overall rates of opioid use are low in adolescents; however, recent increases in mortality from overdose in adolescents have outpaced increases in the general population. This article highlights the importance of expanding evidence-based treatment for adolescent opioid use, especially medication, while also addressing key ethical considerations of harm reduction practices and how application of such practices with adolescents may differ from adults. Concepts related to adolescent populations are discussed, including autonomy, confidentiality, and brain development. Application of harm reduction practices should be age appropriate, express respect for patients' autonomy, include social support, and be accompanied by broader aims to minimize adolescent initiation, escalation, and overall harm caused by opioid use.

Team science and the physician-scientist in the age of grand health challenges.

Despite remarkable advances in medical research, clinicians face daunting challenges from new diseases, variations in patient responses to interventions, and increasing numbers of people with chronic health problems. The gap between biomedical research and unmet clinical needs can be addressed by highly talented interdisciplinary investigators focused on translational bench-to-bedside medicine. The training of talented physician-scientists comfortable with forming and participating in multidisciplinary teams that address complex health problems is a top national priority. Challenges, methods, and experiences associated with physician-scientist training and team building were explored at a workshop held at the Second International Conference on One Medicine One Science (iCOMOS 2016), April 24-27, 2016, in Minneapolis, Minnesota. A broad range of scientists, regulatory authorities, and health care experts determined that critical investments in interdisciplinary training are essential for the future of medicine and healthcare delivery. Physician-scientists trained in a broad, nonlinear, cross-disciplinary manner are and will be essential members of science teams in the new age of grand health challenges and the birth of precision medicine. Team science approaches have accomplished biomedical breakthroughs once considered impossible, and dedicated physician-scientists have been critical to these achievements. Together, they translate into the pillars of academic growth and success.

Is the association of hypertension and panic disorder explained by clustering of autonomic panic symptoms in hypertensive patients?

BACKGROUND: Autonomic nervous system dysfunction may be implicated in the association of hypertension with panic attacks and panic disorder. We hypothesised that panic symptoms of autonomic origin are more common in attacks experienced by hypertensive than normotensive patients, that autonomic panic symptoms cluster together as a distinct factor, and that this factor is more prevalent in hypertensive patients with panic than in normotensives. METHODS: We analysed all 346 structured questionnaires completed by primary care and hospital clinic patients who had reported experiencing full (n=287) or limited symptom panic attacks (n=59) (268 with hypertension, and 78 never having had hypertension). Frequency of sweating, flushes, and racing heart, symptoms selected prospectively as being most likely of autonomic origin, were compared between hypertensive and normotensive patients. Principal component analysis was performed with varimax orthogonal rotation. Using logistic regression, odds ratios were calculated for association of factor scores with hypertension. RESULTS: Sweating and flushes were significantly more common among hypertensive patients than normotensives (sweating; 65% v 46%, p=0.003, flushes; 55% v 40%, p=0.019). There was no significant difference between groups for frequency of racing heart nor any of the remaining panic symptoms analysed as secondary endpoints. Principal component analysis yielded four factors with eigenvalues >1.0. Factor 1 was dominated by autonomic symptoms, notably sweating and flushes, which had loadings of 0.68 and 0.61. On regression only this autonomic factor showed a significant association with hypertension, the odds ratio being 1.37 (95% C.I. 1.05 to 1.77, p=0.018). CONCLUSIONS: These findings support the possibility that autonomic dysfunction contributes to the association of hypertension with panic.

Patients' acceptance of antihypertensive therapy to prevent cardiovascular disease: a comparison between South Asians and Caucasians in the United Kingdom.

BACKGROUND: The importance of patients' involvement in decision-making is because of their right to know the risks and benefits they accept in undertaking treatment and the as yet unproven hope that this will improve compliance. The aim of this study was to establish local people's willingness to receive antihypertensive treatment for primary prevention of cardiovascular disease (CVD) and to explore the role of ethnicity. METHODS: In a cross-sectional study with face-to-face interview South Asian and Caucasian men and women aged 35-74, with and without history of CVD, were interviewed. Minimal clinically important differences were measured for three different baseline CVD risks (10, 20, and 40% in 10 years) using a standard method with risks presented both graphically and numerically and expressed in positive and negative terms. RESULTS: A total of 262 (110 South Asians) participants were interviewed. Overall, South Asians expressed smaller median minimal clinically important differences than Caucasians, 1 and 4%, respectively. Up to 17% of participants in both ethnic groups indicated that they would not take medication regardless of the benefits. The proportion of South Asian men unwilling to take medication regardless of benefit was higher than Caucasian men for all scenarios, 17.2 versus 10.7% for scenario 1 and 12.1 versus 5.6% for scenario 2, respectively. South Asians of both sexes who would consider therapy required less benefit for acceptance in all three scenarios compared with the Caucasians. CONCLUSION: South Asian participants were at least likely as Caucasians to accept antihypertensive treatment as the primary prevention therapy and they should be targeted for this type of therapy.

The effect of GSM and TETRA mobile handset signals on blood pressure, catechol levels and heart rate variability.

An acute rise in blood pressure has been reported in normal volunteers during exposure to signals from a mobile phone handset. To investigate this finding further we carried out a double blind study in 120 healthy volunteers (43 men, 77 women) in whom we measured mean arterial pressure (MAP) during each of six exposure sessions. At each session subjects were exposed to one of six different radio frequency signals simulating both GSM and TETRA handsets in different transmission modes. Blood catechols before and after exposure, heart rate variability during exposure, and post exposure 24 h ambulatory blood pressure were also studied. Despite having the power to detect changes in MAP of less than 1 mmHg none of our measurements showed any effect which we could attribute to radio frequency exposure. We found a single statistically significant decrease of 0.7 mmHg (95% CI 0.3-1.2 mmHg, P = .04) with exposure to GSM handsets in sham mode. This may be due to a slight increase in operating temperature of the handsets when in this mode. Hence our results have not confirmed the original findings of an acute rise in blood pressure due to exposure to mobile phone handset signals. In light of this negative finding from a large study, coupled with two smaller GSM studies which have also proved negative, we are of the view that further studies of acute changes in blood pressure due to GSM and TETRA handsets are not required.

Prevention of coronary heart disease with statins in UK South Asians and Caucasians.

AIMS: To determine the prevalence of subjects eligible for primary and secondary prevention of coronary heart disease (CHD) among the British South Asian population and to compare that with British Caucasians. METHODS AND RESULTS: We used the Health Survey for England 1998 and 1999 datasets, holding data on 9950 Caucasians and 1938 South Asians. Thresholds for treatment were a total cholesterol >3.5 mmol/l and either a history of cardiovascular disease or elevated estimated CHD risk, adjusted where necessary for ethnic differences. Separate analyses were performed for primary prevention risk thresholds of >15% and >30% over 10 years. The prevalence of previous myocardial infarction, angina, or stroke was higher in South Asian men than in Caucasian but the reverse was seen in women. More than 93% [95% confidence interval (CI) 88-97] of South Asian men and nearly 68% (95% CI 66-71) of Caucasian men older than 55 years have a CHD risk greater than 15% (equivalent to cardiovascular risk of 20%) and a cholesterol above 3.5 mmol/l and would be eligible for treatment with lipid-lowering drugs. The equivalent proportions in women are 55% (95% CI 46-65) and 18% (95% CI 16-20) in South Asians and Caucasians, respectively. CONCLUSION: Treating this proportion of the population will have a societal impact, the majority of older people becoming patients, and although it may well be cost-effective for individuals, it will require substantial new resources.

Survey of intensive care physicians on the recognition and management of intra-abdominal hypertension and abdominal compartment syndrome.

OBJECTIVE: To assess current understanding and clinical management of intra-abdominal hypertension and abdominal compartment syndrome among critical care physicians. DESIGN: A ten-question, written survey. SETTING: University health sciences center. SUBJECTS: Physician members of the Society of Critical Care Medicine (SCCM). INTERVENTIONS: The survey was sent to 4,538 SCCM members with a response rate of 35.7% (1622). MEASUREMENTS AND MAIN RESULTS: Primary training, intensive care unit type, and methods for management of abdominal compartment syndrome were assessed. Surgically trained intensivists managed the highest number of abdominal compartment syndrome cases (47% managed 4-10 cases, 16% managed >10 cases). No cases were seen by 25% of medically trained and pediatric trained intensivists. Respondents agreed that bladder pressures and clinical variables were needed to diagnose abdominal compartment syndrome (70%) vs. bladder pressure (7%) or clinical variables (20%) alone. Two percent of surgical intensivists were unaware of a bladder pressure measurement procedure compared with 24% (p < .0001) of pediatric and 23% (p < .0001) of medical intensivists. Forty-two percent of respondents believed bladder pressures of 20-27 mm Hg may cause physiologic compromise. However, 25-27% of pediatric, medicine, or anesthesia trained intensivists believed that compromise occurs between 12 and 19 mm Hg compared with 18% of surgeons. No respondent believed that physiologic compromise occurred at <8 mm Hg. Thirty-eight percent of pediatric intensivists believed that physiologic compromise was patient dependent vs. 7-17% from other specialties (p < .0001; all comparisons). In managing intra-abdominal hypertension, 33% of pediatric intensivists and 19.6% of medical intensivists would never use decompression laparotomy to treat abdominal compartment syndrome compared with 3.6% of intensivists with surgical training (p < .0001; both comparisons). CONCLUSIONS: Significant variation across medical training exists in the management of intra-abdominal hypertension and abdominal compartment syndrome. A significant percentage of intensivists may be unaware of current approaches to abdominal compartment syndrome management including monitoring bladder pressures and decompression laparotomy. Future research and education are necessary to establish clear diagnostic criteria and standards for treatment of this relatively common life-threatening disease process.

Depleting serotonin enhances both cardiovascular and psychological stress reactivity in recovered patients with anxiety disorders.

Serotonin-promoting drugs show cardioprotective properties in patients with anxiety or depression, but it is not known if this is a direct effect of increasing serotonin. We aimed to characterize the effect of serotonin manipulation through acute tryptophan depletion on cardiovascular and psychological responses to stress challenge in recovered patients with anxiety disorders. In 27 recovered patients with anxiety disorders (panic disorder treated by selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy, social anxiety disorder treated by SSRIs), we performed a double-blind randomized crossover study. On 2 separate days, the subjects ingested an acute tryptophan-depleting (aTD) or nondepleting (nD) drink in random order and underwent a stress challenge at time of maximum depletion. Systolic blood pressure (P = 0.007; diff = 9.0 mm Hg; 95% confidence interval (CI), 2.6-15.3 mm Hg) and diastolic blood pressure (P = 0.032; diff = 5.7 mm Hg; 95% CI, 0.6-10.9 mm Hg) responses to stress were significantly greater under aTD than nD, as were the psychological responses to stress (for Spielberger state anxiety, difference in stress response between aTD and nD = 7.11; P = 0.025). Blood pressure responses to stress showed no correlation with psychological responses. The significant increases in acute stress sensitivity in both cardiovascular and psychological domains on serotonin depletion suggest that serotonin is involved in the control of both cardiovascular and psychological aspects of the acute stress response. The lack of correlation in the difference between aTD and nD conditions in cardiovascular and psychological responses suggests that serotonin may have distinct effects on these 2 domains, rather than the cardiovascular responses being merely a secondary consequence of psychological changes.

Predicting coronary risk in UK South Asians: an adjustment method for Framingham-based tools.

BACKGROUND: Although people of South Asian descent appear to be at increased risk of cardiovascular disease (CVD) compared to the general population there is no validated tool for predicting risk in this group. DESIGN: This study was based on an analysis of data from the Health Survey for England (HSE) 1998 and 1999 to identify a simple method for adjusting the Framingham equation to estimate coronary risk in South Asians which could be then applied to existing simple paper-based tools. METHODS: The different adjustments investigated were fixed increments to the age, total cholesterol (TC), and TC:high density lipoprotein (HDL) cholesterol ratio and multipliers for the TC:HDL cholesterol ratio. Framingham risk modified according to a factor derived from an earlier overview of prospective studies was used as a standard to estimate sensitivity and specificity of adjustment methods. The receiver-operating characteristic (ROC) plot was used to compare the different adjustments in the primary role of identifying individuals above or below a given risk threshold. RESULTS: All adjustment methods produced a graded monotonic increase of coronary risk in 4497 eligible subjects from the HSE 1998 dataset. Multiplying TC:HDL cholesterol ratio gave the largest area under the ROC curve. However adding 10 years to the age of South Asian people was the simplest way of calculating coronary heart disease risk using paper-based methods and still provided acceptable accuracy. CONCLUSION: Our result should be used to achieve the systematic evaluation of each individual for primary prevention of CHD in South Asians in primary care.

Coronary risk in South Asians: role of ethnicity and blood sugar.

BACKGROUND: Studies of South Asian immigrants in different countries have reported an increased predisposition to cardiovascular disease in comparison with the native populations. DESIGN: This study is a systematic review of longitudinal studies investigating differences in established risk factors for coronary heart disease (CHD) between Caucasians and South Asians. The aim was to develop a practical tool to estimate CHD risk in individuals. Secondarily data from the Health Survey for England 1999 (HSE 1999) were used to explore a possible role of differences in blood glucose in risk variation. METHODS: We used a systematic search to find relevant published papers. Data from the HSE 1999 were employed to study ethnic differences in blood glucose and glycosylated haemoglobin. RESULTS: Only two out of five longitudinal studies reported independent estimates of relative risks of CHD in South Asians compared to Caucasians. Risk in diabetic South Asians was predicted adequately by classical risk factors whilst risk in a non-diabetic study population was 79% greater than predicted. Non-diabetic South Asians have higher fasting blood glucose (FBG) and HbA1c than Caucasians after adjustment for CHD risk factors. CONCLUSIONS: The difference in risk of CHD between non-diabetic South Asian and Caucasians is not explained by differences in the impact of the traditional risk factors. Part may be due to higher blood sugar concentrations in non-diabetic South Asians.

Drug intolerance due to nonspecific adverse effects related to psychiatric morbidity in hypertensive patients.

BACKGROUND: Poor adherence to antihypertensive drug regimens is common and may increase the risk for cardiovascular morbidity and mortality. Adverse effects of the drugs can contribute to poor adherence, but some patients who discontinue several different antihypertensive drugs may misinterpret nonspecific symptoms as adverse effects of the drug because of psychiatric morbidity. We examined the relationship between intolerance to antihypertensive drugs and the presence of panic disorder, panic attacks, anxiety, and depression. METHODS: We included all patients with hypertension who attended a hospital hypertension clinic during 1 year with at least 2 episodes of intolerance (resulting in reduction of the dosage or stopping an antihypertensive drug) recorded on standardized problem lists and a similar number of patients with no recorded episodes of intolerance. Psychiatric morbidity, assessed by self-administered questionnaires, was analyzed against the number of episodes of nonspecific and drug-specific intolerance, verified by means of individual case-note scrutiny, and scored independently by 2 assessors masked to patient identity. RESULTS: Analyzable questionnaires were returned by 233 (84%) of 276 patients who had experienced 576 (85%) of 679 episodes of intolerance assessed. Five hundred thirty-two episodes (92%) were subjective (patient was symptomatic); of these, 284 were judged to be drug specific; 248, nonspecific. Having more episodes of nonspecific intolerance was associated with significantly higher diastolic blood pressure (P =.003). Episodes of nonspecific intolerance were associated with panic attacks (P =.008), anxiety (Hospital Anxiety and Depression Scale score, P =.04), and depression (Hospital Anxiety and Depression Scale score, P =.005). Drug-specific intolerance was not associated with psychiatric morbidity. CONCLUSIONS: Intolerance to multiple antihypertensive drugs, particularly non-drug-specific intolerance, is strongly associated with psychiatric morbidity. Physicians treating hypertensive patients need to recognize and manage the psychiatric aspects of intolerance to multiple antihypertensive drugs.

Coronary and cardiovascular risk estimation in uncomplicated mild hypertension. A comparison of risk assessment methods.

OBJECTIVE: To compare the accuracy of five risk assessment methods in identifying patients with uncomplicated mild hypertension at high coronary heart disease (CHD) and cardiovascular disease (CVD) risk.DESIGN Comparison of risk estimates using each risk assessment method with CHD risk 15% and CVD risk 20% over 10 years calculated using the Framingham risk functions. SETTING: British population. SUBJECTS: People aged 35-64 years with uncomplicated mild systolic hypertension (systolic blood pressure (SBP) 140-159 mmHg, = 202) from the 1995 Scottish Health Survey. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values. RESULTS: Compared with CHD risk 15% over 10 years, the Sheffield table and Joint British Societies (JBS) Chart had good sensitivity and specificity ( 90%). The New Zealand (NZ) Chart had sensitivity 83% and specificity 89%. Compared with CVD risk 20% over 10 years the Sheffield table had sensitivity 81%, the JBS Chart had sensitivity 63%, and the NZ Chart had sensitivity 75%. All had good specificity ( 90%). For CHD risk and CVD risk the World Health Organization/International Society of Hypertension (WHO-ISH) and United States Joint National Committee VI (JNC-VI) methods had high sensitivity at the cost of very poor specificity ( 50%). CONCLUSION: In patients with uncomplicated mild hypertension, the Sheffield table and JBS Chart both identified CHD risk 15% over 10 years with acceptable accuracy, while the NZ Chart was less accurate. Compared with CVD risk 20% over 10 years, these three risk assessment methods were all less accurate, but the Sheffield table retained the highest sensitivity ( 0.05 versus JBS Chart, = NS versus NZ Chart). The WHO-ISH and JNC-VI methods had unacceptably low specificities compared with both measures of risk and failed to differentiate between those at high and low risk.

What benefit do patients expect from adding second and third antihypertensive drugs?

AIMS: To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. METHODS: This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. RESULTS PARTICIPANTS: required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. CONCLUSIONS: People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients' expectations and informing individual patient decisions.