The effects of short-term omission of daily medication on the pathophysiology of heart failure

Aims Pharmacological therapies for heart failure (HF) aim to improve congestion, symptoms, and prognosis. Failing to take medication is a potential cause of worsening HF. Characterizing the effects of short-term medication omission could inform the development of better technologies and strategies to detect and interpret the reasons for worsening HF. We examined the effect of planned HF medication omission for 48 h on weight, echocardiograms, transthoracic bio-impedance, and plasma concentrations of NT-proBNP. Methods and results Outpatients with stable HF and an LVEF <45% were assigned to take or omit their HF medication for 48 h in a randomized, crossover trial. Twenty patients (16 men, LVEF 32 ± 9%, median NT-proBNP 962 ng/L) were included. Compared with regular medication, omission led to an increase in NT-proBNP by 99% (from 962 to 1883 ng/L, P < 0.001), systolic blood pressure by 16% (from 131 to 152 mmHg, P < 0.001), and left atrial volume by 21% (from 69 to 80 mL, P = 0.001), and reductions in transthoracic bio-impedance by 10% (from 33 to 30 Σ, P = 0.001) and serum creatinine by 8% (from 135 to 118 µmol/L, P = 0.012). No significant changes in body weight, heart rate, or LVEF were observed. Conclusions The characteristic pattern of response to short-term medication omission is of increasing congestion but, in contrast to the pattern reported for disease progression, with a rise in blood pressure and improved renal function. In stable HF, weight is not a sensitive marker of short-term diuretic omission

Graphene-based photovoltaic cells for near-field thermal energy conversion

Thermophotovoltaic devices are energy-conversion systems generating an electric current from the thermal photons radiated by a hot body. In far field, the efficiency of these systems is limited by the thermodynamic Schockley-Queisser limit corresponding to the case where the source is a black body. On the other hand, in near field, the heat flux which can be transferred to a photovoltaic cell can be several orders of magnitude larger because of the contribution of evanescent photons. This is particularly true when the source supports surface polaritons. Unfortunately, in the infrared where these systems operate, the mismatch between the surface-mode frequency and the semiconductor gap reduces drastically the potential of this technology. Here we show that graphene-based hybrid photovoltaic cells can significantly enhance the generated power paving the way to a promising technology for an intensive production of electricity from waste heat.Comment: 5 pages, 4 figure

Adherence with tobramycin inhaled solution and health care utilization

<p>Abstract</p> <p>Background</p> <p>Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization.</p> <p>Methods</p> <p>We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories.</p> <p>Results</p> <p>Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768).</p> <p>Conclusions</p> <p>Use of TIS did not reflect recommended guidelines and may impact other health care utilization.</p

Perceived Discrimination and Adherence to Medical Care in a Racially Integrated Community

BACKGROUND: Past research indicates that access to health care and utilization of services varies by sociodemographic characteristics, but little is known about racial differences in health care utilization within racially integrated communities. OBJECTIVE: To determine whether perceived discrimination was associated with delays in seeking medical care and adherence to medical care recommendations among African Americans and whites living in a socioeconomically homogenous and racially integrated community. DESIGN: A cross-sectional analysis from the Exploring Health Disparities in Integrated Communities Study. PARTICIPANTS: Study participants include 1,408 African-American (59.3%) and white (40.7%) adults (≥18 years) in Baltimore, Md. MEASUREMENTS: An interviewer-administered questionnaire was used to assess the associations of perceived discrimination with help-seeking behavior for and adherence to medical care. RESULTS: For both African Americans and whites, a report of 1–2 and >2 discrimination experiences in one’s lifetime were associated with more medical care delays and nonadherence compared to those with no experiences after adjustment for need, enabling, and predisposing factors (odds ratio [OR] = 1.8, 2.6; OR = 2.2, 3.3, respectively; all P < .05). Results were similar for perceived discrimination occurring in the past year. CONCLUSIONS: Experiences with discrimination were associated with delays in seeking medical care and poor adherence to medical care recommendations INDEPENDENT OF NEED, ENABLING, AND PREDISPOSING FACTORS, INCLUDING MEDICAL MISTRUST; however, a prospective study is needed. Further research in this area should include exploration of other potential mechanisms for the association between perceived discrimination and health service utilization

Tailored preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in the Netherlands

Background Adverse reproductive performance has been linked to unhealthy dietary intake and lifestyles. Our objectives were to investigate the prevalence of unhealthy dietary intake and lifestyles before conception and to evaluate whether tailored preconception counselling modifies these behaviours. Methods Between October 2007 and April 2009, 419 couples received tailored preconception dietary and lifestyle counselling at the outpatient clinic of Obstetrics and Gynaecology of the Erasmus University Medical Center Rotterdam, the Netherlands. A subgroup (n = 110 couples) was counselled twice with a fixed time interval of 3 months. Self-administered questionnaires were used for tailored dietary and lifestyle counselling. A cumulative score based on six Dutch dietary guidelines was displayed in the personal Preconception Dietary Risk score (PDR score). In a similar manner, the Rotterdam Reproduction Risk score (R3 score) was calculated from lifestyle factors (women: 13 items, men: 10 items). Univariate and paired tests were used. Results Most couples (93.8) were subfertile. At the second counselling, the percentage consuming the recommended intake of fruit had increased from 65 to 80 in women and from 49 to 68 in men and the percentage of women getting the recommended intake of fish increased from 39 to 52. As a consequence, the median PDR score was decreased [women: 2.6 (95 CI 2.4-2.9) to 2.4 (95 CI 2.1-2.6), men: 2.5 (95 CI 2.3-2.7) to 2.2 (95 CI 1.9-2.4), both P < 0.05]. The median R3 scores were also lower [women: 4.7 (95 CI 4.3-5.0) to 3.1 (95 CI 2.8-3.4), men: 3.0 (95 CI 2.8-3.3) to 2.0 (95 CI 1.7-2.3), both P < 0.01] due to less alcohol use (-14.6), more physical exercise and folic acid use in women, and less alcohol use in men (-19.4) (all P < 0.01). The R3 scores in women and men were decreased in all ethnicity, educational level, neighbourhood and BMI categories. However, low educated women appeared to show a larger reduction than better educated women and men with a normal BMI to show a larger decrease than overweight men. The reduction in the PDR score of women was similar in both ethnic groups. More than 85 women and men found the counselling useful and around 70 would recommend it to others. Conclusions Tailored preconception counselling about unhealthy dietary and lifestyle behaviours of subfertile couples in an outpatient tertiary clinic is feasible and seems to decrease the prevalence of harmful behaviours in the short term. These Results with subfertile couples are promising and illustrate their opportunities to contribute to reproductive performance and pregnancy outcome

Observed communication skills: how do they relate to the consultation content? A nation-wide study of graduate medical students seeing a standardized patient for a first-time consultation in a general practice setting

<p>Abstract</p> <p>Background</p> <p>In this study, we wanted to investigate the relationship between background variables, communication skills, and the bio-psychosocial content of a medical consultation in a general practice setting with a standardized patient.</p> <p>Methods</p> <p>Final-year medical school students (N = 111) carried out a consultation with an actor playing the role of a patient with a specific somatic complaint, psychosocial stressors, and concerns about cancer. Based on videotapes, communication skills and consultation content were scored separately.</p> <p>Results</p> <p>The mean level of overall communication skills had a significant impact upon the counts of psychosocial issues, the patient's concerns about cancer, and the information and planning parts of the consultation content being addressed. Gender and age had no influence upon the relationship between communication skills and consultation content.</p> <p>Conclusion</p> <p>Communication skills seem to be important for final-year students' competence in addressing sensitive psychosocial issues and patients' concerns as well as informing and planning with patients being representative for a fairly complex case in general practice. This result should be considered in the design and incorporation of communication skills training as part of the curriculum of medical schools.</p

Development of a Single Vector System that Enhances Trans-Splicing of SMN2 Transcripts

RNA modalities are developing as a powerful means to re-direct pathogenic pre-mRNA splicing events. Improving the efficiency of these molecules in vivo is critical as they move towards clinical applications. Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical copy gene called SMN2 produces low levels of functional protein due to alternative splicing. We previously reported a trans-splicing RNA (tsRNA) that re-directed SMN2 splicing. Now we show that reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing. A single vector system was developed that expressed the SMN tsRNA and a splice-site blocking antisense (ASO-tsRNA). The ASO-tsRNA vector significantly elevated SMN levels in primary SMA patient fibroblasts, within the central nervous system of SMA mice and increased SMN-dependent in vitro snRNP assembly. These results demonstrate that the ASO-tsRNA strategy provides insight into the trans-splicing mechanism and a means of significantly enhancing trans-splicing activity in vivo

Five interpersonal factors are predictive of the response to treatment of major depression with antidepressants in primary care

Factors relating to the interpersonal relationship between the patient and their physician and social environment are important components, which contribute to their response to treatment for major depressive disorder. This study aimed to assess the influence of optimism, perfectionism, therapeutic alliance, empathy, social support, and adherence to medication regimen in the response to antidepressant treatments in the context of normal primary care clinical practice. Method: We conducted a prospective study in which 24 primary care physicians administered sertraline or escitalopram to 89 patients diagnosed with major depressive disorder. The response to treatment and remission of the episode was assessed at 4 and 12 weeks by Cox regression. The effect of adherence to the medication regimen was assessed by multiple regression statistical techniques. Results: Adherence to medication (HR = 0.262, 95% CI = 0.125-0.553, p < 0.001) and patient perfectionism (HR = 0.259, 95% CI = 0.017-0.624, p < 0.01) negatively predicted the initial response to treatment, whereas patient optimism (HR = 1.221, 95% CI = 1.080-1.380, p < 0.05) positively predicted it. Patient optimism (HR = 1.247, 95% CI = 1.1-1.4, p < 0.05), empathy perceived by the patient (HR = 1.01, 95% CI = 1001-1002, p < 0.05), and therapeutic alliance (HR = 1.02, 95% CI = 1001-1.04, p < 0.05) positively predicted episode remission, while patient perfectionism (HR = 0.219, 95% CI = 0.093-0.515, p < 0.001) and low adherence to the treatment regimen (HR = 0.293, 95% CI = 0.145-0.595, p < 0.001) negatively predicted it. Finally, social support (p < 0.01) and therapeutic alliance (p < 0.05) predicted adherence to the medication regimen. Conclusions: In addition to taking the antidepressant drug, other factors including the personal interactions between the patient with their primary care physician and with their social environment significantly influenced the patients' initial response and the final rate of episode remission

Spectrum and Inoculum Size Effect of a Rapid Antigen Detection Test for Group A Streptococcus in Children with Pharyngitis

BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection

Changes over time in the effect of marital status on cancer survival

<p>Abstract</p> <p>Background</p> <p>Rates of all-cause and cause-specific mortality are higher among unmarried than married individuals. Cancer survival is also poorer in the unmarried population. Recently, some studies have found that the excess all-cause mortality of the unmarried has increased over time, and the same pattern has been shown for some specific causes of death. The objective of this study was to investigate whether there has been a similar change over time in marital status differences in cancer survival.</p> <p>Methods</p> <p>Discrete-time hazard regression models for cancer deaths among more than 440 000 women and men diagnosed with cancer 1970-2007 at age 30-89 were estimated, using register data encompassing the entire Norwegian population. More than 200 000 cancer deaths during over 2 million person-years of exposure were analyzed.</p> <p>Results</p> <p>The excess mortality of the never-married compared to the married has increased steadily for men, in particular the elderly. Among elderly women, the excess mortality of the never-married compared to the married has increased, and there are indications of an increasing excess mortality of the widowed. The excess mortality of divorced men and women, however, has been stable.</p> <p>Conclusions</p> <p>There is no obvious explanation for the increasing disadvantage among the never-married. It could be due to a relatively poorer general health at time of diagnosis, either because of a more protective effect of partnership in a society that may have become less cohesive or because of more positive selection into marriage. Alternatively, it could be related to increasing differentials with respect to treatment. Today's complex cancer therapy regimens may be more difficult for never-married to follow, and health care interventions directed and adapted more specifically to the broad subgroup of never-married patients might be warranted.</p