A systematic review of the safety information contained within the Summaries of Product Characteristics of medications licensed in the United Kingdom for Attention Deficit Hyperactivity Disorder. how does the safety prescribing advice compare with national guidance?

<p>Abstract</p> <p>Background</p> <p>The safety of paediatric medications is paramount and contraindications provide clear pragmatic advice. Further advice may be accessed through Summaries of Product Characteristics (SPCs) and relevant national guidelines. The SPC can be considered the ultimate independent guideline and is regularly updated. In 2008, the authors undertook a systematic review of the SPC contraindications of medications licensed in the United Kingdom (UK) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). At that time, there were fewer contraindications reported in the SPC for atomoxetine than methylphenidate and the specific contraindications varied considerably amongst methylphenidate formulations. In 2009, the European Medicines Agency (EMA) mandated harmonisation of methylphenidate SPCs. Between September and November 2011, there were three changes to the atomoxetine SPC that resulted in revised prescribing information. In addition, Clinical Guidance has also been produced by the National Institute for Health and Clinical Excellence (NICE) (2008), the Scottish Intercollegiate Guidelines Network (SIGN) (2009) and the British National Formulary for Children (BNFC).</p> <p>Methods</p> <p>An updated systematic review of the Contraindications sections of the SPCs of all medications currently licensed for treatment of ADHD in the UK was undertaken and independent statements regarding contraindications and relevant warnings and precautions were then compared with UK national guidance with the aim of assessing any disparity and potential areas of confusion for prescribers.</p> <p>Results</p> <p>As of November 2011, there were seven medications available in the UK for the treatment of ADHD. There are 15 contraindications for most formulations of methylphenidate, 14 for dexamfetamine and 5 for atomoxetine. Significant differences exist between the SPCs and national guidance part due to the ongoing reactive process of amending the former as new information becomes known. In addition, recommendations are made outside UK SPC licensed indications and a significant contraindication for methylphenidate (suicidal behaviours) is missing from both the NICE and SIGN guidelines. Particular disparity exists relating to monitoring for suicidal and psychiatric side effects. The BNFC has not yet been updated in line with the European Union (EU) Directive on methylphenidate; it does not include any contraindications for atomoxetine but describes contraindications for methylphenidate that are no longer in the SPC.</p> <p>Conclusion</p> <p>Clinicians seeking prescribing advice from critical independent sources of data, such as SPCs and national guidelines, may be confused by the disparity that exists. There are major differences between guidelines and SPCs and neither should be referred to in isolation. The SPC represents the most relevant source of safety data to aid prescribing of medications for ADHD as they present the most current safety data in line with increased exposure. National guidelines may need more regular updates.</p

Barriers to adoption of recent technology in cervical screening

The Pap smear is one of the modern success stories in the field of preventive medicine. Since its introduction as a screening test, there has been a dramatic reduction in the incidence of cervical cancer. However, the search for a better screening test continues. The new technologies, including liquid-based cytology (LBC), Human Papilloma Virus (HPV) testing and automated or machine-assisted screening have been introduced. However, there is continuous debate about whether society's limited resources are better spent on reaching the underserved rather than on these technologies. Another question is whether these technologies create yet another kind of disparity in delivering preventive care. For example, despite the wide use of LBC (99% of tests submitted to our laboratory are LBC), conventional Pap smears are still used to screen/follow up some women. It is not clear why some providers continue to prefer conventional smear over LBC and what are the barriers for adopting LBC in cervical cancer screening. We hypothesize the lower cost of conventional compared to LBC Pap testing, patient's lower socio-economic indices, a patient's medical history and provider's subspecialty/training all appear to play a role in the choice of using conventional Pap testing rather than LBC. Unintentionally, this choice results in repeat testing, delayed treatment and potentially higher costs than intended. The ultimate goal of this review article is to understand and explore possible barriers and disparities to adopting new technology in cancer screening

Diet quality is positively associated with 100% fruit juice consumption in children and adults in the United States: NHANES 2003-2006

<p>Abstract</p> <p>Background</p> <p>One hundred percent fruit juice (100% FJ) has been viewed by some as a sweetened beverage with concerns about its effect on weight. Little regard has been given to the contribution of 100% FJ to diet quality.</p> <p>Methods</p> <p>In this study data from the 2003-2006 National Health and Nutrition Examination Survey were used to examine the association of 100% FJ consumption with diet quality in participants 2-5 years of age (y) (n = 1665), 6-12 y (n = 2446), 13-18 y (n = 3139), and 19+y (n = 8861). Two 24-hour dietary recalls were used to determine usual intake using the National Cancer Institute method. Usual intake, standard errors, and regression analyses (juice independent variable and Healthy Eating Index-2005 [HEI-2005] components were dependent variables), using appropriate covariates, were determined using sample weights.</p> <p>Results</p> <p>The percentage of participants 2-5 y, 6-12 y, 13-18 y, and 19+y that consumed 100% FJ was 71%, 57%, 45%, and 62%, respectively. Usual intake of 100% FJ (ounce [oz]/day) among the four age groups was: 5.8 ± 0.6, 2.6 ± 0.4, 3.7 ± 0.4, and 2.4 ± 0.2 for those in age groups 2-5 y, 6-12 y, 13-18 y, and 19+y, respectively. Consumption of 100% FJ was associated with higher energy intake in 6-12 y, 13-18 y, and 19+y; and higher total, saturated, and discretionary fats in 13-18 y participants. Consumption of 100% FJ was associated with higher total HEI-2005 scores in all age groups (< 0.0001). In 100% FJ consumers, total and whole fruit consumption was higher and intake of added sugars was lower in all age groups.</p> <p>Conclusions</p> <p>Usual intake of 100% FJ consumption exceeded MyPyramid recommendations for children 2-5 y, but was associated with better diet quality in all age groups and should be encouraged in moderation as part of a healthy diet.</p

The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue

In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users

Children's very low food security is associated with increased dietary intakes in energy, fat, and added sugar among Mexican-origin children (6-11 y) in Texas border Colonias

<p>Abstract</p> <p>Background</p> <p>Food insecurity among Mexican-origin and Hispanic households is a critical nutritional health issue of national importance. At the same time, nutrition-related health conditions, such as obesity and type 2 diabetes, are increasing in Mexican-origin youth. Risk factors for obesity and type 2 diabetes are more common in Mexican-origin children and include increased intakes of energy-dense and nutrient-poor foods. This study assessed the relationship between children's experience of food insecurity and nutrient intake from food and beverages among Mexican-origin children (age 6-11 y) who resided in Texas border <it>colonias</it>.</p> <p>Methods</p> <p>Baseline data from 50 Mexican-origin children were collected in the home by trained <it>promotora</it>-researchers. All survey (demographics and nine-item child food security measure) and 24-hour dietary recall data were collected in Spanish. Dietary data were collected in person on three occasions using a multiple-pass approach; nutrient intakes were calculated with NDS-R software. Separate multiple regression models were individually fitted for total energy, protein, dietary fiber, calcium, vitamin D, potassium, sodium, Vitamin C, and percentage of calories from fat and added sugars.</p> <p>Results</p> <p>Thirty-two children (64%) reported low or very low food security. Few children met the recommendations for calcium, dietary fiber, and sodium; and none for potassium or vitamin D. Weekend intake was lower than weekday for calcium, vitamin D, potassium, and vitamin C; and higher for percent of calories from fat. Three-day average dietary intakes of total calories, protein, and percent of calories from added sugars increased with declining food security status. Very low food security was associated with greater intakes of total energy, calcium, and percentage of calories from fat and added sugar.</p> <p>Conclusions</p> <p>This paper not only emphasizes the alarming rates of food insecurity for this Hispanic subgroup, but describes the associations for food insecurity and diet among this sample of Mexican-origin children. Child-reported food insecurity situations could serve as a screen for nutrition problems in children. Further, the National School Lunch and School Breakfast Programs, which play a major beneficial role in children's weekday intakes, may not be enough to keep pace with the nutritional needs of low and very low food secure Mexican-origin children.</p

Is there a demand for physical activity interventions provided by the health care sector? Findings from a population survey

<p>Abstract</p> <p>Background</p> <p>Health care providers in many countries have delivered interventions to improve physical activity levels among their patients. Thus far, less is known about the population's interest to increase their physical activity levels and their opinion about the health care provider's role in physical activity promotion. The aims of this paper were to investigate the self-reported physical activity levels of the population and intention to increase physical activity levels, self-perceived need for support, and opinions about the responsibilities of both individuals and health care providers to promote physical activity.</p> <p>Methods</p> <p>A regional public health survey was mailed to 13 440 adults (aged 18-84 years) living in Östergötland County (Sweden) in 2006. The survey was part of the regular effort by the regional Health Authorities.</p> <p>Results</p> <p>About 25% of the population was categorised as physically active, 38% as moderately active, 27% as somewhat active, and 11% as low active. More than one-third (37%) had no intentions to increase their physical activity levels, 36% had thought about change, while 27% were determined to change. Lower intention to change was mainly associated with increased age and lower education levels. 28% answered that physical activity was the most important health-related behaviour to change "right now" and 15% of those answered that they wanted or needed support to make this change. Of respondents who might be assumed to be in greatest need of increased activity (i.e. respondents reporting poor general health, BMI>30, and inactivity) more than one-quarter wanted support to make improvements to their health. About half of the respondents who wanted support to increase their physical activity levels listed health care providers as a primary source for support.</p> <p>Conclusions</p> <p>These findings suggest that there is considerable need for physical activity interventions in this population. Adults feel great responsibility for their own physical activity levels, but also attribute responsibility for promoting increased physical activity to health care practitioners.</p

Incremental dialysis for preserving residual kidney function-Does one size fit all when initiating dialysis?

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed

Accelerometer-measured sedentary and physical activity time and their correlates in European older adults: The SITLESS study

Background: Sedentary behavior (SB) and physical activity (PA) are important determinants of health in older adults. This study aimed to describe the composition of accelerometer-measured SB and PA in older adults, to explore self-reported context-specific SB, and to assess socio-demographic and functional correlates of engaging in higher levels of SB in participants of a multi-center study including four European countries. Methods: 1360 community-dwelling older adults from the SITLESS study (61.8% women; 75.3±6.3 years) completed a self-reported SB questionnaire and wore an ActiGraph accelerometer for seven days. Accelerometer-determined compositional descriptive statistics were calculated. A fixed effects regression analysis was conducted to assess the socio-demographic (country, age, sex, civil status, education and medications) and functional (BMI and gait speed) correlates. Results: Older adults spent 78.8% of waking time in SB, 18.6% in light-intensity PA (LPA), and 2.6% in moderate to vigorous PA (MVPA). Accelerometry showed that women engaged in more LPA and walking and men engaged in higher amounts of MVPA. Watching television and reading accounted for 47.2% of waking time. Older age, being a man, single, taking more medications, being obese and overweight, and having a slower gait speed were statistically significant correlates of more sedentary time. Conclusions: The high amount of SB of our participants justifies the need to develop and evaluate interventions to reduce sitting time. A clinically relevant change in gait speed can decrease almost 0.45 percentage points of sedentary time. The distribution of context-specific sedentary activities by country and sex showed minor differences, albeit worth noting

Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants

<p>Abstract</p> <p>Background</p> <p>Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.</p> <p>Methods</p> <p>The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).</p> <p>Results</p> <p>Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.</p> <p>Conclusion</p> <p>This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.</p

Credible knowledge: A pilot evaluation of a modified GRADE method using parent-implemented interventions for children with autism

Abstract Background Decision-making in child and youth mental health (CYMH) care requires recommendations that are developed through an efficient and effective method and are based on credible knowledge. Credible knowledge is informed by two sources: scientific evidence, and practice-based evidence, that reflects the "real world" experience of service providers. Current approaches to developing these recommendations in relation to CYMH will typically include evidence from one source or the other but do not have an objective method to combine the two. To this end, a modified version of the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach was pilot-tested, a novel method for the CYMH field. Methods GRADE has an explicit methodology that relies on input from scientific evidence as well as a panel of experts. The panel established the quality of evidence and derived detailed recommendations regarding the organization and delivery of mental health care for children and youth or their caregivers. In this study a modified GRADE method was used to provide precise recommendations based on a specific CYMH question (i.e. What is the current credible knowledge concerning the effects of parent-implemented, early intervention with their autistic children?). Results Overall, it appeared that early, parent-implemented interventions for autism result in positive effects that outweigh any undesirable effects. However, as opposed to overall recommendations, the heterogeneity of the evidence required that recommendations be specific to particular interventions, based on the questions of whether the benefits of a particular intervention outweighs its harms. Conclusions This pilot project provided evidence that a modified GRADE method may be an effective and practical approach to making recommendations in CYMH, based on credible knowledge. Key strengths of the process included separating the assessments of the quality of the evidence and the strength of recommendations, transparency in decision-making, and the objectivity of the methods. Most importantly, this method combined the evidence and clinical experience in a more timely, explicit and simple process as compared to previous approaches. The strengths, limitations and modifications of the approach as they pertain to CYMH, are discussed