Early markers of vulnerable language skill development in galactosaemia

There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative ‘red flag’ behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic development in two 18-month-old infants with GAL (one of each gender). Results identified the male as displaying significantly poorer pre-linguistic skills than both his matched peers and relative to the female infant with GAL, whose pre-linguistic skills were commensurate with or better than her matched peers. The results suggest that by 18 months of age, differential developmental language skills can be identified in infants with GAL when the focus is on pre-linguistic communication behaviours.     

Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum

Rationale

It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings. In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings.

Objectives

To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum.

Methods

Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n?=?42 or 4 mg, n?=?24) or placebo (n?=?66) gum while travelling on a non-smoking train. Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence.

Results

In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F(21,110)?=?1.28, p?=?0.20, $ \eta_{\mathrm{p}}^2 $ ?=?0.20] nor an effect of treatment [F(7,124)?=?0.45, p?=?0.87, $ \eta_{\mathrm{p}}^2 $ ?=?0.03]. There was an effect of time [F(21,110)?=?11.59, p?<?0.001, $ \eta_{\mathrm{p}}^2 $ ?=?0.69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence.

Conclusions

Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence. Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h. Nicotine gum may not have an acute effect on the development of these symptoms.     

The need for pharmaceutical care in the prevention of coronary heart disease: an exploratory study in acute myocardial infarction patients

AIM: To determine guideline-related pharmaceutical care issues for the prevention of coronary heart disease in hospitalised patients admitted for myocardial infarction (MI). METHODS: Consecutive patients admitted with a diagnosis of Q-wave MI to two large teaching hospitals were studied. Relevant patient medical and drug histories, co-morbidities and total cholesterol concentrations were recorded. Primary or secondary prevention treatment prior to admission was assessed using a data collection tool of 16 criteria developed from the Scottish Intercollegiate Guidelines Network (SIGN) guidelines. MAIN OUTCOME MEASURES: Frequency of adherence to defined clinical guideline criteria. RESULTS: There were 167 patients reviewed (mean age 65 years, 111 males), representing possible candidates for primary prevention (n = 98) or secondary prevention (n = 69) based on absence or presence of past history of coronary heart disease (CHD), respectively. Possible primary prevention candidates: eight guideline-based criteria were developed from the SIGN guideline. There were 85 (87%) patients with a total cholesterol concentration available on admission of whom 56 (66%) had a predicted CHD risk > or = 15% and 10 (12%) had CHD risk > or = 30%. Of those with CHD risk > or = 15% 6 (11%) had been receiving an anti-platelet agent and of those with CHD risk > or = 30% only 1 (10%) was recorded as taking a statin. Of known hypertensives with CHD risk > or = 15%, 21% (5/24) were not recorded as having received treatment. Secondary prevention candidates: a further eight guideline-based criteria were developed from the SIGN guidelines. There were 42/65 (65%) candidates for aspirin documented as receiving it. There were 22/47 (47%) of those who had a total cholesterol > or = 5 mmol/l and/or known history of hypercholesterolaemia receiving a statin (representing 76% of the known hypercholesterolaemic patients identified in the community). Of statin-treated patients with a cholesterol measured on admission, 44% (7/16) had cholesterol remaining > or = 5 mmol/l. Beta-blocker use was 27/62 (44%) and ACE inhibitors use was 11/31 (36%) of those eligible. Sublingual GTN was recorded in 36/69 (52%). CONCLUSION: The study has identified opportunities for improved pharmaceutical care in primary and secondary CHD prevention among those destined to suffer an MI. Candidates for secondary prevention are potentially identifiable from community pharmacy patient medication records from which the contribution of pharmacists in primary care might be targeted. The findings were obtained during a period of evolution of the evidence-base and so they establish a baseline for future work.     

Inhaled isobutyl nitrite inhibited macrophage inducible nitric oxide by blocking NFkappaB signaling and promoting degradation of inducible nitric oxide synthase-2

We previously reported that inhaled isobutyl nitrite inhibited macrophage tumoricidal activity by inhibiting inducible nitric oxide (NO) production. In the present study, a much shorter inhalant exposure regimen (five daily exposures) inhibited inducible NO and the NO synthase (NOS2). One of the ways in which NO and NOS2 are regulated is by ubiquitin-dependent NOS2 degradation. Immunoprecipitated NOS2 showed increased poly-ubiquitination, following exposure to the inhalant. In addition, Western blots of macrophage nuclear extracts for the NFkappaB subunit, p65, showed that exposure to the inhalant inhibited NFkappaB signaling, necessary for induction of NOS2. The inhalant blocked phosphorylation of the NFkappaB inhibitor, IkappaBalpha. The inhibition of NFkappaB signaling following inhalant exposure was confirmed using mice transgenic for the kappaB-dependent promoter of the HIV 5' LTR linked to luciferase. The data suggested that inhalant exposure likely inhibited macrophage NO production by blocking NFkappaB-mediated activation signaling and promoting poly ubiquitination of NOS2.     

Suspected GHB overdoses in the emergency department

Blood specimens from 146 suspected gamma-hydroxybutyrate (GHB) overdose cases, presenting to an emergency department in Washington State over a 12-month period, were analyzed for GHB and other drugs. Of these 146 patients, GHB was confirmed in approximately one-third of the patients (N = 54), sometimes in potentially toxic concentrations. These patients were aged between 17 and 59 years (median 28 years), and 83% were male. Blood GHB concentrations ranged from 29 to 490 mg/L (mean 137 mg/L; median 103 mg/L). In 36 (67%) of the 54 patients, other drugs were additionally detected. Ethanol was measured in 22 (41%) patients, with concentrations ranging from 0.01 to 0.26 g/100 mL (median 0.04 g/100 mL). Other commonly co-administered drugs included 3,4-methylenedioxymethamphetamine, marijuana, methamphetamine, cocaine, and citalopram. Frequently observed clinical symptoms on admission for the GHB overdose group included copious vomiting, ataxia, lack of gag reflex, respiratory depression, mild acute respiratory acidosis, unconsciousness, and sudden altered states of consciousness. Many patients required intubation, and several became combative and required restraints. The majority of patients were discharged within 6 h of hospital admission. However, despite presenting with similar clinical symptoms on admission, GHB was not confirmed in 92 of the 146 overdose patients, suggesting that GHB overdose cases may frequently be indistinguishable from other drug overdoses or medical conditions.     

Preteen children and illegal drugs

In this paper we report the results of research on the nature and extent of legal and illegal drug use among preteens and those factors associated with illegal drug use at this young age. The paper is based upon a survey of 2318 ten to twelve year olds in Glasgow and Newcastle. Overall around 30% of children reported having been exposed to illegal drugs and 3.9% had started to use illegal drugs. There was a significant difference in the level of illegal drug use between our two cities. In most cases the illegal drug use identified on the part of preteens related to cannabis although in a small number of instances children were using heroin, cocaine and LSD. On the basis of this research we estimate that around 60 children in the ten to twelve age range will have used heroin in Glasgow and around 34 pupils will have used the drug in Newcastle. Preteen drug use was significantly associated with frequent smoking and alcohol consumption, with preteens' involvement in a range of problem behaviours, and with family difficulties including the presence of someone else within the family using illegal drugs. The paper concludes by noting some of the challenges that are likely to be faced by services seeking to support children who are using illegal drugs by their preteens.     

Chronic pain in South Australia – population levels that interfere extremely with activities of daily living

Objective: The prevalence of chronic pain in Australia has only been previously estimated for the state of New South Wales. The aim of this study was to focus estimates on pain severe enough to interfere markedly with daily function irrespective of contact with health services in another region, South Australia. Methods: A whole of population random face‐to‐face survey method (n=2,973) was used, directly standardised against the whole population for age, gender, country of birth and rurality. Respondents were asked about chronic pain and the degree to which it interfered with daily activities. Results: The prevalence of chronic pain was 17.9%, and pain that interfered extremely with activity 5.0%. Chronic pain was associated with older age, living alone, lower income, not being in full‐time work and lower educational levels in bivariate analyses, however in multifactor analyses the only significant associations were not currently working (p<0.001) and lower levels of educational achievement (p=0.042). Pain that interfered extremely with activity in multifactor analysis was associated with work status where the odds ratio for work‐related injury compared to those in full time work was 19.3 (95% CI 7.30‐51.3; p<0.001). Conclusions: This study highlights the high levels of pain with extreme effects on day‐to‐day life (one in 20 people), the complex inter‐relationships of the factors (educational achievement, work status) associated with chronic pain and the impacts that these factors have on the people experiencing such disabling pain in the long‐term.     

A Systematic Review of Randomized Controlled Trials of Interventions to Improve the Health of Persons During Imprisonment and in the Year After Release

We systematically reviewed randomized controlled trials of interventions to improve the health of people during imprisonment or in the year after release. We searched 14 biomedical and social science databases in 2014, and identified 95 studies.Most studies involved only men or a majority of men (70/83 studies in which gender was specified); only 16 studies focused on adolescents. Most studies were conducted in the United States (n = 57). The risk of bias for outcomes in almost all studies was unclear or high (n = 91). In 59 studies, interventions led to improved mental health, substance use, infectious diseases, or health service utilization outcomes; in 42 of these studies, outcomes were measured in the community after release.Improving the health of people who experience imprisonment requires knowledge generation and knowledge translation, including implementation of effective interventions.Worldwide, more than 11 million people are imprisoned at any given time, and the prison population continues to grow at a rate faster than that of the general population.1 Substantial evidence reveals that people who have experienced imprisonment have poor health compared with the general population, as indicated by the prevalence of mental illness, infectious diseases, chronic diseases, and mortality.2There are several reasons to focus on improving the health of people who experience imprisonment.3 The burden of disease in this population affects the general population directly through increased health care costs and through the transmission of communicable diseases (e.g., HIV, HCV, and tuberculosis) after people are released from detention. Imprisonment has also been associated with worse health in family members of those who are detained, compared with the general population, including chronic diseases4 and poor mental health5,6 in adult relatives and mortality in male children.7 At the community level, higher rates of incarceration have been associated with adverse health outcomes, such as sexually transmitted infections and teen pregnancies.8 There is also evidence that poor health in persons who are released from detention, particularly those with inadequately treated mental illness and substance use disorders,3 may affect public safety and reincarceration rates,3 and that better access to health care is associated with less recidivism.9,10 Finally, the right to health and health care is enshrined in international human rights documents,11,12 and is a legislated responsibility of governments in many countries.Intervening during imprisonment and at the time of release could improve the health of people who experience imprisonment and public health overall.13 Knowledge translation efforts, such as syntheses of effective interventions, could lead to the implementation and further evaluation of interventions,14 and identify areas where further research is needed. To date, only syntheses with a limited focus have been conducted in this population, for example, reviews of interventions related to HIV15 or for persons with serious mental illness.16 Decision makers, practitioners, and researchers in this field would benefit from a broader understanding of the state of evidence regarding interventions to improve health in people who experience imprisonment.To address this gap, we systematically reviewed randomized controlled trials of interventions to improve health in persons during imprisonment and in the year after release. We chose this population because we view imprisonment as a unique opportunity to deliver and to link with interventions for this population, and to highlight interventions that could be implemented by those responsible for the administration of correctional facilities. We limited this study to randomized controlled trials, recognizing that randomized controlled trials provide the highest quality of evidence compared with other study designs.17     

Keeping the focus on children: the challenges of safeguarding children affected by domestic abuse

Safeguarding children affected by domestic abuse is a key responsibility for all professionals working with children and families, but can be difficult to achieve in practice. Despite a policy emphasis on early intervention and child‐centred work, limited attention has been paid to how professionals in universal and additional support services address this important area of work. This paper reports findings from qualitative research undertaken in one local authority area in the north of England during 2011 which examines the challenges facing professionals in safeguarding children affected by domestic abuse. Six mixed professional focus groups were held, attended by a total of 23 participants. Discussion focused upon participants’ awareness of domestic abuse, how they assessed and met children and young peoples’ needs, and their views about service provision and safeguarding processes. Data were transcribed and thematic analysis undertaken. The themes presented in this paper – embodied recognition, someone else's job, service gaps, skills deficits, and focusing upon children and young people – illustrate the scope and limitations of professionals’ work with children and young people affected by domestic abuse. Areas for practice improvement are discussed.     

Structure-activity relationship of neurokinin A(4-10) at the human tachykinin NK(2) receptor: the effect of amino acid substitutions on receptor affinity and function

A structure-activity study of the neurokinin A (NKA) fragment NKA(4-10) was performed to investigate the importance of amino acid residues for receptor efficacy, potency and affinity at the NK(2) receptor in human colon circular muscle. Fourteen analogs of NKA(4-10) were produced with substitutions at positions 4, 5, 7, 9 and/or 10 of NKA. Their potencies were determined by in vitro contractile responses and affinities by radioligand binding using [125I]NKA. Functional potency was enhanced 8-fold by single amino acid substitutions with Lys(5) and MeLeu(9) but not significantly altered by substitutions Glu(4), Arg(5), His(5) and Nle(10). The multiply-substituted analogs [MeLeu(9),Nle(10)]NKA(4-10), [Lys(5),MeLeu(9),Nle(10)]NKA(4-10) and [Lys(5),(Tyr(7)),MeLeu(9),Nle(10)]NKA(4-10) displayed 6-9-fold increase in potency. Although [Arg(5),Nle(10)]NKA(4-10) was similar in potency to NKA(4-10), it was the only analog to show significantly reduced efficacy. All analogs were able to compete fully for [125I]NKA binding. [Lys(5),MeLeu(9)]NKA(4-10), [MeLeu(9),Nle(10)]NKA(4-10), [Lys(5),Nle(10)]NKA(4-10) and analogs containing single substitutions with Glu(4), Arg(5), Lys(5) and MeLeu(9) displayed significantly higher affinity, whereas those with Nle(10) and [Glu(4),Nle(10)] substitutions showed significantly lower affinity than NKA(4-10). There was a positive correlation (r=0.63) between binding affinity and functional potency, which was markedly improved (r=0.95) by removal of three analogs: [Lys(5),MeLeu(9),Nle(10)]NKA(4-10), [Lys(5),Tyr(7),MeLeu(9),Nle(10)]NKA(4-10) and [Lys(5),Tyr(I(2))(7),MeLeu(9),Nle(10)]NKA(4-10). These exhibited similar binding affinities to that of NKA(4-10) but were more potent in functional studies, possibly indicating a different mechanism of receptor interaction. In conclusion, substitution of Ser(5) with Lys, and/or N-methylation of Leu(9), were the most effective changes to increase functional and binding potency of NKA(4-10) at the human colon NK(2) receptor.