Endocardial pacemaker implantation in infants weighing < or = 10 kilograms

Epicardial pacemaker implantation is the most common approach for small children requiring pacemaker implantation, though it is not free from complications. This article reviews the experience with endocardial pacemaker implantation, as an alternative approach, in children < or =10 kg at two centers. Thirty-nine children, median age 3.8 months (2 days-35 months), weight 4.6 kg (2.3-10 kg) underwent endocardial permanent pacing (VVI/R in 38, DDDR in 1). Indications for pacing were complete heart block (CHB) in 34 (congenital in 21, postsurgical in 12, congenitally corrected transposition of the great arteries 1), long QT syndrome in 3, and sinus bradycardia in 2 children. Two children with postsurgical CHB died 7 days and 3 weeks after implantation, respectively, due to heart failure and septicemia, despite appropriate pacemaker therapy. Over a median follow-up of 4.3 years (9 months-15.3 years), 12 patients underwent 18 generator replacements. Five patients were upgraded to physiological pacing. Ten patients underwent 12 ventricular lead advancements. Ventricular lead extraction was attempted 11 times in nine patients and succeeded 10 times. Two patients were converted to epicardial dual chamber systems. Two prepectorally placed generators required resiting due to threatened skin necrosis. Infective endocarditis on the lead, 9 months postimplant required removal of the system in one patient. The subclavian vein was found to be asymptomatically thrombosed in four patients. Endocardial permanent pacing is feasible and effective in children < or = 10 kg and an acceptable alternative to epicardial pacing.     

The Dutch version of the self-report Child Activity and Limitations Interview in adolescents with chronic pain

Purpose: To assess the factor structure, related constructs and internal consistency of the Child Activity Limitation Interview 21-Child version for use in Dutch-language countries.

Methods: Cross-sectional validation study: After forward and back translation of the Dutch version of the Child Activity Limitation Interview 21-Child adolescents (11–21 years old) with chronic musculoskeletal pain completed an assessment. The assessment contained the Dutch Child Activity Limitation Interview, and questionnaires about demographics, pain intensity, functional disability, anxiety and depression. Internal consistency and construct validity were evaluated through exploratory factor analysis (principal axis factoring with oblique rotation) and hypotheses testing using pain intensity, activity limitations, anxiety and depression as comparative constructs.

Results: Seventy-four adolescents completed the assessment. Exploratory factor analysis resulted in a two-factor structure, explaining 50% of the variance. Internal consistency was good (Cronbach’s α?=?0.91 total scale, α?=?0.90 Factor 1, α?=?0.80 Factor 2). All nine hypotheses were confirmed.

Conclusion: The Dutch version can be used to assess pain-related disability in Dutch-speaking adolescents comparable to the study sample. Scores on both subscales provide insight into the severity of the pain-related disability in both daily routine and more physically vigorous activities.

• Implications for Rehabilitation

• Chronic pain is a disabling disorder which not only impacts physically but restricts quality of life.

• This study provides clinicians a questionnaire to measure pain-related disability and quantify the impact of pain on the daily living of adolescents.

• The advantage of the Dutch version of the Child Activity and Limitations Interview over other measurements is that it can distinguish limitations in daily activities from more physically vigorous activities.

     

If you try to stop smoking,should we pay for it? The cost–utility of reimbursing smoking cessation support in the Netherlands

Background Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support (SCS). The short‐term efficiency of reimbursement has been evaluated previously. However, a thorough estimate of the long‐term cost–utility is lacking. Objectives To evaluate long‐term effects of reimbursement of SCS. Methods Results from a randomized controlled trial were extrapolated to long‐term outcomes in terms of health care costs and (quality adjusted) life years (QALY) gained, using the Chronic Disease Model. Our first scenario was no reimbursement. In a second scenario, the short‐term cessation rates from the trial were extrapolated directly. Sensitivity analyses were based on the trial's confidence intervals. In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta‐analyses. Results Intervention costs per QALY gained compared to the reference scenario were approximately €1200 extrapolating the trial effects directly, and €4200 when combining the trial's use of SCS with the cessation rates from the literature. Taking all health care effects into account, even costs in life years gained, resulted in an estimated incremental cost–utility of €4500 and €7400, respectively. In both scenarios costs per QALY remained below €16 000 in sensitivity analyses using a life‐time horizon. Conclusions Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs. Accounting for overheads, administration costs and the costs of SCS, these health gains could be obtained at relatively low cost, even when including costs in life years gained. Hence, reimbursement of SCS seems to be cost‐effective from a health care perspective.     

Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy

Progressive familial intrahepatic cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic cholestasis, referred to as benign recurrent intrahepatic cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with intrahepatic cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent intrahepatic cholestasis as well as intrahepatic cholestasis of pregnancy.     

Quality of life of female caregivers of children with sickle cell disease: a survey

Caring for a child with sickle cell disease poses extra demands on parents, both practically and psychologically, which may influence their quality of life. Since families of children with sickle cell disease in the Netherlands usually belong to immigrant communities with a low socio-economic status, there may be an additional strain on caregivers. The aim of the present study was to evaluate the quality of life of caregivers of children with sickle cell disease. The quality of life of female caregivers of sickle cell disease patients, measured with the TNO-AZL Adult Quality of Life questionnaire, was compared to the norm data of healthy Dutch females (n=700) and female caregivers of healthy children with the same socio-economic status and ethnic background (socio-economic status control group). Groups were compared by the Mann-Whitney U test. Point estimates and 95% confidence intervals of the median difference are presented. The results of questionnaires of 54 caregivers of children with sickle cell disease and 28 caregivers of a control group of the same socio-economic status were analyzed. Caregivers of patients with sickle cell disease had a significantly lower quality of life on all subscales compared to the Dutch norm population. Compared to the control group of the same socio-economic status, the quality of life of caregivers of patients with sickle cell disease was significantly lower on the subscales depressive moods, daily activities and vitality. In this first study reporting on the quality of life of caregivers of children with sickle cell disease, we demonstrate a reduced quality of life in these caregivers compared to the healthy Dutch female population and caregivers of healthy children with the same socio-economic status.     

Longevity for free? Increased reproduction with limited trade-offs in Drosophila melanogaster selected for increased life span

Selection for increased life span in Drosophila melanogaster has been shown to correlate with decreased early fecundity and increased fecundity later in life. This phenomenon has been ascribed to the existence of trade-offs in which limited resources can be invested in either somatic maintenance or reproduction. In our longevity selection lines, we did not find such a trade-off. Rather, we find that females have similar or higher fecundity throughout life compared to non-selected controls. To determine whether increased longevity affects responses in other traits, we looked at several stress resistance traits (chill coma recovery, heat knockdown, desiccation and starvation), geotactic behaviour, egg-to-adult viability, body size, developmental time as well as metabolic rate. Longevity selected flies were more starvation resistant. However, in females longevity and fecundity were not negatively correlated with the other traits assayed. Males from longevity selected lines were slower at recovering from a chill induced coma and resting metabolic rate increased with age, but did not correlate with life span.     

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

Drosophila melanogaster is frequently used in ageing studies to elucidate which mechanisms determine the onset and progress of senescence. Lines selected for increased longevity have often been shown to perform as well as or superior to control lines in life history, stress resistance and behavioural traits when tested in the laboratory. Functional senescence in longevity selected lines has also been shown to occur at a slower rate. However, it is known that performance in a controlled laboratory setting is not necessarily representative of performance in nature. In this study the effect of ageing, environmental temperature and longevity selection on performance in the field was tested. Flies from longevity selected and control lines of different ages (2, 5, 10 and 15 days) were released in an environment free of natural food sources. Control flies were tested at low, intermediate and high temperatures, while longevity selected flies were tested at the intermediate temperature only. The ability of flies to locate and reach a food source was tested. Flies of intermediate age were generally better at locating resources than both younger and older flies, where hot and cold environments accelerate the senescent decline in performance. Control lines were better able to locate a resource compared to longevity selected lines of the same age, suggesting that longevity comes at a cost in early life field fitness, supporting the antagonistic pleiotropy theory of ageing.     

Weight and height z-scores improve after initiating ART among HIV-infected children in rural Zambia: a cohort study

Background  

Deficits in growth observed in HIV-infected children in resource-poor settings can be reversed with antiretroviral treatment (ART). However, many of the studies have been conducted in urban areas with older pediatric populations. This study was undertaken to evaluate growth patterns after ART initiation in a young pediatric population in rural Zambia with a high prevalence of undernutrition.     

Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers

Summary Nicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18–32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscular femoral (FA) and brachial (BA) arteries were investigated. The effects on systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and venous hemodynamics were also assessed. In addition, the subacute effects after 8 days of treatment with N (2×20 mg/day) and ISDN (3×20 mg/day) on these parameters were evaluated. After a 20 mg single oral dose, blood pressure decreased significantly more with ISDN (SBP: 6%; DBP: 14%) than with N (SBP: 2%; DBP: 6%), but after 8 days this decrease in blood pressure was not statistically different between ISDN and N. The diameter of CCA increased more with ISDN (11%) than N (5%) acutely as well as subacutely (ISDN: 12%; N: 9%). Heart rate increased only with ISDN (7% acutely, 3% subacutely). No differences between ISDN and nicorandil were found for acute and subacute effects on SVRI, venous hemodynamics, diameter of muscular arteries (FA, BA), and the distensibility and compliance of elastic (CCA) and muscular (FA, BA) arteries. Day 1 to day 8 changes in heart rate and cardiac index were small but differed between ISDN and nicorandil. These differences were due to a smaller increase in HR and CI at day 8 than at day 1 with ISDN. Data on blood pressure and heart rate are in accordance with drug tolerance seen with ISDN but not with nicorandil. However, ISDN drug tolerance was not seen for the diameter of large arteries. In conclusion, with dosages used in angina, compared to nicorandil—a drug with both a potassium channel opening property and a nitratelike action—the pure nitrate ISDN showed a more pronounced decrease in systolic and diastolic blood pressure, a slight increase in heart rate, and more vasodilation of CCA. ISDN drug tolerance was shown for blood pressure and heart rate. In contrast to the well-known venous tolerance during ISDN, there was no ISDN drug tolerance for the effects on diameter of large arteries. No drug tolerance was seen with nicorandil.     

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

Objective: Iron isomaltoside (Monofer^®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA.

Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000?mg of iron isomaltoside infused in single doses up to 2000?mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters.

Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500?mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0?g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found.

Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000?mg and cumulative doses up to 3000?mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.