Integration of TB into child health policies in Africa's high-burden countries: a normative analysis.

Integration of paediatric TB care into decentralised child health services has the potential to reduce the large proportion of childhood TB that remains undiagnosed. We performed a review of national guidelines and policies for TB and child health to evaluate the normative integration of paediatric TB into existing child health programmes in 15 high TB burden countries in Africa. While integration is addressed in 80% of the national strategic plans for TB, the child health strategies insufficiently address TB in their plans to reduce child mortality. Emphasis needs to be put on multi-sectoral collaboration among national health programmes.

Intégrer la prise en charge antituberculeuse de l'enfant aux services de soins pédiatriques décentralisés pourrait permettre de réduire la proportion élevée de cas de TB pédiatriques qui restent non diagnostiqués. Nous avons examiné les politiques et recommandations nationales en matière de TB et de soins pédiatriques afin d'évaluer l'intégration normative de la TB pédiatrique aux programmes de prise en charge pédiatrique existant dans 15 pays africains à forte prévalence de TB. Cette intégration est abordée dans 80% des plans stratégiques nationaux pour la TB, mais les stratégies relatives aux soins pédiatriques ne tiennent pas suffisamment compte de la TB dans leurs plans visant à réduire la mortalité infantile. Il convient de mettre l'accent sur la collaboration multisectorielle entre les programmes de santé nationaux.

Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing.

ABX464 is a first-in-class, clinical-stage, small molecule for oral administration that has shown strong anti-inflammatory effects in the DSS-model for inflammatory bowel disease (IBD) and also prevents replication of the HIV virus. ABX464 which binds to cap binding complex (CBC) has demonstrated safety and efficacy in a phase 2a proof-of-concept clinical trial in patients with Ulcerative colitis. Previously, with limited technologies, it was not possible to quantify the effect of ABX464 on viral and cellular RNA biogenesis. Here, using RNA CaptureSeq and deep sequencing, we report that ABX464 enhances the splicing of HIV RNA in infected PBMCs from six healthy individuals and also the expression and splicing of a single long noncoding RNA to generate the anti-inflammatory miR-124 both ex vivo and in HIV patients. While ABX464 has no effect on pre-mRNA splicing of cellular genes, depletion of CBC complex by RNAi leads to accumulation of intron retention transcripts. These results imply that ABX464 did not inhibit the function of CBC in splicing but rather strengthens it under pathological condition like inflammation and HIV infection. The specific dual ability of ABX464 to generate both anti-inflammatory miR-124 and spliced viral RNA may have applicability for the treatment of both inflammatory diseases and HIV infection.

[Implantable loop recorders in the diagnosis of syncope]. / Implantierbare Loop-Rekorder in der Synkopendiagnostik.

In syncope patients, it is essential to make the right diagnosis with respect to underlying etiology. Cardiac (arrhythmic and structural) syncopal episodes carry untoward prognostic implication compared with reflex syncope. While rhythm-symptom correlation of a spontaneous syncopal episode is key to making the correct diagnosis, in case of unclear syncope the early implantation of a loop recorder leads to faster, more efficacious, and more cost-effective diagnosis. This review article summarizes the current data regarding diagnostic accuracy and clinical role of implantable loop recorders. It outlines the superiority of loop recorders in the management of unclear syncope according to present knowledge.

TELOMERE AND TELOMERASE MODULATION BY BERGAMOT POLYPHENOLIC FRACTION IN EXPERIMENTAL PHOTOAGEING IN HUMAN KERATINOCYTES.

Photoageing represents the addition of extrinsic chronic ultraviolet radiation-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. In this study, we evaluated the effect of 38% BPF, a highly concentrated extract of the bergamot fruit (Citrus bergamia) on UVB-induced photoageing by examining inflammatory cytokine expression, telomere length/telomerase alterations and cellular viability in human immortalized HaCaT keratinocytes. Our results suggest that 38% BPF protects HaCaT cells against UVB-induced oxidative stress and markers of photoageing in a dose-dependent manner and could be a useful supplement in skin care products. Together with antioxidant properties, BPF, a highly concentrated extract of the bergamot fruit, appears to modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses.

From Birth Control to Sex Control: Unruly Young Women and the Origins of the National Abstinence-Only Mandate.

In the early 1980s, conservative politicians in the United States argued that the federal government was promoting promiscuity by providing teens with confidential access to government-funded family planning services. Claiming the problem was not that young women were getting pregnant but that they were having sex, they promised a new national policy-one that would stress self-discipline and family values over sexual indulgence. As argued in this paper, the resulting abstinence-only federal mandate both draws upon and reinforces traditional sexual scripts, which hold young women responsible for keeping male passion in check, thus selectively burdening them with the work of "doing abstinence."

Short communication: Projecting milk yield using best prediction and the MilkBot lactation model.

The accuracy and precision of 3 lactation models was estimated by summarizing means and variability in projection error for next-test milk and actual 305-d milk yield (M305) for 50-d intervals in a large Dairy Herd Improvement Association data set. Lactations were grouped by breed (Holstein, Jersey, and crossbred) and parity (first vs. later). A smaller, single-herd data set with both Dairy Herd Improvement Association data and daily milk weights was used to compare M305 calculated from test-day data with M305 computed by summing daily milk weights. The lactation models tested were best prediction (BP), the nonlinear MilkBot (MB) model, and a null model (NM) based on a stepwise function. The accuracy of the models was ranked (best to worst) MB, BP, and NM for later-parity cows and MB, NM, and BP for first-parity cows, with MB achieving accuracy in projecting daily milk of 0.5 kg or better in most groups. The models generally showed better accuracy after 50 d in milk. Best prediction and NM had low accuracy for crossbred cows and first-parity Holstein and Jersey cows. The MB model appears to be more precise than BP, and NM had low precision, especially for M305. Regression of model-generated M305 on summed M305 showed BP and MB to be equally efficient in ranking lactations, but MB was better at quantifying differences.

On-farm evaluation of the effect of metabolic diseases on the shape of the lactation curve in dairy cows through the MilkBot lactation model.

The effects of metabolic diseases (MD) occurring during the transition period on milk production of dairy cows have been evaluated in many different ways, often with conflicting conclusions. The present study used a fitted lactation model to analyze specific aspects of lactation curve shape and magnitude in cows that avoided culling or death in the first 120 d in milk (DIM). Production and health records of 1,946 lactations in a 1-yr follow-up study design were collected from a transition management facility in Germany to evaluate both short- and long-term effects of MD on milk production. Milk production data were fitted with the nonlinear MilkBot lactation model, and health records were used to classify cows as healthy (H), affected by one MD (MD), or by multiple MD (MD+). The final data set contained 1,071 H, 348 MD, and 136 MD+ cows, with distinct incidences of 3.7% twinning, 4.8% milk fever, 3.6% retained placenta, 15.4% metritis, 8.3% ketosis, 2.0% displaced abomasum, and 3.7% mastitis in the first 30 DIM. The model containing all healthy and diseased cows showed that lactations classified as H had milk production that increased faster (lower ramp) and also declined faster (lower persistence) compared with cows that encountered one or more metabolic problems. The level of production (scale) was only lowered in MD+ cows compared with H and MD cows. Although the shape of the lactation curve changed when cows encounter uncomplicated (single) MD or complicated MD (more than one MD), the slower increase to a lower peak seemed to be compensated for by greater persistency, resulting in the overall 305-d milk production only being lowered in MD+ cows. In the individual disease models, specific changes in the shape of the lactation curve were found for all MD except twinning. Milk fever, retained placenta, ketosis, and mastitis mainly affected the lactation curve when accompanied by another MD, whereas metritis and displaced abomasum affected the lactation curve equally with or without another MD. Overall, 305-d milk production was decreased in complicated metritis (10,603 ± 50 kg vs. 10,114 ± 172 kg). Although care should be taken in generalizing conclusions from a highly specialized transition management facility, the current study demonstrated that lactation curve analysis may contribute substantially to the evaluation of both short- and long-term effects of metabolic diseases on milk production by detecting changes in the distribution of production that are not apparent when only totals are analyzed.

[Veno-arterial ECMO as bridge to recovery. Cardiogenic shock and suspected myocarditis in a 37-year-old patient]. / Venoarterielle ECMO als "bridge to recovery". Kardiogener Schock und Verdacht auf Myokarditis bei einer 37-Jährigen.

We report a case of a 37-year-old patient presenting with fulminant cardiogenic shock, almost noncontractile ventricles, followed by electromechanical dissociation. During performance of cardiopulmonary resuscitation, a veno-arterial extracorporeal membrane oxygenation device (VA ECMO) was implanted, which became necessary for 13 days. Subsequently, a total arrest of ventricular function was observed and prominent multiple organ failure emerged. A rapid test for respiratory syncytial virus was positive, supporting the suspected diagnosis of myocarditis. Despite numerous complications, complete recovery was achieved.

More safety with more energy: survival of electrical storm with 40-J shocks.

We report the first clinical case of ineffective high-voltage therapy with 36 J and subsequent effective therapy with 40 J in a patient with electrical storm who had previously received a high-energy implantable cardioverter defibrillator (ICD, Fortify VR, 1233-40Q St. Jude Medical, Sylmar, CA, USA). Using a combination of high energy and optimized fixed millisecond duration biphasic waveform shock, successful defibrillation could be achieved at 8 J below the programmed maximum energy level.

[Remodeling by atrial fibrillation and clinical implications for cardioversion]. / Remodeling durch Vorhofflimmern und klinische Implikationen für die Kardioversion.

Atrial fibrillation (AF) most often occurs in pre-diseased hearts. On the other hand substantial alterations (particularly atrial) are induced by the arrhythmia itself. Such remodeling occurs in a time-dependent manner. Remodeling of electrical, contractile, endothelial and structural properties / components has been reported. Medical treatment of AF importantly comprises anticoagulation according to risk stratification scores (CHADS2 or CHA2DS2VASc) besides rate control measures. In patients who remain syptomatic despite rate control a rhythm control strategy is indicated. In order to re-establish sinus rhythm patients may undergo electrical or pharmacological cardioversion. Electrical cardioversion is highly efficient but requires conscious sedation, pharmacological cardioversion should only be performed in hemodynamically stable patients with recent (< 48 h) onset AF. Several anti-arrhythmic options exist for pharmacological cardioversion (amiodarone, flecainide, propafenone and the recently approved atrial-specific agent vernakalant). While amiodarone has low efficacy for rapid restoration of sinus rhythm, it can be given to patients with heart failure or significant structural heart disease. Class-I substances can only be applied to patients without significant structural heart disease but onset of action is more rapid. Vernakalant can be applied to hemodynamically stable patients with structural heart disease and represents a novel alternative option for rapid pharmacological cardioversion.

Evaluation of agreement between intraocular pressure measurements using Goldmann applanation tonometry and Goldmann correlated intraocular pressure by Reichert's ocular response analyser.

PURPOSE: To compare agreement of intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) and Goldmann correlated intraocular pressure generated (IOPg) by the Reichert ocular response analyser (ORA). METHODS: Consecutive patients presenting for glaucoma evaluation underwent ORA assessment followed by examination including GAT. For each ORA assessment, measurements were taken until a waveform score (WS) of 6.5 was obtained or until five measurements were obtained per eye. The relationship between GAT and IOPg and the influence of the WS upon this relationship was evaluated. A Bland-Altman plot and linear regression were used to determine agreement between GAT and IOPg. RESULTS: A total of 518 eyes of 260 patients were included in the final analysis. Increasing WS was found to predict a smaller difference between GAT and IOPg (ß=-0.2, P≤0.001). Selecting the highest WS among ORA assessments of each eye, WS continued to predict concordance between GAT and IOPg (ß=-0.2, P=0.006). The mean IOP difference between methods was 0.1 mm Hg (±0.3), which was found to be statistically insignificant (P=0.391). This relationship between GAT and IOPg was successfully validated using a second distinct data set of 100 eyes. GAT and IOPg measurements varied by 2 mm Hg or less in 53.9% of eyes and 5 mm Hg or less in 92.3% of eyes. CONCLUSION: In clinical practice IOPg is strongly related to GAT. Although higher WS is indicative of greater IOPg/GAT concordance, its influence is minimal. This study does not support the use of a specific WS cutoff to determine quality of an IOPg measurement.

Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium.

AIMS/HYPOTHESIS: Coronary heart disease is the leading cause of mortality among people with type 1 diabetes. Diet is an important lifestyle factor that relates to risk of CHD. The aim of this study was to examine how diet and adherence to dietary guidelines differ between adults with and without type 1 diabetes, and their correlation with CHD risk factors and coronary artery calcium (CAC). METHODS: The study involved 571 people with type 1 diabetes and 696 controls, aged 19 to 56 years, who were asymptomatic for CHD. CAC was measured by electron-beam computed tomography. RESULTS: Compared with the controls, adults with type 1 diabetes reported a diet higher in fat, saturated fat and protein but lower in carbohydrates. Fewer than half of those with type 1 diabetes met dietary guidelines for fat and carbohydrate intake, and only 16% restricted saturated fat to less than 10% of daily energy intake. Adults with type 1 diabetes were significantly less likely to meet dietary guidelines than controls. Fat and saturated fat intakes were positively correlated, but carbohydrate intake was negatively correlated with CHD risk factors and HbA(1c). A high-fat diet and higher intake of protein were associated with greater odds of CAC, while higher carbohydrate intake was associated with reduced odds of CAC. CONCLUSIONS/INTERPRETATION: Adults with type 1 diabetes reported consuming higher than recommended levels of fat and saturated fat. High fat intake was associated with increased CHD risk factors, worse glycaemic control and CAC. An atherogenic diet may contribute to the risk of CHD in adults with type 1 diabetes.

Trends in economic consequences of rheumatoid arthritis over two subsequent years.

OBJECTIVE: To examine changes in direct costs and in working status over 2 yrs in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: In both 1999 and 2000, RA patients (n = 461) filled out a questionnaire retrospectively regarding utilization of health care, other RA-related direct costs and working status. Patients were categorized into four disease duration groups: 0-2 yrs, 2-6 yrs, 6-10 yrs and >10 yrs. At the same time points, disease activity was assessed. Logistic regression analyses were performed to identify a possible association between disease activity (high >66th percentile) measured at start of the second year and high direct costs (high >66th percentile) in the second year. RESULTS: Compared with the first year, a significant decrease in the costs for contacts with health care workers and for costs for laboratory tests was observed in the second year for the <2 yrs group. In the 2-6 yrs group and the >10 yrs group, we found a significant decrease in costs for devices and adaptations, but medication costs increased in the <2 yrs and the >10 yrs group in the second year. In the >10 yrs group, this was mainly due to an increasing number of patients who started to use biological agents during the second year. In all four disease duration groups, worse Visual Analogue Scale (VAS) disease activity and VAS general well-being were significantly associated with high direct costs. Of 97 patients working without disability at time of the first assessment, 12 (12%) patients became (partial) work disabled during follow-up. CONCLUSION: In particular, costs for devices/adaptations and for medication changed during follow-up. The latter was probably due to an increase in the use of biological agents. Hopefully a decrease in direct costs and a reduced percentage of patients getting work disabled by better disease control will outweigh the high costs of biological drugs in the future.

LAVIA--an evaluation of the potential safety benefits of the French intelligent speed adaptation project.

This paper presents the potential safety benefits of the experimental French LAVIA Intelligent Speed Adaptation system, according to road network and system mode, based on observed driving speeds, distributions of crash severity and crash injury risk. Results are given for car frontal and side impacts that together, represent 80% of all serious and fatal injuries in France. Of the three system modes tested (advisory, driver select, mandatory), our results suggest that driver select would most significantly reduce serious injuries and death. We estimate this 100% utilization of cars equipped with this type of speed adaptation system would decrease injury rates by 6% to 16% over existing conditions depending on the type of crash (frontal or side) and road environment considered. Some limitations associated with the analysis are also identified. LAVIA is the acronym for Limiteur s'Adaptant à la VItesse Autorisée, a French Intelligent Speed Adaptation (ISA) project that was set up towards the end of 1999. At the time, 1998 French national road safety statistics recorded 8437 road related deaths, a figure which had shown virtually no positive evolution since 1994. Detailed analysis of the contributory factors involved in fatal road crashes highlighted the time-honoured crash and injury causation mechanisms - alcohol, speed and seatbelts. Of the three, excessive speed (over and above the posted speed limit) was a contributory factor in half of all fatal crashes Inappropriate behaviour such as excessive speeding can be dealt with either by legislative or driver-incentive programmes. The first of these two solutions involves the introduction of new legislation and/or the enforcement of existing laws. This is the domain of Public Authorities and will not be discussed in detail here. Alternatively, incentive schemes can involve the implementation of speed related driver assistance systems, categorised according to their voluntary or mandatory character and the degree of autonomy proposed to or imposed on the driver. The LAVIA project set out to address several possible combinations of these two factors. The generic term Intelligent Speed Adaptation (ISA) encompasses a wide range of different technologies aimed at improving road safety by reducing traffic speed and homogenising traffic flow, within the limit of posted speed limits. "Fixed speed limit" systems inform the vehicle of the posted speed limit whereas "variable speed limit" systems take into account certain locations on the road network where a speed below the posted limit is desirable, such as sharp curves, pedestrian crossings or crash black spots. Taken one step further, speed limit systems may also take into account weather and traffic flow conditions. These systems are known as "dynamic speed limit" systems and benefit from real time updates for a specific location. The different ISA systems are generally characterised by the degree of freedom of choice given to the driver in moderating his or her speed. Speed limit technologies may be advisory (informing drivers of the current speed limit and speed limit changes), voluntary (allowing the driver to decide whether or not to implement speed limitation) or mandatory (imposing the current speed limit). The information supplied may be provided by way of the road infrastructure (and associated equipment), may be acquired autonomously by the vehicle or may be based on an interaction between the infrastructure and the vehicle. Even the most basic of these systems should be considered as a very useful driver aid, helping the driver to stay within the posted speed limit, avoiding "unnecessary" speeding fines through inattention, modelling driver behaviour through the long term reduction of speeds and reducing driver workload by limiting visual speedometer controls. Vehicle-based ISA systems should not be confused with internal systems. These latter systems rely upon the driver entering the desired travel speed, which is then maintained by cruise control or set as a maximum value by automatic speed regulators. Although these systems will not be discussed in detail here, it should be noted that the engine management technologies that they employ are a vital component of ISA systems.

[Difficult AV optimization in a patient with a biventricular implantable cardioverter defibrillator]. / 13. Folge: Schwierigkeiten bei der AV-Zeit-Optimierung einer Patientin mit biventrikulärem implantierbaren Kardioverter/Defibrillator.

This quiz presents the case of a patient who deteriorated clinically after AV delay optimization of a biventricular implantable cardioverter defibrillator. It illustrates that these complex devices require profound knowledge of their function.

[Pharmacological therapy for ventricular arrhythmias: evidence for current treatment strategies and perspectives for the future]. / Pharmakotherapie der ventrikulären Rhythmusstörungen : Was kommt, was bleibt, was geht?

This review summarizes the current status of pharmacological therapy for ventricular arrhythmias in symptomatic patients. The selection of specific drugs for this indication is highly dependent on the underlying heart disease. In primary prevention of sudden death, antiarrhythmic agents do not play a role--except betareceptor antagonists. Similarly, in patients treated for secondary prevention of cardiac arrest or hemodynamically symptomatic ventricular tachycardia, the implantable defibrillator constitutes the therapy of choice with hardly any role left for antiarrhythmic drugs. An emerging role for antiarrhythmic drug therapy is represented by the concomitant pharmacological treatment in ICD recipients who experience shocks from their devices (hybrid therapy). Several randomized clinical trials have recently evaluated this issue and permit an evidence-based treatment strategy. Currently, most patients receive sotalol or amiodarone for hybrid therapy with azimilide as a potential new class III antiarrhythmic drug for this treatment indication.

[Pharmacological cardioversion of atrial fibrillation]. / Medikamentöse Kardioversion von Vorhofflimmern.

Atrial fibrillation is a very common rhythm disorder that can be therapeutically reverted into sinus rhythm by means of pharmacological or electrical cardioversion. This article reviews options for drug therapy and tries to elucidate the mechanisms of AF termination by antiarrhythmics. We will explain the clinical basis of different therapeutic approaches and review the efficacy of selected substances according to recent clinical studies. Finally, we will focus on some important aspects of anticoagulation in the setting of pharmacological cardioversion.