Is there a need for postoperative follow-up after routine urogynaecological procedures? Patients will self-present if they have problems.

INTRODUCTION AND HYPOTHESIS: The value of outpatient appointments for postoperative review has been questioned for many years, and the surgeon practice around this issue is varied. The aim of this study, as part of a larger study assessing postoperative follow-up, was to assess how many patients self-present to their general practitioner (GP) or the emergency department after surgery for urogynaecology procedures. METHODS: A retrospective observational study of postoperative urogynaecology patients between 2007 and 2012 was performed using the British Society of Urogynaecology (BSUG) database to identify patients. These records were correlated with hospital and GP records to assess whether any patient was seen postoperatively for a procedure-related problem. RESULTS: There were 244 patients with complete data on the BSUG database, of whom 25 (10 %) presented to hospital/secondary care in the year following their surgery; only three of these were admitted for problems related to their surgery. There was a response rate of 70 % from GPs for access to their records. This represented 171 patients, 90 of whom (52.3 %) presented to their GP within a year of surgery mostly for a minor procedure-related event: 11 of these were re-referred to secondary care, and the remainder were treated in the community. CONCLUSIONS: The most important aspect of patient care is safety, and this should not be compromised if, for example, postoperative review were to be moved to primary care. As expected, this study shows that patients will self-present if they have problems postoperatively.

Ethical issues in funding research and development of drugs for neglected tropical diseases.

Neglected and tropical diseases, pervasive in developing countries, are important contributors to global health inequalities. They remain largely untreated due to lack of effective and affordable treatments. Resource-poor countries cannot afford to develop the public health interventions needed to control neglected diseases. In addition, neglected diseases do not represent an attractive market for pharmaceutical industry. Although a number of international commitments, stated in the Millennium Development Goals, have been made to avert the risk of communicable diseases, tropical diseases still remain neglected due to delays in international assistance. This delay can be explained by the form international cooperation has generally taken, which is limited to promoting countries' national interests, rather than social justice at a global level. This restricts the international responsibility for global inequalities in health to a humanitarian assistance. We propose an alternative view, arguing that expanding the scope of international cooperation by promoting shared health and economic value at a global level will create new opportunities for innovative, effective and affordable interventions worldwide. It will also promote neglected diseases as a global research priority. We build our argument on a proposal to replace the patenting system that currently regulates pharmaceutical research with a global fund to reward this research based on actual decreases in morbidity and mortality at a global level. We argue that this approach is beneficent because it will decrease global health inequalities and promote social justice worldwide.

Drug prescription patterns in schizophrenia outpatients: analysis of data from a German health insurance fund.

INTRODUCTION: The aim of this study was to investigate routine administrative data from a major German health insurance fund, Techniker Krankenkasse, which covers 5.4 million insured individuals. Using a retrospective cohort design, this study analysed data collected from patients with a hospital diagnosis of schizophrenia in 2003 (index hospitalisation) in order to evaluate prescription patterns of antipsychotic drugs. METHODS: Patients with an ICD-10 diagnosis of schizophrenia, at least one year prior membership with the insurance fund and a follow-up period of one year were identified. Results were standardised by age and stratified by the severity of their illness, defined by the number of hospital bed days during the three years preceding the index hospitalisation. RESULTS: A total of 3,121 patients with schizophrenia (male 56.4%, female 43.6%) received 56 692 single prescriptions of antipsychotics. Of these, 35.4% of the prescriptions were for typical and 64.6% for atypical antipsychotics; 55% were for high-potency, 45% for low-potency typical antipsychotics. The most frequently prescribed drugs were olanzapine (26.6%), clozapine (21.3%) and risperidone (19%). There were no relevant gender differences concerning prescription patterns. During a 12-month follow-up period after the first hospitalisation, 1 372 patients (43.9%) were treated exclusively with an atypical antipsychotic, another 499 patients (16%) had a combination of an atypical plus a low-potency typical antipsychotic. Thus, basal therapy with an atypical was observed in 59.9% of our study population. Only 327 patients (10.5%) were treated exclusively with a typical antipsychotic. A total of 645 patients (20.7%) were treated with a combination of atypical plus typical antipsychotic. Changes of medication within one substance group occurred more often with typical antipsychotics (50%) as compared to atypical antipsychotics (25%). DISCUSSION: At 60%, the proportion of patients in this study treated with atypical antipsychotics was surprisingly high. Of significant interest is the frequent prescription of clozapine (14%). The results are discussed in comparison to comparable studies from other countries.

[Comparison of the legal basis for health prevention and promotion in the school laws of the federal states in Germany]. / Vergleich der Schulgesetze der Länder der Bundesrepublik Deutschland im Hinblick auf die Verankerung von Prävention und Gesundheitsförderung im Gesetzestext.

BACKGROUND: Health prevention and promotion in schools are key public health tasks in most countries. This study focuses on the importance given to prevention and promotion of health in law texts through comparatively analysing school laws for the sixteen federal states in Germany. MATERIAL AND METHODS: The basis for the analysis are the sixteen federal school laws in Germany. A conceptual framework to analyse the law texts has been developed grouped according to the following categories: aims of literacy and education; development of organization; individual and social health; and security and accident prevention. Examples for second level categories include nutrition, motility, alcohol, violence, and road-traffic accident prevention. Based on a point-system of valuation, a ranking for the federal states was derived in terms of an assessment of the importance of health prevention and promotion in federal states' school laws. RESULTS: Berlin, Brandenburg and Mecklenburg-Vorpommern -- three "new" states (i. e. formerly East-German) are leading the ranking. Bavaria and Baden-Württemberg, two states that had been ruled by conservative governments for a long time, had special difficulties to take over new values in their legislation and occupied rank 14 in our ranking. The last place was taken by a state under social-democratic rule -- Nordrhein-Westfalen. However, this law dated from 1952 and a new law has just been passed in August 2005. CONCLUSION AND DISCUSSION: The comparison of the school laws of the federal states in Germany demonstrates that there has been a substantial amount of change in recent years. In some school laws, the impulses of the Ottawa Charta regarding health prevention can be clearly recognised. In others prevention and promotion of health are only subordinated subjects. As in many other areas of social importance, reorientation is taking place. In particular, federal states who have placed little emphasis on school health will have to renew their corresponding legislation.

Chronic alcohol intoxication in rats leads to a strong but transient increase in NGF levels in distinct brain regions.

Nerve growth factor (NGF), a member of the neurotrophin family, is an essential mediator of neuronal activity and synaptic plasticity of basal forebrain cholinergic neurons. In this study NGF-protein levels were determined in areas of the basal forebrain cholinergic system, its projection areas as well as the striatum and the cerebellum after long-term exposure (6 and 9 months) to ethanol and a phase of withdrawal in male Sprague-Dawley rats. 6-month alcohol treatment led to an increase of NGF to 650-850% of controls in the basal forebrain and the septum and to a 210-485% increase in the cholinergic projection areas (anterior cortex, hippocampus and olfactory bulb). After 9 months exposure to ethanol, a decrease of NGF by 16% in the frontal cortex was observed compared to controls. In the other brain regions no differences in NGF expression were detectable at this time-point. These results support the idea of an endogenous neuroprotective mechanism acting through a transient NGF induction followed by a decrease in NGF-levels during the course of further neuronal degeneration.

Ethical issues in funding orphan drug research and development.

This essay outlines the moral dilemma of funding orphan drug research and development. To date, ethical aspects of priority setting for research funding have not been an issue of discussion in the bioethics debate. Conflicting moral obligations of beneficence and distributive justice appear to demand very different levels of funding for orphan drug research. The two types of orphan disease, rare diseases and tropical diseases, however, present very different ethical challenges to questions about allocation of research funds. The dilemma is analysed considering utilitarian and rights based theories of justice and moral obligations of non-abandonment and a professional obligation to advance medical science. The limitations of standard economic evaluation tools and other priority setting tools used to inform health policy decision makers on research funding decisions are outlined.

Comparison of health care financing in Egypt and Cuba: lessons for health reform in Egypt.

Egypt and Cuba are both lower-middle income countries with a history of socialist rule, which have embarked on economic liberalization since the 1990s. Cuba has achieved exemplary health status whereas health status in Egypt is lower than could be expected for its level of income. In this article, health care financing mechanisms in both countries are analysed on their effectiveness, efficiency, and equity, with the objective of identifying the determinants of success in the Cuban health system from which valuable lessons for current health reforms in Egypt may be derived.

Comparison of health care financing in Egypt and Cuba: lessons for health reform in Egypt

Egypt and Cuba are both lower-middle income countries with a history of socialist rule, which have embarked on economic liberalization since the 1990s. Cuba has achieved exemplary health status whereas health status in Egypt is lower than could be expected for its level of income. In this article, health care financing mechanisms in both countries are analysed on their effectiveness, efficiency, and equity, with the objective of identifying the determinants of success in the Cuban health system from which valuable lessons for current health reforms in Egypt may be derived

[A validated questionnaire for measuring patient satisfaction in general and specialist ambulatory medical care: the Qualiskope-A]. / Ein valides Instrument zur Messung der Patientenzufriedenheit in ambulanter haus- und fachärztlicher Behandlung: das Qualiskope-A.

PURPOSE: To develop a reliable and valid questionnaire to measure patient satisfaction in ambulatory care, enabling a detailed analysis of the determinants of patient satisfaction that is applicable in GP and specialist outpatient care. DESIGN: Questionnaire with 27 single items subdivided into four categories: "professional competence", "physician-patient interaction", "information", and "practice organisation". Survey of 3,487 patients in 123 medical practices. 1,151 patients were in specialist care and 2,336 patients in general medical care. RESULTS: Qualiskope-A is a reliable and valid instrument for measuring patient satisfaction in ambulatory care. All item-total correlations for single items were greater than r = 0.40. Coefficients for Cronbach's alpha for the four dimensions ranged between 0.87 and 0.94. CONCLUSIONS: The increasing political importance of patients' attitudes and satisfaction for the development of policy measures to ensure and improve the quality of care is beyond doubt. To make sure that the measurement of patient satisfaction does not only serve to meet regulatory requirements but helps to improve the quality of care and provides reliable data for health services research, a high standard is required for the questionnaires to be used. The Qualiskope-A and only few other instruments meet this high standard.

[When is expensive pharmacotherapy good value for the money?]. / Wann ist eine teure Arzneimitteltherapie preiswert?

Expensive drugs are good value for money if they are effective and safe, and if they have a better cost-effectiveness ratio than the standard therapy. In this article, an overview of commonly used methods, sources and functions of health economic evaluation is presented and illustrated using clinical examples to facilitate interpretation of the health economic information.

Nerve growth factor response to excitotoxic lesion of the cholinergic basal forebrain is slightly impaired in aged rats.

Nerve growth factor (NGF) promotes survival and function of basal forebrain cholinergic neurons. We studied NGF and choline acetyltransferase (ChAT) activity after partial quisqualic acid induced lesions of the basal forebrain in 3 and 27 months-old rats, in order to investigate whether NGF-related regeneration is disturbed in old age. 2 weeks post lesion, ChAT activity decreased by 25 to 32% in adult and old rats. 3 months post lesion, the ChAT deficit receded in adult rats, but remained unchanged in old rats. 2 weeks post lesion, NGF levels were reduced by 36 to 44%, but there was no significant difference between adult and old rats. 3 months post lesion, we found increased NGF levels by 44% in the posterior cortex of adult rats. These results indicate that the compensatory NGF increase in the posterior cortex after partial cholinergic lesion of the basal forebrain is slightly impaired in old age.

Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families.

Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.

Efficacy of lamotrigine in idiopathic generalized epilepsy syndromes: a video-EEG-controlled, open study.

PURPOSE: This prospective, open, video-EEG-controlled study examined the efficacy of lamotrigine (LTG) as add-on and monotherapy in idiopathic generalized epilepsy (IGE). METHODS: 47 patients received LTG either because of insufficient seizure control (n = 35) or serious side effects of prior antiepileptic drugs (AED). Long-term video-EEG recordings were performed before and after the introduction of LTG. The mean follow-up time was 25.5 months. RESULTS: Of 12 patients with refractory childhood absence epilepsy, 9 became seizure free; in one child with absences with eyelid myoclonia, absence frequency was reduced > 50%; in 2 children with absences with a mild atonic component, seizure reduction was only transient. Of 12 patients with juvenile absence epilepsy, 10 became seizure-free and, in 2, a > 50% reduction was obtained. In 15 patients with juvenile myoclonic epilepsy, complete seizure control was achieved in 7 patients, in 6 patients myoclonia persisted. In one patient generalized tonic-clonic seizures also persisted and another patient developed a rash, LTG was therefore stopped. Of 5 patients with grand-mal on awakening, 3 became seizure-free, and a reduction of > 50% was obtained in one patient; LTG was stopped in one patient because of poor compliance. Three patients with pure photosensitive epilepsy became seizure-free. At the end of the study, 11 patients were seizure-free on LTG monotherapy, and in most other patients concomitant AED dosage could be substantially reduced. CONCLUSIONS: Lamotrigine was effective and well tolerated in patients with various IGE syndromes, although differences were observed between individual syndromes and seizure types.

The time course of nerve growth factor content in different neuropsychiatric diseases--a unifying hypothesis.

Nerve growth factor (NGF) is the prototype of related neurotrophic proteins, the so-called neurotrophins. NGF is essential for proper development of sympathetic and neural crest-derived sensory neurons of the peripheral nervous system (PNS) as well as of the neurons in the cholinergic basal forebrain (CBF). In the mature peripheral and central nervous system (CNS) NGF is also biologically active; NGF facilitates neuronal plasticity and regulates synaptic transmission and connectivity. Besides this well established neurotrophic function, recent findings suggest a role of NGF in neuroimmune and stress-associated processes, which NGF imparts not only as the classical "target-derived messenger", that is retrogradely transported within NGF-sensitive neurons, but also as para- and autocrine cytokine modulating the function of non-neuronal cells. Since neurotrophins are produced in very small amounts in vivo, NGF-sensitive cells have to compete for the limited NGF even under physiological conditions, so that normally only less than 10% of NGF receptors (NGFR) are saturated with their endogenous ligand. Consequently, it is feasable that minute changes in NGF concentrations can influence neuronal function in an extensive way. Hence, one plausible pathomechanism of disease(s) may be that a deficiency in NGF leads to malfunction of NGF-sensitive neurons. The change in NGF concentrations in the course of several diseases, namely during alcoholic and diabetic neuropathy as well as in Alzheimer's disease (AD) and several lesion-models of the CBF, indicates that fluctuations of endogenous NGF concentrations in PNS and CNS follow a distinctive pattern. An initial deficit of NGF at the onset of pathological processes is typically followed by its temporary elevation, during which some neuronal deficits may be partially ameliorated. However, if the disease progresses a decrease of NGF is typically observed, which appears to be a "normalization" of formerly elevated NGF concentrations. In our hypothesis we postulate that after acute or chronic injuries NGF is up-regulated as an intrinsic attempt to regenerate NGF-sensitive neurons. After long-term exposure to noxious processes, however, this compensatory increase of NGF cannot be maintained and eventually breaks down. The extent of such a compensatory up-regulation may depend on age and condition of NGF-sensitive neurons as well as on the type of lesion (acute or chronic). Furthermore, we also postulate that an exceeding level of NGF or its chronic elevation could even be detrimental to neuronal functioning under certain conditions. Thus, endogenous NGF has the capacity to modulate and even to compensate different kinds of harmful processes and in this way it may reinstate the homeostatic equilibrium. In our view, it seems to be a more appropriate approach to regard NGF changes as independent of classical constructs of neuropsychiatric diseases. Perhaps our understanding of NGF may even model for a new approach to the aetiology of multifactorial neuropsychiatric disorders.

Comprehensive postictal neuropsychology improves focus localization in epilepsy.

In recent years, new techniques such as single photon emission computed tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI) have been used to improve the localization of epileptic foci during the noninvasive evaluation procedure for epilepsy surgery. Since ictal/or immediate postictal SPECT studies were shown to localize epileptic foci better than interictal SPECT, we addressed the question of whether immediate postictal neuropsychological examination would show the same effect. Neuropsychological examinations were carried out postictally and interictally using a broad range of tests. Postictal results were analyzed with regard to lateralizing and localizing information about the epileptogenic region. Seventeen patients suffering from temporal and extratemporal pharmacoresistant epilepsy were investigated postictally with a subset of tests used for the interictal neuropsychological examination. A significant improvement in focus localization was seen in comparison with interictal neuropsychology (p = 0.014). We conclude that neuropsychology can yield lateralizing and sometimes localizing information, even for extratemporal foci, if carried out during the postictal period and based on a global analysis of the clinical neuropsychological picture.

Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography.

We present a new approach for non-invasive localization of focal epileptogenic discharges in patients considered for surgical treatment. EEG-triggered functional MR imaging (fMRI) and 3D EEG source localization were combined to map the primary electrical source with high spatial resolution. The method is illustrated by the case of a patient with medically intractable frontal lobe epilepsy. EEG obtained in the MRI system allowed triggering of the fMRI acquisition by the patient's habitual epileptogenic discharges. fMRI revealed multiple areas of signal enhancement. Three-dimensional EEG source localization identified the same active areas and provided evidence of onset in the left frontal lobe. Subsequent electrocorticography from subdural electrodes confirmed spike and seizure onset over this region. This approach, i.e. the combination of EEG-triggered fMRI and 3D EEG source analysis, represents a promising additional tool for presurgical epilepsy evaluation allowing precise non-invasive identification of the epileptic foci.

NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease.

There is increasing evidence that in Alzheimer's disease nerve growth factor (NGF) protein and NGF mRNA content in postmortem cortex is not decreased, but may even be elevated although the NGF-sensitive cholinergic basal forebrain neurons are preferentially affected. However, only little is known about the early pathophysiological events leading to Alzheimer's disease. We therefore measured the post-mortem NGF concentrations in temporal and frontal cortex of Alzheimer's disease patients, non-demented controls without Alzheimer's disease-related pathology, as well as non-demented patients with beta A4 plaques who might be classified as 'preclinical' cases. In the Alzheimer's disease group we found up to 43% increase in NGF concentrations in the frontal and temporal cortex as compared to the two other groups. In a subgroup analysis of the non-demented patients with plaques, NGF concentrations were lower in the frontal cortex when beta A4 plaques were present (46% of the control temporal area) than in patients without evidence of frontal plaques (81% of the control temporal area). This NGF decrease was paralleled to a similar decrease of choline acetyltransferase activity, which is regulated by NGF in the cholinergic basal forebrain. These findings support the hypothesis of lower cortical NGF content at the onset of plaque formation and of elevated NGF levels in the clinically manifest and neuropathologically advanced stage of the disease.

Increase of hypoxic tolerance in rat hippocampal slices following 3-nitropropionic acid is not mediated by endogenous nerve growth factor.

Chemical preconditioning with low dose inhibition of succinic dehydrogenase by 3-nitropropionic acid (3-np) increases tolerance against succeeding hypoxia. Supraphysiological doses of nerve growth factor (NGF) repeatedly were shown to protect against ischemic damage. We investigated whether increased tolerance against hypoxia results from increased or accelerated production of endogenous NGF. Average recovery of population spike amplitude after 15 min of hypoxia and 45 min of reoxygenation was 31 +/- 9% (mean +/- SE) in control hippocampal slices. After pretreatment with 3-np (single i.p. injection of 20 mg/kg body weight 1 h to 3 days prior to slice preparation), recovery exceeded 90% (P < 0.01). However, NGF content did not increase upon slice preparation, hypoxia in vitro, and pretreatment with 3-np in vivo 1 h to 1 day prior to slice preparation with and without additional hypoxia in vitro. We conclude that early-onset tolerance to hypoxia induced by 3-np treatment is not caused by induction of endogenous NGF production.