Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Lumbar Spinal Stenosis Severity by CT or MRI Does Not Predict Response to Epidural Corticosteroid versus Lidocaine Injections.

BACKGROUND AND PURPOSE: Epidural steroid injections may offer little-to-no short-term benefit in the overall population of patients with symptomatic spinal stenosis compared with lidocaine alone. We investigated whether imaging could identify subgroups of patients who might benefit most. MATERIALS AND METHODS: A secondary analysis of the Lumbar Epidural Steroid Injections for Spinal Stenosis prospective, double-blind trial was performed, and patients were randomized to receive an epidural injection of lidocaine with or without corticosteroids. Patients (n = 350) were evaluated for qualitative and quantitative MR imaging or CT measures of lumbar spinal stenosis. The primary clinical end points were the Roland-Morris Disability Questionnaire and the leg pain numeric rating scale at 3 weeks following injection. ANCOVA was used to assess the significance of interaction terms between imaging measures of spinal stenosis and injectate type on clinical improvement. RESULTS: There was no difference in the improvement of disability or leg pain scores at 3 weeks between patients injected with epidural lidocaine alone compared with corticosteroid and lidocaine when accounting for the primary imaging measures of qualitative spinal stenosis assessment (interaction coefficients for disability score, -0.1; 95% CI, -1.3 to 1.2; P = .90; and for the leg pain score, 0.1; 95% CI, -0.6 to 0.8; P = .81) or the quantitative minimum thecal sac cross-sectional area (interaction coefficients for disability score, 0.01; 95% CI, -0.01 to 0.03; P = .40; and for the leg pain score, 0.01; 95% CI, -0.01 to 0.03; P = .33). CONCLUSIONS: Imaging measures of spinal stenosis are not associated with differential clinical responses following epidural corticosteroid injection.

[The pain situation for residents of nursing homes. Results of a study in Münster]. / Die Schmerzsituation von Bewohnern in der stationären Altenhilfe. Ergebnisse einer Studie in Münster.

BACKGROUND: Little is known about the phenomenon of pain in German nursing homes. In particular, it is unknown to what extent and severity pain occurs among residents and how their pain can be described. MATERIAL AND METHODS: A total of 13 nursing homes located in the city of Münster, Germany, were included as part of the health services research project "Action Alliance Pain-free City Münster." Data were collected from 436 residents over 65 years old via self-report or the observational pain tool pain assessment in advanced dementia, german version (PAINAD-G), according to the cognitive status of the residents. RESULTS: At the time of the interview, the majority of the residents questioned reported suffering from pain at rest and/or during movement. Approximately one quarter of residents complained about moderate to intolerable pain at rest and nearly 45% during movement. Residents encountered pain most often when standing up, sitting, resting in bed and walking and three quarters of residents had suffered from pain for more than 1 year. Many residents experienced pain in several body regions. Among residents assessed solely by the observational pain scale PAINAD-G, signs indicating pain existed in 21% (≥ 6) or 69% (≥ 2), respectively, depending on the cut-off value chosen on the PAINAD-G scale. CONCLUSION: Pain in nursing homes is a challenge that needs more attention as it has considerable negative consequences for the persons concerned. The extent of pain in the studied facilities indicates an urgent need for action on the part of all professionals caring for residents in nursing homes.

[Non-pharmacologic measures in pain therapy. Application in 25 German hospitals]. / Nichtmedikamentöse Massnahmen in der Schmerztherapie. Anwendung in 25 deutschen Krankenhäusern.

BACKGROUND: The application of non-pharmacologic therapy (NPT) within pain therapy increases patient satisfaction and is, in addition to pharmacologic methods, recommended in the National Expert Standard on Pain Management in Nursing of the German Network of Quality Development in Nursing. If and to what extent non-pharmacologic methods are applied within pain therapy in German hospitals has as yet been unknown. MATERIALS AND METHODS: Within the project "Pain-Free Hospital" 2,840 nurses in 25 hospitals were interviewed via questionnaire forms and oral interviews about the use of NPT. RESULTS: Of the nurses 80% confirmed the use of NPT. The majority of the interviewed nurses applied superficial cold, bedding and heat for pain relief. We identified barriers to the implementation of NPT, such as the scarce knowledge of nurses about these therapeutic areas and the uncertainty whether NPT needs to be described by doctors or not. CONCLUSION: Some of the NPTs are well established in hospitals. For nationwide use of NPT their systematic training and implementation is necessary.

[Health services research project "action alliance pain-free city Münster" : Objectives and methods]. / Versorgungsforschungsprojekt "aktionsbündnis schmerzfreie stadt Münster" : zielsetzung und methodik.

Inadequate pain care in health care facilities is still a major concern. Due to structural and organizational shortcomings the potential of modern analgesia is far from being exhausted. The project "Action Alliance Pain-free City Münster" is designed to analyze the multiprofessional pain management in health care facilities in the model City of Münster in an epidemiologic study and aims to optimize pain management in accordance with nursing standards and medical guidelines. Hospitals, nursing homes, outpatient nursing services, hospices and pain care centers will be examined. After an analysis of the current state on the basis of a pre-test, the necessary optimization measures will be developed and implemented. Subsequently, the pain management will be reevaluated in a post-test. In partly still unexplored health care areas of Germany, epidemiologic data will be generated, barriers to the implementation of standards and guidelines revealed and measures of improvements developed and tested. In addition, interface problems between the evaluated sectors will be identified. In this article the objective and the methods of the project are described.

Sensitivity of different ecotypes and mutants of Arabidopsis thaliana toward the bacterial elicitor flagellin correlates with the presence of receptor-binding sites.

Flagellin, the main building block of the bacterial flagellum, acts as potent elicitor of defense responses in different plant species. Genetic analysis in Arabidopsis thaliana identified two distinct loci, termed FLS1 and FLS2, that are essential for perception of flagellin-derived elicitors. FLS2 was found to encode a leucine-rich repeat transmembrane receptor-like kinase with similarities to Toll-like receptors involved in the innate immune system of mammals and insects. Here we used a radiolabeled derivative of flg22, a synthetic peptide representing the elicitor-active domain of flagellin, to probe the interaction of flagellin with its receptor in A. thaliana. The high affinity binding site detected in intact cells and membrane preparations exhibited specificity for flagellin-derived peptides with biological activity as agonists or antagonists of the elicitor responses. Specific binding activity was measurable in all ecotypes of A. thaliana that show sensitivity to flagellin but was barely detectable in the flagellin-insensitive ecotype Ws-0 affected in FLS1. A strongly impaired binding of flagellin was observed also in several independent flagellin-insensitive mutants isolated from the flagellin-sensitive ecotype La-er. In particular, no binding was found in plants carrying a mutation in the LRR domain of FLS2. These data indicate that the formation of functional receptor-binding sites depends on genes encoded by both loci, FLS1 and FLS2. The tight correlation between the presence of the binding site and elicitor response provides strong evidence that this binding site acts as the physiological receptor of flagellin.

Both the extracellular leucine-rich repeat domain and the kinase activity of FSL2 are required for flagellin binding and signaling in Arabidopsis.

In Arabidopsis, activation of defense responses by flagellin is triggered by the specific recognition of the most conserved domain of flagellin, represented by the peptide flg22, in a process involving the FLS2 gene, which encodes a leucine-rich repeat serine/threonine protein kinase. We show here that the two fls2 mutant alleles, fls2-24 and fls2-17, which were shown previously to confer insensitivity to flg22, also cause impaired flagellin binding. These features are rescued when a functional FLS2 gene is expressed as a transgene in each of the fls2 mutant plants, indicating that FLS2 is necessary for flagellin binding. The point mutation of the fls2-17 allele lies in the kinase domain. A kinase carrying this missense mutation lacked autophosphorylation activity when expressed in Escherichia coli. This indicates that kinase activity is required for binding and probably affects the stability of the flagellin receptor complex. We further show that overexpression of the kinase-associated protein phosphatase (KAPP) in Arabidopsis results in plants that are insensitive to flagellin treatment, and we show reduced flg22 binding in these plants. Furthermore, using the yeast two-hybrid system, we show physical interaction of KAPP with the kinase domain of FLS2. These results suggest that KAPP functions as a negative regulator of the FLS2 signal transduction pathway and that the phosphorylation of FLS2 is necessary for proper binding and signaling of the flagellin receptor complex.

Presence of acetyl coenzyme A (CoA) carboxylase and propionyl-CoA carboxylase in autotrophic Crenarchaeota and indication for operation of a 3-hydroxypropionate cycle in autotrophic carbon fixation.

The pathway of autotrophic CO2 fixation was studied in the phototrophic bacterium Chloroflexus aurantiacus and in the aerobic thermoacidophilic archaeon Metallosphaera sedula. In both organisms, none of the key enzymes of the reductive pentose phosphate cycle, the reductive citric acid cycle, and the reductive acetyl coenzyme A (acetyl-CoA) pathway were detectable. However, cells contained the biotin-dependent acetyl-CoA carboxylase and propionyl-CoA carboxylase as well as phosphoenolpyruvate carboxylase. The specific enzyme activities of the carboxylases were high enough to explain the autotrophic growth rate via the 3-hydroxypropionate cycle. Extracts catalyzed the CO2-, MgATP-, and NADPH-dependent conversion of acetyl-CoA to 3-hydroxypropionate via malonyl-CoA and the conversion of this intermediate to succinate via propionyl-CoA. The labelled intermediates were detected in vitro with either 14CO2 or [14C]acetyl-CoA as precursor. These reactions are part of the 3-hydroxypropionate cycle, the autotrophic pathway proposed for C. aurantiacus. The investigation was extended to the autotrophic archaea Sulfolobus metallicus and Acidianus infernus, which showed acetyl-CoA and propionyl-CoA carboxylase activities in extracts of autotrophically grown cells. Acetyl-CoA carboxylase activity is unexpected in archaea since they do not contain fatty acids in their membranes. These aerobic archaea, as well as C. aurantiacus, were screened for biotin-containing proteins by the avidin-peroxidase test. They contained large amounts of a small biotin-carrying protein, which is most likely part of the acetyl-CoA and propionyl-CoA carboxylases. Other archaea reported to use one of the other known autotrophic pathways lacked such small biotin-containing proteins. These findings suggest that the aerobic autotrophic archaea M. sedula, S. metallicus, and A. infernus use a yet-to-be-defined 3-hydroxypropionate cycle for their autotrophic growth. Acetyl-CoA carboxylase and propionyl-CoA carboxylase are proposed to be the main CO2 fixation enzymes, and phosphoenolpyruvate carboxylase may have an anaplerotic function. The results also provide further support for the occurrence of the 3-hydroxypropionate cycle in C. aurantiacus.

[Morphological and cytochemical investigation of Ehrlich ascites tumor cells of the solid form as compared with peritoneal exudate in mice (author's transl)]. / Morphologische und zytochemische Untersuchung der Zellen des soliden Tumors und der Zellen dieses Tumors in der Peritonealflüssigkeit der Mäuse mit einem Ehrlich-Aszites-Tumor.

Ehrlich ascites tumor cells in peritoneal exudate of mice show a more regular round shape, greater and multiple nucleoli and more abundant and dark cytoplasma in comparison with cells of the same tumor transplanted in the limb. In solid tumor cells activity of naphthol-AS-acetate esterase is significantly higher than in exudate cells which demonstrate higher activity of PAS reaction. Other cytochemical reactions show no significant differences between the two cell forms. It seems that exudate cells are biologically more active than cells from the solid tumor.

The results of some cytochemical reactions in metastatic malignant tumor cells in pleural and peritoneal effusions.

The cytomorphologic and cytochemical investigation of 59 samples of pleural and peritoneal effusions with malignant tumor cells was performed and the results were compared. The diagnosis was confirmed histologically in most cases. The cytomorphologic method gave very good results not only in the determination of malignant tumor cells but also in the differentiation of various kinds of tumors. A diagnosis was made of differentiated carcinoma (adenocarcinoma and squamous carcinoma) in 40 cases, undifferentiated carcinoma in five, sarcoma or hemoblastosis in nine and undifferentiated malignant tumor in five cases. The results of cytochemical reactions investigated demonstrated a significant difference between the cells of carcinoma and sarcoma, and in various kinds of carcinoma the most important difference was found between the positive reaction of the alkaline phosphatase and negative reaction of the acid phosphatase in the cells of ovarina and uterine carcinoma. Although we consider the morphologic examination of effusions the most important for the diagnosis of malignancy, the cytochemical methods can sometimes be helpful in a more precise differentiation.