The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy.

The current study assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS, a condition characterized by sudden-onset obsessive-compulsive, tic, or restrictive eating symptoms following infection. We conducted an anonymous survey between February and June 2021 of 254 self-reported caregivers of minors with PANS/PANDAS. Caregivers answered questions regarding PANS/PANDAS symptoms, telehealth care, and intention to vaccinate their child against COVID-19. PANS/PANDAS symptoms during COVID-19 infections were assessed when applicable. Children's OCD symptoms and coercive behaviors towards caregivers, along with the caregivers' mental health, relationship satisfaction, and burden, were assessed using standardized questionnaires. A majority of respondents endorsed a negative impact on their child's friendships, relationships with extended family, hobbies, and academic skills due to the pandemic. Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety. Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS. A majority of caregivers reported high levels of relationship dissatisfaction and caregiver burden. As expected, these data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.

Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya.

PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5-9-year-olds, 25/86 (29.1%) vaccinations in 13-59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups. These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373).

International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder - USA and Canada, 2013-2014.

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

An overview of foodborne outbreaks in Canada reported through Outbreak Summaries: 2008-2014.

BACKGROUND: Enteric outbreak investigation in Canada is performed at the local, provincial/territorial (P/T) and federal levels. Historically, routine surveillance of outbreaks did not occur in all jurisdictions and so the Public Health Agency of Canada, in partnership with P/T public health authorities, developed a secure, web-based Outbreak Summaries (OS) Reporting System to address this gap. OBJECTIVE: This analysis summarizes the foodborne outbreak investigations reported to the OS Reporting System between 2008 and 2014. METHODS: Finalised reports of investigations between 2008 and 2014 for all participating jurisdictions in Canada were extracted and descriptive analysis was carried out for foodborne outbreaks on etiological agent, severity of illness, outbreak duration, exposure setting and outbreak source. RESULTS: There were 115 reported foodborne outbreaks included in the analysis. This represents 11.2% of all outbreaks reported in the enteric module of the OS Reporting System between 2008 and 2014. Salmonella was the most commonly reported cause of foodborne outbreak (40.9%) and Enteritidis was the most common serotype reported. Foodborne outbreaks accounted for 3,301 illnesses, 225 hospitalizations and 30 deaths. Overall, 38.3% of foodborne outbreaks were reported to have occurred in a community and 32.2% were associated with a food service establishment. Most foodborne outbreak investigations (63.5%) reported a specific food associated with the outbreak, most frequently meat. CONCLUSION: The OS Reporting System supports information sharing and collaboration among Canadian public health partners and offers an opportunity to obtain a national picture of foodborne outbreaks. This analysis has demonstrated the utility of the OS Reporting System data as an important and useful source of information to describe foodborne outbreak investigations in Canada.

First TDCR measurements at low energies using a miniature x-ray tube.

Developed for radionuclide standardization using liquid scintillation, the Triple to Double Coincidence Ratio (TDCR) method is applied using coincidence counting obtained with a specific three-photomultiplier system. For activity determination, a statistical model of light emission is classically used to establish a relation between the detection efficiency and the experimental TDCR value. At LNE-LNHB, a stochastic approach of the TDCR modeling was developed using the Monte Carlo code Geant4. The interest of this TDCR-Geant4 model is the possibility to simulate the propagation of optical photons from their creation in the scintillation vial to the production of photoelectrons in photomultipliers. As an alternative to the use of radionuclide sources, first TDCR measurements are presented using a miniature x-ray tube closely coupled to the scintillation vial. The objective of this new set-up was to enable low-energy depositions (lower than 20 keV) in liquid scintillator in order to study the influence of both time and geometrical dependence between PMTs already observed with radioactive sources. As for the statistical TDCR model, the non-linearity of light emission is implemented in the TDCR-Geant4 model using the Birks formula which depends on the kB factor and the scintillation yield. Measurements performed with the x-ray tube are extended to the assessment of these parameters and they are tested afterwards in the TDCR-Geant4 model for activity measurements of (3)H.

A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue.

PURPOSE: The purpose of the present systematic review was to develop a practice guideline to inform health care providers about screening, assessment, and effective management of cancer-related fatigue (crf) in adults. METHODS: The internationally endorsed adapte methodology was used to develop a practice guideline for pan-Canadian use. A systematic search of the literature identified a broad range of evidence: clinical practice guidelines, systematic reviews, and other guidance documents on the screening, assessment, and management of crf. The search included medline, embase, cinahl, the Cochrane Library, and other guideline and data sources to December 2009. RESULTS: Two clinical practice guidelines were identified for adaptation. Seven guidance documents and four systematic reviews also provided supplementary evidence to inform guideline recommendations. Health professionals across Canada provided expert feedback on the adapted recommendations in the practice guideline and algorithm through a participatory external review process. CONCLUSIONS: Practice guidelines can facilitate the adoption of evidence-based assessment and interventions for adult cancer patients experiencing fatigue. Development of an algorithm to guide decision-making in practice may also foster the uptake of a guideline into routine care.

The influence of primary health care organizational models on patients' experience of care in different chronic disease situations.

OBJECTIVES: To examine the extent to which experience of care varies across chronic diseases, and to analyze the relationship of primary health care (PHC) organizational models with the experience of care reported by patients in different chronic disease situations. METHODS: We linked a population survey and a PHC organizational survey conducted in two regions of Quebec. We identified five groups of chronic diseases and contrasted these with a no-chronic-disease group. RESULTS: Accessibility of care is low for all chronic conditions and shows little variation across diseases. The contact and the coordination-integrated models are the most accessible, whereas the single-provider model is the least. Process and outcome indices of care experience are much higher than accessibility for all conditions and vary across diseases, with the highest being for cardiovascular-risk-factors and the lowest for respiratory diseases (for people aged 44 and under). However, as we move from risk factors to more severe chronic conditions, the coordination-integrated and community models are more likely to generate better process of care, highlighting the greater potential of these two models to meet the needs of more severely chronically ill individuals within the Canadian health care system.

Development of an x-ray imaging system for the Laser Megajoule (LMJ).

This imaging system aims at recording images of the core size and shape of an imploding deuterium-tritium (DT) microballoon on LMJ inertial confinement fusion (ICF) experiments. Image acquisition is difficult due to the harsh surrounding created by the fusion reaction, which affects system specifications. This one is made of a scintillator, an optical relay, and a CCD camera shielded from the surrounding. The system was tested on different facilities at CEA/DIF, where a spatial resolution of 120 µm was achieved and gamma dose up to 20 rad effects were measured. Setup and performed test are described.

[Exercise therapy in the treatment of chronic back pain. An integral part of interdisciplinary therapy]. / Medizinische Trainingstherapie beim chronischen Rückenschmerz. Ein integraler Bestandteil der interdisziplinären Therapie.

Chronic low back pain requires interdisciplinary and biopsychosocial treatment. Apart from the medical, psychological, and physiotherapeutic aspects of therapy, exercise therapy is an important component. Together with"work hardening," it represents the elements for reconditioning. The isolated effect is scientifically difficult to specify with the available data, but in most analytical studies, exercise therapy is an important component in an interdisciplinary setting. A nonspecific, diversified training program is superior to exercise solely of the trunk muscles. The primary tasks are to recover load capacity and diminish pain-avoidance behaviors, with consideration of the principles of"functional restoration." Thorough information and cooperation with the patient, continuous motivation, ratio control, a systematic increase in load, and permanent feedback are necessary. Close communication within the team makes immediate accompanying interventions of other specialized groups possible.

["Work hardening" for chonic back pain. An integral component of multimodal therapy programs]. / "Work hardening" bei chronischen Rückenschmerzen. Ein integraler Bestandteil multimodaler Therapieprogramme.

Work hardening is aimed at a reestablishment of the potentials needed in occupational everyday life. Fundamental motor abilities, such as strength, stability, flexibility and persistence, are restored and merged into the everyday life so that psychological contents, such as fear avoidance behavior will be positively affected. The design of work hardening is interdisciplinary in the sense of a holistic approach to back pain. Handling the pain under load requires sophisticated treatment and the training demands a high degree of individual design. A trusting and mutual agreement between therapist and patient is essential. Work hardening represents an important part of the therapy of chronic back pain and greatly supports regaining confidence in the physical efficiency and the ability to control the body.

Daily trimethoprim-sulfamethoxazole prophylaxis rapidly induces corresponding resistance among intestinal Escherichia coli of HIV-infected adults in Kenya.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMZ) has been recommended by World Health Organization (WHO) as daily prophylaxis for Africans with AIDS to prevent opportunistic infections. Daily TMP-SMZ may reduce its susceptibility to commensal intestinal Escherichia coli (E coli), increasing the burden of TMP-SMZ-resistant pathogens. METHODS: Participants received either daily TMP-SMZ (CD4 <350 cells/mm(3)) or daily multivitamins (MVIs; CD4 > or =350 cells/mm(3)) for 6 months. Stool was collected at baseline, 2 weeks, 2 months, and 6 months. A random E coli was tested for susceptibility. RESULTS: Baseline prevalence of TMP-SMZ resistance ranged from 71% to 81% and was not different across CD4 strata. At 2 weeks, prevalence of TMP-SMZ-resistant E coli increased significantly from 78% to 98% (P < .001) among persons taking daily TMP-SMZ and did not change among persons taking MVIs. CONCLUSIONS: Daily prophylaxis with TMP-SMZ induced in vivo resistance to the drug after 2 weeks. Empiric therapy for diarrhea with agents other than TMP-SMZ should be considered for HIV-infected persons receiving daily TMP-SMZ prophylaxis.

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya.

OBJECTIVES: To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS: Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6-59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS: The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrollment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION: Although artemether-lumefantrine (Coartem) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardize the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.

Causes of deaths using verbal autopsy among adolescents and adults in rural western Kenya.

OBJECTIVE: To establish causes and patterns of deaths among adolescents and adults (age >11 years) using verbal autopsy (VA) in a rural area of western Kenya where malaria and HIV are common. METHODS: Village reporters reported all deaths in Asembo and Gem (population 135 000), an area under routine demographic surveillance. After an interval of >/=1 month, a trained interviewer used a structured questionnaire to ask the caretaker about signs and symptoms that preceded death. Three clinical officers independently reviewed the interviews and assigned two unranked causes of death; a common cause was designated as the cause of death. RESULTS: In 2003, 1816 deaths were reported from residents; 48% were male and 72% were between 20 and 64 years of age. Most residents (97%) were ill before death, with 60% of illnesses lasting more than 2 months; 87% died at home. Care was sought by 96%; a health facility was the most common source, visited by 73%. For 1759 persons (97%), a common cause of death was designated. Overall, 74% of deaths were attributed to infectious causes. HIV (32%) and tuberculosis (TB) (16%) were the most frequent, followed by malaria, respiratory infections, anaemia and diarrhoeal disease (approximately 6% each). Death in a health facility was associated with young age, higher education, higher SES, a non-infectious disease cause and a shorter duration of illness. CONCLUSION: In this area, the majority of adult and adolescent deaths were attributed to potentially preventable infectious diseases. Deaths in health facilities were not representative of deaths in the community. Programmes to prevent HIV and TB infection and to decrease mortality have started. Their impact can be evaluated against this baseline information.

The effect of health care worker training on the use of intermittent preventive treatment for malaria in pregnancy in rural western Kenya.

BACKGROUND: In 1998, Kenya adopted intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) for malaria prevention during pregnancy. We conducted a survey in 2002 among women who had recently delivered in the rural neighbouring areas Asembo and Gem and reported coverage of 19% of at least one dose and 7% of two or more doses of SP. Health care workers (HCW) in Asembo were retrained on IPTp in 2003. OBJECTIVES: To evaluate if IPTp coverage increased and if the training in Asembo led to better coverage than in Gem, and to identify barriers to the effective implementation of IPTp. METHODS: Community-based cross-sectional survey among a simple random sample of women who had recently delivered in April 2005, interviews with HCW of antenatal clinics (ANC) in Asembo and Gem. RESULTS: Of the 724 women interviewed, 626 (86.5%) attended the ANC once and 516 (71.3%) attended two or more times. Overall IPTp coverage was 41% for at least one dose, and 21% for at least two doses of SP. In Asembo, coverage increased from 19% in 2002 to 61% in 2005 for at least one dose and from 7% to 17% for two doses of SP. In Gem, coverage increased from 17% to 28% and 7% to 11%, respectively. Interviews of HCW in both Asembo and Gem revealed confusion about appropriate timing, and lack of direct observation of IPTp. CONCLUSION: Training of HCW and use of simplified IPTp messages may be a key strategy in achieving Roll Back Malaria targets for malaria prevention in pregnancy in Kenya.

Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro.

The objective of this study was to determine the major intracellular signalling pathways used by FSH and insulin to stimulate cytochrome P450 aromatase (Cyp19) mRNA and oestradiol accumulation in oestrogenic bovine granulosa cells in vitro. Bovine granulosa cells from small follicles (2-4 mm diameter) were cultured for 6 days under non-luteinizing conditions in the presence of insulin at 100 ng/ml, or insulin (10 ng/ml) and FSH (1 ng/ml). On day 4 of culture, specific inhibitors of phosphatidylinositol 3-kinase (PI3K; LY-294002), protein kinase C (PKC; GF-109203X), protein kinase A (PKA; H-89) or mitogen-activated protein (MAP) kinase activation (PD-98059) were added. The addition of PI3K and PKC inhibitors, but not of PKA inhibitor, significantly decreased insulin-stimulated Cyp19 mRNA levels and oestradiol accumulation (P < 0.001). The PKA inhibitor significantly decreased FSH-stimulated Cyp19 mRNA abundance and oestradiol secretion, whereas PI3K and PKC inhibitors decreased oestradiol secretion without affecting Cyp19 mRNA accumulation. Inhibition of MAP kinase pathway significantly increased Cyp19 mRNA abundance in insulin- and FSH-stimulated cells. P450scc mRNA levels and progesterone secretion were not affected by any inhibitor in either experiment. Although FSH stimulates Cyp19 expression predominantly through PKA, oestradiol secretion is altered by PI3K and PKC pathways independently of Cyp19 mRNA levels. In addition, we suggest that Cyp19 is under tonic inhibition mediated through a MAP kinase pathway.

Mental imagery. Effects on static balance and attentional demands of the elderly.

BACKGROUND AND AIMS: Several studies have demonstrated the effectiveness of mental imagery in improving motor performance. However, no research has studied the effectiveness of such a technique on static balance in the elderly. This study evaluated the efficiency of a mental imagery technique, aimed at improving static balance by reducing postural oscillations and attentional demands in the elderly. METHODS: Twenty subjects aged 65 to 90 years old, divided into two groups (8 in Control group and 12 in Experimental group) participated in the study. The experimental participants underwent daily mental imagery training for a period of six weeks. Antero-posterior and lateral oscillations, reaction times during the use of the double-task paradigm were measured, and the Berg Balance Scale, Activities-specific Balance Confidence Scale, and VMIQ questionnaire were answered during both pre-test and post-test. RESULTS: Attentional demands and postural oscillations (antero-posterior) decreased significantly in the group with mental imagery training compared with those of the Control group. Subjects in the mental imagery group became significantly better in their aptitudes to generate clear vivid mental images, as indicated by the VMIQ questionnaire, whereas no significant difference was observed for the Activities-specific Balance Confidence Scale or Berg Scale. CONCLUSION: The results support psychoneuromuscular and motor coding theories associated with mental imagery.

[Lengthening temporalis myoplasty and transfacial nerve graft (VII-V). Technical note]. / Myoplastie d'allongement du temporal et greffe nerveuse transfaciale (VII-V). Note technique.

Authors report the first five cases of lengthening temporalis myoplasty associated with transfacial nerve grafting. After a follow-up period of 10 months and 8 months for the 2 first cases, temporalis reinnervation by the facial nerve could be observed. Nerve growth was documented by electromyography. Three other cases have been performed using this technique and are in the nerve growth phase. Operative technique is described in detail. Transfacial nerve grafting seems to help the transposed temporalis muscle obtain more facial function and therefore, improve the quality of the spontaneous smile. The temporalis muscle become double innervated (trigeminal and facial nerve). It should be indicated in children, young adults or in patients in whom physical therapy will be difficult.

Malaria control in Bungoma District, Kenya: a survey of home treatment of children with fever, bednet use and attendance at antenatal clinics.

OBJECTIVE: To lay the basis for planning an improved malaria control programme in Bungoma District, Kenya. METHODS: By means of a cluster sample household survey an investigation was conducted into the home management of febrile children, the use of bednets, and attendance at antenatal clinics. FINDINGS: Female carers provided information on 314 recently febrile children under 5 years of age, of whom 43% received care at a health facility, 47% received an antimalarial drug at home, and 25% received neither. Of the antimalarial treatments given at home, 91% were started by the second day of fever and 92% were with chloroquine, the nationally recommended antimalarial at the time. The recommended dosage of chloroquine to be administered over three days was 25 mg/kg but the median chloroquine tablet or syrup dosage given over the first three days of treatment was 15 mg/kg. The total dosages ranged from 2.5 mg/kg to 82 mg/kg, administered over one to five days. The dosages were lower when syrup was administered than when tablets were used. Only 5% of children under 5 years of age slept under a bednet. No bednets had been treated with insecticide since purchase. At least two antenatal visits were made by 91% of pregnant women. CONCLUSIONS: Carers are major and prompt providers of antimalarial treatment. Home treatment practices should be strengthened and endorsed when prompt treatment at a health facility is impossible. The administration of incorrect dosages, which proved common with chloroquine, may occur less frequently with sulfadoxine-pyrimethamine, as its dosage regimen is simpler. High levels of utilization of antenatal clinics afford the opportunity to achieve good coverage with presumptive intermittent malaria treatments during pregnancy, and to reach the goal of widespread bednet use by pregnant women and children by distributing nets during antenatal clinic visits.

[Actions of standardized extracts of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure]. / Wirksamkeit eines standardisierten Extraktes aus frischen Crataegus-Beeren auf Belastungstoleranz und Lebensqualität bei Patienten mit Herzinsuffizienz (NYHA II).

Standardized extracts of Crataegus leaves and blossoms are said to have positive inotropic, positive dromotropic and negative bathmotropic effects. Clinical trials produce evidence for an improvement of symptoms in patients with congestive heart failure (NYHA II). In this trial the efficacy of a standardized extract of fresh Crataegus berries (Rob 10) on exercise tolerance and quality of life was studied in 88 patients. In a three-month placebo-controlled, randomized, double-blind trial these patients were treated with Rob 10 (3 x 25 drops daily). Total exercise time in bicycle ergometry was defined as primary efficacy variable, while quality of life (Minnesota Questionnaire), Dyspnea-Fatigue Index and the assessment of dyspnea by the patient on a visual analogous scale were chosen as secondary parameters. Investigations were performed after a two week placebo run-in period as well as 6 and 12 weeks after the onset of the study. Treatment with Rob 10 led to a increase of exercise time of 38.9 s vs placebo (95% confidence interval 5.7-72.1 s). Quality of life improved accordingly in favour of Rob 10. In the Minnesota Questionnaire, the total score fell by 31% (30.6 vs 44.1) under Rob 10 vs 18% (34.6 vs 42.4) under placebo. The Dyspnea-Fatigue Index demonstrated an increase of the total score of 12% (9.41 vs 8.37) vs 8% (8.92 vs 8.26) under administration of placebo. According to findings of the assessment of dyspnea by the patient, dyspnea decreased by 11% (50.5 vs 56.6 mm) vs 4% (54.8 vs 57.3 mm) under placebo. The present study proves the efficacy and safety of a standardized extract of fresh Crataegus berries (Rob 10) in patients with congestive heart failure (NYHA II) regarding the parameters evaluated.