The role of a labial salivary gland biopsy in the diagnostic procedure for Sjögren's syndrome: a study of 94 cases

Objectives: The purpose of the present study is to examine the role of the outcome of the labial salivary gland biopsy (LSGB) in the diagnostic procedure of patients suspected of suffering from Sjögren's syndrome (SS). Material and Methods: In a retrospective study the result of histopathological assessment of 94 consecutively taken labial salivary gland biopsies has been examined. For the diagnosis of SS the American-European Consensus Group classification (AECG, 2002) have been used. The outcome of the assessment has been discussed in relation to a recently reported classification provided by the American College of Rheumatology (ACR, 2012). Results: In the 94 LSGBs support for a diagnosis of SS has been encountered in 24 out of 26 patients with SS. In the 68 patients with a negative diagnosis of SS only six positive LSGBs were observed. The sensitivity of the labial biopsy amounted 0.92; the specificity was 0.91, while the positive predictive value and the negative predictive value amounted 0.80 and 0.97 respectively. LSGBs taken by or on the request of the departments of Rheumatology or Internal Medicine had a significant higher yield compared to LSGBs taken in other clinical departments. Conclusion s : The LSGB may play a role in the diagnostic procedure of Sjögren's syndrome when using either the AECG classification or the ACR classification. A LSGB should preferably taken after counseling for the possible presence of SS by a department of Rheumatology or Internal Medicine since the yield of such biopsies is much higher than in patients who have not been counseled by these departments prior to the taking of a LSGB. When using the ACR classification, a positive serologic result and a positive ocular test make the taking of a LSGB redundant. Only in case of a negative serologic outcome or a negative result of the ocular test a LSGB is indicated. Since both the serologic test and the ocular test carry hardly any morbidity, these tests should, indeed, be performed first before considering to take a LSGB

Antioxidant intervention in rheumatoid arthritis: results of an open pilot study

There is evidence that reactive oxygen species play a causal role in auto-immune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. To determine the potential beneficial effects of an antioxidant intervention on clinical parameters for RA, an open pilot study was designed. Eight non-smoking female patients with rheumatoid factor + RA and a Disease Activity Score (DAS 28) higher than 2.5 were enrolled in the study. Patients had to be receiving stable non-steroidal anti-inflammatory drug treatment and/or ‘second line’ medication for at least 3 months. The pilot group consumed 20 g of antioxidant-enriched spread daily during a period of 10 weeks. The intervention was stopped after 10 weeks and was followed by a ‘wash-out’ period of 4 weeks. At t = 0, t = 10 weeks and t = 14 weeks, patients’ condition was assessed by means of DAS. In addition, standard laboratory analyses were performed, and blood-samples for antioxidants were taken. The antioxidant-enriched spread was well tolerated. All laboratory measures of inflammatory activity and oxidative modification were generally unchanged. However, the number of swollen and painful joints were significantly decreased and general health significantly increased, as reflected by a significantly improved (1.6) DAS at t = 10 weeks. The antioxidant effect was considered beneficial as, compared to the scores at t = 0, the DAS significantly reduced at t = 10 weeks. Increase of the DAS (0.7) after the “wash-out period” at t = 14 confirmed a causal relation between changes in clinical condition and antioxidants. This open pilot study aimed to assess the clinical relevance of an antioxidant intervention as a first step in assessing potential beneficial effects of antioxidants on rheumatoid arthritis. These conclusions need to be validated in a larger controlled study population

Illness perception and related behaviour in lower respiratory tract infections—a European study

Background. Lower respiratory tract infection (LRTI) is a common presentation in primary care, but little is known about associated patients’ illness perception and related behaviour. Objective. To describe illness perceptions and related behaviour in patients with LRTI visiting their general practitioner (GP) and identify differences between European regions and types of health care system. Methods. Adult patients presenting with acute cough were included. GPs recorded co morbidities and clinical findings. Patients filled out a diary for up to 4 weeks on their symptoms, illness perception and related behaviour. The chi-square test was used to compare proportions between groups and the Mann-Whitney U or Kruskal Wallis tests were used to compare means. Results. Three thousand one hundred six patients from 12 European countries were included. Eighty-one per cent (n = 2530) of the patients completed the diary. Patients were feeling unwell for a mean of 9 (SD 8) days prior to consulting. More than half experienced impairment of normal or social activities for at least 1 week and were absent from work/school for a mean of 4 (SD 5) days. On average patients felt recovered 2 weeks after visiting their GP, but 21% (n = 539) of the patients did not feel recovered after 4 weeks. Twenty-seven per cent (n = 691) reported feeling anxious or depressed, and 28% (n = 702) re-consulted their GP at some point during the illness episode. Reported illness duration and days absent from work/school differed between countries and regions (North-West versus South-East), but there was little difference in reported illness course and related behaviour between health care systems (direct access versus gate-keeping). Conclusion. Illness course, perception and related behaviour in LRTI differ considerably between countries. These finding should be taken into account when developing International guidelines for LRTI and interventions for setting realistic expectations about illness course

Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>The choice of appropriate artemisinin-based combination therapy depends on several factors (cost, efficacy, safety, reinfection rate and simplicity of administration). To assess whether the combination dihydroartemisinin-piperaquine (DP) could be an alternative to artemether-lumefantrine (AL), the efficacy and the tolerability of the two products for the treatment of uncomplicated falciparum malaria in sub-Saharan Africa have been compared.</p> <p>Methods</p> <p>A multicentric open randomized controlled clinical trial of three-day treatment of DP against AL for the treatment of two parallel groups of patients aged two years and above and suffering from uncomplicated falciparum malaria was carried out in Cameroon, Côte d'Ivoire and Senegal. Within each group, patients were randomly assigned supervised treatment. DP was given once a day for three days and AL twice a day for three days. Follow-up visits were performed on day 1 to 4 and on day 7, 14, 21, 28 to evaluate clinical and parasitological results. The primary endpoint was the recovery rate by day 28.</p> <p>Results</p> <p>Of 384 patients enrolled, 197 were assigned DP and 187 AL. The recovery rates adjusted by genotyping, 99.5% in the DP group and 98.9% in the AL group, were not statistically different (p = 0.538). No Early Therapeutic Failure (ETF) was observed. At day 28, two patients in the DP group and five in AL group had recurrent parasitaemia with <it>Plasmodium falciparum</it>. In the DP group, after PCR genotyping, one of the two recurrences was classified as a new infection and the other as recrudescence. In AL group, two recurrences were classified after correction by PCR as recrudescence. All cases of recrudescence were classified as Late Parasitological Failure (LPF). In each group, a rapid recovery from fever and parasitaemia was noticed. More than 90% of patients did no longer present fever or parasitaemia 48 hours after treatment. Both drugs were well tolerated. Indeed, no serious adverse events were reported during the follow-up period. Most of the adverse events which developed were moderate and did not result in the treatment being stopped in either treatment group.</p> <p>Conclusions</p> <p>Dihydroartemisinin-piperaquine was as effective and well-tolerated as artemether-lumefantrine in the treatment of uncomplicated falciparum malaria. In addition, dihydroartemisinin-piperaquine, a single daily dose, could be an advantage over artemether-lumefantrine in Africa because of better treatment observance.</p

Expanding the role of village malaria workers in Cambodia: Implementation and evaluation of four health education packages

Background: Early access to correct diagnosis and appropriate treatment is essential for malaria elimination, and in Cambodia this relies on village malaria workers (VMWs). Decreasing malaria transmission leave VMWs with diminished roles. Activities related to the control of other health conditions could keep these community health workers relevant. Methods: During 2022, 120 VMWs attended training at local health centres on four health education packages: 1. hygiene and sanitation; 2. disease surveillance; 3. management of mild illness; 4. vaccination and antenatal care. All training and evaluation sessions were documented through meeting minutes, and 19 focus group discussions (FGDs) were conducted among VMWs and health centre personnel. Audio-records of FGDs were transcribed and translated in English and underwent thematic analysis. Results: VMWs reported strong interest in the training and welcomed the expansion of their roles thus assuring their continued relevance. VMWs prioritized disease surveillance and management of mild illness among the available training packages because these topics were seen as most relevant. While training was considered comprehensible and important, the low literacy among VMWs was an impediment suggesting training materials need to be delivered visually. Since VMWs have limited resources, incentives could ensure that VMWs are motivated to undertake additional roles and responsibilities. Conclusions: The transformation of VMWs into community health workers with roles beyond malaria is a promising approach for sustaining health care provision in remote areas. Training needs to consider the low scientific literacy, time constraints and limited resources of VMWs

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Systematic care for caregivers of people with dementia in the ambulatory mental health service: designing a multicentre, cluster, randomized, controlled trial

Contains fulltext : 81435.pdf (publisher's version ) (Open Access)BACKGROUND: Care for people with dementia and their informal caregivers is a challenging aim in healthcare. There is an urgent need for cost-effective support programs that prevent informal caregivers of people with dementia from becoming overburdened, which might result in a delay or decrease of patient institutionalization. For this reason, we have developed the Systematic Care Program for Dementia (SCPD). The SCPD consists of an assessment of caregiver's sense of competence and suggestions on how to deal with competence deficiencies. The efficiency of the SCPD will be evaluated in our study. METHODS AND DESIGN: In our ongoing, cluster, randomized, single-blind, controlled trial, the participants in six mental health services in four regions of the Netherlands have been randomized per service. Professionals of the ambulatory mental health services (psychologists and social psychiatric nurses) have been randomly allocated to either the intervention group or the control group. The study population consists of community-dwelling people with dementia and their informal caregivers (patient-caregiver dyads) coming into the health service. The dyads have been clustered to the professionals. The primary outcome measure is the patient's admission to a nursing home or home for the elderly at 12 months of follow-up. This measure is the most important variable for estimating cost differences between the intervention group and the control group. The secondary outcome measure is the quality of the patient's and caregiver's lives. DISCUSSION: A novelty in the SCPD is the pro-active and systematic approach. The focus on the caregiver's sense of competence is relevant to economical healthcare, since this sense of competence is an important determinant of delay of institutionalization of people with dementia. The SCPD might be able to facilitate this with a relatively small cost investment for caregivers' support, which could result in a major decrease in costs in the management of dementia. Implementation on a national level will be started if the SCPD proves to be efficient. TRIAL REGISTRATION: NCT00147693

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>efficacy assessments of the first-line treatments for <it>Plasmodium falciparum </it>malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated <it>P. falciparum </it>malaria since 2004.</p> <p>Methods</p> <p>Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for <it>P. falciparum </it>in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented <it>P. falciparum </it>mono-infection were enrolled and followed according to the standard 2009 World Health Organization <it>in vivo </it>drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.</p> <p>Results</p> <p>Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight <it>P. falciparum </it>patients (6.7%) presented with <it>Plasmodium vivax </it>infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.</p> <p>Conclusions</p> <p>AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with <it>P. vivax </it>possibly from relapse or new infection was observed.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052584">NCT01052584</a></p