Feasibility, safety, and efficacy of early prophylactic donor lymphocyte infusion after T cell-depleted allogeneic stem cell transplantation in acute leukemia patients.

Prophylactic donor lymphocyte infusion (DLI) starting at 6 months after T cell-depleted allogeneic stem cell transplantation (TCD-alloSCT) can introduce a graft-versus-leukemia (GvL) effects with low risk of severe graft-versus-host-disease (GvHD). We established a policy to apply low-dose early DLI at 3 months after alloSCT to prevent early relapse. This study analyzes this strategy retrospectively. Of 220 consecutive acute leukemia patients undergoing TCD-alloSCT, 83 were prospectively classified to have a high relapse risk and 43 were scheduled for early DLI. 95% of these patients received freshly harvested DLI within 2 weeks of the planned date. In patients transplanted with reduced intensity conditioning and an unrelated donor, we found an increased cumulative incidence of GvHD between 3 and 6 months after TCD-alloSCT for patients receiving DLI at 3 months compared to patients who did not receive this DLI (0.42 (95%Confidence Interval (95% CI): 0.14-0.70) vs 0). Treatment success was defined as being alive without relapse or need for systemic immunosuppressive GvHD treatment. The five-year treatment success in patients with acute lymphatic leukemia was comparable between high- and non-high-risk disease (0.55 (95% CI: 0.42-0.74) and 0.59 (95% CI: 0.42-0.84)). It remained lower in high-risk acute myeloid leukemia (AML) (0.29 (95% CI: 0.18-0.46)) than in non-high-risk AML (0.47 (95% CI: 0.42-0.84)) due to an increased relapse rate despite early DLI.

Routine hoof-trimming data provides insight into the occurrence of claw lesions in Holstein herds in the central region of South Africa.

Claw lesions in dairy cows contribute significantly to lameness, causing distress and discomfort for affected cows and raising welfare concerns. Despite increased awareness, lameness incidence continues to rise. Defining and recording claw traits are particularly problematic. In South Africa (SA), claw data is limited to paper-based records kept by private hoof trimmers. This research analysed claw-trimming data from five dairy farms over 6 years to examine the occurrence and recording of claw lesions in SA Holstein cattle. Lesion identification followed the Claw Lesion Identification in Dairy Cattle brochure. Among the recorded lesions, digital dermatitis (DD) had the highest prevalence (64.02%), followed by sole ulcers (SU; 8.59%), white line disease (WLD; 6.27%), and sole haemorrhage (SH; 4.28%), and most lesions occurred in the rear feet. Chi-square tests and correspondence analysis (CA) were employed to explore the relationships between lesions, feet, and housing. Results indicated that the prevalence of SU and SH showed high similarity for foot and lesion association, and that these were more highly associated with the rear feet. Additionally, the prevalence of DD and interdigital phlegmon were strongly associated, and closely associated with SU, and all these lesions were associated with both dirt lot and free-stall housing systems. CA further confirmed a close association between WLD and SH, and the prevalence of these lesions in the combination housing system. Results of this study highlight the complexity of lesion data and that specific associations between lesions could lead to simplifying the recording thereof. Consolidating the most informative claw lesions into categories will aid in the practical prevention, management, and treatment of lameness on-farm.

A within- and across-country assessment of the genomic diversity and autozygosity of South African and eSwatini Nguni cattle.

In southern Africa, the Nguni cattle breed is classified as an indigenous and transboundary animal genetic resource (AnGR) that manifests unique adaptation abilities across distinct agroecological zones. The genetic integrity of various ecotypes is under potential threat due to both indiscriminate crossbreeding and uncontrolled inbreeding. The aim of this study was to assess the genetic diversity and autozygosity that exist both across countries (ES: eSwatini; SA: South Africa) and within countries (SA), between purebred stud animals (SA-S) and research herds (SA-R). Subsets of 96 ES, 96 SA-S, and 96 SA-R genotyped for 40,930 common SNPs were used to study genome-wide profiles of runs of homozygosity (ROH) and heterozygosity (ROHet) as well as inbreeding levels and population structure. The highest percentage (39.8%) of the 2168 ROH segments was 4-8 Mbp in length, whereas 65% of the 935 ROHet segments fell within the 0.5-1 Mbp length category. Inbreeding coefficients indicated positive but low inbreeding (FROH>1Mbp range: 0.025 for SA-S to 0.029 for SA-R). Principal component (PCA) and population structure analyses illustrated genome-level distinctness of (1) the Nguni from global indicine (Boran) and taurine (Hereford) breeds (K = 3), (2) the SA Nguni populations from the ES Nguni population (K = 4), and (3) different Nguni ecotypes within countries (K = 8). Furthermore, greater admixture was observed for the SA-R population compared to purebred SA-S population (shared ancestry = 0.631 ± 0.353 compared to 0.741 ± 0.123), and fewer genomics-defined ES ecotypes were observed than phenotypically (pre)defined. Overall, the results illustrated that genetic uniqueness within the sampled Nguni cattle resulted from both geographic isolation and exposure to different breeding strategies (and, selection pressures). A further loss of genetic variability should be monitored to prevent the endangerment of unique and beneficial ecotypes.

Moving towards sustainable breeding objectives and cow welfare in dairy production: a South African perspective.

Genetic advancements have resulted in improved dairy production over many decades, due to the focus of breeding objectives on production as the driving force for genetic progress and overall farm profitability. Major advancements were made in the easy-to-measure traits with moderate to high heritability, which resulted in unintended consequences on herd fertility, health, and welfare of cows. In addition, climate change and animal welfare concerns demanded balanced breeding objectives and selection approaches for sustainable production-including health and longevity. The inclusion of genomic information into genetic evaluations has been proved to benefit traits associated with welfare and sustainable production. Cow welfare traits remain complex and suitable phenotypes are not always easy to measure or readily available for genetic evaluations. The challenge for improvement of cow welfare often lies within implementation of sensitive and measurable parameters. The aim of this review was to explore the reconsideration of breeding objectives in the dairy industry towards sustainable dairy production and cow welfare with reference to selection of dairy animals in South Africa.

[The impact of comorbid personality disorders on the effectiveness of acute phase treatments for depression: a meta-analysis and meta-regression]. / De impact van comorbide persoonlijk­heidsstoornissen op de effectiviteit van acute-fasebehandeling van depressie: een meta-analyse en metaregressie.

BACKGROUND: Results from previous meta-analyses of the impact of comorbid personality disorders (PD's) on treatment outcomes for depressive disorder are contradictory and biased by methodological differences between included studies. AIM: To investigate the impact of comorbid PD on the outcome of depression treatments, using only studies with controlled treatments and structured measurement instruments (PROSPERO, CRD42019120200). METHOD: Studies were searched in PubMed, PsycINFO and Embase, and in reference lists of selected articles and previous meta-analyses. Treatment studies for depression with a subset of individuals with comorbid PD were included. Primary outcome was depression severity change during treatment. Effect sizes were estimated using random effect models, study-level variables were examined with meta-regression. Bias was assessed with the Risk of Bias tool. RESULTS: Six studies involving 942 individuals (447 with PD) were included. There was no significant difference in depression severity reduction between individuals with and without PD (g = 0.03, 95% CI -0.15-0.20, p = 0.27). Heterogeneity and risk of bias were low. The meta-regression did not yield significant results. CONCLUSION: Findings don't indicate an impact of comorbid PD on the outcome of acute phase treatment for depression. Depressed patients with and without comorbid PD should receive the same evidence-based depression treatments.

Population structure of indigenous southern African goats based on the Illumina Goat50K SNP panel.

In this study, the genetic structure of indigenous Tswana and Swazi goats using the Illumina Goat50K SNP array was investigated. Two South African commercial goat breeds were included to investigate admixture with the indigenous populations in southern Africa. A total of 144 DNA samples including Boer goats (n = 24), Kalahari Red (n = 24), Swazi (n = 48), and Tswana goats (n = 48) were genotyped. Statistical analysis was performed using PLINK version 1.07. Genetic diversity, measured as expected heterozygosity, was estimated at 0.390, 0.398, 0.413, and 0.387 for Boer, Kalahari Red, Tswana, and Swazi goats, respectively. The individual inbreeding coefficient varied from 0.019 ± 0.05 to 0.011 ± 0.06 for the Tswana and Swazi goats, respectively. The Principal component analysis clustered the populations according to geographical origin and breed type. Linkage disequilibrium (LD) for shorter intervals (0-10 kb) ranged from 0.44 to 0.56 and commercial breeds had higher values. Effective population sizes decreased with generations and at the 13th generation ranged between 87 for Boer to 266 for Tswana goats. The Tswana population exhibited the highest level of genetic variation and effective population size, which holds potential for improved production in marginal regions. A national strategy is required to maintain genetic diversity in communal goat production systems through well-structured breeding and conservation programs.

[Ten years of cognitive control training for depression: an overview of findings and challenges]. / Tien jaar cognitieve controletraining voor depressie: een overzicht van verwezenlijkingen en uitdagingen.

BACKGROUND: 2007 marks a shift in scientific literature on the cognitive vulnerabilities of depression. Preceded by a vast amount of studies exploring neuroplasticity and cognitive transfer effects, Siegle e.a. (Cognit Ther Res 2007; 31: 235-62) published the findings of a proof-of-principle study in which cognitive control training (cct) was applied to treat depression. This denotes an evolution towards clinically oriented cct studies targeting reduction of the vulnerability mechanisms of depression. Following this publication, several studies tested the effects of cct on emotional vulnerability. These studies show great variability.
AIM: This article provides an overview summarizing the findings of cct for depression published in the last 10 years.
METHOD: The results of a recently conducted systematic review were reviewed, with a particular interest in clinical implications and challenges.
RESULTS: cct shows beneficial effects on indicators of depression vulnerability (e.g., stress reactivity, rumination, symptomatology). Associated literature underlines the importance of intensive training procedures, use of an affective task context and task motivation.
CONCLUSION: cct shows potential as a clinical intervention for depression. However, several questions still need to be addressed before implementation into clinical practice is warranted.

Health status in Europe: comparison of 24 urban areas to the corresponding 10 countries (EURO-URHIS 2).

Background: : In Europe, over 70% of the population live in urban areas (UAs). Most international comparative health research is done using national level data, as reliable and comparable urban data are often unavailable or difficult to access. This study aims to investigate whether population health is different in UAs compared with their corresponding countries. : Routinely available health-related data were collected by the EURO-URHIS 2 project, for 10 European countries and for 24 UAs within those countries. National and UA level data for 11 health indicators were compared through the calculation of relative difference, and geographical patterns within Europe were investigated using the Mann Whitney U test. Linear regression modelling was used to adjust for population density, gross domestic product and urbanicity. : In general, the urban population in Eastern Europe is less healthy than the Western European urban population. However, people in Eastern Europe have significantly better broad health outcomes in UAs as compared with the corresponding country as a whole, whereas people in Western Europe have generally worse broader health outcomes in UAs. : For most European countries and UAs that were investigated, the national level health status data does not correspond with the health status at UA level. In order to identify health problems in UAs and to provide information for local health policy, health monitoring and international benchmarking should also be conducted at the local level.

Problems with continuity of care identified by community pharmacists post-discharge.

WHAT IS KNOWN AND OBJECTIVE: Medication discrepancies are common at hospital discharge, and medication reconciliation is widely endorsed as a preventive strategy. However, implementation is difficult for instance due to the unreliability of patients medication histories. In the Netherlands, community pharmacies are well-informed about their patients' pre-admission medication status which enables thorough post-discharge reconciliation. Our aim was to study the frequency and nature of medication discrepancies, missing patient's knowledge and administrative problems at admission to primary care. METHODS: A cross-sectional study was conducted in pharmacies belonging to the Utrecht Pharmacy Practice network for Education and Research in the Netherlands. Structured checklists were used to evaluate all discharge prescriptions presented by adult patients discharged from the hospital to their own home during the study period. The primary outcome was all possible problems with continuity of care, defined as (i) the number and type of medication discrepancies, (ii) administrative problems and (iii) the necessity for patient education. RESULTS AND DISCUSSION: In forty-four pharmacies, checklists were completed for 403 patients. Most discharge prescriptions (92%) led to one or more problems with continuity of care (n = 1154, mean 2·9 ± 2·0), divided into medication discrepancies (31%), administrative problems (34%) and necessity for further education (35%). Medication discrepancies (n = 356) resulted mainly from missing pre-admission medication (n = 106) and dose regimen changes (n = 55) on the discharge prescription. Administrative problems (n = 392) originated mainly from administrative incompleteness (n = 177), for example missing reimbursement authorization forms, or supply issues (n = 150), for example insufficient pharmacy stock. The patients' lack of medication knowledge post-discharge was illustrated by the high need for patient education (n = 406). WHAT IS NEW AND CONCLUSION: Community pharmacists are still confronted with problems due to inadequate documentation at discharge which can inflict harm to patients if not properly addressed. To reduce these problems, a rigorous implementation of the medication reconciliation process at all transition points, standardized electronic transfer of all medication-related information and interdisciplinary collaboration are crucial.

A survey analysis of indigenous goat production in communal farming systems of Botswana.

A total of 153 communal farmers in four agro-ecological regions of Botswana were interviewed using a structured questionnaire. The aims of the survey were to characterise existing communal goat production systems, evaluate the importance of goats to farmers and identify breeding practices and constraints encountered in goat production in Botswana. Data was collected on socio-economic parameters, general and breeding management practices and major constraints limiting goat production in Botswana. All respondents were small-scale communal farmers with 63% respondents practising mixed crop-livestock farming and 37% keeping livestock as their primary activity. The majority (33%) of respondents were older than 60 years. Over 80% of the farmers kept goats for cash required for tuition, school uniforms and household commodities as well as re-stocking of animals. Most farmers (62%) kept indigenous crossed genotypes. Generally, uncontrolled mating was practised with the majority of farmers (41%) using on-farm reared bucks for more than two years of breeding and communal bucks (36%) as an alternative. The major constraints limiting goat productivity in communal areas included uncontrolled breeding, predators, theft and diseases. Issues raised by farmers should be considered in designing and implementing effective breeding programs for goats to improve their overall productivity and contribution to poverty alleviation in these communities.

Polyceraty (multi-horns) in Damara sheep maps to ovine chromosome 2.

Polyceraty (presence of multiple horns) is rare in modern day ungulates. Although not found in wild sheep, polyceraty does occur in a small number of domestic sheep breeds covering a wide geographical region. Damara are fat-tailed hair sheep, from the south-western region of Africa, which display polyceraty, with horn number ranging from zero to four. We conducted a genome-wide association study for horn number with 43 Damara genotyped with 606 006 SNP markers. The analysis revealed a region with multiple significant SNPs on ovine chromosome 2, in a location different from the mutation for polled in sheep on chromosome 10. The causal mutation for polyceraty was not identified; however, the region associated with polyceraty spans nine HOXD genes, which are critical in embryonic development of appendages. Mutations in HOXD genes are implicated in polydactly phenotypes in mice and humans. There was no evidence for epistatic interactions contributing to polyceraty. This is the first report on the genetic mechanisms underlying polyceraty in the under-studied Damara.

ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults.

BACKGROUND: The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS. METHODS: We performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory effects (n = 357, age: 4-12 years, the Netherlands), BREATHE (n = 820, age: 3-22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n = 172, age: 5-12 years, USA), the Genes- environment and Mixture in Latino Americans II- study (n = 745, age: 8-21, USA) and the Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5-18, UK) to test the robustness of the findings. Finally, all results were meta-analysed. RESULTS: Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013) and OR = 1.22 (P = 0.0017), respectively. CONCLUSION AND CLINICAL RELEVANCE: A novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.

Cognitive processes in pharmacists' clinical decision-making.

BACKGROUND: Pharmacists' clinical decision-making is a core process in pharmaceutical care. However, the practical aspects and effective teaching methods of this process remain largely unexplored. OBJECTIVE: To examine the cognitive processes involved in pharmacists' perceptions of how they make clinical decisions in pharmacy practice. METHODS: Semi-structured, face-to-face interviews were conducted with pharmacists working in community, outpatient, and hospital care in the Netherlands between August and December 2021. Participants were explicitly asked for examples when asked how they make clinical decisions in practice and how they teach this to others. After transcribing audio-recorded interviews, an inductive thematic analysis was conducted to identify cognitive processes. A theoretical model of clinical decision-making was then used and adapted to structure the identified processes. RESULTS: In total, 21 cognitive processes were identified from interviews with 16 pharmacists working in community (n = 5), outpatient (n = 2), and hospital care (n = 9). These cognitive processes were organized into 8 steps of the adapted theoretical model, i.e. problem and demand for care consideration, information collection, clinical reasoning, clinical judgment, shared decision-making, implementation, outcomes evaluation, and reflection. Pharmacists struggled to articulate their clinical decision-making and went back-and-forth in their explanations of this process. All pharmacists emphasized the importance of identifying the problem and described how they collect information through reviewing, gathering, recalling, and investigating. Clinical reasoning entailed various cognitive processes, of which comprehending the problem in the patient's context was deemed challenging at times. Pharmacists seemed least active in evaluating patient outcomes and reflecting on these outcomes. CONCLUSIONS: Pharmacists use multiple cognitive processes when making clinical decisions in pharmacy practice, and their back-and-forth explanations emphasize its dynamic nature. This study adds to a greater understanding of how pharmacists make clinical decisions and to the development of a theoretical model that describes this process, which can be used in pharmacy practice and education.

Communication and relationship building in pharmacy education: Experiences from a student-patient buddy project.

BACKGROUND AND PURPOSE: In order to deliver patient-centred pharmaceutical care, pharmacy students need to develop the appropriate competences and skills. During their regular study program, they have limited long-term patient contact. We therefore implemented a student-patient buddy project to give students opportunity to practice and learn from the patient contact. EDUCATIONAL ACTIVITY AND SETTING: A student-patient buddy project was implemented in a 10-week first-year master experiential learning course, including a community pharmacy internship. The pharmacist paired the student with a community-dwelling patient. Student learning activities included: (1) three meetings at the university to prepare and discuss buddy contact moments, (2) three buddy contact moments, (3) discussion with the internship providing pharmacist, and (4) a written reflection report. FINDINGS: In total, 66 students participated from April to June 2021. Most students found patient contact fun and a useful learning experience. Students mentioned that patients were very open and there was opportunity to build a relationship. The first conversation was experienced as exciting and sometimes difficult. Understanding the person was perceived as important. Internship pharmacists were positive about the project and saw learning benefits for students, as well as added value for the pharmacy, mainly because patients seemed to appreciate the contact. SUMMARY: A student-patient buddy project is a good way to expand the limited long-term "real" patient care experiences of pharmacy students. This enables them to practice communication and building relationships with patients.

Factors influencing pharmacists' clinical decision making in pharmacy practice.

BACKGROUND: Pharmacists' clinical decision-making is considered a core process of pharmaceutical care in pharmacy practice, but little is known about the factors influencing this process. OBJECTIVE: To identify factors influencing clinical decision-making among pharmacists working in pharmacy practice. METHODS: Semi-structured interviews were conducted with pharmacists working in primary, secondary, and tertiary care settings in the Netherlands between August and December 2021. A thematic analysis was conducted using an inductive approach. The emerged themes were categorized into the Capability-Opportunity-Motivation-Behaviour (COM-B) model domains. RESULTS: In total, 16 pharmacists working in primary care (n = 7), secondary care (n = 4) or tertiary care (n = 5) were interviewed. Factors influencing pharmacists' capability to make clinical decisions are a broad theoretical knowledge base, clinical experience, and skills, including contextualizing data, clinical reasoning, and clinical judgment. The pharmacy setting, data availability, rules and regulations, intra- and interprofessional collaboration, education, patient perspectives, and time are mentioned as factors influencing their opportunity. Factors influencing pharmacists' motivation are confidence, curiosity, critical thinking, and responsibility. CONCLUSIONS: The reported factors covered all domains of the COM-B model, implying that clinical decision-making is influenced by a combination of pharmacists' capability, opportunity, and motivation. Addressing these different factors in pharmacy practice and education may improve pharmacists' clinical decision-making, thereby improving patient outcomes.

Exploring the effect of auditory stimuli on activity levels, milk yield and faecal glucocorticoid metabolite concentrations in Holstein cows.

Health and welfare are inextricably linked within efficient and sustainable dairy production, and several potential risk factors may affect the well-being of dairy cows, including chronic stress. Although auditory stimuli could be used as a tool to decrease the potential stress that cows might experience, it is seldom applied to livestock production systems due to the perception that enrichment is an unnecessary expense. This study aimed to explore the effect of auditory stimuli as a form of enrichment in a Holstein herd by monitoring fecal glucocorticoid metabolite (fGCM) concentrations (a non-invasive, stress-associated biomarker). Cow activity level and milk yield were also measured. Nine cows in their second and third lactation were divided into 3 groups, using a Latin Square experimental design, exposing each cow group to each of the 3 treatments, namely constant exposure (CE), limited exposure (LE), and no exposure (NE) to classical music. FGCMs were quantified using a group-specific enzyme immunoassay detecting 11,17-dioxoandrostanes. Compared to LE and NE animals, cows exposed to constant music had significantly lower fGCM concentrations (P = 0.012), as well as higher milk yields (P < 0.0001) and lowered activity levels during the morning (P = 0.005) and the evening activity period (P = 0.048). These findings indicate that auditory stimuli in the form of classical music may have a positive effect on the welfare of cows as well as milk yield, which hold economic benefits for the producer and potentially reduces the number of cows needed for profitable production.

Tracking the progeny of adoptively transferred virus-specific T cells in patients posttransplant using TCR sequencing.

Adoptive cellular therapies with T cells are increasingly used to treat a variety of conditions. For instance, in a recent phase 1/2 trial, we prophylactically administered multivirus-specific T-cell products to protect recipients of T-cell-depleted allogeneic stem cell grafts against viral reactivation. To establish treatment efficacy, it is important to determine the fate of the individual transferred T-cell populations. However, it is difficult to unequivocally distinguish progeny of the transferred T-cell products from recipient- or stem cell graft-derived T cells that survived T-cell depletion during conditioning or stem cell graft manipulation. Using messenger RNA sequencing of the T-cell receptor ß-chains of the individual virus-specific T-cell populations within these T-cell products, we were able to track the multiple clonal virus-specific subpopulations in peripheral blood and distinguish recipient- and stem cell graft-derived virus-specific T cells from the progeny of the infused T-cell products. We observed in vivo expansion of virus-specific T cells that were exclusively derived from the T-cell products with similar kinetics as the expansion of virus-specific T cells that could also be detected before the T-cell product infusion. In addition, we demonstrated persistence of virus-specific T cells derived from the T-cell products in most patients who did not show viral reactivation. This study demonstrates that virus-specific T cells from prophylactically infused multiantigen-specific T-cell products can expand in response to antigen encounter in vivo and even persist in the absence of early viral reactivation.

Multicenter survey of routine determinations of resistance of Helicobacter pylori to antimicrobials over the last 20 years (1990 to 2009) in Belgium.

We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.

Biomarkers of therapy responsiveness in asthma: pitfalls and promises.

Asthma is one of the most common chronic diseases worldwide. There is a large inter-individual variability in response to asthma treatment. Most patients respond well to standard therapy; however, a small proportion of the patients remain symptomatic despite treatment with high dosages of corticosteroids. Uncontrolled asthma leads to a decreased quality of life. Therefore, it is important to identify individuals who will respond poorly to standard asthma medication, especially to standard maintenance therapy with inhaled corticosteroids, at an early stage. Response to anti-inflammatory therapy is generally monitored by the assessment of clinical symptoms, which only partially correlates with underlying airway inflammation. The identification of specific inflammatory biomarkers might help to guide treatment or predict a corticosteroid response more accurately. Some inflammatory biomarkers are already finding their way into clinical practice (e.g. fraction of nitric oxide in exhaled breath), whereas others are predominantly used as a research tool (e.g. profiles of volatile organic compounds). Currently, there is no inflammatory biomarker used in routine clinical practice to predict a corticosteroid response. More knowledge on the underlying biological mechanism(s) of heterogeneous therapeutic responses could help to identify novel biomarkers. This review will focus on inflammatory patterns and genetic variations that may underlie differences in treatment response in patients with asthma, and will provide an overview of inflammatory biomarkers that could potentially serve as response predictors.