Characterization of the gut bacterial and viral microbiota in latent autoimmune diabetes in adults.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.

Comment on Grabala et al. Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study. J. Clin. Med. 2024, 13, 1529.

We read with great interest the study titled "Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study" by Grabala and colleagues [...].

Health-related quality of life in early onset scoliosis patients treated with the spring distraction system: what to expect in the first 2 years after surgery.

PURPOSE: The Spring Distraction System (SDS) is a novel "growth-friendly" implant for the treatment of Early-Onset Scoliosis (EOS). This prospective study aims to determine the evolution of the "24-Item Early-Onset Scoliosis Questionnaire" (EOSQ-24) scores during 2-year follow-up after SDS surgery. Secondary aims include investigating the relation between EOSQ-24 scores and EOS etiology, and evaluating the impact of an unplanned return to the operating room (UPROR) on HRQoL. METHODS: All SDS patients with at least 2-year follow-up were included. Caregivers completed the EOSQ-24 pre-operatively, post-operatively, and at 6, 12, and 24 month follow-up. Mean total and -domain scores were graphed over time. Repeated-measures ANOVA analyzed the influence of etiology on EOSQ-24 scores. Multiple regression analyzed associations between UPRORs and EOSQ-24 scores. RESULTS: Forty-nine patients were included. Mean total EOSQ-24 scores decreased from 70 pre-operatively to 66 post-operatively, then gradually increased to 75 (24 months). Most domains exhibited changes over time, with initial declines, but eventually surpassing pre-operative levels after 2-year follow-up. Neuromuscular/Syndromic patients had lower scores, but showed similar improvements over time compared with other etiologies. Multiple regression showed lower Parental Burden domain score (- 14 points) in patients with UPRORs, although no significant reductions were found in total score, or in other domains. CONCLUSION: HRQoL decreases immediately following SDS surgery but quickly recovers and exceeds pre-operative levels at 2-year follow-up in all domains. Neuromuscular/Syndromic patients have lower initial scores, but progress similarly over time. UPRORs do not influence EOSQ-24 scores, except for a negative impact on the Parental Burden domain in the short term. LEVEL OF EVIDENCE: III.

Therapeutic drug monitoring to personalize dosing of imatinib, sunitinib, and pazopanib: A mixed methods study on barriers and facilitators.

BACKGROUND: Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib. METHODS: We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. RESULTS: In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). CONCLUSION: We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.

Surgical treatment of neuromuscular Early Onset Scoliosis with a bilateral posterior one-way rod compared to the Spring Distraction System: study protocol for a limited-efficacy Randomized Controlled Trial (BiPOWR).

BACKGROUND: Early Onset Scoliosis (EOS) is a progressive spinal deformity in children, and a potentially life-threatening disease. "Growth-friendly" surgical techniques aim to control the deformity, while allowing the spine and trunk to maintain growth. Current "growth-friendly" systems such as the traditional growing rod (TGR) and magnetically controlled growing rod (MCGR) have limitations that reduce their efficacy and cost-effectiveness. Recently, two "growth-friendly" systems have been developed that mitigate many of these limitations, the Spring Distraction System (SDS) and the One Way Self-Expanding Rod (OWSER). The purpose of the multicenter BiPOWR trial is to investigate, describe and compare the 1-year limited-efficacy and -safety of both strategies in the treatment of neuromuscular EOS. METHODS: After informed consent, 28 neuromuscular EOS patients will be randomized to receive either the SDS or the OWSER. Patients and caregivers will be blinded to allocation until after surgery. Primary outcomes will be maintenance of coronal curve correction and the occurrence of serious adverse events. In addition, spinal growth, implant lengthening, and perioperative findings are recorded systematically. At each follow-up moment, the Early Onset Scoliosis Questionnaire (EOSQ-24) will be used to assess health-related quality of life. All outcomes will be compared between groups. DISCUSSION: The BiPOWR trial is the first randomized controlled trial that compares two specific "growth-friendly" implants in a specified EOS population. It will determine the 1-year limited-efficacy and safety of the SDS and OWSER implants. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04021784 (13-06-2019). CCMO registry: NL64018.041.17 (06-05-2019).

The gut microbiota in multiple sclerosis varies with disease activity.

BACKGROUND: Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. METHODS: Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. RESULTS: We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-ß, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. CONCLUSIONS: Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.

Reducing Shoulder Complaints in Employees with High Occupational Shoulder Exposures: A Cluster-Randomised Controlled Study (The Shoulder-Café Study).

PURPOSE: To evaluate if a group-based Shoulder-Café intervention could reduce shoulder complaints more effectively than an individual-based control intervention in employees with shoulder complaints and high occupational shoulder exposures. METHODS: A cluster-randomised controlled study of 109 participants from 60 companies in Central Denmark Region. Companies were randomised and allocated to either Shoulder-Café or control intervention. Participants in both interventions received a pamphlet on home-based shoulder exercises and a pamphlet with general information on reducing occupational shoulder exposures. They also had their occupational shoulder exposures assessed. Shoulder-Café participants additionally received three café-meetings with casual discussion, clinical shoulder evaluation, education about shoulder anatomy and occupational shoulder exposures, supervised exercises, workplace-oriented counselling, and an optional workplace visit. The primary outcome measure was the Oxford Shoulder Score (OSS) at 6-month follow-up. Secondary outcome measures were the OSS at 12 months, Fear-Avoidance Beliefs Questionnaire - Physical Activity at 6 and 12 months, and Patients' Global Impression of Change at 6 months. The study also included seven supplementary outcome measures. RESULTS: Both groups improved from baseline to 6 months with respect to the primary outcome (P < 0.01). No group differences were found for the primary outcome (mean difference (MD) [95% confidence interval]: 0.3 [- 1.6; 2.2]) or secondary outcomes. The supplementary outcomes "felt informed about handling shoulder complaints" and "felt informed about reducing occupational exposures" at 6 months, and "Patients' Global Impression of Change" and "overall satisfaction" at 12 months favoured the Shoulder-Café intervention. CONCLUSION: The Shoulder-Café intervention did not reduce shoulder complaints more effectively than the control intervention. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov on 19 May 2017 (ID: NCT03159910).

The Spring Distraction System for Growth-Friendly Surgical Treatment of Early Onset Scoliosis: A Preliminary Report on Clinical Results and Safety after Design Iterations in a Prospective Clinical Trial.

Background: The Spring Distraction System (SDS) is a dynamic growth-friendly implant to treat early onset scoliosis (EOS). Previous SDS studies showed promising results in terms of curve correction and complication profile. Nevertheless, complications did occur, which led to modifications in the implant design. The main iterations were a larger rod diameter and a more sagittal stable sliding mechanism. The purpose of this study was to investigate the performance of these iterations. Methods: All patients treated with the modified SDS and >1 year follow-up were included. Radiographic outcomes, severe adverse events (SAEs), unplanned returns to the operating room (UPRORs) and health-related quality of life (HRQoL) were investigated. Results: Seventeen EOS patients (three congenital, four idiopathic, nine neuromuscular, one syndromic) were included. Mean age at surgery was 9.5 ± 2.5 years. Similar to the first generation SDS, about 50% initial correction was achieved and maintained, and spinal growth was near physiological. Most importantly, SAEs and UPRORs were diminished and favorable with 0.10/patient/year. In addition, HRQoL increased during the first year postoperatively, indicating the implant was well accepted. Conclusion: These preliminary results indicate that the iterations of the SDS are effective in terms of reducing SAEs and UPRORs and increasing HRQoL in patients with EOS.

Library Preparation and Sequencing Platform Introduce Bias in Metagenomic-Based Characterizations of Microbiomes.

Metagenomics is increasingly used to describe microbial communities in biological specimens. Ideally, the steps involved in the processing of the biological specimens should not change the microbiome composition in a way that it could lead to false interpretations of inferred microbial community composition. Common steps in sample preparation include sample collection, storage, DNA isolation, library preparation, and DNA sequencing. Here, we assess the effect of three library preparation kits and two DNA sequencing platforms. Of the library preparation kits, one involved a PCR step (Nextera), and two were PCR free (NEXTflex and KAPA). We sequenced the libraries on Illumina HiSeq and NextSeq platforms. As example microbiomes, two pig fecal samples and two sewage samples of which aliquots were stored at different storage conditions (immediate processing and storage at -80°C) were assessed. All DNA isolations were performed in duplicate, totaling 80 samples, excluding controls. We found that both library preparation and sequencing platform had systematic effects on the inferred microbial community composition. The different sequencing platforms introduced more variation than library preparation and freezing the samples. The results highlight that all sample processing steps need to be considered when comparing studies. Standardization of sample processing is key to generating comparable data within a study, and comparisons of differently generated data, such as in a meta-analysis, should be performed cautiously. IMPORTANCE Previous research has reported effects of sample storage conditions and DNA isolation procedures on metagenomics-based microbiome composition; however, the effect of library preparation and DNA sequencing in metagenomics has not been thoroughly assessed. Here, we provide evidence that library preparation and sequencing platform introduce systematic biases in the metagenomic-based characterization of microbial communities. These findings suggest that library preparation and sequencing are important parameters to keep consistent when aiming to detect small changes in microbiome community structure. Overall, we recommend that all samples in a microbiome study are processed in the same way to limit unwanted variations that could lead to false conclusions. Furthermore, if we are to obtain a more holistic insight from microbiome data generated around the world, we will need to provide more detailed sample metadata, including information about the different sample processing procedures, together with the DNA sequencing data at the public repositories.

Disc and Vertebral Body Morphology From Birth to Adulthood.

STUDY DESIGN: Cross-sectional. OBJECTIVE: The aim of this study was to describe the morphology of intervertebral discs and vertebral bodies during growth in asymptomatic children and adolescents. SUMMARY OF BACKGROUND DATA: Earlier studies demonstrated that spinal growth occurs predominantly in vertebral bodies. This axiom introduced a vertebral-body-focus for unravelling etiological questions and achieve growth-modulation in young spinal deformity patients. Recent studies show the importance of the intervertebral discs in the early phases and possible etiology of pediatric spinal deformities. There is presently a paucity of 3D morphometric data of spinal elements during growth. METHODS: A database of 298 patients aged 0 to 21 that have received a computed tomography scan for indications not related to the spine was analyzed. Custom made software was used to semi-automatically measure intervertebral disc and vertebral body morphology, corrected for orientation in all 3 planes. RESULTS: Vertebral body height increased from birth up to adulthood, from 4-to-14 mm in the cervical, 6 to 20 mm in the thoracic, and 9 to 28 mm in the lumbar spine. This increase was 0.70 mm/year in males, more pronounced than females with 0.62 mm/year (P = 0.001). Lumbar discs increased throughout growth from 4.4 to 9.0 mm, whereas thoracic discs only increased from 3.5 to 4.9 mm at age 4 and remained stable afterwards, similarly for cervical discs. The disc transverse surface area increased greatly and consistently throughout growth. Disc slenderness was stable in the lumbar spine during growth, but decreased in the thoracic and cervical spine. Overall, discs were more slender in females, especially around early adolescence. CONCLUSION: The spine grows predominantly in the vertebral bodies. Thoracic discs increase in height only during the first years, whereas the transverse surface area continues to increase throughout growth, thus discs slenderness decreases. Relatively, female discs remained slenderer around growth-spurt. These measurements may assist future studies on the role of disc morphology in the etiology and treatment of spinal deformity.Level of Evidence: 4.

Identifying complications and failure modes of innovative growing rod configurations using the (hybrid) magnetically controlled growing rod (MCGR) and the spring distraction system (SDS).

BACKGROUND: Magnetically controlled growing rods (MCGRs) offer non-invasive distractions in Early-Onset Scoliosis (EOS). However, implant-related complications are common, reducing its cost-effectiveness. To improve MCGRs functionality and cost-effectiveness, we often combine a single MCGR with a contralateral sliding rod (hybrid MCGR). Recently, we developed the spring distraction system (SDS) as an alternative, which provides continuous distraction forces through a helical spring. This study aims to identify complication rates and failure modes of EOS patients treated with either of these innovative systems. METHODS: This single-centre retrospective study included EOS patients treated with a (hybrid) MCGR or SDS between 2013 and 2018. Baseline demographics, and data regarding complications and implant growth were measured. Complication rate, complication profile, complication-free survival and implant growth were compared between groups. RESULTS: Eleven hybrid- and three bilateral MCGR patients (4.1-year follow-up) and one unilateral, eleven hybrid and six bilateral SDS patients (3.0-year follow-up) were included. Groups had similar age, sex, aetiology distribution, and pre-operative Cobb angle. Complication rate was 0.35 complications/patient/year for MCGR patients and 0.33 complications/patient/year for SDS patients. The most common complications were failure to distract (MCGR-group; 8/20 complications) and implant prominence (SDS-group; 5/18 complications). Median complication-free survival was 2.6 years, with no differences between groups (p = 0.673). Implant growth was significantly higher in the SDS-group (10.1 mm/year), compared to the MCGR-group (6.3 mm/year). CONCLUSION: (Hybrid) MCGR and SDS patients have similar complication rates and complication-free survival. Complication profile differs between the groups, with frequent failure to distract leading to significantly reduced implant growth in (hybrid) MCGR patients, whereas SDS patients frequently exhibit implant prominence and implant kyphosis. LEVEL OF EVIDENCE: III.

Enhancing African low-resource languages: Swahili data for language modelling.

Language modelling using neural networks requires adequate data to guarantee quality word representation which is important for natural language processing (NLP) tasks. However, African languages, Swahili in particular, have been disadvantaged and most of them are classified as low resource languages because of inadequate data for NLP. In this article, we derive and contribute unannotated Swahili dataset, Swahili syllabic alphabet and Swahili word analogy dataset to address the need for language processing resources especially for low resource languages. Therefore, we derive the unannotated Swahili dataset by pre-processing raw Swahili data using a Python script, formulate the syllabic alphabet and develop the Swahili word analogy dataset based on an existing English dataset. We envisage that the datasets will not only support language models but also other NLP downstream tasks such as part-of-speech tagging, machine translation and sentiment analysis.

Pinguicula rosmarieae Casper, Bussmann & T.Henning (Lentibulariaceae), a new butterwort from the Amotape-Huancabamba Zone (northern Peru).

The insectivorous genus Pinguicula occurs along the whole Andean mountain chain from Colombia-Venezuela in the north to Tierra del Fuego in the south with a short interruption in the Peruvian-Chilean desert range. This paper describes a new and striking species of Pinguicula that occurs in the south-eastern part of the Amotape-Huancabamba Zone in north Peru. It grows either as a lithophyte on moist rocks or as an epiphyte on Polylepis multijuga Pilg. in the wet highlands of the Cordillera Central. Pinguicula rosmarieae Casper, Bussmann & T.Henning, sp. nov. is clearly distinguished by a basal rosette of ovate-obovate leaves spread out flat on the ground and especially by a two-partite corolla with a straight uniform tube-spur complex, two features unknown from other Andean Pinguicula species. The morphological similarity to P. calyptrata Kunth is discussed and the habitat and distribution of P. rosmarieae are characterised.

ResumenEl género insectívoro Pinguicula se encuentra a lo largo Andes desde Colombia y Venezuela en el norte hasta Tierra Fuego en el sur, con una breve interrupción en el los desiertos peruano-chilenos. Este artículo describe una nueva y distintiva especie de Pinguicula que se encuentra en la parte sur de la zona Amotape-Huancabamba en el norte del Perú. Puede crecer tanto como litófita sobre rocas húmedas o como epífita sobre Polylepis multijuga Pilg. en las tierras altas y húmedas de la Cordillera Central. Pinguicula rosmarieae Casper, Bussmann & T.Henning, sp. nov. se distingue claramente por tener una roseta basal de hojas ovadas-obovadas, postradas sobre el suelo y, especialmente, por la corola bipartida con un espolón uniforme recto, una combinación de características desconocidas de otras especies andinas de Pinguicula. Se discute la similitud morfológica con P. calyptrata Kunth y se caracterizan el hábitat y la distribución de P. rosmarieae.

Acceptable Success Rate in Patients With Periprosthetic Knee Joint Infection Treated With Debridement, Antibiotics, and Implant Retention.

BACKGROUND: Acute periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) surgery can be treated with debridement, antibiotics, and implant retention (DAIR). However, varying results have been reported in the literature and optimal timing of the procedure is still debated. In this retrospective cohort study, we investigate (a) success rate of DAIR for treating PJI following primary TKA surgery and (b) whether time after primary surgery until DAIR and (c) type of isolated microorganism influence outcome. METHODS: Sixty-seven patients with PJI following primary TKA surgery treated with DAIR were identified. Patients with insufficient data and patients who did not fulfill Musculoskeletal Infection Society PJI criteria were excluded, leaving 58 patients for analysis. Minimum follow-up was 2 years. A DAIR was considered a success if the patient was infection free after 2 years. RESULTS: The overall success rate of PJI treated with DAIR was 84%. Median time until DAIR was 21 days (7-1092). Thirty-four patients (59%) were revised within 28 days, 42 patients (72%) within 42 days, while 10 patients (17%) were revised more than 90 days after primary TKA surgery. The success rates were 85%, 88%, and 60%, respectively. In the patients revised within 90 days, our success rate was 90% (43/48) regardless of the involved microorganism. CONCLUSION: We find DAIR to be a viable and safe treatment option for PJI following primary TKA surgery, when performed early after primary surgery and with the addition of a relevant postrevision antibiotic regime.

Epidemiological Aspects of Blastocystis Colonization in Children in Ilero, Nigeria.

This study aimed to elucidate aspects of the epidemiology of Blastocystis in Nigerian school children, including the distribution of subtypes (STs) and ST alleles. A total of 199 genomic DNAs extracted from fecal samples from 199 Nigerian children aged 2-14 years were tested by real-time polymerase chain reaction for Blastocystis Positive DNAs were submitted to barcoding by PCR and sequencing to obtain information on STs and ST alleles. A total of 167 (84%) samples were positive for Blastocystis, with prevalence increasing by age. No association between Blastocystis colonization and gender (P = 0.51) or type/presence of toilet facilities (P = 0.21) was observed. Blastocystis carriers were more prone to using water collected from wells than from sachets (P = 0.0044). Moreover, Blastocystis positivity was associated with positivity for fecal-orally transmitted protozoa (P = 0.018) and helminths (P < 0.0001). A clear inverse association of Blastocystis colonization and malaria infection was observed (P < 0.0001); however, malaria-positive children being younger than malaria-negative children, this finding was attributed to the age effect of Blastocystis colonization. ST data were available for 127/167 (76%) samples. Fifty-one children were positive for ST1, while 42 and 33 children were colonized with ST2 and ST3, respectively; a single case of ST7 was observed. By and large, the ST alleles identified for ST1 and ST2 did not differ from those observed in humans in other regions of the world; meanwhile, the distribution of ST3 alleles was remarkably distinct and potentially specific to humans in sub-Saharan Africa.

Validation of a visual analogue score (LRTI-VAS) in non-CF bronchiectasis.

BACKGROUND AND AIM: Quality of life in patients with non-cystic fibrosis (non-CF) bronchiectasis is largely defined by respiratory symptoms. To date, no disease-specific tool for symptom measurement in this patient group was available. We developed the lower respiratory tract infections - visual analogue scale (LRTI-VAS) in order to quickly and conveniently quantify symptoms in non-CF bronchiectasis. This study aimed to validate LRTI-VAS for use in non-CF bronchiectasis. METHODS: This study included outpatients with radiologically proven bronchiectasis and no evidence of CF. Results of LRTI-VAS were compared with other markers of disease activity {lung function parameters, oxygen saturation and three health-related quality of life questionnaires [Medical Outcomes Study Short-Form 36 Health Survey (SF-36), St Georges Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ)]} and validity, reliability and responsiveness were assessed. RESULTS: Thirty stable and 30 exacerbating participants completed the LRTI-VAS questionnaire. When testing for repeatability on two separate occasions, no statistically significant difference between total scores was found {1.4 [standard deviation (SD)] 5.3}, P = 0.16). Internal consistency was high across items (Cronbach's alpha 0.86). Correlation with SGRQ, SF-36 and LCQ total scores was high. Following antibiotic treatment, mean (SD) LRTI-VAS total score improved from 18.1 (SD 9.9) to 26.1 (SD 6.6) (P < 0.001). CONCLUSIONS: LRTI-VAS showed excellent validity, reliability and responsiveness to change and therefore appears a reliable tool for symptom measurement in non-CF bronchiectasis.

Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial.

IMPORTANCE: Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis. OBJECTIVE: To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis. DESIGN, SETTING, AND PARTICIPANTS: The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year. INTERVENTIONS: Azithromycin (250 mg daily) or placebo for 12 months. MAIN OUTCOME MEASURES: Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life. RESULTS: Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group. CONCLUSIONS AND RELEVANCE: Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00415350.

Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial.

RATIONALE: Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia (CAP), possibly by diminishing local and systemic antiinflammatory host response. OBJECTIVES: To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP. METHODS: Hospitalized patients, clinically and radiologically diagnosed with CAP using standard clinical and radiological criteria, were randomized to receive 40 mg prednisolone for 7 days or placebo, along with antibiotics. Primary outcome was clinical cure at Day 7. Secondary outcomes were clinical cure at Day 30, length of stay, time to clinical stability, defervescence, and C-reactive protein. Disease severity was scored using CURB-65 (a severity index for community-acquired pneumonia evaluating Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, and age 65 or older) and Pneumonia Severity Index. MEASUREMENTS AND MAIN RESULTS: We enrolled 213 patients. Fifty-four (25.4%) patients had a CURB-65 score greater than 2, and 93 (43.7%) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104 (66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109 (77.1%) in the placebo group (P = 0.38 and P = 0.08). Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo. Subanalysis of patients with severe pneumonia did not show differences in clinical outcome. Late failure (>72 h after admittance) was more common in the prednisolone group (20 patients, 19.2%) than in the placebo group (10 patients, 6.4%; P = 0.04). Adverse events were few and not different between the two groups. CONCLUSIONS: Prednisolone (at 40 mg) once daily for a week does not improve outcome in hospitalized patients with CAP. A benefit in more severely ill patients cannot be excluded. Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP.