The patient-reported outcomes measurement information systems (PROMIS®) physical function and its derivative measures in adults: a systematic review of content validity.

PURPOSE: This study aims to systematically review and critically appraise the content validity of the adult versions of the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) item bank and its derivative measures in any adult population. METHODS: MEDLINE and EMBASE were searched in October 2021 for studies on measurement properties of PROMIS-PF measures in an adult population. Studies were included if the study described the development of a PROMIS-PF measure or investigated its relevance, comprehensiveness, or comprehensibility. Assessment of the methodological quality of eligible studies, rating of results, and summarizing evidence was performed following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology for assessing content validity. A modified GRADE approach was used to determine the level of evidence. RESULTS: Three development studies and eight studies on the content validity of one or more of the PROMIS-PF measures were identified. The methodological quality of most studies was rated doubtful. There was low to high level evidence for sufficient relevance, comprehensiveness, and comprehensibility of most PROMIS-PF measures for healthy seniors and various disease populations. We found low to moderate level evidence for insufficient relevance of PROMIS-PF measures for patients with conditions that affected only one body part, and insufficient comprehensibility of the PROMIS-PF measures for minority elderly. CONCLUSION: Most PROMIS-PF measures demonstrate sufficient content validity in healthy seniors and various disease populations. However, the quality of this evidence is generally low to moderate, due to limitations in the methodological quality of the studies.

Deceleration and Trapping of SrF Molecules.

We report on the electrostatic trapping of neutral SrF molecules. The molecules are captured from a cryogenic buffer-gas beam source into the moving traps of a 4.5-m-long traveling-wave Stark decelerator. The SrF molecules in X^{2}Σ^{+}(v=0,N=1) state are brought to rest as the velocity of the moving traps is gradually reduced from 190 m/s to zero. The molecules are held for up to 50 ms in multiple electric traps of the decelerator. The trapped packets have a volume (FWHM) of 1 mm^{3} and a velocity spread of 5(1) m/s, which corresponds to a temperature of 60(20) mK. Our result demonstrates a factor 3 increase in the molecular mass that has been Stark decelerated and trapped. Heavy molecules (mass>100 amu) offer a highly increased sensitivity to probe physics beyond the standard model. This work significantly extends the species of neutral molecules of which slow beams can be created for collision studies, precision measurement, and trapping experiments.

Transition of care in stroke patients discharged home: a single-center prospective cohort study.

INTRODUCTION: Approximately two-thirds of the patients admitted to the hospital with an ischemic stroke are discharged directly home. Discontinuity of care may result in avoidable patient harm, re-admissions and even death. We hypothesized that the transfer of information is most essential in this patient group since any future care for these patients relies solely on the information that is available to the care provider responsible at that time. AIM: The objective of this study was to evaluate the continuity of transmural care in ischemic stroke patients by assessing 1) the transfer of clinical information through discharge letters to general practitioners (GPs), 2) subsequent documentation of this information and early follow-up by GPs and 3) the documentation of medication-related information in discharge letters, at GPs and community pharmacies (CPs). METHODS: This prospective cohort study was conducted from September 2019 through March 2020 in OLVG, Amsterdam, the Netherlands, in patients with a first stroke discharged directly home. Outcome measures were derived from national guidelines and regional agreements. Results were analyzed using descriptive analysis. RESULTS: A total of 33 patients were included. Discharge letters (n = 33) and outpatient clinic letters (n = 24) to GPs contained most of the essential items, but 16% (n = 9) of the letters were sent in time. GPs (n = 31) infrequently adhered to guidelines since 10% (n = 3) of the diagnoses were registered using the correct code and 55% (n = 17) of the patients received follow-up shortly after discharge. Medication overviews were inaccurately communicated to GPs since 62% (n = 150) of all prescriptions (n = 243) were correctly noted in the discharge letter. Further loss of information was seen as only 39% (n = 95) of all prescriptions were documented correctly in GP overviews. We found that 59% (n = 144) of the prescriptions were documented correctly in CP overviews. CONCLUSION: In this study, we found that discontinuity of care occurred to a varying extent throughout transmural care in patients with a first stroke who were discharged home.

Aspirated bile: a major host trigger modulating respiratory pathogen colonisation in cystic fibrosis patients.

Chronic respiratory infections are a leading global cause of morbidity and mortality. However, the molecular triggers that cause respiratory pathogens to adopt persistent and often untreatable lifestyles during infection remain largely uncharacterised. Recently, bile aspiration caused by gastro-oesophageal reflux (GOR) has emerged as a significant complication associated with respiratory disease, and cystic fibrosis (CF) in particular. Based on our previous finding that the physiological concentrations of bile influence respiratory pathogens towards a chronic lifestyle in vitro, we investigated the impact of bile aspiration on the lung microbiome of respiratory patients. Sputum samples (n = 25) obtained from a cohort of paediatric CF patients were profiled for the presence of bile acids using high-resolution liquid chromatography-mass spectrometry (LC-MS). Pyrosequencing was performed on a set of ten DNA samples that were isolated from bile aspirating (n = 5) and non-bile aspirating (n = 5) patients. Both denaturing gradient gel electrophoresis (DGGE) and pyrosequencing revealed significantly reduced biodiversity and richness in the sputum samples from bile aspirating patients when compared with non-aspirating patients. Families and genera associated with the pervasive CF microbiome dominated aspirating patients, while bacteria associated with the healthy lung were most abundant in non-aspirating patients. Bile aspiration linked to GOR is emerging as a major host trigger of chronic bacterial infections. The markedly reduced biodiversity and increased colonisation by dominant proteobacterial CF-associated pathogens observed in the sputum of bile aspirating patients suggest that bile may play a major role in disease progression in CF and other respiratory diseases.

Neurological complications of excessive recreational nitrous oxide use: a case series based on a text mining algorithm.

BACKGROUND: The recreational use of nitrous oxide (N2O) has gained popularity over recent years. We present a case series of excessive N2O users with neurological complications. METHODS: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N2O recreationally and visited a neurologist. RESULTS: We identified 251 patients. The median duration of N2O use was 11 months (interquartile range [IQR], 3-24) and the median amount of N2O used per occasion 1.6 kg (IQR 0.5-4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery. CONCLUSIONS: In this case series of excessive N2O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N2O use.

The non-classical ArsR-family repressor PyeR (PA4354) modulates biofilm formation in Pseudomonas aeruginosa.

PyeR (PA4354) is a novel member of the ArsR family of transcriptional regulators and modulates biofilm formation in Pseudomonas aeruginosa. Characterization of this regulator showed that it has negative autoregulatory properties and binds to a palindromic motif conserved among PyeR orthologues. These characteristics are in line with classical ArsR-family regulators, as is the fact that PyeR is part of an operon structure (pyeR-pyeM-xenB). However, PyeR also exhibits some atypical features in comparison with classical members of the ArsR family, as it does not harbour metal-binding motifs and does not appear to be involved in metal perception or resistance. Hence, PyeR belongs to a subgroup of non-classical ArsR-family regulators and is the second ArsR regulator shown to be involved in biofilm formation.

Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

The relationship between psychological distress and impairment of disease-specific quality-of-life compared between liquid sclerocompression therapy and invasive treatments in patients with superficial venous disease during a one-year follow-up.

INTRODUCTION: Superficial venous disease (SVD) is a very common disease and much research has been done towards finding the ideal treatment and discovering the pathophysiology of SVD. Not much is known about the psychological burden of SVD. Current guidelines and scientific publications tend to focus on clinical and physiological aspects of SVD. The aim of this study was to relate the changes in Quality-of-Life (QoL) after SVD treatment to possible changes in psychological distress (PD). METHODS: A prospective cohort was set up with the assistance of 5 specialized vein clinics in the Netherlands. Inclusion criteria were: 18 years of age or older, fluent in Dutch language, C1 to C6 (CEAP) class intended to be primary treated with either endovenous laser(LA), radiofrequency ablation (RFA) and phlebectomy(PHL) or sclerocompression therapy alone (SCT). Patients were divided in two groups:1. C1-C3 patients treated by SCT2. C1-C6 patients treated invasively (LA, RFA and PHL)Outcomes were a disease specific QoL questionnaire (CIVIQ-20) and a questionnaire to assess PD (Hospital Anxiety and Depression Scales (HADS)). This study was approved by the local institutional review board, following the principles outlines in the Declaration to Helsinki. This trial was registered in the ISRCTN registry with study ID ISRCTN12085308. RESULTS: 442 patients were included in the study and completed the T0 measurements. Mean age of these patients is 54.4 years (s.d. 12.9, 17-90). Number of females: 349 (79.0%), of males: 93 (21.0%). The mean baseline (T-0) HADS depression (0-3) scale scores is 2.54 (s.d. 0.51, n = 412). The mean one-year difference between T-12 HADS depression (0-3) scale scores and baseline T-0 scores is +0.06. The mean baseline (T-0) HADS anxiety (0-3) scale scores is 2.19 (s.d. 0.5, n = 283). The mean one-year difference between T-12 HADS anxiety (0-3) scale scores and baseline T-0 scores is +0.06. Controlled for baseline scores, gender, age, weight and length(BMI), patients in group 2 (receiving invasive treatment) show significantly higher one-year improvement in the QoL of their psychological state of mind than patients in group 1 (receiving SCT and having C1,2,3) (beta 0.158 p = 0.002). CONCLUSIONS: The significant improvement in psychological, QoL and clinical scores that we observe after successful invasive treatment compared to no significant improvement after SCT and the lack of psychological distress in patients with "simple" SVD indicates that SCT is mainly performed for cosmetic reasons. One could thus argue that reimbursement of SCT as a stand-alone medical treatment is debatable.

A supersonic laser ablation beam source with narrow velocity spreads.

A supersonic beam source for SrF and BaF molecules is constructed by combining the expansion of carrier gas (a mixture of 2% SF6 and 98% argon) from an Even-Lavie valve with laser ablation of a barium/strontium metal target at a repetition rate of 10 Hz. Molecular beams with a narrow translational velocity spread are produced at relative values of Δv/v = 0.053(11) and 0.054(9) for SrF and BaF, respectively. The relative velocity spread of the beams produced in our source is lower in comparison with the results from other metal fluoride beams produced in supersonic laser ablation sources. The rotational temperature of BaF is measured to be 3.5 K. The source produces 6 × 108 and 107 molecules per steradian per pulse in the X2Σ+ (ν = 0, N = 1) state of BaF and SrF molecules, respectively, a state amenable to Stark deceleration and laser cooling.

Randomised controlled trial comparing sapheno-femoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anaesthesia: one year results.

OBJECTIVES: Comparison of sapheno-femoral ligation and stripping (SFL/S) versus endovenous laser ablation (EVLA, 980-nm) in the treatment of great saphenous vein (GSV) insufficiency, using local tumescent anaesthesia. DESIGN: Randomised, single centre trial. MATERIALS AND METHODS: Patients with GSV incompetence and varicose veins were randomised to either SFL/S or EVLA. At days 1, 2, 3, 7, 10, and 14 post-treatment, patients completed questionnaires on pain and quality of life. Recurrent varicose veins were evaluated by Duplex ultrasound (DUS) performed at 1 and 6 weeks, and 6 and 12 months. RESULTS: 130 legs in 121 patients were treated by SFL/S (n=68) or EVLA (n=62). Significantly more post-treatment pain was noted after EVLA at days 7, 10 and 14 (p<0.01; p<0.01; p=0.01), more hindrance in mobility at days 7 (p<0.01) and 10 (p=0.01), and in self care (p=0.03) and daily activities (p=0.01) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9% recurrences (5/56) after EVLA and 10% (5/49) after SFL/S. CONCLUSION: Both SFL/S and EVLA, using local tumescent anaesthesia, were well tolerated, with no difference in short-term recurrence rate. In the second week after EVLA, patients experienced significantly more pain resulting in restricted mobility, self care and daily activity compared to SFL/S.

Bacterial aetiology and mortality in COPD patients with CAP: results from the German Competence Network, CAPNETZ.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality, and chronic obstructive pulmonary disease (COPD) is a frequent comorbidity. The bacterial aetiology of CAP-COPD and its possible associations with serum markers and mortality are incompletely understood. OBJECTIVES: 1) To assess the bacterial aetiology of CAP only and CAP-COPD, and 2) to study the association between bacterial aetiology, empirical antibiotic treatment, serum markers and mortality. METHODS: Of 1288 patients with CAP (57.0% males, age 59.0 years ± 18.5), 262 (20.3%) fulfilled the diagnostic criteria for COPD. Differences between subgroups were investigated using univariate analyses and corrected for multiple comparisons. RESULTS: Streptococcus pneumoniae was the most common pathogen (30.8% CAP only vs. 26.0% CAP-COPD, not significant). Haemophilus influenzae was significantly more frequent in CAP-COPD (5.6% CAP only vs. 26.0% CAP-COPD, P < 0.001). The number given adequate empirical antibiotic treatment was comparable (83.3% CAP only vs. 83.6% CAP-COPD, P > 0.05). The CAP-COPD group had worse CURB-65 and partial pressure of arterial oxygen levels than the CAP only group (P < 0.001). Partial pressure of arterial carbon dioxide levels were increased in CAP-COPD patients without pathogen detection (P < 0.001). Short- (P = 0.011) and long-term mortality (P = 0.006) were highest in CAP-COPD without pathogen detection. CONCLUSION: It is important to identify COPD patients with CAP. In particular, those without bacterial pathogen detection have more severe CAP and are at higher risk of dying. Better understanding of the aetiology could contribute to improved management and treatment of CAP in COPD patients.

Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti-Saccharomyces cerevisiae antibodies in serum of patients with IBD.

AIM: To investigate the correlation between ASCA and presence of mucosal S. cerevisiae DNA in a population of CD, ulcerative colitis (UC) patients and controls. METHODS: S. cerevisiae-specific primers and a fluorescent probe were designed for a 5' exonuclease real time PCR (TaqMan) assay, which is a homogenous system using a fluorescent-labelled probe for the detection of PCR product in real time. We analyzed the relation of the PCR results with the ASCA findings in a group of 76 inflammatory bowel disease (IBD) patients (31 CD, 45 UC) and 22 healthy controls (HC). RESULTS: ASCA (IgA or IgG) were positive in 19 (61%) patients with CD, 12 (27%) with UC and none of the HC. PCR amplification was inhibited and excluded from the final results in 10 (22%) UC patients, 7 (22%) CD patients, and 6 (30%) HC. In only 15 of the mucosal samples, S. cerevisiae DNA was detected by real time PCR, including 7 (29%) in CD, 7 (19%) in UC, 1 (6%) in HC. In 4 CD and in 4 UC patients, ASCA and mucosal S. cerevisiae were positive. Mucosal S. cerevisiae was present in combination with negative ASCA IgA and IgG in 3 UC, and 3 CD patients. CONCLUSION: We conclude that since the presence of S. cerevisiae in colonic mucosal biopsy specimens is very rare, ASCA is unlikely to be explained by continuous exposure to S. cerevisiae in the mucosa. Therefore, ASCA formation must occur earlier in life and levels remain relatively stable thereafter in immunological susceptible persons.

Class 1 integrons in ciprofloxacin-resistant Escherichia coli strains from two Dutch hospitals.

A significant increase in the isolation frequency of ciprofloxacin-resistant Escherichia coli was observed in the haematology departments of two university hospitals in The Netherlands. Amplified fragment length polymorphism analysis revealed that this increase was not caused by the emergence of unique ciprofloxacin-resistant clones. Determination of the presence of class 1 integrons indicated that 81% of the ciprofloxacin-resistant isolates contained an intI1 gene, compared with 11% of the ciprofloxacin-susceptible isolates (p<0.0001). The quinolone resistance gene qnrA was not present in any of the integrons characterised and could not be detected using dot-blot hybridisation of total DNA. In addition, conjugation experiments showed that ciprofloxacin resistance was not co-transferred with class 1 integrons. Ciprofloxacin-resistant isolates harboured mutations in the gyrA gene, which are known to encode ciprofloxacin resistance. In conclusion, an association was observed between ciprofloxacin resistance and the presence of class 1 integrons, which could not be explained by the currently known genetic determinants of quinolone resistance.

Pediatric microdose and microtracer studies using 14C in Europe.

Important information gaps remain on the efficacy and safety of drugs in children. Pediatric drug development encounters several ethical, practical, and scientific challenges. One barrier to the evaluation of medicines for children is a lack of innovative methodologies that have been adapted to the needs of children. This article presents our successful experience of pediatric microdose and microtracer studies using (14) C-labeled probes in Europe to illustrate the strengths and limitations of these approaches.

Sapheon: the solution?

Less invasive endovenous techniques have been shown to be as effective as open surgery in the treatment of varicose veins. Furthermore, they cause less postoperative bruising and pain and enable early return to normal activities and work. Tumescent anaesthesia is safe and obviates complications of general or spinal anaesthesia. Drawbacks are a steep learning curve and painful administration during treatment. Tumescentless techniques like Clarivein™ or VenaSeal™ Sapheon Closure System are recently under investigation. Short-term results of VenaSeal™ are comparable with thermal ablation. The procedure is safe without serious adverse events. Perioperative pain and patient discomfort with this tumescentless approach is minimal but postoperative recovery is temporarily hindered by thrombophlebitis in 14-15 % of patients. One-year results in a small feasibility study has demonstrated durable closure at this endpoint. No longer-term results are available. A randomized control trial between VenaSeal™ and Covidien ClosureFast™ is in a preparatory phase.

Detection of varicose vein recurrence by duplex ultrasound: intra- and interobserver reproducibility.

In a long-term follow-up study comparing saphenofemoral ligation and stripping with endovenous laser ablation, the groin is examined yearly by duplex ultrasound (DUS) to detect postoperative varicose vein recurrence. Clear criteria are needed for the uniformity of DUS observations. Physicians taking care of the follow-up were evaluated by an intra- and interobserver analysis. DUS films of 22 patients with no recurrence and 22 patients with recurrence of varicose veins were twice interpreted in two sessions. Observations were analysed by a kappa test. Interpretations of DUS by experienced observers show a kappa >7. Improved kappa results were measured over time in our physician in training. In conclusion, the reproducibility of DUS studies performed by the experienced observers of the study is excellent.

Biomechanical responses of the back of riding horses to water treadmill exercise.

There is a lack of evidence for the presumed beneficial effects of water treadmills on the movement of the horse's back. The aim of the study was to evaluate the effects of water treadmill exercise on axial rotation (AR), lateral bending (LB) and pelvic flexion (PF) in horses. The back kinematics of a group of riding horses were studied at the walk in a water treadmill at different depths of water (hoof, fetlock, carpus, elbow and shoulder joint levels) over a period of 10 days. Skin markers were placed at anatomical locations on the back. AR, LB and PF were measured on days 1 and 10 using two high-speed video cameras. There was a significant increase in AR compared to baseline at the level of the carpus and at higher water levels, whereas LB was significantly lower than baseline values at water levels that reached the elbow and shoulder joints. PF was significantly higher than baseline values at each water depth other than hoof water depth. At increasing water depths, there were significant increases in flexion and rotation of the back. At the highest water levels, there was reduced bending of the back. After 10 days, horses exhibited more bending of the back.

Characterization of imipenem resistance mechanisms in Pseudomonas aeruginosa isolates from Turkey.

The emergence of carbapenem resistance in Pseudomonas aeruginosa threatens the efficacy of this important anti-pseudomonal antibiotic class. Between 2003 and 2006, an increase in the number of carbapenem-resistant P. aeruginosa isolates at the Zonguldak Karaelmas University Hospital was observed (Zonguldak, Turkey). To assess the imipenem resistance mechanisms emerging in these P. aeruginosa isolates, they were characterized by amplified fragment length polymorphism typing, which revealed diversity among imipenem-resistant isolates as well as two clonally related outbreak groups. The molecular mechanism of carbapenem resistance was characterized in a representative isolate from each clonal group. Mutational disruption of oprD was the most frequently encountered resistance mechanism (23/27 isolates).