The validity of the interviewer severity ratings in groups of ASI interviewers with varying training

Aims. This study evaluated the hypothesis that the subjective interviewer severity rating (ISR) summary indices of the intake Addiction Severity Index (ASI) of less trained interviewers are less valid than those of more highly trained interviewers.
Design. Baseline ASIs from three completed studies whose interviewers varied in degree of initial ASI training and subsequent quality assurance monitoring were examined. Associations between baseline ISRs and three other sets of ASI summary indices not based on interviewer ratings—composite scores, clinical indices and evaluation indices—were compared for three groups of interviewers with varying amounts of training. The assumption underlying these analyses was that more reliable ISRs, found in more trained interviewers, would be more highly associated with the other more objective indices.
Setting. Methadone maintenance patients in the Philadelphia and New York City areas.
Participants. Thirty-five interviewers with the most intense training who administered 295 interviews; 10 interviewers with an intermediate level of training who administered 763 interviews; and eight identified (and other unidentified) least trained interviewers who administered a total of 276 interviews.
Measurements and methods. Four sets of summary indices from the above ASIs. Both bivariate and multivariate analyses were performed.
Findings. The study found that the validity of the validity of ISRs was greater in more trained interviewers.
Conclusions. Greater training and subsequent monitoring of ASI interviewers generally appears to be associated with increased ISR validity.     

Long-term outcomes of grade I/II skull base chondrosarcoma: an insight into the role of surgery and upfront radiotherapy

Journal of Neuro-Oncology - To clarify the need for post-operative radiation treatment in skull base chondrosarcomas (SBCs). A retrospective analysis of patients with grade I or II SBC. Patients...     

Factors affecting short-term rehabilitation outcomes of disabled elderly patients with proximal hip fracture

OBJECTIVE: To identify factors associated with postacute rehabilitation outcome of disabled elderly patients with proximal hip fracture. SETTING: Geriatric rehabilitation center. PARTICIPANTS: One hundred thirty-three older patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM instrument, motor FIM score, absolute functional gain on the FIM and motor FIM scores, relative functional gain on the FIM and motor FIM scores, rate of improvement on the FIM and motor FIM scores, proportion of patients discharged to home, and length of stay (LOS). RESULTS: Mean FIM score improved by 14 points (22%) with a functional gain rate of .56 point per day. No significant differences (P>.05) were found between weight-bearing and non-weight-bearing patients regarding the above outcome measures. Functionally independent and cognitively intact patients achieved significantly better score changes and rates of improvement and showed a higher ability to extract their rehabilitation potential than dependent and cognitively impaired patients. Their LOSs were significantly shorter. Patients with latency time (time delay from fracture to operation) of more than 5 days and patients with a history of stroke had significantly longer LOSs. Mini-Mental State Examination score, albumin levels on admission, and prefracture functional status were the most important parameters associated with FIM discharge scores (r=.756) and relative functional gain on the FIM (r=.583). Depression was the most important factor associated with LOS in patients with weight-bearing instructions on admission. The presence of a caregiver was the significant predictive value variable for returning home. CONCLUSIONS: Cognitive function, nutritional status, preinjury functional level, and depression were the most important prognostic factors associated with rehabilitation success of older patients with proximal hip fracture. Of these, depression and nutritional status are correctable, and early intervention may improve rehabilitation outcome.     

Hold your pauses: external globus pallidus neurons respond to behavioural events by decreasing pause activity

Awareness of its rich structural pathways has earned the external segment of the globus pallidus (GPe) recognition as a central figure within the basal ganglia circuitry. Interestingly, GPe neurons are uniquely identified by the presence of prominent pauses interspersed among a high‐frequency discharge rate of 50–80 spikes/s. These pauses have an average pause duration of 620 ms with a frequency of 13/min, yielding an average pause activity (probability of a GPe neuron being in a pause) of (620 × 13)/(60 × 1000) = 0.13. Spontaneous pause activity has been found to be inversely related to arousal state. The relationship of pause activity with behavioural events remains to be elucidated. In the present study, we analysed the electrophysiological activity of 200 well‐isolated GPe pauser cells recorded from four non‐human primates (Macaque fascicularis) while they were engaged in similar classical conditioning tasks. The isolation quality of the recorded activity and the pauses were determined with objective automatic methods. The results showed that the pause probability decreased by 9.09 and 10.0%, and the discharge rate increased by 2.96 and 1.95%, around cue and outcome presentation, respectively. Analysis of the linear relationship between the changes in pause activity and discharge rate showed r² = 0.46 and r² = 0.66 upon cue onset and outcome presentation, respectively. Thus, pause activity is a pertinent element in short‐term encoding of relevant behavioural events, and has a significant, but not exclusive, role in the modulation of GPe discharge rate around these events.     

Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program: Acute otitis media microbiology in Costa Rican children

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009).This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction).Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction.Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.     

CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency

Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ⁹-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3–4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [³H]CP55,940 displacement and its effect on [³⁵S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [³⁵S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes.The CB2 cannabinoid receptor functions as an endogenous protective entity (1). Thus, it is an important regulator of bone mass and inflammation. It represents a therapeutic target that avoids the undesired psychotropic effects caused by CB1 receptor activation. CB2 is expressed in osteoblasts, the bone-forming cells, and in osteoclasts, the bone-resorbing cells (2). Monocytes/macrophages, B cells, certain T-cell subtypes, and mast cells also express CB2 (3–7). In the skeleton, activation of CB2 favors bone formation over resorption, thus protecting the skeleton against age-related bone loss. Inflammatory responses are restrained by CB2 agonists in several instances such as hepatic ischemia-reperfusion injury (8), uveitis (9), and contact dermatitis (10). With their terpene and resorcinol-derived moieties, some synthetic CB2 agonists, such as HU-308 (10), JWH-133 (11), and HU-910 (12), structurally resemble the phytocannabinoids Δ⁹-tetrahydrocannabinol and cannabidiol. Other, non-phytocannabinoid-type agonists have been also reported (13). HU-308 was one of the first fully characterized, highly selective, and highly efficacious cannabinoid type-2 agonist (10). It has three chiral centers, namely, at carbon atoms in positions 3, 4, and 6 (Scheme 1). HU-308 has a 3R, 4S, 6S configuration; that of its enantiomer (HU-433) is 3S, 4R, 6R.Open in a separate windowScheme 1.Structures of HU-433 and -308.In most experiments, the optimal HU-308 mitogenic activity in osteoblasts, as well as its antiosteoclastogenic effect, was obtained by using concentrations in the nanomolar range (2, 14). Surprisingly, testing a new HU-308 batch, we noticed a 3- to 4-magnitude decrease in the dose that triggers optimal proliferative response in osteoblasts, reasoning that this preparation contained a significant amount of the HU-308 enantiomer, presumably responsible for the enhanced activity. We report here that this enantiomer, designated HU-433, was synthesized and compared with HU-308, and indeed showed markedly enhanced bone-anabolic and antiinflammatory activities, but inferior CB2 receptor binding affinity. Although both enantiomers seem to target the same binding pocket, two different orientations relative to the binding site are possible, leading to different behavior of the two enantiomers due to their different occupancy of these orientations. This observation appears to reflect a situation in which relatively small differences in possible binding conformations of the ligands within the receptor—referred to as poses—lead to significant diminution of receptor-binding properties and a marked increase in biological activity.     

Severe malnutrition due to systemic lupus erythematosus associated protein losing enteropathy

Systemic lupus erythematosus most often targets organs such as joints, serosa, skin, bone marrow, and the kidneys. Gastrointestinal complications are uncommon, and among these, protein losing enteropathy is particularly rare. We present a young woman who suffered from chronic abdominal pain and diarrhea, developed severe malnutrition, and was eventually diagnosed with systemic lupus erythematosus and associated protein losing enteropathy.     

Cardiac surgery in patients on chronic hemodialysis: short and long-term survival

OBJECTIVE: Open-heart surgery carries a high risk for hemodialysis patients. This study focuses on the short and long-term outcomes of hemodialysis patients undergoing heart surgery. DESIGN: The study was carried out as a retrospective analysis in the Department of Cardiothoracic Surgery in a large university-affiliated hospital. PATIENTS: 115 hemodialysis patients underwent cardiac surgery in our department between 1 July 1996 and 31 July 2006. 67.5 % (77 patients) underwent isolated coronary artery bypass grafting (CABG), 13.2 % (15 patients) underwent isolated aortic valve replacement (AVR) and 20.2 % (23 patients) underwent mitral valve surgery or combined valve and coronary artery bypass grafting or multiple valve surgery. METHODS: The relationship between several variables (age, sex, hypertension, diabetes, and previous myocardial infarction, type of disease, preoperative ejection fraction, and congestive heart failure) and operative (30 days) mortality and late survival was analyzed. RESULTS: The overall 30-day mortality was 18.3 % (21 patients). It was 13 % (10/77 patients) for the isolated CABG group and 13.3 % (2/15) for the isolated AVR group. Patients undergoing combined valve and coronary surgery or multiple valve surgery had a higher perioperative mortality of 39.1 % (9/23) compared to the isolated CABG and isolated AVR patients. Perioperative death was also higher in patients with moderate and severe LV dysfunction, and in patients with diabetes. The duration of dialysis periods was not related to perioperative death. Mean follow-up was 26.4 +/- 29.7 months (0.1 to 104 months). Actuarial survival at 1 year and 5 years was 76 % and 55 % for isolated CABG, 59 % and 21 % for isolated AVR, and 44 % and 33 % for all other cases, respectively (log rank P = 0.001). CONCLUSION: Patients on dialysis have a high risk of perioperative mortality and poor long-term survival rates. Mortality is higher and survival is worse after combined CABG and valve-related procedures or multiple valve surgery than after isolated CABG and AVR.