[Pneumonia: what's new?]

Pneumonia continues to be one of the most important infectious diseases which often leads to hospital admissions and is occasionally fatal. The spectrum of causative organisms, their sensitivity pattern to antibiotics, diagnostic tools, and available antibiotics are continually changing. Currently, the most disquieting trend is the increasing development of resistance to commonly used antibiotics by the pneumococcus. Although this trend has thus far been observed primarily in other countries, it will most likely not spare Switzerland. Rational empiric therapy must include careful clinical assessment of the patient, knowledge of the spectrum of organisms locally causing pneumonias, including their resistance patterns, as well as a prognostic assessment of the patient. Using these factors, possible antibiotic schemes for empiric therapy of community-acquired pneumonia are reviewed.

Development of a screening tool predicting the transition from acute to chronic low back pain for patients in a GP setting: protocol of a multinational prospective cohort study

BACKGROUND: Low back pain (LBP) is by far the most prevalent and costly musculoskeletal problem in our society today. Following the recommendations of the Multinational Musculoskeletal Inception Cohort Study (MMICS) Statement, our study aims to define outcome assessment tools for patients with acute LBP and the time point at which chronic LBP becomes manifest and to identify patient characteristics which increase the risk of chronicity. METHODS: Patients with acute LBP will be recruited from clinics of general practitioners (GPs) in New Zealand (NZ) and Switzerland (CH). They will be assessed by postal survey at baseline and at 3, 6, 12 weeks and 6 months follow-up. Primary outcome will be disability as measured by the Oswestry Disability Index (ODI); key secondary endpoints will be general health as measured by the acute SF-12 and pain as measured on the Visual Analogue Scale (VAS). A subgroup analysis of different assessment instruments and baseline characteristics will be performed using multiple linear regression models. This study aims to examine: 1. Which biomedical, psychological, social, and occupational outcome assessment tools are identifiers for the transition from acute to chronic LBP and at which time point this transition becomes manifest. 2. Which psychosocial and occupational baseline characteristics like work status and period of work absenteeism influence the course from acute to chronic LBP. 3. Differences in outcome assessment tools and baseline characteristics of patients in NZ compared with CH. DISCUSSION: This study will develop a screening tool for patients with acute LBP to be used in GP clinics to access the risk of developing chronic LBP. In addition, biomedical, psychological, social, and occupational patient characteristics which influence the course from acute to chronic LBP will be identified. Furthermore, an appropriate time point for follow-ups will be given to detect this transition. The generalizability of our findings will be enhanced by the international perspective of this study. TRIAL REGISTRATION: [Clinical Trial Registration Number, ACTRN12608000520336].

Türkische Übersetzung und erste psychometrische Überprüfung der deutschsprachigen FAMOS (Fragebogen zur Analyse Motivationaler Schemata) und INK (Inkongruenzfragebogen)

Theoretischer Hintergrund: Standardisierte psychologische Messinstrumente in der Psychotherapie für Personen mit Migrationshintergrund fehlen weitgehend. Fragestellungen: Die türkischsprachigen Übersetzungen des Fragebogens zur Analyse Motivationaler Schemata (FAMOS) und des Inkongruenzfragebogens (INK) wurden in die türkische Sprache übersetzt und psychometrisch überprüft. Methode: Insgesamt füllten 73 türkischsprachige Patienten und 230 gesunde türkischsprachige Personen mit Migrationshintergrund in der Schweiz FAMOS und INK aus. Ergebnisse: Die Skalen von FAMOS und INK zeigen gute Reliabilität und Validität. Patienten weisen stärker ausgeprägte Vermeidungsziele und Inkongruenzwerte als gesunde Personen auf. Schlussfolgerungen: Die türkischen Versionen von FAMOS und INK eignen sich sowohl für die klinisch-psychologische Forschung als auch für die Praxis.

Does subjective burden of early breast cancer and its treatment affect immune measures during adjuvant therapy?

Psychosocial factors have been described as affecting cellular immune measures in healthy subjects. In patients with early breast cancer we explored bi-directional psycho-immune effects to determine whether subjective burden has an impact on immune measures, and vice versa. Patients (n = 239) operated for early breast cancer and randomized into International Breast Cancer Study Group (IBCSG) adjuvant clinical trials were assessed immediately before the beginning of adjuvant treatment (baseline) and 3 and 6 months thereafter, at the beginning of the corresponding treatment cycle. Cellular immune measures (leukocytes, lymphocytes, lymphocyte subset counts), markers of activation of the cellular immune system (beta2-microglobulin, soluble interleukin-2 receptor serum levels), and self-report subjective burden (global indicators of physical well-being, mood, coping effort) were assessed concurrently. The relationship between subjective burden and gradients of immune measures was investigated with regression analyses controlling for adjuvant treatment. There was a pattern of small negative associations between all variables assessing subjective burden before the beginning of adjuvant therapy with the gradients of the markers of activation of the cellular immune system and NK cell counts. In particular, better mood predicted a decline in the course of beta2-microglobulin and IL-2r at months 3 and 6. The gradient of beta2-microglobulin was associated with mood and coping effort at month 3. However, the effect sizes were very small. In conclusion, in this explorative investigation, there was an indication for subjective burden affecting and being affected by markers of activation of the cellular immune system during the first 3 and 6 months of adjuvant therapy. The question of clinical significance remains unanswered. These associations have to be investigated with refined assessment tools and schedules.

Interventions for the management of mandibular fractures

BACKGROUND Fractures of the mandible (lower jaw) are a common occurrence and usually related to interpersonal violence or road traffic accidents. Mandibular fractures may be treated using open (surgical) and closed (non-surgical) techniques. Fracture sites are immobilized with intermaxillary fixation (IMF) or other external or internal devices (i.e. plates and screws) to allow bone healing. Various techniques have been used, however uncertainty exists with respect to the specific indications for each approach. OBJECTIVES The objective of this review is to provide reliable evidence of the effects of any interventions either open (surgical) or closed (non-surgical) that can be used in the management of mandibular fractures, excluding the condyles, in adult patients. SEARCH METHODS We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 28 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE via OVID (1950 to 28 February 2013), EMBASE via OVID (1980 to 28 February 2013), metaRegister of Controlled Trials (to 7 April 2013), ClinicalTrials.gov (to 7 April 2013) and the WHO International Clinical Trials Registry Platform (to 7 April 2013). The reference lists of all trials identified were checked for further studies. There were no restrictions regarding language or date of publication. SELECTION CRITERIA Randomised controlled trials evaluating the management of mandibular fractures without condylar involvement. Any studies that compared different treatment approaches were included. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed trial quality and extracted data. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated to include both clinical and methodological factors. MAIN RESULTS Twelve studies, assessed as high (six) and unclear (six) risk of bias, comprising 689 participants (830 fractures), were included. Interventions examined different plate materials and morphology; use of one or two lag screws; microplate versus miniplate; early and delayed mobilization; eyelet wires versus Rapid IMF™ and the management of angle fractures with intraoral access alone or combined with a transbuccal approach. Patient-oriented outcomes were largely ignored and post-operative pain scores were inadequately reported. Unfortunately, only one or two trials with small sample sizes were conducted for each comparison and outcome. Our results and conclusions should therefore be interpreted with caution. We were able to pool the results for two comparisons assessing one outcome. Pooled data from two studies comparing two miniplates versus one miniplate revealed no significant difference in the risk of post-operative infection of surgical site (risk ratio (RR) 1.32, 95% CI 0.41 to 4.22, P = 0.64, I(2) = 0%). Similarly, no difference in post-operative infection between the use of two 3-dimensional (3D) and standard (2D) miniplates was determined (RR 1.26, 95% CI 0.19 to 8.13, P = 0.81, I(2) = 27%). The included studies involved a small number of participants with a low number of events. AUTHORS' CONCLUSIONS This review illustrates that there is currently inadequate evidence to support the effectiveness of a single approach in the management of mandibular fractures without condylar involvement. The lack of high quality evidence may be explained by clinical diversity, variability in assessment tools used and difficulty in grading outcomes with existing measurement tools. Until high level evidence is available, treatment decisions should continue to be based on the clinician's prior experience and the individual circumstances.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Systematic reviews and meta-analyses of randomized trials: principles and pitfalls

Systematic reviews and meta-analyses allow for a more transparent and objective appraisal of the evidence. They may decrease the number of false-negative results and prevent delays in the introduction of effective interventions into clinical practice. However, as for any other tool, their misuse can result in severely misleading results. In this article, we discuss the main steps that should be taken when conducting systematic reviews and meta-analyses, namely the preparation of a review protocol, identification of eligible trials, and data extraction, pooling of treatment effects across trials, investigation of potential reasons for differences in treatment effects across trials, and complete reporting of the review methods and findings. We also discuss common pitfalls that should be avoided, including the use of quality assessment tools to derive summary quality scores, pooling of data across trials as if they belonged to a single large trial, and inappropriate uses of meta-regression that could result in misleading estimates of treatment effects because of regression to the mean or the ecological fallacy. If conducted and reported properly, systematic reviews and meta-analyses will increase our understanding of the strengths and weaknesses of the available evidence, which may eventually facilitate clinical decision making.

Clinical decision rules and D-Dimer in venous thromboembolism: current controversies and future research priorities

Venous thromboembolism (VTE) is a potentially lethal clinical condition that is suspected in patients with common clinical complaints, in many and varied, clinical care settings. Once VTE is diagnosed, optimal therapeutic management (thrombolysis, IVC filters, type and duration of anticoagulants) and ideal therapeutic management settings (outpatient, critical care) are also controversial. Clinical prediction tools, including clinical decision rules and D-Dimer, have been developed, and some validated, to assist clinical decision making along the diagnostic and therapeutic management paths for VTE. Despite these developments, practice variation is high and there remain many controversies in the use of the clinical prediction tools. In this narrative review, we highlight challenges and controversies in VTE diagnostic and therapeutic management with a focus on clinical decision rules and D-Dimer.

Sharp neck injuries in suicidal intention

Sharp neck injuries in suicidal intention often present as serious emergency situations with the need for an immediate diagnosis and treatment. We report our study of the clinical evolution of this emergency condition. This study investigates the cases of sharp neck injuries in suicidal intention treated at our institution between 2000 and 2010. Patient records were collected in a retrospectively reviewed and analyzed database. The current literature was compared to our findings. We found 36 cases (10 female and 26 male). The neck injuries were superficial and profound in 16 and 20 patients, respectively. Twenty-two patients were seen by the Head and Neck surgeon. A surgical neck exploration was necessary in 19 cases. Tracheal, laryngeal, pharyngeal and vascular injuries were found in one, five, three and three cases, respectively. The hospital stay ranged from 1 to 47 days. All the patients underwent emergency psychiatric assessment and were subsequently referred for psychiatric treatment. One patient died in the emergency room from an additional arterial injury to the wrist. Sharp neck injuries in suicidal intention treated with an interdisciplinary medical, surgical and psychiatric emergency assessment and treatment have low mortality and morbidity.

Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.

AIMS A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis.

Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.

An examination chair to measure internal rotation of the hip in routine settings: a validation study

OBJECTIVE: To determine the performance of a newly developed examination chair as compared with the clinical standard of assessing internal rotation (IR) of the flexed hip with a goniometer. METHODS: The examination chair allowed measurement of IR in a sitting position simultaneously in both hips, with hips and knees flexed 90 degrees, lower legs hanging unsupported and a standardized load of 5 kg applied to both ankles using a bilateral pulley system. Clinical assessment of IR was performed in supine position with hips and knees flexed 90 degrees using a goniometer. Within the framework of a population-based inception cohort study, we calculated inter-observer agreement in two samples of 84 and 64 consecutive, unselected young asymptomatic males using intra-class correlation coefficients (ICC) and determined the correlation between IR assessed with examination chair and clinical assessment. RESULTS: Inter-observer agreement was excellent for the examination chair (ICC right hip, 0.92, 95% confidence interval [CI] 0.89-0.95; ICC left hip, 0.90, 95% CI 0.86-0.94), and considerably higher than that seen with clinical assessment (ICC right hip, 0.65, 95% CI 0.49-0.77; ICC left hip, 0.69, 95% CI 0.54-0.80, P for difference in ICC between examination chair and clinical assessment clinical assessment were similar (difference 1.1 degrees, 95% CI - 0.7-2.8 degrees, P=0.23), and the correlation was strong (Pearson's coefficient, 0.75, 95% CI 0.62-0.84). CONCLUSIONS: The use of the examination chair resulted in a precise assessment of hip IR in our population-based inception cohort study of young asymptomatic males. It was strongly correlated with standard clinical assessment of IR but was considerably more reliable.

Aesthetic outcome and oncological safety of nipple-areola complex replantation after mastectomy and immediate breast reconstruction

Immediate breast reconstruction (IBR) has become an established procedure for women necessitating mastectomy. Traditionally, the nipple-areola complex (NAC) is resected during this procedure. The NAC, in turn, is a principal factor determining aesthetic outcome after breast reconstruction, and due to its particular texture and shape, a natural-looking NAC can barely be reconstructed with other tissues. The aim of this study was to assess the oncological safety as well as morbidity and aesthetic outcome after replantation of the NAC some days after IBR. Retrospective analysis of 85 patients receiving 88 mastectomies and IBR between 1998 and 2007 was conducted. NAC (n=29) or the nipple alone (n=23) were replanted 7 days (median, range 2-10 days) after IBR in 49 patients, provided the subareolar tissue was histologically negative for tumour infiltration. Local recurrence rate was assessed after 49 months (median, range 6-120 months). Aesthetic outcome was evaluated by clinical assessment during routine follow-up at least 12 months after the last intervention. Malignant involvement of the subareolar tissue was found in eight cases (9.1%). Patients qualifying for NAC replantation were in stage 0 in 29%, stage I in 15%, stage IIa in 31%, stage IIb in 17% and stage III in 8%. Total or partial necrosis occurred in 69% and 26% if the entire NAC or only the nipple were replanted, respectively (P<0.01). Depigmentation was seen in 52% and corrective surgery was done in 11 out of 52 NAC or nipple replantations. Local recurrence and isolated regional lymph node metastasis were observed in one single case each. Another 5.8% of the patients showed distant metastases. We conclude that the replantation of the NAC in IBR is oncologically safe, provided the subareolar tissue is free of tumour. However, the long-term aesthetic outcome of NAC replantation is not satisfying, which advocates replanting the nipple alone.

Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain

Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR-T) and the electrical pain threshold (EP-T) are reliable measures in pain-free populations. However, it is necessary to investigate the reliability of these measures in patients with chronic pain in order to translate these techniques from laboratory to clinic. The aims of this study were to determine the test-retest reliability of the NWR-T and EP-T after single and repeated (temporal summation) electrical stimulation in a group of patients with chronic low back pain, and to investigate the association between the NWR-T and the EP-T. To this end, 25 patients with chronic pain participated in three identical sessions, separated by 1 week in average, in which the NWR-T and the EP-T to single and repeated stimulation were measured. Test-retest reliability was assessed using intra-class correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis. The association between the thresholds was assessed using the coefficient of determination (r (2)). The results showed good-to-excellent reliability for both NWR-T and EP-T in all cases, with average ICC values ranging 0.76-0.90 and average CV values ranging 12.0-17.7%. The association between thresholds was better after repeated stimulation than after single stimulation, with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR-T and the EP-T are reliable assessment tools for assessing the sensitivity of spinal nociceptive pathways in patients with chronic pain.

Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse

Alcohol-induced liver disease (ALD) is a leading cause of nonaccident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively nonspecific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study, the metabolic changes associated with ALD were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-beta-d-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of a metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model.