Don't forget asking the others! - The added value of significant other's reports on patient interpersonal style for the prediction of therapy process and outcome

Theory: Interpersonal factors play a major role in causing and maintaining depression. It is unclear, however, to what degree significant others of the patient need to be involved for characterizing the patient's interpersonal style. Therefore, our study sought to investigate how impact messages as perceived by the patients' significant others add to the prediction of psychotherapy process and outcome above and beyond routine assessments, and therapist factors. Method: 143 outpatients with major depressive disorder were treated by 24 therapists with CBT or Exposure-Based Cognitive Therapy. Interpersonal style was measured pre and post therapy with the informant‐based Impact Message Inventory (IMI), in addition to the self‐report Inventory of Interpersonal Problems (IIP‐32). Indicators for the patients' dominance and affiliation as well as interpersonal distress were calculated from these measures. Depressive and general symptomatology was assessed at pre, post, and at three months follow‐up, and by process measures after every session. Results: Whereas significant other's reports did not add significantly to the prediction of the early therapeutic alliance, central mechanisms of change, or post‐therapy outcome including therapist factors, the best predictor of outcome 3 months post therapy was an increase in dominance as perceived by significant others. Conclusions: The patients' significant others seem to provide important additional information about the patients' interpersonal style and therefore should be included in the diagnostic process. Moreover, practitioners should specifically target interpersonal change as a potential mechanism of change in psychotherapy for depression.

Accuracy of diagnostic testing in primary ciliary dyskinesia.

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

Simulation-based cost-utility analysis of population screening-based alendronate use in Switzerland

A simulation model adopting a health system perspective showed population-based screening with DXA, followed by alendronate treatment of persons with osteoporosis, or with anamnestic fracture and osteopenia, to be cost-effective in Swiss postmenopausal women from age 70, but not in men. INTRODUCTION: We assessed the cost-effectiveness of a population-based screen-and-treat strategy for osteoporosis (DXA followed by alendronate treatment if osteoporotic, or osteopenic in the presence of fracture), compared to no intervention, from the perspective of the Swiss health care system. METHODS: A published Markov model assessed by first-order Monte Carlo simulation was refined to reflect the diagnostic process and treatment effects. Women and men entered the model at age 50. Main screening ages were 65, 75, and 85 years. Age at bone densitometry was flexible for persons fracturing before the main screening age. Realistic assumptions were made with respect to persistence with intended 5 years of alendronate treatment. The main outcome was cost per quality-adjusted life year (QALY) gained. RESULTS: In women, costs per QALY were Swiss francs (CHF) 71,000, CHF 35,000, and CHF 28,000 for the main screening ages of 65, 75, and 85 years. The threshold of CHF 50,000 per QALY was reached between main screening ages 65 and 75 years. Population-based screening was not cost-effective in men. CONCLUSION: Population-based DXA screening, followed by alendronate treatment in the presence of osteoporosis, or of fracture and osteopenia, is a cost-effective option in Swiss postmenopausal women after age 70.

Evidence-based diagnosis

Making an accurate diagnosis is essential to ensure that a patient receives appropriate treatment and correct information regarding their prognosis. Characteristics of diagnostic tests are quantified in test accuracy studies, but many such studies have methodological flaws. The HSRC evidence-based diagnosis programme has focused on methods for systematic reviews of test accuracy studies, and the wider context in which tests are ordered and interpreted. We carried out a range of projects relating to literature searching, quality assessment, meta-analysis, presentation of results, and interactions between doctors and patients during the diagnostic process. We have shown that systematic reviews of test accuracy studies should search a range of databases and that current diagnostic filters do not have sufficient accuracy to be used in test accuracy reviews. Summary quality scores should not be used in test accuracy reviews; the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QUADAS) tool for assessing test accuracy studies is acceptable for quality assessment. We have shown that the hierarchical summary receiver operating characteristic (HSROC) and bivariate models for meta-analysis of test accuracy are statistically equivalent in many circumstances, and have developed an add-on module for the statistical software package Stata that enables these statistically rigorous models to be fitted by those without expert statistical knowledge. Three areas that would benefit from further research are literature searching, synthesis of results from individual patient data and presentation of results.

L’hépatite auto-immune

Autoimmune hepatitis is a systemic disease, difficult to diagnose due the high variability of the clinical presentation and some non specific histological features. The recent identification of additional autoantibodies used as serological markers, as well as simplified diagnostic criteria should help the primary care physician to advance with the diagnostic process. These progresses are crucial as undiagnosed and therefore untreated autoimmune hepatitis has a poor prognosis, whereas immunosuppressive therapy leads to remission in a majority of cases.

Intraoral hyperplastic Fordyce granule with destruction of bone: a case presentation.

Fordyce granules of the oral mucosa are often discovered during routine dental examinations. They are considered anatomic variations and are typically seen on the labial and buccal mucosa in adults. The present case report describes for the first time in the literature an atypical location of an enlarged Fordyce granule with local bone destruction. The diagnostic process, surgical treatment, and follow-up are presented and discussed.

The Neuropsychological Assessment of Cognitive Deficits Considering Measures of Performance Variability

Neuropsychologists often face interpretational difficulties when assessing cognitive deficits, particularly in cases of unclear cerebral etiology. How can we be sure whether a single test score below the population average is indicative of a pathological brain condition or normal? In the past few years, the topic of intra-individual performance variability has gained great interest. On the basis of a large normative sample, two measures of performance variability and their importance for neuropsychological interpretation will be presented in this paper: the number of low scores and the level of dispersion.We conclude that low scores are common in healthy individuals. On the other hand, the level of dispersion is relatively small. Here, base rate information about abnormally low scores and abnormally high dispersion across cognitive abilities are providedto improve the awareness of normal variability and to serve clinicians as additional interpretive measures in the diagnostic process.

Clinical acid-base pathophysiology: disorders of plasma anion gap.

The plasma anion gap is a frequently used parameter in the clinical diagnosis of a variety of conditions. The commonest application of the anion gap is to classify cases of metabolic acidosis into those that do and those that do not leave unmeasured anions in the plasma. While this algorithm is useful in streamlining the diagnostic process, it should not be used solely in this fashion. The anion gap measures the difference between the unmeasured anions and unmeasured cations and thus conveys much more information to the clinician than just quantifying anions of strong acids. In this chapter, the significance of the anion gap is emphasized and several examples are given to illustrate a more analytic approach to using the clinical anion gap; these include disorders of low anion gap, respiratory alkalosis and pyroglutamic acidosis.

High intratumoral levels of FoxP3+ lymphocytes are associated with better prognosis in primary resected esophageal adenocarcinomas.

Background: Tumor infiltrating T-lymphocytes (TILs) have been shown to play an important prognostic role in many carcinomas. The identification of prognostic relevant morphological or molecular factors is a major area of interest in the diagnostic process and for the treatment of highly aggressive esophageal adenocarcinoma. Studies about the impact of TILs in this tumor have not shown completely congruent results yet. We present a comprehensive study about the clinical and pathological impact of TIL in esophageal adenocarcinomas. Methods: A next generation tissue microarray (TMA) of 117 primary resected esophageal adenocarcinomas was analyzed for CD3+, CD8+ and FoxP3+ TIL using immunohistochemistry. The TMA contained three cores of the tumor center and the tumor periphery per each case. Slides were scanned with a high-resolution scanner (ScanScope CS; Aperio) and an image analysis software (Aperio Image Scope) was used to determine the TIL counts. The results were correlated with clinicopathological parameters. Results: CD3+, CD8+ and FoxP3+ TIL counts showed a significant correlation among each other (p<0.001 each, range: 0.27-0.77). TIL counts were categorized as high and low levels, according to the median. Tumors with high FoxP3+ intratumoral lymphocyte counts were more frequently of lower pT category (p<0.001) and without lymph node metastasis (p=0.04). High levels of FoxP3+ lymphocytes in the tumor center and the periphery were also associated with better prognosis (p<0.001 and p=0.041, respectively) in univariate analysis. A similar prognostic impact was seen for high levels of CD3+ and CD8+ TIL in the tumor center, but not in the periphery (p=0.047 and p=0.011, respectively). In multivariate analysis high central FoxP3+TIL levels were an independent prognostic factor (HR=0.4; p=0.023) which was similar to a combination score of CD3+/CD8+/FoxP3+ TIL (HR=0.54; p=0.027) or CD8+/Foxp3+ TIL (HR=0.052; p=0.020) and superior to pT- and pN category (p>0.05 each). Conclusion: This study demonstrates a significant beneficial prognostic impact of high TIL counts in the tumor center of esophageal adenocarcinomas, in particular with regards to the subpopulation of FoxP3+ and CD8+ T-regulatory cells. The determination of intratumoral lymphocytic counts and application of TIL scores can improve prognostic accuracy of pathologic reports of these tumors and may be helpful for better risk stratification of esophageal adenocarcinoma patients.

Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group

BACKGROUND AND OBJECTIVES: There are no widely accepted criteria for the definition of hematopoietic stem cell transplant -associated microangiopathy (TAM). An International Working Group was formed to develop a consensus formulation of criteria for diagnosing clinically significant TAM. DESIGN AND METHODS: The participants proposed a list of candidate criteria, selected those considered necessary, and ranked those considered optional to identify a core set of criteria. Three obligatory criteria and four optional criteria that ranked highest formed a core set. In an appropriateness panel process, the participants scored the diagnosis of 16 patient profiles as appropriate or not appropriate for TAM. Using the experts' ratings on the patient profiles as a gold standard, the sensitivity and specificity of 24 candidate definitions of the disorder developed from the core set of criteria were evaluated. A nominal group technique was used to facilitate consensus formation. The definition of TAM with the highest score formed the final PROPOSAL. RESULTS: The Working Group proposes that the diagnosis of TAM requires fulfilment of all of the following criteria: (i) >4% schistocytes in blood; (ii) de novo, prolonged or progressive thrombocytopenia (platelet count <50 x 109/L or 50% or greater reduction from previous counts); (iii) sudden and persistent increase in lactate dehydrogenase concentration; (iv) decrease in hemoglobin concentration or increased transfusion requirement; and (v) decrease in serum haptoglobin. The sensitivity and specificity of this definition exceed 80%. INTERPRETATION AND CONCLUSIONS: The Working Group recommends that the presented criteria of TAM be adopted in clinical use, especially in scientific trials.

A review identifies and classifies reasons for ordering diagnostic tests

OBJECTIVE: To consider the reasons and context for test ordering by doctors when faced with an undiagnosed complaint in primary or secondary care. STUDY DESIGN AND SETTING: We reviewed any study of any design that discussed factors that may affect a doctor's decision to order a test. Articles were located through searches of electronic databases, authors' files on diagnostic methodology, and reference lists of relevant studies. We extracted data on: study design, type of analysis, setting, topic area, and any factors reported to influence test ordering. RESULTS: We included 37 studies. We carried out a thematic analysis to synthesize data. Five key groupings arose from this process: diagnostic factors, therapeutic and prognostic factors, patient-related factors, doctor-related factors, and policy and organization-related factors. To illustrate how the various factors identified may influence test ordering we considered the symptom low back pain and the diagnosis multiple sclerosis as examples. CONCLUSIONS: A wide variety of factors influence a doctor's decision to order a test. These are integral to understanding diagnosis in clinical practice. Traditional diagnostic accuracy studies should be supplemented with research into the broader context in which doctors perform their work.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range).Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.

[Implementation of a routine gradual psycho-diagnostic programme in somatic rehabilitation centres - results of a pilot study]

STUDY AIM: A pilot study was conducted to implement and evaluate a routine gradual psycho-diagnostic programme to improve diagnostics and treatment of mental disorders in somatic rehabilitation centres. First of all, implementation strategies were acquired in trainings together with psychologists and physicians. The psycho-diagnostic programme consists of a screening instrument (PHQ-9) designed to permit time-effective detection of comorbid mental disorders. Besides evaluation of the training, the aim of the study was to analyze the extent to which it is possible to implement the routine gradual psycho-diagnostic programme in practice. Additionally, it was intended to identify beneficial and obstructive conditions for implementation. METHODOLOGY: The pilot study was conducted in two orthopaedic and one cardiological rehabilitation centre. The training was evaluated directly after its completion using a questionnaire. Three months after its implementation, the introduction of the psycho-diagnostic programme was evaluated using interviews with n=11 physicians and psychologists. RESULTS: The training was rated positively by the participants . Implementation of the entire gradual psycho-diagnostic programme was possible in one centre and to some degree in the other two. Beneficial for implementation were a frank organisational climate, sufficient time resources, and physicians' biopsychosocial understanding of disease. A dismissive attitude towards psycho-diagnostics, little communication between staff members, little perceived advantage for one's own work and fear to stigmatise patients by psychiatric diagnoses were obstructive. CONCLUSION: Essential for a successful implementation are sufficient time and personal resources, a motivation for change in staff and centre management, and a positive attitude regarding psycho-diagnostics in clinic staff. Furthermore, flexibility in implementation strategies and the opportunity to participate in the implementation process are important.

[The patent nasopalatine duct. A rare anomaly and diagnostic pitfall]

The patent nasopalatine duct is a rare anomaly in the anterior maxilla. During the early fetal period, a bilateral and epithelium-lined duct is formed within the primary palatal process as an oro-nasal communication. However, the duct obliterates and degenerates before birth. A persisting patent or through-and-through nasoplatine duct is therefore considered a developmental anomaly. A patent nasopalatine duct normally presents as one (or two) tiny openings lateral or posterior to the incisive papilla. In such a case, the ducts can be partially or completely probed with gutta-percha points with subsequent radiographic imaging. The patients report strange sensations such as squeaking noise, palatal drainage, nasal regurgitation, or airway communication between nasal and oral cavities; however, patients rarely complain about pain. About 40 cases have been documented in the literature. We describe two patients who have been referred to our department for evaluation of "sinus tracts" in the anterior palate. Since a patent nasopalatine duct can become a diagnostic pitfall, a thorough inspection of the mucosa around the incisive papilla is essential to avoid unnecessary endodontic or surgical interventions in the area of the central maxillary incisors.