What is the evidence for the use of probiotics in functional disorders?

A rationale for the use of probiotics for a number of functional gastrointestinal symptoms and syndromes can be developed, and an experimental basis for their use continues to emerge, but data from well-conducted clinical trials of probiotics in this area remain scarce. Irritable bowel syndrome (IBS) has attracted the most attention; recent revelations regarding the potential pathogenic roles of the enteric flora and immune activation have led to reawakened interest in bacteriotherapy for this common and challenging disorder. Some recent randomized, controlled studies attest to the efficacy of some probiotics in alleviating individual IBS symptoms, and selected strains have a more global impact. Evidence for long-term efficacy is also beginning to emerge, though more studies are needed in this regard. In other functional syndromes, data are far from adequate to make recommendations, but there is evidence for efficacy of probiotics in treating individual symptoms such as diarrhea, constipation, and bloating. The interpretation of much of the literature in this area is complicated by lack of quality control, use of many different species and strains, and, above all, significant deficiencies in trial methodology.     

Does the granular matter?

Granular materials, such as sand, gravel, powders, and pharmaceutical pills, are large aggregates of macroscopic, individually solid particles, or "grains." Far from being simple materials with simple properties, they display an astounding range of complex behavior that defies their categorization as solid, liquid, or gas. Just consider how sand can stream through the orifice of an hourglass yet support one's weight on the beach; how it can form patterns strikingly similar to a liquid when vibrated, yet respond to stirring by "unmixing" of large and small grains. Despite much effort, there still is no comprehensive understanding of other forms of matter, like ordinary fluids or solids. In what way, therefore, is granular matter special, and what makes it so difficult to understand? An emerging interdisciplinary approach to answering these questions focuses directly on the material's discontinuous granular nature.     

Does retention matter? Treatment duration and improvement in drug use

Aim This study examines whether there is a minimum threshold, continuous or non‐linear relationship between the duration of addiction treatment and improvements in drug use. Design Longitudinal cohort study of 62 drug treatment units and 4005 clients in the US National Treatment Improvement Evaluation Study, fielded from 1993 to 1995. Subjects Baseline and 1‐year follow‐up interviews with clients in methadone maintenance, out‐patient non‐methadone, short‐term residential and long‐term residential treatment programs. Measures Improvement in drug use is the difference between the client‐reported peak frequency of drug use (in days per month) in the year prior to the baseline interview minus the peak frequency in the year after discharge. Primary drug, and overall use of the major illicit drugs (heroin, cocaine powder, crack cocaine, and marijuana) are considered separately. Results Controlling for multiple factors, treatment duration had a positive linear relationship with primary drug use improvement among methadone clients and an inverted‐U‐shaped relationship with overall and primary drug use improvements among out‐patient and long‐term residential clients. Improvement with longer duration is greatest for long‐term residential clients. Conclusions Contrary to previous arguments for a sharp retention threshold for onset of treatment effects, we find smooth curves relating treatment duration to drug use improvements in methadone maintenance, out‐patient non‐methadone and long‐term residential modalities. These relationships are effectively linear for durations typically observed in single treatment episodes, but unusually long retention in out‐patient non‐methadone and long‐term residential units appear steadily less predictive of improvement.     

Does practice mirror the evidence base in the treatment of rheumatoid arthritis?

A large base of evidence exists regarding treatments for rheumatoid arthritis (RA) and how they may be used to preserve long-term function and improve patient outcomes. However, little is known about whether real-life rheumatology practice reflects the evidence base. This survey aimed to capture differing perceptions among rheumatologists in the identification and treatment of patients and to understand how their management of and treatment decisions for patients with RA may be influenced by the current published literature. Rheumatologists from five European countries and Canada participated in a survey between April and May 2006 to establish how rheumatologists identify and treat particular patient types in everyday practice. In total, 458 rheumatologists responded to the online and telephone survey. Rapidly progressing disease was overwhelmingly recognized (97%) as a distinct subtype among patients with RA, and the majority (88%) of respondents make treatment decisions based on this distinction. Most rheumatologists use measures including C-reactive protein, erythrocyte sedimentation rate, tender/swollen joint counts, and X-ray progression to diagnose and monitor this particular group of patients; a minority (30%) used magnetic resonance imaging to identify and monitor patients with rapidly progressing disease. Although treatment goals for these patients were similar among rheumatologists, the treatment approach varied considerably across countries. Overall, rheumatologists agree on the management goals for patients with rapidly progressing RA; however, their treatment patterns have some dissimilarities.     

Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of adrenocortical tumors?

Adrenal incidentalomas are detected more frequently with high-resolution imaging modalities. It is difficult to distinguish between benign and malignant lesions despite the so-called histologic Weiss criteria, imaging features, and molecular studies. We here present a 52 yr-old man who was found to have an adrenal incidentaloma during an annual check-up at his urologist. An 8 cm large adrenal lesion was detected on ultrasound, computed tomography, and magnetic resonance imaging with imaging features suggestive of malignancy. The lesion was hormonally inactive. A left-sided adrenalectomy was performed and histologic grading revealed a Weiss score of 2, suggesting a benign tumor. However, on further follow-up, the patient developed a local recurrence and pulmonary metastases diagnosed 6 yr after initial presentation. After repeat surgery in the left adrenal bed adrenocortical tumor tissue had a Weiss score of 8, clearly suggesting histologic malignancy. The patient received adjuvant mitotane therapy. Under this therapy, he developed a right-sided adrenal mass (contralateral from the primary tumor) of 2 cm size which disappeared during the following 9 months, whereas the pulmonary metastases remained unchanged, suggesting tumor clones with a variable response to treatment or spontaneous apoptosis. This case suggests that adrenal incidentalomas larger than 6 cm with imaging features such as intratumoral necrosis suggestive of malignancy, should be managed as potential cancers independent of the so-called Weiss criteria. In such patients, close follow-up examinations including high-resolution imaging (preferably 3 monthly) are needed and should be carried out by a physician familiar/specialized in endocrine oncology.     

Morphological heterogeneity in ductal adenocarcinoma of the pancreas – Does it matter?

Morphological heterogeneity is a common finding in pancreatic ductal adenocarcinoma. Inter- and intra-tumour heterogeneity relates not only to the microscopic appearances of the tumour cell population, but pertains also to other essential aspects of the cancer, including the grade of differentiation, growth pattern and desmoplastic stroma. While the existence of considerable morphological variation is well known among pathologists, it is usually not fully appreciated by the wider community. Morphological heterogeneity in pancreatic cancer is only partially represented in the WHO classification, and current pathology guidelines do not recommend reporting on morphological variation other than the conventional variants of ductal adenocarcinoma. Although tumour heterogeneity is increasingly recognized as a major determinant of therapeutic response, morphological heterogeneity has been left unconsidered as a possible proxy for underlying aberrations – genomic or otherwise – that determine the effect of treatment. Various aspects of morphological heterogeneity in pancreatic ductal adenocarcinoma are illustrated in this article and discussed along with the possible implications for patient management and research.     

Does aging affect the use of shifting standards?

Prior research on the use of stereotypes in social judgments has shown that whether young adults make stereotype-consistent or -inconsistent judgments depends in part upon the response scale that is used. This shifting standards effect in stereotype use was examined in the present study to determine whether older adults, who tend to rely on stereotypes more than younger adults, would also show a similar effect. Young and older adults evaluated the height of male and female targets using either an objective or subjective scale. No age differences were found, with both age groups producing stereotype-consistent judgments (i.e., men are taller than women) on an objective scale, but stereotype-inconsistent judgments (i.e., men and women are equally tall) on a subjective scale. These results suggest that the shifting standards effect holds across the adult life span.