The Hampshire Depression Project: development and piloting of clinical practice guidelines and education about depression in primary health care

This paper describes the development and piloting of a comprehensive educational programme about recognition and management of depressive illness in primary care. Full evaluation of the effectiveness of the programme is currently underway in a randomized controlled trial, the Hampshire Depression Project (HDP), involving 56 general practices. The programme consists of clinical practice guidelines, practice-based seminars and follow-up sessions. Each part of the programme has been designed to be flexible, clinically oriented and relevant to all members of the multidisciplinary primary care team. The pilot study established the need for a systematic approach to the access of practices and practice teams, and the organization and process of the seminars. Application of this approach was associated with excellent attendance in the main programme.     

Energy cost of running during a specific transition in duathlon]

The aim of the present study was to investigate the variability of the energy cost of running (Cr) during a simulated duathlon performed in outdoor conditions by elite duathletes. This duathlon consisted of 5 km of running, 30 km of cycling, and 5 km of running. The main result was the lack of significant difference in Cr between the two running bouts (210 +/- 10 mL d'O2.km-1.kg-1 vs. 217 +/- 10 mL d'O2.km-1.kg-1). This result is different from those observed during a triathlon, where an increase of energy cost of running bout has been reported. Furthermore, during a short-distance duathlon performed by well-trained subjects, none of the physiological (ventilation alteration, metabolic changes, or dehydration) or biomechanical factors that are classically evoked in triathlon research to explain Cr variability seem to be affected by the run-cycle-run transition. These results seem to minimize the negative effect of the cycle-to-run transition during a short-duration event in well-trained subjects.     

Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes

Peroxisome proliferator-activated receptor (PPAR)-gamma is one of the key actors of adipocyte differentiation. This study demonstrates 1) that PPAR-gamma mRNA expression is not altered in subcutaneous adipose tissue (n = 44) or in skeletal muscle (n = 19) of subjects spanning a wide range of BMIs (20-53 kg/m2) and 2) that insulin acutely increases PPAR-gamma mRNA expression in human adipocytes both in vivo and in vitro. The effect of insulin was investigated in abdominal subcutaneous biopsies obtained before and at the end of a 3-h euglycemic-hyperinsulinemic clamp. Insulin significantly increased PPAR-gamma mRNA levels in lean subjects (88 +/- 17%, n = 6), in type 2 diabetic patients (100 +/- 19%, n = 6), and in nondiabetic obese patients (91 +/- 20%, n = 6). Both PPAR-gamma1 and PPAR-gamma2 mRNA variants were increased (P < 0.05) after insulin infusion. In isolated human adipocytes, insulin induced the two PPAR-gamma mRNAs in a dose-dependent manner, with half-maximal stimulation at a concentration of approximately 1-5 nmol/l. However, PPAR-gamma2 mRNA was rapidly (2 h) and transiently increased, whereas a slow and more progressive induction of PPAR-gamma1 was observed during the 6 h of incubation. In explants of human adipose tissue, PPAR-gamma protein levels were significantly increased (42 +/- 3%, P < 0.05) after 12 h of incubation with insulin. These data demonstrate that PPAR-gamma belongs to the list of the insulin-regulated genes and that obesity and type 2 diabetes are not associated with alteration in the expression of this nuclear receptor in adipose tissue.     

Variability in vitamin D assays impairs clinical assessment of vitamin D status

Background: Measuring serum 25(OH)D concentration is common in clinical practice despite the questionable reliability of assays. Aims: The aim of the present study was to examine agreement in 25(OH)D concentrations measured by different assays and laboratories, and consider related clinical implications. Methods: Serum samples from 813 participants in the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study) were assayed for 25(OH)D concentration. Duplicate samples from subsets of subjects were sent to different laboratories, two using DiaSorin Liaison (Laboratory A and B) and one using Liquid Chromatography‐Tandem Mass Spectrometry (LC‐MS/MS – selected here as the nominal gold standard). Pairwise within‐assay (both within‐laboratory and between‐laboratories) and between‐assay agreement was examined using Deming regression and Bland‐Altman plots. Common 25(OH)D cut‐points for classification of vitamin D deficiency were used to compare the different assays. Results: 25(OH)D concentrations measured using Liaison were substantially lower at Laboratory A than at Laboratory B (mean bias ?11.60 nmol/L, 95% limits of agreement ?46.39, 23.18). Both Liaison assays returned much lower 25(OH)D concentrations than LC‐MS/MS (mean bias up to ?26.05 nmol/L, 95% limits of agreement of ?13.21, 65.31). For Laboratory A participants, 46% (355/765) were classified as vitamin D deficient (25(OH)D <50 nmol/L) using Liaison compared with 17% (128/765) using LC‐MS/MS. For Laboratory B participants, the respective figures were 36% (76/209) and 20% (41/209). Hence, between 1‐in‐5 and 1‐in‐3 participants were misclassified as ‘deficient’. Conclusion: Bias and variability in 25(OH)D measurements sufficient to affect significantly clinical decision‐making were found both between‐laboratories and between‐assays. The adoption of common standards to allow assay calibration is required urgently.     

Residual ridge resorption, lower denture stability and subjective complaints among edentulous individuals

Residual ridge resorption in the mandible after tooth loss may lead to worsening of complete denture stability and to various subjective complaints. The aim was to evaluate the association between radiologically assessed residual ridge resorption in the mandible, clinically assessed stability of lower complete denture and subjective complaints among elderly denture wearers. The study population consisted of 326 (115 men and 211 women) edentulous subjects aged 60-78years, all of whom were wearing complete dentures in the mandible. Data on subjective complaints were obtained from questionnaires and interviews. Denture stability was assessed clinically. Residual ridge resorption was analysed from panoramic radiographs. The results showed that women were significantly more often satisfied with their lower dentures and reported fewer problems with eating than men. They also had significantly more often residual ridge resorption than men. Among women, residual ridge resorption was significantly associated with poor chewing ability, low satisfaction with dentures and poor denture stability. Among men, residual ridge resorption did not associate with subjective complaints or denture stability. Poor satisfaction with dentures associated significantly with poor denture stability in both genders. In conclusion, these results highlight the importance of denture maintenance treatment. As the extent of residual ridge resorption in the mandible was the most important factor that increased dissatisfaction with lower complete dentures, it is also important to inhibit the progression of resorption by preventing tooth loss or by using implant-retained dentures.     

Differential response to H. pylori eradication therapy of co-existing diffuse large B-cell lymphoma and MALT lymphoma of stomach-significance of tumour cell clonality and BCL10 expression

We recently reported that low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori-independent status is closely associated with nuclear translocation of BCL10. However, co-existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co-existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction-based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co-existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori-independent component and cytoplasmic expression of BCL10 in the H. pylori-dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co-existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co-existence of these components.     

External validation of the Heidenreich criteria for patient selection for unilateral or bilateral retroperitoneal lymph node dissection for post-chemotherapy residual masses of testicular cancer

Objective

To validate the Heidenreich criteria for patient selection for unilateral retroperitoneal lymph node dissection (RPLND) for residual masses after chemotherapy for nonseminomatous germ cell tumor (NSGCT).

Subjects/patients and methods

For validation, the data of 59 patients who underwent RPLND for residual masses of NSGCT were used. Of these patients, 23 (39 %) qualified for a modified RPLND, the others had an indication for a bilateral dissection. Results from histopathology after RPLND and follow-up data for relapse inside or outside the zone of the resection template were considered for validation.

Results

In the study cohort, median age at time of RPLND was 31 years. The 2-year disease-free survival was 90 and 96 % for the bilateral and the unilateral RPLND patients, respectively. Overall, 8 (14 %) relapses were observed after a median follow-up of 54 month. Of these, 6 were outside of the resection field and 2 were in-field. Of the 23 patients with indication for a modified RPLND, 1 patient relapsed in the contralateral testis and 1 inside the modified RPLND template. No relapse was observed outside the modified RPLND field and inside the untouched contralateral RPLND field. The Heidenreich criteria did therefore not misclassify a single patient.

Conclusion

The Heidenreich criteria for the selection of candidates for unilateral RPLND for residual masses after chemotherapy allow a highly reliable selection of patients. The application of the Heidenreich criteria can help to reduce comorbidity and invasiveness of RPLND.