Clinical and cost-effectiveness of computerised cognitive behavioural therapy for depression in primary care: Design of a randomised trial

Background  

Major depression is a common mental health problem in the general population, associated with a substantial impact on quality of life and societal costs. However, many depressed patients in primary care do not receive the care they need. Reason for this is that pharmacotherapy is only effective in severely depressed patients and psychological treatments in primary care are scarce and costly. A more feasible treatment in primary care might be computerised cognitive behavioural therapy. This can be a self-help computer program based on the principles of cognitive behavioural therapy. Although previous studies suggest that computerised cognitive behavioural therapy is effective, more research is necessary. Therefore, the objective of the current study is to evaluate the (cost-) effectiveness of online computerised cognitive behavioural therapy for depression in primary care.     

Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity

PURPOSE: Gastrointestinal stromal tumors (GIST) are commonly regarded as solitary tumors. The occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions. Beyond these well-defined situations, the presentation of multiple synchronous lesions is commonly viewed as the result of the metastatic spreading of a single primary GIST. Based on this axiom, patients with multifocal disease are classified as advanced stage and treated as such. Whether, indeed, the detection of several lesions in sporadic adult GIST patients may be suggestive of phenomena of tumor multiplicity still needs to be clarified. EXPERIMENTAL DESIGN: From a multicentric series of 442 consecutive cases, 26 of which with advanced disease, we selected 5 patients who presented up to three distinct GIST nodules. Five additional cases with similar characteristics were also contributed by two other institutions. The clonal relationship between the synchronous lesions was assessed by comparing KIT/PDGFRA mutation and microsatellite pattern. RESULTS: An independent origin of the synchronous lesions was established in 6 of 10 cases. Notably, in one patient, one lesion arose in the peritoneum, which is ordinarily regarded as a site of metastasis. CONCLUSIONS: Our data indicate that a significant fraction of GIST patients with multifocal presentation are actually affected by multiple primary tumors, suggesting that mesenchymal GIST precursor cells of these individuals are somehow primed to transformation. Thus, in the presence of multifocal GIST manifestations, an accurate characterization of the different tumor sites should be undertaken for a proper patient staging and therapy planning.     

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae)

Ethnopharmacological relevance

Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats.

Material and methods

The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H₂O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na⁺, K⁺, Cl⁻ and HCO₃⁻ were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined.

Results

Water and Na⁺ excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2′,5′-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment.

Conclusion

The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway.     

Prospective Changes in the Distribution of Movement Behaviors Are Associated With Bone Health in the Elderly According to Variations in their Frailty Levels

Frailty is associated with poor bone health and osteoporosis, and physical activity (PA) is one of the best treatments for both pathologies in older adults. Nonetheless, because daily time is limited, how the time is distributed during the waking hours is critical. The waking hours are spent according to different movement behaviors: sedentary behaviors (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). The aim of this study was to use compositional data analyses to examine the effects of the change in movement behaviors on bone health during aging in older people, related to the changes in their frailty levels. We analyzed 227 older people aged 65 to 94 (125 women and 102 men) over a 4-year period. Movement behaviors were assessed using accelerometry. Both bone mineral density (BMD) and bone mineral content (BMC) were determined using bone densitometry. The Frailty Trait Scale was used to divide the sample by frailty level evolution during aging. The R statistical system was used for the compositional data analysis and, in addition, all models were adjusted for several covariates. The changes in the distribution of all movement behaviors within a waking hour period were significantly associated with spine and femoral neck BMD changes in the subgroup with a positive change in frailty level and spine BMC in the subgroup with no change in frailty level (p ≤ .05). Likewise, MVPA relative to the change in other movement behaviors was also associated in both subgroups with higher BMD and BMC, respectively, in the same body areas (p ≤ .05). No significant associations were found in the negative change in frailty level subgroup. Older people who achieved a positive change in frailty level during a 4-year period showed higher BMD changes compared to those with no changes or increases in their frailty level. Therefore, increasing MVPA relative to the change in the other movement behaviors during a 4-year period could perhaps produce bone health improvements in the elderly that do not worsen their frailty level. © 2020 American Society for Bone and Mineral Research.     

Serotonin synthesis protects the mouse colonic crypt from DNA damage and colorectal tumorigenesis

Serotonin (5-HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5-HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1^fl/flVillin^Cre) mouse models defective in 5-HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post-treatment followed a timeline designed to understand how disruption of 5-HT synthesis affects the initial steps leading to CRT. We found Tph1KO mice had decreased development of both allograft tumors and colitis-related CRT. Interestingly, carcinogenic exposure alone induced multiple colon tumors and increased cyclooxygenase-2 (Ptgs2) expression in Tph1KO mice. Deletion of interleukin 6 (Il6) in Tph1KO mice confirmed that inflammation was a part of the process. 5-HT deficiency increased colonic DNA damage but inhibited genetic repair of specific carcinogen-related damage, leading to CRT-related inflammatory reactions and dysplasia. To validate a secondary effect of 5-HT deficiency on another DNA repair pathway, we exposed Tph1KO mice to ionizing radiation and found an increase in DNA damage associated with reduced levels of ataxia telangiectasia and Rad3 related (Atr) gene expression in colonocytes. Restoring 5-HT levels with 5-hydroxytryptophan treatment decreased levels of DNA damage and increased Atr expression. Analysis of Tph1^fl/flVillin^Cre mice with intestine-specific loss of 5-HT synthesis confirmed that DNA repair was tissue specific. In this study, we report a novel protective role for 5-HT synthesis that promotes DNA repair activity during the early stages of colorectal carcinogenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Proximal tubular cells contain a phenotypically distinct,scattered cell population involved in tubular regeneration

Regeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre‐existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24‐, CD133‐, and vimentin‐positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent ‘normal’ proximal tubular cells, these CD24‐positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co‐localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24‐positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24‐positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24‐positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre‐existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

CT‐measured bone attenuation in patients with chronic obstructive pulmonary disease: Relation to clinical features and outcomes

Osteoporosis is highly prevalent in chronic obstructive pulmonary disease (COPD) patients and has been related to several clinical features. However, most studies have been in relatively small COPD cohorts. Therefore, the objectives of this study were to compare bone attenuation measured on low‐dose chest computed tomography (CT) between COPD subjects and smoker and nonsmoker controls, and to relate bone attenuation to clinical parameters, inflammatory biomarkers, and outcomes in a large, well‐characterized COPD cohort. We studied 1634 COPD subjects, 259 smoker controls, and 186 nonsmoker controls who participated in a large longitudinal study (ECLIPSE). We measured bone attenuation, extent of emphysema, and coronary artery calcification (Agatston score) on baseline CT scans, and clinical parameters, inflammatory biomarkers, and outcomes. Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls (164.9 ± 49.5 Hounsfield units [HU] versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU, p < 0.001). Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation correlated positively with forced expiratory volume in 1 second (FEV₁, r = 0.062, p = 0.014), FEV₁/forced vital capacity (FVC) ratio (r = 0.102, p < 0.001), body mass index (r = 0.243, p < 0.001), fat‐free mass index (FFMI, r = 0.265, p < 0.001), and C‐reactive protein (r = 0.104, p < 0.001), and correlated negatively with extent of emphysema (r = ?0.090, p < 0.001), Agatston score (r = ?0.177, p < 0.001), and interleukin‐8 (r = ?0.054, p = 0.035). In a multiple regression model, older age, lower FFMI and higher Agatston score were associated with lower bone attenuation. Lower bone attenuation was associated with higher exacerbation (r = ?0.057, p = 0.022) and hospitalization (r = ?0.078, p = 0.002) rates but was not associated with all‐cause mortality. In conclusion, CT‐measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls, after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation was associated with age, body composition, and coronary artery calcification but was not associated with all‐cause mortality.     

Camel-related pancreatico-duodenal injuries: a report of three cases and review of literature

Background

Human pancreatico-duodenal injuries caused by camels are extremely rare.

Objective

We report three patients who sustained camel-related pancreatico-duodenal injuries and review the literature on this topic.

Results

A 32-year camel caregiver was kicked by a camel which then stepped on his abdomen trying to kill him. The patient''s abdomen was soft and lax. CT scan of the abdomen showed free retroperitoneal air. Laparotomy revealed a complete tear of the anterior wall of the second part of duodenum which was primarily repaired. A 40-year camel caregiver was directly kicked into his abdomen by a camel. He developed traumatic pancreatitis which was treated conservatively. A 31-year-old male fell down on his abdomen while riding a camel. Abdominal examination revealed tenderness and guarding. Abdominal CT Scan showed complete transection of the neck of the pancreas which was confirmed by laparotomy. The patient had distal pancreatectomy with preservation of the spleen. All patients were discharged home in good condition.

Conclusion

These cases demonstrate the misleading presentation of the camel-realted pancreatico-duodenal injuries and their unique mechanism of injury.