A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data

Background: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. Methods: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. Results: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). Conclusion: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease

The cell biology of polycystic kidney disease

Polycystic kidney disease is a common genetic disorder in which fluid-filled cysts displace normal renal tubules. Here we focus on autosomal dominant polycystic kidney disease, which is attributable to mutations in the PKD1 and PKD2 genes and which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis. The mechanisms that connect the underlying genetic defects to disease pathogenesis are poorly understood, but their exploration is shedding new light on interesting cell biological processes and suggesting novel therapeutic targets

Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2

<p>Abstract</p> <p>Background</p> <p>Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genes <it>PKD1 </it>and <it>PKD2 </it>account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product of <it>PKD2</it>. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.</p> <p>Methods</p> <p>Here we utilized different kidney cell-lines expressing wild-type and mutant <it>PKD2 </it>as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.</p> <p>Results</p> <p>Surprisingly, over-expression of wild-type <it>PKD2 </it>in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutated <it>PKD2 </it>augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57^KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.</p> <p>Conclusion</p> <p>Our results indicate the probable involvement of p57^KIP2on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21.</p

Emerging evidence of a link between the polycystins and the mTOR pathways

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by the formation of renal cysts. This disease can be caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC-1) and -2 (PC-2), respectively

Healthcare utilization and symptom variation among veterans using behavioral telehealth center services

Substance use and mental health problems are often underdiagnosed and undertreated in primary care. Veterans affairs facilities are using the Behavioral Telehealth Center (BTC) to provide evidence-based assessments for primary care patients via telephone. Whether participation in BTC services is associated with (1) increases in healthcare utilization and (2) decreases in symptoms based on behavioral health screening instruments, post-BTC services compared with pre-BTC services were investigated. Retrospective data were extracted for 1,820 patients who were referred to the BTC. Differences in utilization rates and symptom scores pre- and post-BTC services were tested using repeated measures analysis of covariance while controlling for relevant sociodemographic variables. Participants (1) utilized significantly more substance use and mental health treatment services and (2) had significantly lower alcohol and depression screening scores post-BTC services compared with pre-BTC services. This initial evaluation provides support that BTC services are associated with increased healthcare utilization and decreased alcohol and depressive symptoms. </p

Healthcare utilization and symptom variation among veterans using behavioral telehealth center services

Substance use and mental health problems are often underdiagnosed and undertreated in primary care. Veterans affairs facilities are using the Behavioral Telehealth Center (BTC) to provide evidence-based assessments for primary care patients via telephone. Whether participation in BTC services is associated with (1) increases in healthcare utilization and (2) decreases in symptoms based on behavioral health screening instruments, post-BTC services compared with pre-BTC services were investigated. Retrospective data were extracted for 1,820 patients who were referred to the BTC. Differences in utilization rates and symptom scores pre- and post-BTC services were tested using repeated measures analysis of covariance while controlling for relevant sociodemographic variables. Participants (1) utilized significantly more substance use and mental health treatment services and (2) had significantly lower alcohol and depression screening scores post-BTC services compared with pre-BTC services. This initial evaluation provides support that BTC services are associated with increased healthcare utilization and decreased alcohol and depressive symptoms. </p

Impact of the COVID-19 pandemic on gastrointestinal endoscopy in the Netherlands: Analysis of a prospective endoscopy database

Background: COVID-19 has dramatically affected gastrointestinal endoscopy practice. We aimed to investigate its impact on procedure types, indications, and findings. Methods: We retrospectively analyzed endoscopies performed in 15 Dutch hospitals by comparing periods 15 March to 25 June of 2019 and 2020 using the prospective Trans.IT database. Results: During lockdown in 2020, 9776 patients underwent endoscopy compared with 19296 in 2019. Gastroscopies decreased by 57% (from 7846 to 4467) and colonoscopies by 45% (from 12219 to 5609), whereas endoscopic retrograde cholangiopancreatography volumes remained comparable (from 578 to 522). Although endoscopy results indicative of cancer decreased (from 524 to 340), the likelihood of detecting cancer during endoscopy increased (2.7% [95% confidence interval (CI) 2.5-3.0] in 2019 versus 3.5% [95%CI 3.1-3.9] in 2020; P <0.001). After lifting of lockdown, endoscopy volumes started to return to normal, except for colorectal cancer screening. Conclusions: Fewer endoscopies were performed during the COVID-19 lockdown, leading to a significant reduction in the absolute detection of cancer. Endoscopies increased rapidly after lockdown, except for colorectal cancer screening