Background

Genetic analysis of gastrointestinal malignancies shows a great number of mutations. Most mutations found in gastric tumors are also found in colorectal and esophageal tumors. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors.

Methods

Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Pathologic stage and histology were compared between subjects with and without a specific mutated gene using two-sample t-tests, adjusted for multiple gene testing. Sequence convergence and functional impact of genetic mutations were analyzed using permutation test and PolyPhen-2 score.

Results

Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD =10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rates of missing data (44%). Pathologic stage: 20% stage I, 35% stage II, 31% stage III, and 14% stage IV. Anatomical location: 30% gastric, 59% colorectal, and 11% esophageal. Histology of gastric cancer: 61% intestinal, 23% diffuse, 15% mixed, and 1% missing. Two mutated genes-CDH1, RHOA-distinguished gastric from colorectal and esophageal tumors. These mutations were highly specific to diffuse histology and advanced stages of gastric tumors and recurrent in transcribed regions known to impact protein functions.

Conclusions

CDH1 and RHOA regulate cell-cell adhesion which is vital to cell growth and proliferation. Identification of these potential driver mutations is critical to better define therapeutic vulnerabilities for the rational design of gastric cancer therapies.

Background

While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. There is paucity in the literature for direct comparison of various practices. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study in patients with gastric cancer who had multimodality treatment for non-metastatic gastric cancer.

Methods

We gathered clinical data (patient demographics, pathology reports, type of surgical intervention, chemotherapy, and radiation therapy) for patients diagnosed with gastric adenocarcinoma who underwent gastrectomy at five sites from 2010-2017 using Electronic Health Records and California Cancer Registry databases. Medical chart reviews were conducted to validate patient outcomes. We performed multivariate Cox regression analyses to determine predictors for cancer recurrence and survival. We also performed logistic regression analyses to determine predictors of positive resection margins and hospitalization.

Results

One hundred and sixteen patients met eligibility criteria to be included. Mean age was 65.7±11.6 years. About 65.5% were male. The most common ethnicities were Asian (44.0%) and Caucasian (37.9%). About 58.6% of the patients had localized disease (defined as pT1-3, pN0) and the remaining 41.4% had loco-regional disease (i.e., pT4 or pN+). About 41.4% of the tumors were diffuse, 27.6% intestinal, 12.0% mixed, and 19.0% unknown histology. Surgery included laparoscopic (94.8%) and open gastrectomy (5.2%). Chemotherapy and radiation therapy were given in 51.7% and 19.0% of the patients, respectively. After a median follow-up time of 19 months after gastrectomy, 16.4% of patients had recurrence and 19.8% had died. Patients who had loco-regional tumors were more likely to have recurrence and death than those who had localized tumors (hazard ratios =7.0, P=0.0228 for recurrence and hazard ratios =3.3, P=0.0160 for death). Positive resection margins were seen in 9% of the patients and were associated with diffuse histology (odds ratio =6.6, P=0.0207). Hospitalization within six months of gastrectomy was seen in 22% of the patients. Peri-operative chemotherapy was the only significant predictor for re-hospitalization (odds ratio =3.5, P=0.0415).

Conclusions

In this contemporary cohort of patients with localized gastric cancer, only the pathological stage was significantly associated with survival while positive resection margins were associated with diffuse histology. Closer monitoring of patients undergoing perioperative chemotherapy within 6 months of surgery is warranted based on our observation of higher rate of re-hospitalization.

An algorithm was developed that identifies patients with new diagnoses of HIV infection by the use of electronic health records. It was based on the sequence of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at four large urban Veterans Health Administration (VHA) facilities. Source data were obtained from the VHA National Corporate Data Warehouse. Chart review was done by a single trained abstractor to validate site-level data regarding new diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test within the VHA. Of these, 57% were determined to have prior knowledge of their HIV status from testing at non-VHA facilities. An algorithm based on the sequence and results of available laboratory tests and ICD-9-CM entries identified new HIV diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90%. There were no meaningful demographic or clinical differences between newly diagnosed patients who were correctly or incorrectly classified by the algorithm. We have validated a method to identify cases of new diagnosis of HIV infection in large administrative datasets. This method, which has a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90% can be used in analyses of the epidemiology of newly diagnosed HIV infection.

Background

We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis - a point of substantial importance to the VA, which is the largest provider of HIV care in the United States.

Methods

Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation.

Results

Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3-5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations.

Discussion

This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).

The CDC recommends routine voluntary HIV testing of all patients 13-64 years of age. Despite this recommendation, HIV testing rates are low even among those at identifiable risk, and many patients do not return to receive their results. To examine the costs and benefits of strategies to improve HIV testing and receipt of results. Cost-effectiveness analysis based on a Markov model. Acceptance of testing, return rates, and related costs were derived from a randomized trial of 251 patients; long-term costs and health outcomes were derived from the literature. Primary-care patients with unknown HIV status. Comparison of three intervention models for HIV counseling and testing: Model A = traditional HIV counseling and testing; Model B = nurse-initiated routine screening with traditional HIV testing and counseling; Model C = nurse-initiated routine screening with rapid HIV testing and streamlined counseling. Life-years, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness. Without consideration of the benefit from reduced HIV transmission, Model A resulted in per-patient lifetime discounted costs of $48,650 and benefits of 16.271 QALYs. Model B increased lifetime costs by $53 and benefits by 0.0013 QALYs (corresponding to 0.48 quality-adjusted life days). Model C cost $66 more than Model A with an increase of 0.0018 QALYs (0.66 quality-adjusted life days) and an incremental cost-effectiveness of $36,390/QALY. When we included the benefit from reduced HIV transmission, Model C cost $10,660/QALY relative to Model A. The cost-effectiveness of Model C was robust in sensitivity analyses. In a primary-care population, nurse-initiated routine screening with rapid HIV testing and streamlined counseling increased rates of testing and receipt of test results and was cost-effective compared with traditional HIV testing strategies.

Objective

To determine predictors and variations in the rate of newly diagnosed HIV infection among persons who underwent routine (ie, non-risk based) rather than risk-based HIV testing in Veterans Health Administration (VHA) facilities.

Methods

Retrospective observational study of the HIV infection new rates during the period when VHA policy called for routine (2009-2012) versus risk-based (2006-2009) HIV testing. Source data for testing results at 18 VHA facilities were obtained from the VHA National Corporate Data Warehouse.

Results

New HIV diagnoses were established in 0.14% (95% confidence interval (CI): 0.12 to 0.46) of the 210,957 patients tested in the routine testing period versus 0.46% (95% CI: 0.42 to 1.29) of the 89,652 patients tested in the risk-based testing period. Among persons aged 65-74 years and 75 years or older, the new diagnosis rates were 0.07% (95% CI: 0.04 to 0.09) and 0.02% (95% CI: 0.00 to 0.03), respectively, and thus less than the generally accepted cost-effective threshold of 0.10%. Among African Americans, the upper bound of the 95% CI of the crude rate of new diagnoses during the routine-testing period was greater than 0.1% across all age strata. When assessed by year of testing, the adjusted rates of new diagnoses fell from 0.20% in 2010 to 0.10% in 2012.

Conclusions

Routine HIV testing is cost-effective among persons younger than 65 years. Among older patients, risk-based testing may be a more efficient and cost-effective approach. This will be increasingly relevant if rates of new HIV diagnoses in persons undergoing routine testing continue to decrease.

Sustainability—the routinization and institutionalization of processes that improve the quality of healthcare—is difficult to achieve and not often studied. To evaluate the sustainability of increased rates of HIV testing after implementation of a multi-component intervention in two Veterans Health Administration healthcare systems. Quasi-experimental implementation study in which the effect of transferring responsibility to conduct the provider education component of the intervention from research to operational staff was assessed. Persons receiving healthcare between 2005 and 2006 (intervention year) and 2006 and 2007 (sustainability year). Monthly HIV testing rate, stratified by frequency of clinic visits. The monthly adjusted testing rate increased from 2% at baseline to 6% at the end intervention year and then declined reaching 4% at the end of the sustainability year. However, the stratified, visit-specific testing rate for persons newly exposed to the intervention (i.e., having their first through third visits during the study period) increased throughout the intervention and sustainability years. Increases in the proportion of visits by patients who remained untested despite multiple, prior exposures to the intervention accounted for the aggregate attenuation of testing during the sustainability year. Overall, the percentage of patients who received an HIV test in the sustainability year was 11.6%, in the intervention year 11.1%, and in the pre-intervention year 5.0% Provider education combined with informatics and organizational support had a sustainable effect on HIV testing rates. The effect was most pronounced during patients’ early contacts with the healthcare system.

Background

While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the USA. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary across geographic locations. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions.

Methods

California Cancer Registry data were collected for nmGC patients who underwent gastrectomy with curative intent from 2010 to 2018. We conducted chart reviews of the patients' electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes.

Results

Demographics of study cohort (n=326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) vs. 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: 34% open gastrectomy, 48% laparoscopic, 18% unknown; number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant alone, 25% adjuvant alone, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median post-surgical follow-up of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries were associated with fewer recovered lymph nodes (mean =18 vs. 25, P=0.0042). Fewer recovered lymph nodes were associated with a significant decrease in 5-year overall survival [hazard ratio (HR) =1.9, 95% confidence interval (CI): 1.3-2.8]. Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival; in contrast, greater lymph node recovery plus chemotherapy were associated with a significant increase in survival (HR =0.3, 95% CI: 0.1-0.6).

Conclusions

This study highlights major practice differences in the management of nmGC patients across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.

Background

Pilot data suggest that a multifaceted approach may increase HIV testing rates, but the scalability of this approach and the level of support needed for successful implementation remain unknown.

Objective

To evaluate the effectiveness of a scaled-up multi-component intervention in increasing the rate of risk-based and routine HIV diagnostic testing in primary care clinics and the impact of differing levels of program support.

Design

Three arm, quasi-experimental implementation research study.

Setting

Veterans Health Administration (VHA) facilities.

Patients

Persons receiving primary care between June 2009 and September 2011 INTERVENTION: A multimodal program, including a real-time electronic clinical reminder to facilitate HIV testing, provider feedback reports and provider education, was implemented in Central and Local Arm Sites; sites in the Central Arm also received ongoing programmatic support. Control Arm sites had no intervention

Main measures

Frequency of performing HIV testing during the 6 months before and after implementation of a risk-based clinical reminder (phase I) or routine clinical reminder (phase II).

Key results

The adjusted rate of risk-based testing increased by 0.4 %, 5.6 % and 10.1 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). During phase II, the adjusted rate of routine testing increased by 1.1 %, 6.3 % and 9.2 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). At study end, 70-80 % of patients had been offered an HIV test.

Conclusions

Use of clinical reminders, provider feedback, education and social marketing significantly increased the frequency at which HIV testing is offered and performed in VHA facilities. These findings support a multimodal approach toward achieving the goal of having every American know their HIV status as a matter of routine clinical practice.

BACKGROUND: Limited English Proficiency (LEP) Latinxs experience a longer duration of untreated depression and anxiety. LEP Latinxs have difficulty accessing mental healthcare due to insufficient Spanish-speaking behavioral/mental health clinicians to meet demand. These under-resourced healthcare systems are less likely to be the site for the implementation of innovations. Digital interventions can provide an effective option for overcoming these barriers; yet, when digital evidence-based treatments are available, uptake and engagement is often low. This manuscript presents the protocol for the SUPERA (SUpport from PEeRs to expand Access) study which will evaluate the implementation of an evidence-based, Spanish language, digital cognitive-behavioral therapy (dCBT) intervention (i.e., SilverCloud) in safety-net primary care clinics for LEP Latinx patients with depression or anxiety. METHODS: We will conduct an effectiveness-implementation hybrid trial (Type 2) design comparing engagement and clinical outcomes in two modalities of dCBT delivery (peer-supported vs. unsupported). We will also compare provider-level outreach (using a clinic patient registry) versus inreach (traditional provider referral) to compare rates of initiation, completion, and cost. Participants will be 426 LEP Latinx adults ≥18 years of age, PHQ-9 ≥ 10 or GAD-7 ≥ 8, with access to the internet via smartphone, and not currently receiving individual psychotherapy. We will collect baseline, post-intervention (8 weeks), and follow up (3 months) data. CONCLUSION: The long-term goal of this research is to aid in the implementation of digital mental health interventions that can be sustainably implemented in low-resourced settings, while reducing the reliance on professionals, overcoming workforce deficits, and increasing relevance for diverse populations.