Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Atypical use of PICC as centrally inserted central catheter in infants and neonates: Report of a 10-year experience.

PURPOSE: The aim was to determine the success, safety and post procedure complications of peripherally inserted central catheters as centrally inserted central catheters (CICC). MATERIALS AND METHOD: One hundred and sixty-one consecutive infants and neonates, who underwent image guided tunnelled central venous catheter insertion were retrospectively evaluated between April 2008 and April 2018. Patient's demographics, site of access and procedure details were recorded. Outcomes included technical success and post procedure complications. RESULTS: One hundred and eighty-two CICCs were inserted in 161 patients (49.7%, n = 80 male). Mean patient age was 100 days (range: 0-342) with a mean weight of 4.20 kg (range 1.80-9.40). The most common indication was for antibiotics administration (41%; n = 66). Technical success was 99% (181/182). Early complications (<7 days) were seen in 8.8% (n = 13). This included inadvertent line removal in 5.5%, catheter-related bloodstream infection in 1.1% and catheter occlusion in 2.2% (n = 4). Average line functional duration prior to removal was 26 days (range 0-180). 77.5% of the lines lasted for the intended duration of treatment. In the neonate subgroup, 84.1% (37/44 lines) of lines remained in situ for the intended duration of treatment. CONCLUSION: Tunnelled central venous catheters using non-cuffed peripherally inserted central catheters in infants is a safe technique with excellent success rate and minimal complications rates.

Process of Engaging Community and Scientific Partners in the Development of the CIRCL-Chicago Study Protocol.

Objectives: Hypertension affects 1 in 3 adults in the United States and disproportionately affects African Americans. Kaiser Permanente demonstrated that a "bundle" of evidence-based interventions significantly increased blood pressure control rates. This paper describes a multiyear process of developing the protocol for a trial of the Kaiser bundle for implementation in under-resourced urban communities experiencing cardiovascular health disparities during the planning phase of this biphasic award (UG3/UH3). Methods: The protocol was developed by a collaboration of faith-based community members, representatives from community health center practice-based research networks, and academic scientists with expertise in health disparities, implementation science, community-engaged research, social care interventions, and health informatics. Scientists from the National Institutes of Health and the other grantees of the Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance also contributed to developing our protocol. Results: The protocol is a hybrid type 3 effectiveness-implementation study using a parallel cluster randomized trial to test the impact of practice facilitation on implementation of the Kaiser bundle in community health centers compared with implementation without facilitation. A central strategy to the Kaiser bundle is to coordinate implementation via faith-based and other community organizations for recruitment and navigation of resources for health-related social risks. Conclusions: The proposed research has the potential to improve identification, diagnosis, and control of blood pressure among under-resourced communities by connecting community entities and healthcare organizations in new ways. Faith-based organizations are a trusted voice in African American communities that could be instrumental for eliminating disparities.

Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial.

BACKGROUND: Over half of patients with elevated blood pressure require multi-drug treatment to achieve blood pressure control. However, multi-drug treatment may lead to lower adherence and more adverse drug effects compared with monotherapy. OBJECTIVE: The Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET) USA trial was designed to evaluate whether initiating treatment with ultra-low-dose quadruple-combination therapy will lower office blood pressure more effectively, and with fewer side effects, compared with initiating standard dose monotherapy in treatment naive patients with SBP < 180 and DBP < 110 mm Hg and patients on monotherapy with SBP < 160 and DBP < 100 mm Hg. METHODS/DESIGN: QUARTET USA was a prospective, randomized, double-blind trial (ClinicalTrials.gov NCT03640312) conducted in federally qualified health centers in a large city in the US. Patients were randomly assigned (1:1) to either ultra-low-dose quadruple combination therapy or standard dose monotherapy. The primary outcome was mean change from baseline in office systolic blood pressure at 12-weeks, adjusted for baseline values. Secondary outcomes included measures of blood pressure change and variability, medication adherence, and health related quality of life. Safety outcomes included occurrence of serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. A process evaluation aimed to understand provider experiences of implementation and participant experiences around side effects, adherence, and trust with clinical care. DISCUSSION: QUARTET USA was designed to evaluate whether a novel approach to blood pressure control would lower office blood pressure more effectively, and with fewer side effects, compared with standard dose monotherapy. QUARTET USA was conducted within a network of federally qualified healthcare centers with the aim of generating information on the safety and efficacy of ultra-low-dose quadruple-combination therapy in diverse groups that experience a high burden of hypertension.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): A point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. METHODS: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): a point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: Rapid and accurate testing for SARS-CoV-2 is an essential tool in the medical and public health response to the COVID-19 pandemic. An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR combined with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. METHODS: To evaluate the performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC PCR (sample insertion to result time of 16 minutes), we conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites. We collected two bilateral anterior nasal swabs from each participant and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard." RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently COVID-19 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R=0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR. Its compact design and ease of use are optimal for a variety of healthcare, and potentially community settings, including areas with lack of access to central laboratory-based PCR testing. SUMMARY: DASH is an accurate, easy to use, and fast point-of-care test with applications for diagnosis and screening of SARS-CoV-2 infection.

The Complex Interplay of Communication and Trust in Healthcare Delivery.

Effective communication in clinician-patient relationships is an essential part of improving health outcomes. Ineffective communication in clinical settings leaves patients feeling undervalued and unheard. Breakdowns in communication can have particularly profound effects on minority or underserved populations, where health disparities already exist. Effective communication is critical for establishing trust, which allows individuals to feel they can share their concerns and questions. Distrust is a particularly important issue in maternal health, where current US rates of maternal mortality and morbidity are 3.1 times higher in Black and African American (AA) pregnant and birthing persons than their non-Hispanic white counterparts. To address the widespread issue of medical distrust and its connection with maternal health outcomes, the OPTIMIZE study is currently implementing an innovative intervention aimed at improving perinatal care for Black/AA pregnant persons. This intervention prompts clinician-patient conversations to enhance communication and repair trust, including a focus on patients' goals, concerns, social determinants of health, and safety. The implications of this intervention are broad, including the potential to improve trust and communication in other clinical specialties.

Extravascular findings during upper limb computed tomographic angiography focusing on undiagnosed malignancy.

BACKGROUND: Computer tomography angiography (CTA) has been an established method for diagnostic vascular disease of lower limbs. Recently, the method is widely used for diagnosis of vascular pathologies in the upper limbs too. It also has increased the possibilities of this scans being reviewed by no specially trained radiologists. This increases the risk of incidental non vascular findings to be missed or misinterpreted. The study is focusing in the frequency of extravascular incidental finding (EVIF) and highlights the importance for both the reporting radiologist and the referring physician recognizing the frequency of EVIFs. AIM: To analyse the frequency of EVIF identified on computed angiography (CT) of the upper limb. METHODS: A total of 1383 CT angiographic studies of the peripheral arterial system were performed between August 2015 and August 2017. All upper limb CTAs (n = 79) were retrospectively reviewed for the presence of non-vascular incidental findings within the chest, abdomen/pelvis, musculoskeletal system or head and neck. These EVIFs were subsequently grouped into 3 categories based on clinical significance. EVIFs of immediate clinical relevance were included in category A, findings considered indeterminate but most likely benign were placed in category B, while incidental findings of no clinical significance were included in category C. RESULTS: Complete imaging datasets were available in 74/79 (93.7%). Patient demographics included 39 (52.7%) females and 35 (47.2%) males with a mean age of 59 ± 19.5 years (range 19-93 years). A total of 153 EVIFs were reported in 52 patients (70.3%). Of these, 44 EVIFs (28.7%) were found in the chest, 83 (54.2%) in the abdomen, 14 (9.2%) in the musculoskeletal system and 9 (5.8%) in the head and neck. Thirteen EVIFs (8.4%) identified in 11 patients were noted to be of immediate clinical significance (Category A), 50 EVIFs (32.3%) were identified in 20 patients and were considered indeterminate but most likely benign, while the remaining 91 EVIFs (59.5%) identified in 21 patients were determined to be of no clinical significance (Category C). One index case of malignancy (1.3%) and four cases of new disseminated metastatic disease (5.4%) were identified. CONCLUSION: Our study of upper limb CTA examinations demonstrated a frequency of 8.4% for extravascular incidental findings of immediate clinical significance. We highlight the importance for both the reporting radiologist and the referring physician of the need to recognize the frequency with which EVIFs are identified in the upper limb peripheral arterial system and of the necessity for further clinical and imaging work-up.

Breast cancer liver metastases in a UK tertiary centre: Outcomes following referral to tumour board meeting.

INTRODUCTION: To assess the outcomes from multidisciplinary board meetings (MDM) for patients with breast cancer liver metastases (BCLM) and identify prognostic factors for survival. MATERIALS AND METHODS: A retrospective review of MDM records for patients referred with BCLM to a tertiary centre between 2005 and 2016. Patient demographics, clinicopathological factors and intervention type were analysed to find predictive factors for overall survival. RESULTS: 61 patients with BCLM were referred to the MDM. Treatment pathways included surgical resection (n = 23), radiofrequency ablation (RFA, n = 11), or chemotherapy (n = 27). Surgical resection patients had an improved median overall survival compared to chemotherapy (49 v 20mo; p < 0.001). RFA showed comparable survival benefit (37 v 20mo; p = 0.011). Resection and RFA showed no significant difference in survival over one another (49 v 37mo; p = 0.854). Survival analysis identified that resection (p = 0.002) and RFA (p = 0.001) were associated with improved overall survival compared to chemotherapy. Multivariate analysis identified extrahepatic disease (HR = 14.21; p = 0.044) and R0 resection (HR = 0.068; p = 0.023) as prognostic factors. CONCLUSIONS: Surgical resection of BCLM may improve the overall survival in selected patient groups. This study identifies a cohort of patients, without extrahepatic disease and responsive to chemotherapy, who may particularly benefit from surgery.