IL28B Genotype Does Not Correlate with HIV Control in African Americans

Background: HIV‐1 natural viral suppressors (NVS) are individuals that control HIV replication without antiretrovirals (also know as HIV elite controllers). We have recently shown that these individuals have an elevated rate of hepatitis C virus (HCV) clearance. Given the association of IL28B genotype, specifically the rs12979860 single nucleotide polymorphism (SNP) based CC genotype, with HCV clearance, we studied its association with HIV control in 172 African American HIV subjects and 173 race‐matched controls. Findings: The frequency of the CC genotype was 12.5% in the NVS, 14.7% in the LVL (“low viral load” cohort with 400–20,000 HIV‐1 RNA copies/mL), 17.8% in the MHVL (“medium/high viral load” cohort with >20,000 HIV‐1 RNA copies/mL), and 11.6% in an HIV‐negative cohort. There was no statistical significance in the CC genotype distribution between these cohorts (p= 0.48 between the NVS and non‐NVS HIV positive controls, p= 0.85 between NVS and HIV‐negatives). We also did not observe any association between CC genotype distribution and HIV RNA viral load, as a continuous measure. Conclusions: The IL28B CC genotype does not account for the noted HIV control in our specific NVS cohort. Further studies will be needed to determine if a common genetic factor can primarily account for any joint clearance of HCV and control of HIV. Clin Trans Sci 2011; Volume 4: 282–284     

Impact of population management with direct physician feedback on care of patients with type 2 diabetes

OBJECTIVE: Population-level strategies may improve primary care for diabetes. We designed a controlled study to assess the impact of population management versus usual care on metabolic risk factor testing and management in patients with type 2 diabetes. We also identified potential patient-related barriers to effective diabetes management. RESEARCH DESIGN AND METHODS: We used novel clinical software to rank 910 patients in a diabetes registry at a single primary care clinic and thereby identify the 149 patients with the highest HbA(1c) and cholesterol levels. After review of the medical records of these 149 patients, evidence-based guideline recommendations regarding metabolic testing and management were sent via e-mail to each intervention patient's primary care provider (PCP). Over a 3-month follow-up period, we assessed changes in the evidence-based management of intervention patients compared with a matched cohort of control patients receiving usual care at a second primary care clinic affiliated with the same academic medical center. RESULTS: In the intervention cohort, PCPs followed testing recommendations more often (78%) than therapeutic change recommendations (36%, P = 0.001). Compared with the usual care control cohort, population management resulted in a greater overall proportion of evidence-based guideline practices being followed (59 vs. 45%, P = 0.02). Most intervention patients (62%) had potential barriers to effective care, including depression (35%), substance abuse (26%), and prior nonadherence to care plans (18%). CONCLUSIONS: Population management with clinical recommendations sent to PCPs had a modest but statistically significant impact on the evidence-based management of diabetes compared with usual care. Depression and substance abuse are prevalent patient-level adherence barriers in patients with poor metabolic control.     

The ATEAM study: Advances in technology to enhance PrEP adherence monitoring (ATEAM) among young men who have sex with men

Young age has consistently correlated with lower adherence to pre‐exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real‐time feedback among cisgender YMSM and transgender women. One hundred HIV‐negative young men and transgender women ages 16–24 years were enrolled in a 24‐week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard‐of‐care. Participants in the 12‐week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4‐week intervals for tenofovir diphosphate (TFV‐DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30‐day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%–60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV‐DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real‐time monitoring.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Lack of efficacy to pre‐exposure prophylaxis (PrEP) is due almost exclusively to low drug adherence and the failure of traditional adherence metrics to precisely document drug adherence, identify patterns of adherence behaviors, and facilitate timely intervention when lapses in adherence occurred.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What is the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real‐time feedback among cisgender young men who have sex with men (YMSM) and transgender women?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study successfully developed an integrated system that confirms ingestion of oral PrEP, monitors adherence both in real‐time and longitudinally, and provides feedback mechanisms to promote enhanced adherence behaviors for YMSM.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study warrants further exploration in the use of digital medicine and real‐time monitoring to optimize PrEP adherence for youth.     

Patient randomized trial of a targeted navigation program to improve rates of follow-up colonoscopy in community health centers

BackgroundColorectal cancer (CRC) screening by annual fecal immunochemical test (FIT) is an accessible and cost-effective strategy to lower CRC incidence and mortality. However, this mode of screening depends on follow-up colonoscopy after a positive FIT result. Unfortunately, nearly one-half of FIT-positive patients fail to complete this essential screening component. Patient navigation may improve follow-up colonoscopy adherence. To deliver patient navigation cost-effectively, health centers could target navigation to patients who are unlikely to complete the procedure on their own.ObjectivesThe Predicting and Addressing Colonoscopy Non-adherence in Community Settings (PRECISE) clinical trial will validate a risk model of follow-up colonoscopy adherence and test whether patient navigation raises rates of colonoscopy adherence overall and among patients in each probability stratum (low, moderate, and high probability of adherence without intervention).MethodsPRECISE is a collaboration with a large community health center whose patient population is 37% Latino. Eligible patients will be aged 50–75, have an abnormal FIT result in the past month, and be due for a follow-up colonoscopy. Patients will be randomized to patient navigation or usual care. Primary outcomes will be colonoscopy completion within one year of a positive FIT result, cost, and cost-effectiveness. Secondary outcomes will include time to colonoscopy receipt, adequacy of bowel prep, and communication of results to primary care providers. Primary and secondary outcomes will be reported overall and by probability stratum.DiscussionThis innovative clinical trial will test the effectiveness and financial feasibility of using a precision health intervention to improve CRC screening completion in community health centers.Trial RegistrationNational Clinical Trial (NCT) Identifier: NCT03925883.     

COVID‐19 in HIV‐positive patients: A systematic review of case reports and case series

IntroductionCoronavirus disease 2019 (COVID‐19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system''s focus on the COVID‐19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID‐19 in HIV‐positive patients.Material and MethodsUsing the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: “Human Immunodeficiency Virus,” “acquired immune deficiency syndrome,” “HIV,” “AIDS,” “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus,” “SARS‐CoV‐2,” “nCoV disease,” “SARS2,” and “2019‐nCoV disease.”ResultsTwenty‐one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID‐19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID‐19. The total death rate in HIV‐positive patients with COVID‐19 was about 9%.ConclusionIn the current systematic review, we demonstrated that HIV‐positive patients co‐infected with COVID‐19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID‐19 co‐infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID‐19 pandemic.     

Physiotherapy screening of patients referred for orthopaedic consultation in primary healthcare – A randomised controlled trial

A large proportion of patients who consult primary healthcare for musculoskeletal pain are referred for orthopaedic consultation, but only a small number of these patients are appropriate for orthopaedic intervention. Experienced physiotherapists have the appropriate knowledge to manage musculoskeletal disorders. The primary aim of this randomised study was therefore to evaluate a screening by a physiotherapist of patients referred for orthopaedic consultation compared to standard practice in primary care.Patients referred for orthopaedic consultation (n = 203) were randomised to physiotherapy screening or standard practice. Selection accuracy for orthopaedic intervention and other referrals were analysed with proportion analysis. Patient views of the quality of care were analysed with Mann–Whitney U-test, waiting time with Independent t-test.There was higher selection accuracy for orthopaedic intervention in the physiotherapy screening group (p = 0.002). A smaller proportion of patients in the screening group were referred back to their general practitioner (GP) (p < 0.001) and a larger proportion to the physiotherapy clinic (p < 0.001) compared to standard practice. The proportion of patients referred for further investigations was significantly lower in the physiotherapy screening group (p < 0.039). Waiting time was shorter in the screening group (p < 0.001). A large proportion of the patients reported no hesitation to attend the clinic for future care, no difference between the groups (p < 0.95).The findings in this study suggest that an experienced physiotherapist effectively can screen patients referred for orthopaedic consultation in primary healthcare.     

The abnormal level and prognostic potency of multiple inflammatory cytokines in PCI‐treated STEMI patients

ObjectiveInflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST‐segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)‐treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.MethodsSerum tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) of 212 PCI‐treated STEMI patients and 30 angina pectoris patients were determined using enzyme‐linked immunosorbent assay.ResultsTNF‐α (52.5 (43.9–62.6) pg/ml versus 46.4 (39.0–59.1) pg/ml, p = 0.031), IL‐8 (61.6 (49.6–81.7) pg/ml versus 46.7 (32.5–63.1) pg/ml, p = 0.001), IL‐17A (57.4 (45.7–77.3) pg/ml versus 43.2 (34.2–64.6) pg/ml, p = 0.001), and VCAM‐1 (593.6 (503.4–811.4) ng/ml versus 493.8 (390.3–653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL‐1β (p = 0.069), IL‐6 (p = 0.110), IL‐10 (p = 0.052), and ICAM‐1 (p = 0.069) were of no difference. Moreover, both IL‐17A high (vs. low) (p = 0.026) and VCAM‐1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox''s analysis exhibited that IL‐17A high (vs. low) (p = 0.034) and VCAM‐1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C‐reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.ConclusionIL‐17A and VCAM‐1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.     

Normalisation of airflow limitation in asthma: Post‐hoc analyses of TRIMARAN and TRIGGER

BackgroundIn asthma, persistent airflow limitation (PAL) is associated with poorer control, lung function decline and exacerbations. Using post‐hoc analyses we evaluated: the relationship between post‐salbutamol PAL at screening, airflow limitation (AL) during 52 weeks treatment with extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) versus BDP/FF and the risk of moderate/severe asthma exacerbations.MethodsTRIMARAN and TRIGGER were double‐blind studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium‐dose ICS; TRIGGER high‐dose) in adults with uncontrolled asthma. Patients were subgrouped according to post‐salbutamol PAL status at screening, and AL over the 52‐week treatment period.ResultsMost patients with post‐salbutamol PAL at screening had AL at all on‐treatment visits (TRIMARAN 62.8%; TRIGGER 66.8%). A significantly higher proportion of patients had normalised airflow on ≥1 follow‐up visit when receiving BDP/FF/G than BDP/FF (TRIMARAN 44.1 vs. 33.1% [p = 0.003]; TRIGGER 40.1 vs. 26.0% [p < 0.001]). In patients with post‐salbutamol PAL at screening and normalised AL at ≥1 follow‐up visit, exacerbation rates were 15% (p = 0.105) and 19% (p = 0.039) lower in TRIMARAN and TRIGGER versus those with AL on all visits. There was a trend to lower exacerbation rates in patients receiving BDP/FF/G than BDP/FF, particularly in patients in whom AL was normalised.ConclusionIn these analyses, AL in asthma was associated with an increased exacerbation incidence. Inhaled triple therapy with extrafine BDP/FF/G was more likely to normalise airflow, and was associated with a trend to a lower exacerbation rate than BDP/FF, particularly in the subgroup of patients in whom treatment was associated with airflow normalisation.ClinicalTrials.gov: TRIMARAN, {"type":"clinical-trial","attrs":{"text":"NCT02676076","term_id":"NCT02676076"}}NCT02676076; TRIGGER, {"type":"clinical-trial","attrs":{"text":"NCT02676089","term_id":"NCT02676089"}}NCT02676089.     

Reducing severe cutaneous adverse and type B adverse drug reactions using pre‐stored human leukocyte antigen genotypes

BackgroundSeveral type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre‐stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre‐stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs.MethodsWe analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA‐B*57:01, HLA‐B*58:01, HLA‐A*31:01, HLA‐B*15:02, HLA‐B*15:11, HLA‐B*13:01, HLA‐B*59:01, and HLA‐A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre‐stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts'' consensus.ResultsAmong 11,988 HLA‐tested transplant patients, 4092 (34.1%) had high‐risk HLA alleles, 4583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA‐B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA‐B*58:01 (17.2% vs. 11.9%, odds ratio [OR] 1.53 [95% confidence interval {CI} 1.09–2.13], p = 0.001, 2.3% versus 0.3%, OR 7.13 [95% CI 2.19–22.69], p < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA‐A*31:01, HLA‐B*15:02, or HLA‐B*15:11 alleles. Vancomycin and dapsone use in HLA‐A*32:01 and HLA‐B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs.ConclusionUtilization of pre‐stored HLA data can prevent type B ADRs including SCARs by screening high‐risk patients.     

An audit of dermatology in a paediatric accident and emergency department.

Two studies were undertaken of patients with dermatological disorders who attended the Accident and Emergency (A&E) Department of the Royal Belfast Hospital for Sick Children during 1990-1991. The aims were to review diagnostic accuracy and assess the benefits of an open-access consultant dermatology clinic. A retrospective survey of 14,340 new attendances at the A&E department over a 7-month period found that 540 of these (4%) had a primary dermatological disorder. In 26% no diagnosis had been made although only 10% were referred for a specialist opinion. A 2-month prospective study of patients who attended the department and were referred to a consultant dermatology open-access clinic revealed overall diagnostic accuracy of 66% (+/- 2 SEM). Individual rates of diagnostic concordance between junior doctor and consultant were 59% for skin infections and 77% for papulosquamous disorders. The open-access clinic allowed prompt referral for correct diagnosis and initiation of appropriate management.     

Impact of a low intensity and broadly inclusive ED care coordination intervention on linkage to primary care and ED utilization

Objective

We aim to evaluate the effectiveness of a broadly inclusive, comparatively low intensity intervention linking ED patients to a primary care home.

Identification of Depression in an Inner-city Population Using a Simple Screen

Objectives: The purpose of this study was to compare a brief screening tool with physicians' usual practice in detecting depressive symptoms in patients presenting with somatic complaints to an inner-city emergency department. Depression is a major cause of morbidity and mortality in the United States. Underprivileged patients who rely on emergency departments for primary care remain at risk for undetected depression. Methods: This prospective observational study included all patients older than 18 years presenting to an urgent care clinic staffed by emergency physicians in an urban public hospital during an eight-week period. Clinically unstable patients and those with a chief complaint of depression were excluded. After consenting, patients completed a previously validated two-question screening tool for depression. Patients identified as having depressive symptoms were referred to social workers for evaluation for possible psychiatric intervention. Results: Of the 226 patients enrolled, 55% (124/226; 95% confidence interval [CI] = 48% to 61%) screened positive for depressive symptoms. Physicians identified 14% (31/226; 95% CI = 10% to 19%) as having depressive symptoms. The κ value was 0.22 (95% CI = 0.14 to 0.29). All patients but one identified as positive by the physicians screened positive on the screening tool. Patients who screened positive were referred to social workers. The physicians failed to identify 19 of the patients who needed further psychiatric care. Conclusions: Depressive symptoms are common among patients in urgent care settings with somatic complaints. A simple screening tool identified more patients for further evaluation than does physicians' usual practice.     

The veterans' study to improve the control of hypertension (V-STITCH): design and methodology

BACKGROUND: Among the 60 million Americans with hypertension, only approximately 31% have their blood pressure (BP) under control (<140/90 mm Hg). Despite the damaging impact of hypertension and the availability of evidence-based target values for BP, interventions to improve BP control have had limited success. OBJECTIVES: A randomized controlled health services intervention trial with a split-plot design is being conducted to improve BP control. This 4-year trial evaluates both a patient and a provider intervention in a primary care setting among diagnosed hypertensive veterans. METHODS: In a cluster-randomization, 30 primary care providers in the Durham VAMC Primary Care Clinic were randomly assigned to receive the provider intervention or control. The provider intervention is a patient-specific electronically generated hypertension decision support system (DSS) delivering guideline-based recommendations to the provider at each patient's visit, designed to improve guideline-concordant therapy. For these providers, a sample of their hypertensive patients (n=588) was randomly assigned to receive a telephone-administered patient intervention or usual care. The patient intervention incorporates patients' need assessments and involves tailored behavioral and education modules to promote medication adherence and improve specific health behaviors. All modules are delivered over the telephone bi-monthly for 24 months. In this trial, the primary outcome is the proportion of patients who achieve a BP < or =140/90 mm Hg at each outpatient clinic visit over 24 months. CONCLUSION: Despite the known risk of poor BP control, a majority of adults still do not have their BP controlled. This study is an important step in testing the effectiveness of a patient and provider intervention to improve BP control among veterans in the primary care setting.     

No implication of HIV coinfection on the plasma exposure to rifampicin,pyrazinamide, and ethambutol in tuberculosis patients

There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first‐line anti‐tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB‐HIV− group; n = 15) and HIV positive (TB‐HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB‐HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB‐HIV+ patients, dose‐normalized plasma exposure area under the curve from zero to 24 h (nAUC_0–24; geometric mean and 95% confidence interval [CI]) values at steady‐state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74–24.59), 238.21 (95% CI 191.09–296.95), and 18.33 (95% CI 14.56–23.09) µg∙h/ml, respectively. Similar plasma exposure was found in the TB‐HIV− patients. The geometric mean and 90% CI of the ratios between TB‐HIV− and TB‐HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

First‐line anti‐tubercular drugs (FLATDs) plasma exposure is an important variable of tuberculosis (TB) outcome; however, there are contrasting findings regarding the effect of HIV on the pharmacokinetics of FLATDs due to a lack of prospective controlled clinical studies, including HIV positive and HIV negative patients with TB.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study evaluates the effect of HIV coinfection on the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients who are on stable therapy in the second month of FLATDs treatment.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study shows no evidence that the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients with TB are affected by HIV coinfection or by any of the standard of care HIV comedications allowed in the study (lamivudine, zidovudine, tenofovir, efavirenz, or raltegravir).

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

HIV coinfection does not require dose adjustment of rifampicin, pyrazinamide, and ethambutol in patients with TB.     

Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications

IntroductionRegular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations).Methods/study designThis group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results.ConclusionThe novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial.     

Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression

BackgroundChronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma.MethodsHospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow‐up measures were collected 16 weeks after omalizumab treatment.ResultsHADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS‐anxiety scores. Abnormal HADS‐depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test‐22 (SNOT‐22) versus HADS total was r = 0.59 p < 0.0001, HADS‐anxiety r = 0.56 p < 0.0001 and HADS‐depression r = 0.49 p < 0.0001. Omalizumab improved anxiety in CRS (p < 0.0001) regardless of nasal polyp status (CRSwNP p = 0.0042 and CRSsNP p = 0.0078). Depression scores did not improve in either group. SNOT‐22 (p = 0.0006), asthma control questionnaire‐7 (p = 0.0019) and mini‐asthma quality of life questionnaire including emotional function (p = 0.0003 and p = 0.0009, respectively) all improved in both subgroups.ConclusionIn CRS and asthma, anxiety scores but not depression improved after omalizumab treatment. Anxiety may be closely related to airway disease severity, but depression may be independent of airway disease itself. If so, a separate mental health care pathway is needed for CRS patients with depression.     

Adherence to triple‐component antihypertensive regimens is higher with single‐pill than equivalent two‐pill regimens: A randomized controlled trial

AbstractUsing a single‐pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free‐equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple‐component SPC compared with an equivalent two‐pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open‐label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple‐component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two‐pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single‐ and two‐pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single‐pill group had significantly higher PDT and PDTc than the two‐pill group: median (25–75 percentile) PDT 95.1 (86.7–100.0) versus 92.1 (73.0–97.3); and PDTc 91.0 (79.4–96.5) versus 88.6 (69.2–96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single‐pill combination of the triple‐component antihypertensive regimen showed better adherence than the equivalent two‐pill therapy. Reducing pill burden by means of a single‐pill combination is an effective strategy for enhancing adherence to multiple‐agent antihypertensive therapy. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Previous studies suggested that the use of a single‐pill combination (SPC) in hypertension (HTN) treatment produced better adherence and persistence than a free‐equivalent combination. However, supportive data are confined to dual‐component SPC and came from observational studies using medication possession ratio as an outcome.

• WHAT QUESTION DID THIS STUDY ADDRESS?

The objective of this study is to investigate whether a triple‐component SPC improved medication adherence over an equivalent two‐pill combination therapy in a randomized controlled trial using medication event monitoring systems.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Medication adherence in the SPC group was superior to that of two‐pill group, confirming previous findings from observational studies.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.     

Clinical value of YKL‐40 in patients with polymyositis/dermatomyositis: A cross‐sectional study and a systematic review

IntroductionWe performed a cross‐sectional study to investigate the clinical usefulness of YKL‐40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL‐40 in patients with polymyositis (PM)/DM.Materials and methodsA cross‐sectional study and a systematic review were performed to study the clinical value of YKL‐40 in patients with PM/DM. Serum YKL‐40 level was detected using enzyme‐linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL‐40 in patients with PM/DM.ResultsIn the cross‐sectional study, serum YKL‐40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72–176.4] ng/ml versus 27.37 [12.30–53.58] ng/ml, p < 0.0001). Serum levels of YKL‐40 were associated with the course of DM (r = −0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751–0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL‐40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death.ConclusionSerum YKL‐40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.