Immunologic profiles in patients with chronic limb-threatening ischemia undergoing endovascular revascularization.

BACKGROUND: Inflammation and immune dysregulation have been associated with adverse outcomes in cardiovascular disease. There is limited understanding of the association of different profiles of white blood cell (WBC) subsets and red cell distribution width (RDW) in patients with chronic limb-threatening ischemia (CLTI). METHODS: Patients with CLTI undergoing endovascular revascularization in our single-center, tertiary care hospital from 2017 to 2019, who had a preceding complete blood count (CBC) with WBC differentials (n =213), were included in the analysis. Patient characteristics, laboratory values, and clinical outcomes were collected. Cox proportional hazards regression models were used to assess for associations between all-cause mortality and leukocyte subset; multivariate analysis was used to account for confounders. Kaplan-Meier curves were generated to depict survival censored at 1 year postrevascularization using baseline CBC indices. RESULTS: Adjusting for confounders, elevated RDW was associated with increased mortality (continuous per % increase, adjusted hazard ratio [HR] 1.33, p < 0.001). Baseline lymphopenia was associated with mortality in univariate analysis. Other leukocyte subtypes were not associated with mortality outcomes in our population. Exploratory analysis showed negative deflections in ∆WBC from pre- to postprocedure day 1 were affiliated with increased mortality when adjusted for age, sex, race, chronic kidney disease, and baseline hemoglobin (∆WBC HR 1.16, p = 0.004). Further exploratory analysis showed an association between RDW and all-comers readmission. CONCLUSIONS: The utilization of a periprocedural WBC subset differential can be a useful adjunct to risk-stratify patients with CLTI undergoing endovascular revascularization. Further studies are needed to understand potential ways to modulate immune dysregulation so as to improve mortality outcomes.

Novel intracardiac echocardiography-guided catheter-based removal of inoperable tricuspid valve vegetation.

With the ongoing intravenous drug abuse (IVDA) epidemic, the number of IVDA patients with infective endocarditis is increasing. These cases are often characterized by large vegetations complicated by valvular dysfunction, heart failure, and recurrent septic pulmonary emboli demanding surgical intervention. Latter cannot be offered in a good proportion of the patients due to challenging medical and social complexities. Hence, AngioVac system has been used as an alternative therapy; however, it is associated with high procedural mortality. In this document, we describe in detail the successful treatment of a case of large tricuspid valve vegetation, with prohibitive risk for surgery, using a percutaneous catheter-based system, the Triever aspiration catheter with FLEX technology, with the guidance of intracardiac echocardiogram.

The utility of geriatric nutritional risk index to predict outcomes in chronic limb-threatening ischemia.

OBJECTIVES: To assess geriatric nutritional risk index (GNRI) in patients with chronic limb-threatening ischemia (CLTI). BACKGROUND: The prevalence of CLTI continues to rise, with major amputation and mortality remaining prominent. Frailty is a vital risk factor for adverse outcomes in cardiovascular care. The GNRI is a nutrition-based surrogate for frailty that has been utilized in Southeast Asia to predict adverse events in CLTI. It has not yet been evaluated in a primarily Western population, nor in the context of wound healing. METHODS: Between 8August 2017 and April 2019, we identified patients undergoing endovascular interventions for CLTI at our institution, categorized into low GNRI (≤ 94, frail) versus normal GNRI (> 94, reference). We analyzed the risks of major adverse limb events (MALE), its individual components [mortality, major amputation, and target vessel revascularization (TVR)], amputation free survival (AFS), and wound healing using Kaplan-Meier and multivariate cox-proportional hazard regression analyses. RESULTS: A total of 255 patients were included in the analysis, with follow up of 14 ± 9.1 months. Lower GNRI was associated with higher cumulative event rates for MALE (71.0% vs. 43.3%, p < 0.001), mortality (34.3% vs. 15.2%, p < 0.001), major amputation (31.2% vs. 15.8%, p = 0.002), and freedom from AFS (56.0% vs. 28.2%, p < 0.001). There was a trend toward lower TVR and higher wound healing with higher GNRI score. CONCLUSIONS: Our single-center, retrospective evaluation of GNRI (as a surrogate for frailty) correlated with increased risks of MALE, mortality, and major amputation. Future directions should focus not only on the recognition of these patients, but risk-factor modification to optimize long-term outcomes.

Predictors and potential advantages of PERT and advanced therapy use in acute pulmonary embolism.

OBJECTIVES: We sought to examine predictors of pulmonary embolism response team (PERT) utilization and identify those who could benefit from advanced therapy. BACKGROUND: PERT and advanced therapy use remain low. Current risk stratification tools heavily weight age and comorbidities, which may not always correlate with presentation's severity. METHODS: We prospectively studied patients with CT-confirmed PE between January 2019 and December 2019 at our hospital. PERT activation was left to the treating physician. Multivariable analyses were utilized to identify predictors of PERT activation and advanced therapy. Using the log odd ratio of each significant predictor of advanced therapy, we created a scoring system and a score of 2 was associated with the highest use. Primary outcomes were 30- and 90-day all-cause mortality, readmission, and major bleed. RESULTS: Of the 307 patients, PERT was activated in 22.5%. While abnormal vital signs and right ventricular (RV) strain were associated with PERT activation, pulmonary embolism severity index (PESI) was not. Advanced therapy use was significantly higher in the PERT cohort (35% vs 2%). Predictors of advanced therapy use were composite variable (heart rate > 110 or systolic blood pressure < 100 or respiratory rate > 30 or oxygen saturation < 90%) and right-to-left ventricular ratio > 0.9. PERT patients with advanced therapy use, when compared to the no-PERT patients who could have qualified (score of 2), had significantly lower 30- and 90-day mortality and 30-day readmission without difference in major bleed. CONCLUSION: PERT has important therapeutic impact, yet no guidelines to direct activation. We recommend a multidisciplinary approach for higher acuity pulmonary embolism cases and physician education regarding PERT and the scope of advanced therapy use.

Impact of COVID-19 pandemic on ST-elevation myocardial infarction in a non-COVID-19 epicenter.

OBJECTIVES: We sought to study the impact of COVID-19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST-elevation myocardial infarction (STEMI) in a non-hot-spot region. BACKGROUND: COVID-19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain. METHODS: From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18-hospital system. Pre- and post-COVID-19 cohorts were based on March 23rd, 2020, whenstay-at-home orders were initiated in Ohio. We used presenting heart rate, blood pressure, troponin, new Q-wave, and left ventricle ejection fraction (LVEF) to assess severity. Duration of intensive care unit stay, total length of stay, door-to-balloon (D2B) time, and radial versus femoral access were used to assess patterns of care. RESULTS: Post-COVID-19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q-wave, and higher initial troponin; however, these did not reach statistical significance. Among post-COVID-19 patients, those with >12-hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs. 8.5 ng/ml, p = .03). Of these, 27% avoided the hospital due to fear of COVID-19, 18% believed symptoms were COVID-19 related, and 9% did not want to burden the hospital during the pandemic. CONCLUSIONS: COVID-19 has remarkably affected STEMI presentation and care. Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis.

Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results.

Purpose: To present the 6-month results of the Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial (ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy.

The utility of real-world evidence for benefit-risk assessment, communication, and evaluation of pharmaceuticals: Case studies.

PURPOSE: In recent years, novel types of real-world evidence (RWE) have played a role in various decision-making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post-approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit-risk (BR) assessment, communication/risk minimization and evaluation ("BRACE"). METHODS: A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision-making. RESULTS: Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post-approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance. CONCLUSIONS: RWE has an important role in informing regulatory decision-making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision-making.

Associations of exercise ankle-brachial index, pain-free walking distance and maximum walking distance with the Peripheral Artery Questionnaire: Finding from the PORTRAIT PAD Registry.

An exercise ankle-brachial index (ABI) test can provide further insight into the functional significance of peripheral artery disease (PAD). The variability in its use, associated patient factors and its relation to patients' symptoms are unknown. From the international PORTRAIT registry, we identified 1131 patients with PAD. We fit a hierarchical logistic regression model, adjusting for patient factors, country and site, to examine predictors of and variation in ordering exercise ABI testing. We also examined the associations between test components and health status as quantified by the Peripheral Artery Questionnaire (PAQ) using semi-parametric regression methods. Testing was ordered in 22% in the United States versus 80% in the Netherlands and 90% in Australia. Testing was likely to be performed if the patient was male, younger, had typical symptoms and a higher resting ABI, with substantial variability across sites (median odds ratio=5.9, 95% CI: 3.2-19.5). Adjusting for country and site, the resting ABI and all exercise ABI metrics were associated with the PAQ Physical Limitation score. In addition, important components of the test, namely time to onset of claudication, pain-free walking distance (PFWD), and maximum walking distance (MWD), were also associated with PAQ Symptoms and Summary scores. More importantly, even after adjusting for resting ABI, a patient with a post-exercise ABI of 0.29 (25th percentile), compared to 0.61 (75th percentile), achieved 4.4 (95% CI: 0.4-8.4, p=0.031) points less on the PAQ Physical Limitation score. Exercise ABI test use is remarkably variable, and less used in the United States. Its data, specifically PFWD and MWD, might help in objectively assessing the impact of PAD on patients' functioning and quality of life.

SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial.

The efficacy of biologic therapies in critical limb ischemia (CLI) remains elusive, in part, due to limitations in trial design and patient selection. Using a novel design, we examined the impact of complementing revascularization therapy with intramuscular JVS-100 - a non-viral gene therapy that activates endogenous regenerative repair pathways. In this double-blind, placebo-controlled, Phase 2B trial, we randomized 109 patients with CLI (Rutherford class V or VI) to 8 mg or 16 mg intramuscular injections of placebo versus JVS-100. Patients were eligible if they persistently had reduced forefoot perfusion, by toe-brachial index (TBI) or skin perfusion pressure (SPP), following successful revascularization with angiographic demonstration of tibial arterial flow to the ankle. The primary efficacy end point was a 3-month wound healing score assessed by an independent wound core laboratory. The primary safety end point was major adverse limb events (MALE). Patients' mean age was 71 years, 33% were women, 79% had diabetes, and 8% had end-stage renal disease. TBI after revascularization was 0.26, 0.27, and 0.26 among the three groups (placebo, 8 mg, and 16 mg injections, respectively). Only 26% of wounds completely healed at 3 months, without any differences between the three groups (26.5%, 26.5%, and 25%, respectively). Similarly, there were no significant changes in TBI at 3 months. Three (2.8%) patients died and two (1.8%) had major amputations. Rates of MALE at 3 months were 8.8%, 20%, and 8.3%, respectively. While safe, JVS-100 failed to improve wound healing or hemodynamic measures at 3 months. Only one-quarter of CLI wounds healed at 3 months despite successful revascularization, highlighting the need for additional research in therapies that can improve microcirculation in these patients. ClinicalTrials.gov Identifier: NCT02544204.

Personalized benefit-risk assessments combining clinical trial and real-world data provide further insights into which patients may benefit most from therapy: Demonstration for a new oral antiplatelet therapy.

PURPOSE: Quantitative benefit-risk (B-R) assessments are used to characterize treatment by combining key benefits and risks into a single metric but have historically been done for the "average" patient. Our aim was to conduct an individualized assessment for the oral antiplatelet vorapaxar by combining trial and real-world data to further personalize the treatment profiles. METHODS: Using linked UK health care databases, we developed risk prediction equations for key ischemic and bleeding events using Cox proportional hazards models. Trial hazard ratios, relative to placebo, were applied to baseline risk estimates to compute expected attributable risks, summed to derive a per-patient net clinical benefit (NCB). High risk subgroups were defined a priori, and Gaussian mixture models (GMM) were fit to characterize the NCB distribution and identify subgroups with similar NCBs. RESULTS: NCB was consistently positive for all subgroups, likely due to the outcome correlation, and would remain positive with a 12-fold increase in bleeding risk. GMMs identified three distinct NCB subgroups. Compared with the middle/lower NCB subgroups, those with a higher NCB tended to be older, female, and have higher CV disease burden. CONCLUSIONS: Personalized B-R assessments are feasible and clinically valuable and can be used to better predict who would benefit most from therapy.

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for cancer. Due to the mechanism of action of ICIs, inflammatory reactions against normal tissue were an anticipated side effect of these agents; these immune-related adverse events have been documented and are typically low grade and manageable. Myocarditis has emerged as an uncommon but potentially life-threatening adverse reaction in patients treated with ICIs. Assessment and characterization of ICI-associated myocarditis is challenging because of its low incidence and protean manifestations. Nevertheless, the seriousness of ICI-associated myocarditis justifies a coordinated effort to increase awareness of this syndrome, identify patients who may be at risk, and enable early diagnosis and appropriate treatment. The "Checkpoint Inhibitor Safety Working Group," a multidisciplinary committee of academic, industry, and regulatory partners, convened at a workshop hosted by Project Data Sphere, LLC, on December 15, 2017. This meeting aimed to evaluate the current information on ICI-associated myocarditis, determine methods to collect and share data on this adverse reaction, and establish task forces to close the identified knowledge gaps. In this report, we summarize the workshop findings and proposed steps to address the impact of ICI-associated myocarditis in patients with cancer.

Analysis of IN.PACT DEEP trial on the association between changes in perfusion from pre- to postrevascularization and clinical outcomes in critical limb ischemia.

OBJECTIVES: To quantify changes in ankle and toe pressure from pre- to post-endovascular revascularization for critical limb ischemia (CLI) and examine their association with major adverse limb events (MALE). BACKGROUND: Despite societal guidelines recommendation of routine hemodynamic surveillance following revascularization, little is known about hemodynamic assessment in CLI. METHODS: Among the 358 patients with CLI from the international multicenter IN.PACT DEEP trial, ankle and toe pressures measurements were available at both baseline and after intervention in 270 and 44 patients, respectively. The change in ankle and toe pressures in response to endovascular revascularization and its association with 1-year MALE (target limb revascularization, amputation, or death) were examined using Kaplan-Meier curves and multivariable Cox proportional hazard analyses. Corresponding optimal cutoff points were also identified. RESULTS: The mean increase in ankle and toe pressures following revascularization was 33 and 13 mmHg, respectively. Patients with an improvement of ankle pressure >73 mmHg or toe pressure >1 mmHg had similarly the lowest incidence of MALE (23%), while the highest rate of MALE (50%) was found in those whose toe pressure failed to improve by at least 1 mmHg following intervention. In addition, an increase in ankle pressure >73 mmHg was numerically protective against MALE, and more importantly, an increase in toe pressure of >1 mmHg provided statistically significant protection from MALE (adjusted HR = 0.15, 95% CI: 0.04-0.57, P = 0.005). CONCLUSIONS: Improvements in toe pressure post revascularization are incremental and rarely normalize. Toe pressure, compared to ankle pressure, is more useful in CLI and predicts future MALE.

Prognostic value of an increase in post-exercise ankle-brachial index.

Prior studies have assessed the prognostic value of a decrease, not an increase, of the post-exercise ankle-brachial index (ABI) among patients with normal resting results. Thus, we sought to evaluate the prognostic significance of an increase in post-exercise ABI among these patients. From a single center vascular laboratory database between September 2005 and January 2010, we retrospectively identified 1437 consecutive patients with a normal resting ABI (1.00-1.40) and available post-exercise results. We classified them into group 1 (normal subjects; post-exercise ABI drop ⩽ 20%, 58%) and group 2 (post-exercise ABI increase, 42%) after excluding those with an ABI drop > 20% (peripheral artery disease) as they had known disease ( n=192). The primary outcome was to assess the risk of ischemic events, defined as a composite of unadjudicated death, stroke, or myocardial infraction (MACE). Associations between groups and outcomes were examined using multivariable Cox proportional hazard and propensity analyses. Both groups had similar prevalence of cardiovascular comorbidities. In unadjusted analysis, group 2 was more likely to have MACE ( p = 0.001). After adjusting for all baseline characteristics, an increase in post-exercise ABI compared to normal subjects was associated with a higher MACE (adjusted HR: 1.70, 95% CI: 1.14-2.53; p=0.009). This association stayed statistically significant after propensity matching (adjusted HR: 1.80, 95% CI: 1.17-2.76; p=0.007). This hypothesis-generating analysis showed that an increase in post-exercise ABI appears to identify a population with a higher risk for MACE. A prospective study of this association and mechanisms of risk should be conducted.

The Contemporary Role of Stents and Angioplasty for the Treatment of Infrapopliteal Disease in Critical Limb Ischemia.

PURPOSE OF REVIEW: Critical limb ischemia (CLI) is associated with significant morbidity, mortality, and increased health care expenses. Revascularization has a central role in the treatment of CLI. Following publication of BASIL (bypass versus angioplasty in severe ischemia of the leg) trial a decade ago, an "endovascular first" approach had gained momentum and the technologies available for endovascular therapy have exponentially increased. Both the development of technology and technique, highlighted in this review, have allowed operators to treat complex infrapopliteal lesions which are central to CLI pathology. RECENT FINDINGS: The role of atherectomy remains controversial but for calcified lesions it has become an accepted adjunctive tool for plaque modification. The place of drug delivery technologies requires further trials. The use of a drug-coated balloon (DCB) makes intuitive sense; however, choice of excipient, lower limit of vessel size, and impact on remodeling and thrombosis remain uncertain. The optimal treatment of infrapopliteal disease remains an area of active investigation. The endpoints in CLI trials continue to be challenging and calibration of patency in relation to wound healing remains a moving target. In addition, unaccounted variables continue to confound interpretation of CLI trials-including quality and nature of wound care, status of pedal-plantar loop patency, and management of underlying diabetes and other comorbidities. In summary, these challenges will also need to be addressed as the CLI field continues to mature in the twenty-first century.

An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia.

OBJECTIVE: Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. METHODS: Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available ankle-brachial index (ABI), and only 40 of the latter had available toe pressure measurements. The associations between ABI, ankle pressure, and toe pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (≥70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. RESULTS: Only 14 of 237 patients (6%) had an ABI <0.4. Abnormal ankle pressure, defined as <50 mm Hg if Rutherford category 4 and <70 mm Hg if Rutherford category 5 or 6, was found only in 37 patients (16%). Abnormal toe pressure, defined as <30 mm Hg if Rutherford category 4 and <50 mm Hg if Rutherford category 5 or 6, was found in 24 of 40 patients (60%) with available measurements. Importantly, 29% of these 24 patients had an ABI within normal reference ranges. A univariate multinomial logistic regression found no association between the above hemodynamic parameters and the number of diseased infrapopliteal vessels. However, there was a significant paradoxic association where patients with Rutherford category 6 had higher ABI and ankle pressure than those with Rutherford category 5. Similarly, there was no association between ABI and pedal arch patency. CONCLUSIONS: The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe pressure has better sensitivity and should be considered in all patients with critical limb ischemia.

The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease.

Peripheral artery disease (PAD) is associated with increased mortality and concomitant coronary artery disease (CAD). However, it is unclear whether uncovering the presence of functional coronary ischemia by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk. From January 2000 to 2009, 4294 individuals underwent cardiac stress testing within 180 days of ankle-brachial index (ABI) measurements. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ⩽ 0.9 or prior lower extremity arterial revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by the summed difference score (SDS) and summed stress score (SSS), respectively. Univariate and multivariable Cox proportional hazard analyses were used to study the impact of SDS and SSS on all-cause mortality. Additionally, using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and lower extremity arterial revascularizations as time-varying covariates on outcomes. We found no significant difference in all-cause mortality between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0) (adjusted HR: 0.94, 95% CI: 0.53-1.69; p = 0.84). Similarly, the presence of jeopardized myocardium (SSS > 0) did not have a significant impact on mortality (adjusted HR: 1.16, 95% CI: 0.67-2.00; p = 0.59). Moreover, adjustment for post-testing coronary and lower extremity arterial revascularizations did not affect our results. In conclusion, ischemic and jeopardized myocardia are not predictors of all-cause mortality in PAD; thus, SPECT MPI does not appear to be a useful risk stratification tool in these patients.

Evaluating the validity of clinical codes to identify cataract and glaucoma in the UK Clinical Practice Research Datalink.

PURPOSE: The aim of this study is to determine (i) the positive predictive value (PPV) of an algorithm using clinical codes to identify incident glaucoma and cataract events in the Clinical Practice Research Datalink (CPRD) and (ii) the ability to capture the correct timing of these clinical events. METHODS: A total of 21,339 and 5349 potential cataract and glaucoma cases, respectively, were identified in CPRD between 1 January 1990 and 31 December 2010. Questionnaires were sent to the general practitioners (GP) of 1169 (5.5%) cataract and 1163 (21.7%) glaucoma cases for validation. GPs were asked to verify the diagnosis and the timing of the diagnosis and to provide other supporting information. RESULTS: A total of 986 (84.3%) valid cataract questionnaires and 863 (74.2%) glaucoma questionnaires were completed. 92.1% and 92.4% of these used information beyond EMR to verify the diagnosis. Cataract and glaucoma diagnoses were confirmed in the large majority of the cases. The PPV (95% CI) of the cataract and glaucoma Read code algorithm were 92.0% (90.3-93.7%) and 84.1% (81.7-86.6%), respectively. However, timing of diagnosis was incorrect for a substantial proportion of the cases (20.3% and 32.8% of the cataract and glaucoma cases, respectively) among whom 30.4% and 49.2% had discrepancies in diagnosis timing greater than 1 year. CONCLUSIONS: High PPV suggests that the algorithms based on the clinical Read codes are sufficient to identify the cataract and glaucoma cases in CPRD. However, these codes alone may not be able to accurately identify the timing of the diagnosis of these eye disorders. Ltd.

Patterns of prescription of antidepressants and antipsychotics across and within pregnancies in a population-based UK cohort.

Although antidepressant and antipsychotic utilization by gestational trimester has been described, longitudinal prescription patterns within pregnancies have received less attention. All mothers in the Clinical Practice Research Datalink's Mother Baby Link enrolled from 6 months before pregnancy to 3 months after delivery, with delivery date between 01/1989 and 12/2010 were included (n = 421,645). Drug use prevalence was calculated as the number of women with prescriptions for antidepressants or antipsychotics in capsules/tablets in the 3 months before pregnancy (T0), the first (T1), second (T2), or third (T3) pregnancy trimesters, or the 3 months after delivery (T4). In each pregnancy, prescriptions in T0 and T3 were compared to identify treatment discontinuation, simplification (some drugs discontinued or dose lowered), no treatment change, intensification (drugs added to prior treatment or dose increased), and start. Antidepressant use in T0 through T4 was 4.69, 2.81, 1.31, 1.34, and 5.46 %, respectively. Of 19,774 T0 antidepressant users, 79.57 % discontinued, 5.13 % simplified, 9.06 % did not change, and 2.19 % intensified treatment. 0.40 % of non-users in T0 started antidepressants by T3. Antipsychotic use in T0 through T4 was 0.57, 1.34, 0.54, 0.28 and 0.38 %. Excluding prochlorperazine, it was 0.15, 0.13, 0.08, 0.07 and 0.15 %, respectively; of 639 T0 users, 72.30 % discontinued, 7.51 % simplified, 11.11 % did not change, and 4.07 % intensified treatment. 0.03 % of non-users in T0 started antipsychotics by T3. Cross-sectional and longitudinal analyses identified a post-conception decrease in antidepressant and antipsychotic prescribing. Longitudinal treatment assessment additionally captured several treatment patterns among those who do not discontinue treatment that usually stay unrecognized.

The prevalence and trends of antiviral medication use during pregnancy in the US: a population-based study of 664,297 deliveries in 2001-2007.

To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15-45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy.