Predictors of left ventricular ejection fraction in high-risk percutaneous coronary interventions.

Revascularization completeness after percutaneous coronary intervention (PCI) is associated with improved long-term outcomes. Mechanical circulatory support [intra-aortic balloon pump (IABP) or Impella] is used during high-risk PCI (HR-PCI) to enhance peri-procedural safety and achieve more complete revascularization. The relationship between revascularization completeness [post-PCI residual SYNTAX Score (rSS)] and left ventricular ejection fraction (LVEF) in HR-PCI has not been established. We investigated LVEF predictors at 90 days post-PCI with Impella or IABP support. Individual patient data (IPD) were analyzed from PROTECT II (NCT00562016) in the base case. IPD from PROTECT II and RESTORE-EF (NCT04648306) were naïvely pooled in the sensitivity analysis. Using complete cases only, linear regression was used to explore the predictors of LVEF at 90 days post-PCI. Models were refined using stepwise selection based on Akaike Information Criterion and included: treatment group (Impella, IABP), baseline characteristics [age, gender, race, New York Heart Association Functional Classification, LVEF, SYNTAX Score (SS)], and rSS. Impella treatment and higher baseline LVEF were significant predictors of LVEF improvement at 90 days post-PCI (p ≤ 0.05), and a lower rSS contributed to the model (p = 0.082). In the sensitivity analysis, Impella treatment, higher baseline LVEF, and lower rSS were significant predictors of LVEF improvement at 90 days (p ≤ 0.05), and SS pre-PCI contributed to the model (p = 0.070). Higher baseline LVEF, higher SS pre-PCI, lower rSS (i.e. completeness of revascularization), and Impella treatment were predictors of post-PCI LVEF improvement. The findings suggest potential mechanisms of Impella include improving the extent and quality of revascularization, and intraprocedural ventricular unloading.

Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review.

BACKGROUND: Patients with chronic kidney disease, especially those receiving hemodialysis (HD), are at risk of hyperkalemia (HK). This systematic review aimed to evaluate the prevalence of HK in patients with renal disease receiving HD and collate evidence on the effect of HK and differing HD patterns (i.e., long vs. short inter-dialytic intervals [LIDI and SIDI, respectively] in a thrice weekly schedule) on mortality. METHODS: Comprehensive searches were conducted across six databases and selected conference proceedings by two independent reviewers up to September 2020. A hundred and two studies reporting frequency of HK, mortality, or cardiovascular (CV) outcomes in adult patients with acute, chronic or end-stage renal disease in receipt of HD were included. Narrative synthesis of results was undertaken with key findings presented in tables and figures. RESULTS: Median prevalence of HK in patients with renal disease receiving HD was 21.6% and increased in patients receiving concomitant medications - mainly renin-angiotensin-aldosterone system inhibitors and potassium-sparing diuretics. Associations between elevated potassium levels and increased risk of both all-cause and CV mortality in the HD population were consistent across the included studies. In addition, there was a rise in all-cause and CV mortality on the day following LIDI compared with the day after the two SIDIs in patients on HD. CONCLUSIONS: Evidence identified in this systematic review indicates a relationship between HK and LIDI with mortality in patients with renal disease receiving HD, emphasizing the need for effective monitoring and management to control potassium levels both in emergency and chronic HD settings.

Randomized Noninferiority Trial of Telephone Delivery of BRCA1/2 Genetic Counseling Compared With In-Person Counseling: 1-Year Follow-Up.

PURPOSE: The ongoing integration of cancer genomic testing into routine clinical care has led to increased demand for cancer genetic services. To meet this demand, there is an urgent need to enhance the accessibility and reach of such services, while ensuring comparable care delivery outcomes. This randomized trial compared 1-year outcomes for telephone genetic counseling with in-person counseling among women at risk of hereditary breast and/or ovarian cancer living in geographically diverse areas. PATIENTS AND METHODS: Using population-based sampling, women at increased risk of hereditary breast and/or ovarian cancer were randomly assigned to in-person (n = 495) or telephone genetic counseling (n = 493). One-sided 97.5% CIs were used to estimate the noninferiority effects of telephone counseling on 1-year psychosocial, decision-making, and quality-of-life outcomes. Differences in test-uptake proportions for determining equivalency of a 10% prespecified margin were evaluated by 95% CIs. RESULTS: At the 1-year follow-up, telephone counseling was noninferior to in-person counseling for all psychosocial and informed decision-making outcomes: anxiety (difference [d], 0.08; upper bound 97.5% CI, 0.45), cancer-specific distress (d, 0.66; upper bound 97.5% CI, 2.28), perceived personal control (d, -0.01; lower bound 97.5% CI, -0.06), and decisional conflict (d, -0.12; upper bound 97.5% CI, 2.03). Test uptake was lower for telephone counseling (27.9%) than in-person counseling (37.3%), with the difference of 9.4% (95% CI, 2.2% to 16.8%). Uptake was appreciably higher for rural compared with urban dwellers in both counseling arms. CONCLUSION: Although telephone counseling led to lower testing uptake, our findings suggest that telephone counseling can be effectively used to increase reach and access without long-term adverse psychosocial consequences. Further work is needed to determine long-term adherence to risk management guidelines and effective strategies to boost utilization of primary and secondary preventive strategies.

Economic Evaluation Alongside a Clinical Trial of Telephone Versus In-Person Genetic Counseling for BRCA1/2 Mutations in Geographically Underserved Areas.

PURPOSE: BRCA1/2 counseling and mutation testing is recommended for high-risk women, but geographic barriers exist, and no data on the costs and yields of diverse delivery approaches are available. METHODS: We performed an economic evaluation with a randomized clinical trial comparing telephone versus in-person counseling at 14 locations (nine geographically remote). Costs included fixed overhead, variable staff, and patient time costs; research costs were excluded. Outcomes included average per-person costs for pretest counseling; mutations detected; and overall counseling, testing, and disclosure. Sensitivity analyses were performed to assess the impact of uncertainty. RESULTS: In-person counseling was more costly per person counseled than was telephone counseling ($270 [range, $180 to $400] v $120 [range, $80 to $200], respectively). Counselors averaged 285 miles round-trip to deliver in-person counseling to the participants (three participants per session). There were no differences by arm in mutation detection rates (approximately 10%); therefore, telephone counseling was less costly per positive mutation detected than was in-person counseling ($37,160 [range, $36,080 to$38,920] v $40,330 [range, $38,010 to $43,870]). In-person counseling would only be less costly than telephone counseling if the most favorable assumptions were applied to in personc ounseling and the least favorable assumptions were applied to telephone counseling. CONCLUSION: In geographically underserved areas, telephone counseling is less costly than in-person counseling.

The effects of study order and backward associative strength on illusory recollection: A source-strength effect does not always occur.

We investigated illusory recollection by dividing lists of associated words into three subsets (high, medium and low) based on their backward associative strength (BAS) to an unstudied theme. Participants studied these subsets at different visual locations on a computer screen and afterwards were given a source memory test. In Experiment 1, we varied the order in which high- and medium-BAS subsets were studied. In Experiment 2, we again manipulated study order as well as the associative strength of the medium-BAS subsets (strong or weak). Across both experiments, illusory recollection was constrained by both study order and BAS. Source attributions to the high-BAS location were more likely (a source-strength effect) when high-BAS items were studied first or studied following items of relatively low associative strength. However, attributions to the strong medium-BAS studied location were more likely when these items were studied before high-BAS items. These findings are interpreted as resulting from misbinding of source details at encoding which can be explained by the activation-monitoring theory of illusory recollection.

Expanding access to BRCA1/2 genetic counseling with telephone delivery: a cluster randomized trial.

BACKGROUND: The growing demand for cancer genetic services underscores the need to consider approaches that enhance access and efficiency of genetic counseling. Telephone delivery of cancer genetic services may improve access to these services for individuals experiencing geographic (rural areas) and structural (travel time, transportation, childcare) barriers to access. METHODS: This cluster-randomized clinical trial used population-based sampling of women at risk for BRCA1/2 mutations to compare telephone and in-person counseling for: 1) equivalency of testing uptake and 2) noninferiority of changes in psychosocial measures. Women 25 to 74 years of age with personal or family histories of breast or ovarian cancer and who were able to travel to one of 14 outreach clinics were invited to participate. Randomization was by family. Assessments were conducted at baseline one week after pretest and post-test counseling and at six months. Of the 988 women randomly assigned, 901 completed a follow-up assessment. Cluster bootstrap methods were used to estimate the 95% confidence interval (CI) for the difference between test uptake proportions, using a 10% equivalency margin. Differences in psychosocial outcomes for determining noninferiority were estimated using linear models together with one-sided 97.5% bootstrap CIs. RESULTS: Uptake of BRCA1/2 testing was lower following telephone (21.8%) than in-person counseling (31.8%, difference = 10.2%, 95% CI = 3.9% to 16.3%; after imputation of missing data: difference = 9.2%, 95% CI = -0.1% to 24.6%). Telephone counseling fulfilled the criteria for noninferiority to in-person counseling for all measures. CONCLUSIONS: BRCA1/2 telephone counseling, although leading to lower testing uptake, appears to be safe and as effective as in-person counseling with regard to minimizing adverse psychological reactions, promoting informed decision making, and delivering patient-centered communication for both rural and urban women.

Age differences in voluntary task switching.

Task choice processes in older (60+ years) and younger (18-30 years) adults were compared using a voluntary task switching procedure (Arrington & Logan, 2004). To assess age-related differences in task representation maintenance, preparation times were varied across a large range of response-to-stimulus intervals (100, 500, 1,000, and 5,000 ms) and the environmental influence on task selection was varied by repeating or changing stimuli from trial to trial. Older adults switched less frequently than younger adults and this effect was the same at each RSI. Younger adults were more likely to switch tasks when the stimulus changed than when it repeated suggesting that they used a different process to determine task choices, either endogenous task selection or environmentally supported task repetitions. Older adults' task selection was unaffected by stimulus repetitions indicating that they were less flexible with the processing they used to guide task selection. These findings are consistent with previous observations of age-related increases in goal shielding, but not with age-related deficits in task goal maintenance. Robust age differences in switch costs were observed across RSIs suggesting that task reconfiguration processes are different following endogenous than exogenous task selection.

The role of verbal short-term memory in task selection: how articulatory suppression influences task choice in voluntary task switching.

The roles of verbal short-term memory (vSTM) in task selection and task performance processes were examined when individuals were asked to voluntarily choose which of two tasks to perform on each trial randomly. Consistent with previous voluntary task-switching (VTS) research, we hypothesized that vSTM would support random task selection by maintaining a sequence of previously executed tasks that would be used by a representativeness heuristic. Furthermore, because using a representativeness heuristic requires sufficient time for updating and comparison processes, we expected that vSTM would have a greater effect on task selection when more time was available. Participants completed VTS under concurrent articulatory suppression and foot tapping at short and long response-to-stimulus intervals (RSIs). Task selection in VTS was more repetitive under suppression than under foot tapping, but this effect did not vary with RSI, suggesting that vSTM does not maintain the sequence of executed tasks to guide task selection. Instead, vSTM is critical for maintaining the intended task and ensuring that it is carried out. In contrast to the finding that a working memory load impairs task performance, we found no difference in reaction times and no switch costs between suppression and foot-tapping conditions, suggesting that vSTM is not critical for task performance.

Variation in individuals' semantic networks for common knowledge is associated with false memory.

Three experiments assessed the relationships between false memories of words and their degree of connectedness within individual semantic networks. In the first two experiments, participants studied associated word lists (e.g., hot, winter, ice), completed a recognition test that included related nonstudied words (e.g., cold, snow), and then rated the semantic relatedness of all word pairs including studied and nonstudied words. In the third experiment, the task order was reversed; participants completed pairwise ratings and then, two weeks later, completed the false memory task. The relatedness ratings were analysed using the Pathfinder scaling algorithm. In all experiments, items that an individual falsely recognized had higher semantic Pathfinder node densities than those items correctly rejected.

Working memory capacity modulates task performance but has little influence on task choice.

Variation in the ability to maintain internal goals while resolving competition from multiple information streams has been related to individual differences in working memory capacity (WMC). In a multitask environment, task choice and task performance are influenced by internal goals, prior behavior within the environment, and the availability of relevant and irrelevant information in the environment. Using the voluntary task-switching procedure, task performance, as measured by switch costs, was related to WMC, but only at short preparation intervals. Task choice processes were only weakly related to WMC. These findings are consistent with models of cognitive control that separate task choice processes from the processes of activating and maintaining task readiness. WMC is related to regulation of specific task parameters but not to choice processes integral to the coordination of multiple sources of information.

The influence of distinctive processing manipulations on older adults' false memory.

Covertly generating item-specific characteristics for each studied word from DRM (Deese-Roediger-McDermott) lists decreases false memory in young adults. The typical interpretation of this finding is that item-specific characteristics act as additional unique source information bound to each studied item at encoding, and at retrieval young adults can use the absence of this type of information to reject non-presented associated words that might otherwise be falsely remembered. In two experiments, we examined whether healthy older adults could use this strategy to reduce their false memories in the DRM paradigm. In Experiment 1, low frontal lobe functioning was associated with increased false memory in the item-specific strategy condition. Experiment 2 found more memory intrusions under item-specific encoding and the same amount of false memory in auditory and visual presentation conditions, i.e., no modality effect, even with 8 s of encoding time. Both findings are consistent with impaired distinctive processing by older adults.

Age-related deficits in reality monitoring of action memories.

The authors describe 3 theoretical accounts of age-related increases in falsely remembering that imagined actions were performed (A. K. Thomas & J. B. Bulevich, 2006). To investigate these accounts and further explore age-related changes in reality monitoring of action memories, the authors used a new paradigm in which actions were (a) imagined only, (b) actually performed, or (c) both imagined and performed. Older adults were more likely than younger adults to misremember the source of imagined-only actions, with older adults more often specifying that the action was imagined and also that it was performed. For both age groups, illusions that the actions were only performed decreased as repetitions of the imagined-only events increased. These patterns suggest that both older and younger adults use qualitative characteristics when making reality-monitoring judgments and that repeated imagination produces richer records of both sensory details and cognitive operations. However, sensory information derived from imagination appears to be more similar to that derived from performance for older adults than for younger adults.

Implementation intentions facilitate prospective memory under high attention demands.

An implementation intention is a planning technique that involves specifying a situation for initiating an intended action and linking these specific cues to the intention. In two experiments with young adults, we found significant increases in prospective memory with implementation intentions. With an implementation intention, but not with standard instructions, prospective memory performance was maintained under demanding attentional conditions (Experiment 2). Ongoing task performance did not decline, however, in relation with a no prospective memory control. Positive effects were not observed when the imagery component of the implementation intention was isolated from the verbal component. We suggest that implementation intention planning (relative to standard instructions) increases the likelihood that people will encode a robust associative link between the target cue and the intended action, thereby promoting reflexive triggering of the intended action on presentation of the target cue.

Age deficits in the control of prepotent responses: evidence for an inhibitory decline.

Older adults have more difficulty than younger adults appropriately directing their behavior when the required response is in competition with a prepotent response. The authors varied the difficulty of inhibiting a prepotent eye movement response by varying the response cue (peripheral onset or central arrow). The response cue manipulation did not affect prosaccade accuracy and latency for either age group and did not affect younger adults' antisaccades. Older adults' antisaccades were slower in the peripheral cue condition than in the central arrow condition. These findings are taken as support for the inhibitory deficit hypothesis of aging (L. Hasher, R. T. Zacks, & C. P. May, 1999).

Considerations in catheter retrieval from the arterial system.

Catheter-based techniques have become commonplace in the diagnosis and treatment of cardiovascular disease. Despite the significant improvements in materials and techniques, catheter separation or fracture may occur and result in catheter embolization or intravascular retention. We present such an occurrence during antegrade access to the common femoral artery. Although the sheared catheter was visualized fluoroscopically, attempts at percutaneous recovery were futile. Our findings at exploration confirmed total intravascular retention and impaction of the catheter. Practitioners should recognize this problem and avoid the dangers associated with percutaneous recovery.

Age differences in veridical and false recall are not inevitable: the role of frontal lobe function.

The relationship of neuropsychological measures of frontal lobe function to age differences in false recall was assessed using the Deese/Roediger-McDermott associative false memory paradigm (Deese, 1959; Roediger & McDermott, 1995). As other studies have found, older adults were less likely to correctly recall studied items and more likely to falsely recall highly related but nonpresented items than were younger adults. When older adults were divided based on a composite measure of frontal lobe functioning, this age difference was found only for low frontal lobe functioning individuals. High frontal lobe functioning older adults and young adults had equivalent levels of false recall, as well as equivalent levels of veridical recall. These results suggest that age differences in memory may be due to declines in frontal lobe function. More important, our findings indicate that declines in veridical recall and increases in false recall are not an inevitable consequence of aging.

Inhibitory processes in adults with persistent childhood onset ADHD.

The theory that attention-deficit/hyperactivity disorder (ADHD) stems from a deficit in an executive behavioral inhibition process has been little studied in adults, where the validity of ADHD is in debate. This study examined, in high-functioning young adults with persistent ADHD and a control group, 2 leading measures of inhibitory control: the antisaccad task and the negative priming task. ADHD adults showed weakened ability to effortfully stop a refle ve or anticipated oculomotor response but had normal ability to automatically suppress irrelevant information. Results suggest that an inhibitory deficit in ADHD is confined to effortful inhibition of motor response, that antisaccade and negative priming tasks index distinct inhibition systems, and that persistence of ADHD symptoms into adulthood is associated with persistence of executive motor inhibition deficits.