ABSTRACT
BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3â×â1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.
Subject(s)
Adenoviridae/genetics , BCG Vaccine/administration & dosage , Carcinoma in Situ/therapy , Drug Resistance, Neoplasm , Genetic Therapy , Genetic Vectors , Interferon alpha-2/genetics , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Aged , BCG Vaccine/adverse effects , Carcinoma in Situ/genetics , Carcinoma in Situ/mortality , Carcinoma in Situ/pathology , Disease Progression , Female , Genetic Therapy/adverse effects , Genetic Therapy/mortality , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Time Factors , Treatment Outcome , United States , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVE: Vinpocetine has been shown to enhance memory in animal models, with possible cognitive benefit in humans. The present study sought to demonstrate if vinpocetine can enhance cognition in healthy volunteers or patients with epilepsy. In addition, we compare blood levels of vinpocetine and its active metabolite (apovincaminic acid; AVA) in humans and animals to further characterize factors related to possible therapeutic benefit. METHODS: The cognitive effects of vinpocetine were assessed in healthy adult volunteers (nâ¯=â¯8) using a double-blind, randomized, crossover design at single doses (placebo, 10, 20, and 60â¯mg oral). Cognitive effects of vinpocetine in patients with focal epilepsy (nâ¯=â¯8) were tested using a double-blind, randomized, crossover design at single doses (placebo, 20â¯mg oral) followed by one-month open label at 20â¯mg oral three times a day. The neuropsychological battery included both computerized and non-computerized tests. Levels of vinpocetine and AVA in the human studies were compared to levels in 45 mice across time dosed at 5-20â¯mg/kg intraperitoneal of vinpocetine. RESULTS: No significant cognitive benefits were seen in healthy volunteers or patients with epilepsy. No appreciable side effects occurred. Vinpocetine and AVA levels were lower in humans than animals. CONCLUSIONS: Vinpocetine was well tolerated, but was not associated with positive cognitive effects. However, blood levels obtained in humans were substantially less than levels in animals obtained from dosages known to be effective in one model. This suggests that higher dosages are needed in humans to assess vinpocetine's cognitive efficacy.
Subject(s)
Cognition/drug effects , Epilepsies, Partial , Epilepsy , Vinca Alkaloids/therapeutic use , Adult , Animals , Humans , Memory , MiceABSTRACT
ABSTRACT: Locally advanced or metastatic basal cell carcinomas (laBCCs or mBCCs) are rare, with few case series providing information on their epidemiology. We aimed to describe the clinical and histologic features of locally advanced and metastatic basal cell carcinomas. Forty cases of laBCC or mBCC were identified by searching Vanderbilt's database from 1984 to January 2019. A retrospective chart review was performed. Pathology slides were available for 23 cases (13 mBCCs and 10 laBCCs). Twenty-one of 23 cases were Clark level IV or V, with a mean depth of invasion of >7 mm for both types. The mean mitotic rate was 4.4 mitoses/mm2 for laBCCs and 3.3 mitoses/mm2 for mBCCs. Ulceration was identified in 7 laBCC and 8 mBCC cases. Perineural invasion was present in 2 laBCC and 6 mBCC cases, with 3 mBCCs invading nerves >0.1 mm. Of 13 mBCC cases, histologic subtypes included infiltrative (n = 9), nodular (n = 7), morpheaform (n = 4), and superficial (n = 2), with multiple patterns present in some specimens. 10 of 13 patients with mBCC had local recurrence before metastasis. In summary, we identified several potential markers of high-risk BCC, including perineural invasion, deep invasion, elevated mitotic rate, and local recurrence of the primary tumor.
Subject(s)
Carcinoma, Basal Cell/pathology , Skin Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Internationally, there has been substantial growth in temporary working, including in the medical profession where temporary doctors are known as locums. There is little research into the implications of temporary work in health care. In this paper, we draw upon theories concerning the sociology of the medical profession to examine the implications of locum working for the medical profession, healthcare organisations and patient safety. We focus particularly on the role of organisations in professional governance and the positioning of locums as peripheral to or outside the organisation, and the influence of intergroup relationships (in this case between permanent and locum doctors) on professional identity. Qualitative semi-structured interviews were conducted between 2015 and 2017 in England with 79 participants including locum doctors, locum agency staff, and representatives of healthcare organisations who use locums. An abductive approach to analysis combined inductive coding with deductive, theory-driven interpretation. Our findings suggest that locums were perceived to be inferior to permanently employed doctors in terms of quality, competency and safety and were often stigmatised, marginalised and excluded. The treatment of locums may have negative implications for collegiality, professional identity, group relations, team functioning and the way organisations deploy and treat locums may have important consequences for patient safety.
Subject(s)
Medicine , Physicians, Family , England , Humans , Patient SafetyABSTRACT
We simulated the effect of several automatic gain control (AGC) and AGC-like systems and head movement on the output levels, and resulting interaural level differences (ILDs) produced by bilateral cochlear-implant (CI) processors. The simulated AGC systems included unlinked AGCs with a range of parameter settings, linked AGCs, and two proprietary multi-channel systems used in contemporary CIs. The results show that over the range of values used clinically, the parameters that most strongly affect dynamic ILDs are the release time and compression ratio. Linking AGCs preserves ILDs at the expense of monaural level changes and, possibly, comfortable listening level. Multichannel AGCs can whiten output spectra, and/or distort the dynamic changes in ILD that occur during and after head movement. We propose that an unlinked compressor with a ratio of approximately 3:1 and a release time of 300-500 ms can preserve the shape of dynamic ILDs, without causing large spectral distortions or sacrificing listening comfort.
Subject(s)
Cochlear Implantation , Cochlear Implants , Sound Localization , Speech Perception , Auditory Perception , Head MovementsABSTRACT
BACKGROUND: Many countries use external evaluation programmes such as accreditation in order to improve quality and safety in their healthcare settings. Hospital accreditation has developed in many low-and-middle-income countries (LMICs); however, the implementation and sustainability of these programmes vary in each country. This study addresses design and implementation issues of national hospital accreditation programmes. It identifies factors which may explain why programmes can be implemented successfully in one country but not in another and derives lessons for the design and implementation of national accreditation programmes in poor-resource settings. METHODS: A multiple case study design was used, comprising three countries in the Eastern Mediterranean Region: Egypt, Lebanon and Jordan. In-depth semi-structured interviews were conducted with 27 key stakeholders in the three countries and experts from international organisations concerned with accreditation activities in LMICs. RESULTS: The hospital accreditation programme was successful and sustainable in Jordan but experienced some difficulties in Egypt and Lebanon. The premature end of external funding and devastating political instability after the Arab Spring were problematic for the programmes in Egypt and Lebanon, but continuous funding and strong political will supported the implementation and sustainability of the programme in Jordan. CONCLUSIONS: LMICs striving to improve their hospitals' performance through accreditation programmes should consider their vulnerability to a scarcity of financial resources and political instability. An important factor underpinning sustainability is recognising that the accreditation programme is an ongoing and developing quality improvement process that needs continuing and careful attention from funders and political systems if it is to survive and thrive.
Subject(s)
Accreditation , Hospitals , Egypt , Jordan , Lebanon , Mediterranean RegionABSTRACT
Cutaneous metastases from solid tumor malignancies often emanate from breast, gastrointestinal, and lung tumors. Adenocarcinomas from minor salivary gland cancers may involve the skin contiguously but rarely as metastatic deposits. Furthermore, these metastases are usually locoregional and not distal. Recently, an uncommon neoplasm termed cribriform adenocarcinoma of the minor salivary glands has been described, and although it often spreads to cervical lymph nodes, metastatic involvement of the skin has not been reported.
Subject(s)
Adenocarcinoma/secondary , Salivary Gland Neoplasms/pathology , Salivary Glands, Minor/pathology , Skin Neoplasms/secondary , Adult , Central Nervous System Neoplasms/secondary , Humans , Lung Neoplasms/secondary , MaleABSTRACT
BACKGROUND: In the regulation of healthcare, the subject of patient and family involvement figures increasingly prominently on the agenda. However, the literature on involving patients and families in regulation is still in its infancy. A systematic analysis of how patient and family involvement in regulation is accomplished across different health systems is lacking. We provide such an overview by mapping and classifying methods of patient and family involvement in regulatory practice in four countries; Norway, England, the Netherlands, and Australia. We thus provide a knowledge base that enables discussions about possible types of involvement, and advantages and difficulties of involvement encountered in practice. METHODS: The research design was a multiple case study of patient and family involvement in regulation in four countries. The authors collected 1) academic literature if available and 2) documents of regulators that describe user involvement. Based on the data collected, the authors from each country completed a pre-agreed template to describe the involvement methods. The following information was extracted and included where available: 1) Method of involvement, 2) Type of regulatory activity, 3) Purpose of involvement, 4) Who is involved and 5) Lessons learnt. RESULTS: Our mapping of involvement strategies showed a range of methods being used in regulation, which we classified into four categories: individual proactive, individual reactive, collective proactive, and collective reactive methods. Reported advantages included: increased quality of regulation, increased legitimacy, perceived justice for those affected, and empowerment. Difficulties were also reported concerning: how to incorporate the input of users in decisions, the fact that not all users want to be involved, time and costs required, organizational procedures standing in the way of involvement, and dealing with emotions. CONCLUSIONS: Our mapping of user involvement strategies establishes a broad variety of ways to involve patients and families. The four categories can serve as inspiration to regulators in healthcare. The paper shows that stimulating involvement in regulation is a challenging and complex task. The fact that regulators are experimenting with different methods can be viewed positively in this regard.
Subject(s)
Delivery of Health Care/legislation & jurisprudence , Family/psychology , Patient Participation/methods , Australia , England , Humans , Netherlands , NorwayABSTRACT
People with epilepsy are at increased risk for neuropsychological dysfunction due to multiple factors, of which the most amendable are antiseizure medications (ASMs). Antiseizure medication effectiveness is frequently determined by tolerability. In this study, we compared the neuropsychological effects of eslicarbazepine acetate (ESL) and carbamazepine immediate-release (CBZ) using a randomized, double-blind, crossover design in healthy volunteers with a 2-week titration and 4-week maintenance phase in each treatment arm (CBZâ¯=â¯400â¯mg BID and ESLâ¯=â¯800â¯mg qAM). Neuropsychological testing was performed at the initial visit, repeated at 1st baseline nondrug condition, end treatment #1, 2nd nondrug condition one month after treatment #1, end treatment #2, and 3rd nondrug condition one month after treatment #2. Neuropsychological testing was conducted 2â¯h after morning dose and included computer (i.e., dual task test, selective attention test, symbol digit, verbal memory, visuospatial memory, and 1- & 2-back continuous performance) and noncomputer tasks (i.e., Medical College of Georgia (MCG) paragraph memory, Stroop, Symbol Digit Modalities Test, Profile of Mood States). z-Scores calculated from nondrug conditions were used to compare ESL and CBZ for the 23 completers. Follow-up analyses included individual test scores and distribution of individual raw means. Mean blood levels on test day were CBZâ¯=â¯8.9⯵g/ml and ESLâ¯=â¯15.3⯵g/ml. Omnibus z-score was significantly better for ESL (pâ¯=â¯.0001). For individual measures, executive function and selective attention tests were statistically significantly better for ESL. Individual test raw means favored ESL over CBZ on 22 of 30 measures (pâ¯=â¯.016, 2-tailed sign test). Eslicarbazepine acetate demonstrated less adverse neuropsychological effects than CBZ.
Subject(s)
Anticonvulsants/adverse effects , Carbamazepine/adverse effects , Dibenzazepines/adverse effects , Epilepsy/drug therapy , Epilepsy/psychology , Adolescent , Adult , Affect/drug effects , Attention/drug effects , Cross-Over Studies , Double-Blind Method , Female , Healthy Volunteers , Humans , Male , Memory/drug effects , Middle Aged , Neuropsychological Tests , Psychomotor Performance/drug effects , Spatial Memory/drug effects , Stroop Test , Treatment Outcome , Young AdultABSTRACT
Pathologists and dermatopathologists commonly encounter tumors with adipocyte differentiation. Most are of minimal clinical significance. Those exhibiting atypical spindle cell morphology have been reported but the terminology for such neoplasms is unsettled. Tumors with both spindle cell and pleomorphic morphology are rare, with equally unsettled descriptive nomenclature. Recently, a series of such tumors, termed atypical pleomorphic lipomatous tumor, has been published. They resided in the deep soft tissue or subcutis. To date, such a tumor has not been reported with dermal involvement.
Subject(s)
Cheek/pathology , Liposarcoma/immunology , Liposarcoma/pathology , Antigens, CD34/immunology , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Humans , Lost to Follow-Up , Male , Middle Aged , Referral and Consultation , Surgical OncologyABSTRACT
BACKGROUND: High profile failures of care in the NHS have raised concerns about regulatory systems for health-care professionals and organizations. In response, the Care Quality Commission (CQC), the regulator of health and social care in England overhauled its regulatory regime. It moved to inspections which made much greater use of expert knowledge, data and views from a range of stakeholders, including service users. OBJECTIVE: We explore the role of service users and citizens in health and social care regulation, including how CQC involved people in inspecting and rating health and social care providers. DESIGN: We analyse CQC reports and documents, and 61 interviews with CQC staff and representatives of groups of service users and citizens and voluntary sector organizations to explore the place of service user voice in regulatory processes. RESULTS: Care Quality Commission invited comments and facilitated the sharing of existing service user experiences and engaged with representatives of groups of service users and voluntary sector organizations. CQC involved service users in their inspections as "experts by experience." Information from service users informed both the inspection regime and individual inspections, but CQC was less focused on giving feedback to service users who contributed to these activities. DISCUSSION AND CONCLUSIONS: Service users can make an important contribution to regulation by sharing their experiences and having their voices heard, but their involvement was somewhat transactional, and largely on terms set by CQC. There may be scope for CQC to build more enduring relationships with service user groups and to engage them more effectively in the regulatory regime.
Subject(s)
Advisory Committees , Patient Participation , Patient Safety , Quality Assurance, Health Care , England , Humans , Qualitative Research , State MedicineABSTRACT
We report here a case of a young girl with pancreatitis and pancreatic fat necrosis (PFN). This condition is rare in the pediatric age group, and its etiopathogenesis is different from disease in adults. Whereas PFN in adults typically results from pancreatitis secondary to pancreatic duct obstruction, alcohol abuse, and pancreatic adenocarcinoma, in children it appears to arise in a setting of systemic disease, often involving a genetic disorder.
Subject(s)
Fat Necrosis/pathology , Pancreas/pathology , Child , Female , Humans , Lipase/blood , Multimorbidity , Pancreatitis/complications , Subcutaneous Fat, Abdominal/pathologyABSTRACT
We report the case of an infant born with perioral vesicles that rapidly spread to involve his mouth and the majority of his body. Histopathology, immunofluorescence, and enzyme-linked immunohistochemistry assays confirmed a diagnosis of epidermolysis bullosa acquisita (EBA). His mother had no history of EBA, and serum indirect immunofluorescence was negative. The patient improved rapidly with local wound care and oral dapsone.
Subject(s)
Dapsone/therapeutic use , Epidermolysis Bullosa Acquisita/diagnosis , Folic Acid Antagonists/therapeutic use , Enzyme-Linked Immunosorbent Assay , Epidermolysis Bullosa Acquisita/therapy , Fluorescent Antibody Technique, Indirect , Humans , Immunohistochemistry , Infant, Newborn , Male , Skin/pathologyABSTRACT
This study simulated the effect of unlinked automatic gain control (AGC) and head movement on the output levels and resulting inter-aural level differences (ILDs) produced by bilateral cochlear implant (CI) processors. The angular extent and velocity of the head movements were varied in order to observe the interaction between unlinked AGC and head movement. Static, broadband input ILDs were greatly reduced by the high-ratio, slow-time-constant AGC used. The size of head-movement-induced dynamic ILDs depended more on the velocity and angular extent of the head movement than on the angular position of the source. The profiles of the dynamic, broadband output ILDs were very different from the dynamic, broadband input ILD profiles. Short-duration, high-velocity head movements resulted in dynamic output ILDs that continued to change after head movement had stopped. Analysis of narrowband, single-channel ILDs showed that static output ILDs were reduced across all frequencies, producing low-frequency ILDs of the opposite sign to the high-frequency ILDs. During head movements, low- and high-frequency ILDs also changed with opposite sign. The results showed that the ILDs presented to bilateral CI listeners during head turns were highly distorted by the interaction of the bilateral, unlinked AGC and the level changes induced by head movement.
ABSTRACT
BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the United States and is more prevalent in older populations. OBJECTIVE: The aim of this study was to investigate BCC risk factors in male patients younger than 40 years. MATERIALS AND METHODS: A consecutive series of male patients with pathology-proven BCC and younger than 40 years at time of diagnosis were retrospectively identified along with matched controls. Phone interviews were conducted using a structured questionnaire, and differences between patients with and without BCC were investigated. RESULTS: A total of 50 patients with BCC and 27 controls were included in this study. Compared with controls, patients with BCC worked outdoor jobs for longer lengths of time (43.2 vs 15.6 months; p = .04), were more likely to have a family history of skin cancer (66% vs 44%; p = .02), and were more likely to use sunscreen heavily after biopsy (p = .02). Patients with multiple BCCs (n = 20) were more likely to have a history of substantial recreational sun exposure (p = .01) than patients with solitary lesions (n = 30). CONCLUSION: The authors conclude that outdoor sun exposure in patients with underlying genetic susceptibility is the most likely mechanism of BCC formation in young male patients.
Subject(s)
Carcinoma, Basal Cell/etiology , Skin Neoplasms/etiology , Adult , Age Factors , Carcinoma, Basal Cell/pathology , Case-Control Studies , Genetic Predisposition to Disease , Humans , Male , Retrospective Studies , Risk Factors , Skin Neoplasms/pathology , Sunlight/adverse effects , Sunscreening Agents/therapeutic use , Surveys and QuestionnairesABSTRACT
BACKGROUND: Accelerating the implementation of new technology in healthcare is typically complex and multi-faceted. One strategy is to charge a national agency with the responsibility for facilitating implementation. This study examines the role of such an agency in the English National Health Service. In particular, it compares two different facilitation strategies employed by the agency to support the implementation of insulin pump therapy. METHODS: The research involved an empirical case study of four healthcare organisations receiving different levels of facilitation from the national agency: two received active hands-on facilitation; one was the intended recipient of a more passive, web-based facilitation strategy; the other implemented the technology without any external facilitation. The primary method of data collection was semi-structured qualitative interviews with key individuals involved in implementation. The integrated-PARIHS framework was applied as a conceptual lens to analyse the data. RESULTS: The two sites that received active facilitation from an Implementation Manager in the national agency made positive progress in implementing the technology. In both sites there was a high level of initial receptiveness to implementation. This was similar to a site that had successfully introduced insulin pump therapy without facilitation support from the national agency. By contrast, a site that did not have direct contact with the national agency made little progress with implementation, despite the availability of a web-based implementation resource. Clinicians expressed differences of opinion around the value and effectiveness of the technology and contextual barriers related to funding for implementation persisted. The national agency's intended roll out strategy using passive web-based facilitation appeared to have little impact. CONCLUSIONS: When favourable conditions exist, in terms of agreement around the value of the technology, clinician receptiveness and motivation to change, active facilitation via an external agency can help to structure the implementation process and address contextual barriers. Passive facilitation using web-based implementation resources appears less effective. Moving from initial implementation to wider scale-up presents challenges and is an issue that warrants further attention.
Subject(s)
Biomedical Technology/organization & administration , Health Systems Agencies , Inventions/statistics & numerical data , Data Collection , England , Humans , Organizations , State Medicine/statistics & numerical dataABSTRACT
Upon publication of the original article [1], Gregory Maniatopoulos' name was incorrectly given as 'Greg Maniatopoulous'. This has now been corrected in the original article.
ABSTRACT
Psychophysical tests of spectro-temporal resolution may aid the evaluation of methods for improving hearing by cochlear implant (CI) listeners. Here the STRIPES (Spectro-Temporal Ripple for Investigating Processor EffectivenesS) test is described and validated. Like speech, the test requires both spectral and temporal processing to perform well. Listeners discriminate between complexes of sine sweeps which increase or decrease in frequency; difficulty is controlled by changing the stimulus spectro-temporal density. Care was taken to minimize extraneous cues, forcing listeners to perform the task only on the direction of the sweeps. Vocoder simulations with normal hearing listeners showed that the STRIPES test was sensitive to the number of channels and temporal information fidelity. An evaluation with CI listeners compared a standard processing strategy with one having very wide filters, thereby spectrally blurring the stimulus. Psychometric functions were monotonic for both strategies and five of six participants performed better with the standard strategy. An adaptive procedure revealed significant differences, all in favour of the standard strategy, at the individual listener level for six of eight CI listeners. Subsequent measures validated a faster version of the test, and showed that STRIPES could be performed by recently implanted listeners having no experience of psychophysical testing.
Subject(s)
Cochlear Implantation/instrumentation , Cochlear Implants/adverse effects , Speech Perception/physiology , Acoustic Stimulation/methods , Adult , Aged , Aged, 80 and over , Auditory Perception/physiology , Bionics , Cochlear Implantation/rehabilitation , Cues , Female , Hearing Tests/methods , Humans , Male , Middle Aged , Noise/adverse effects , Noise/prevention & control , Pitch Discrimination , Psychoacoustics , Psychometrics/methods , Time FactorsABSTRACT
BACKGROUND AND OBJECTIVE: Initiation of response in a simple reaction time (RT) task may precede conscious perception of the stimulus. Since volitionally delayed responses may require conscious perception of the stimulus before response initiation, it has been hypothesized that volitionally delayed responses will markedly delay RT. METHODS: We conducted two experiments with separate groups of healthy volunteers (n=16; n=13) who performed computerized simple and choice RT tasks. In the standard condition, we instructed the participants to respond to a visual stimulus by pushing a button as quickly as possible. In the second condition, we instructed the participants to respond after a slight volitional delay. The second experiment had an additional volitional delay condition in which we asked participants to delay their responses by an estimated 50% above their usual standard response. RESULTS: We found marked delays and increased variability when participants volitionally delayed their responses, averaging 322 ms for standard and 861 ms for delayed simple RTs (267% increase), and 650 ms for standard and 1018 ms for delayed choice RTs (157% increase). Effects did not differ across age, sex, or handedness. However, a minority of participants did not meaningfully delay their RT during the volitional delay conditions. CONCLUSIONS: On average, participants had marked delays when they tried to delay their responses slightly, but a subset of participants exhibited essentially no delay despite trying to delay. We suggest some potential mechanisms that future investigations might delineate.