ABSTRACT
OBJECTIVE: People with severe and persistent mental illness (SPMI) may be excluded from community-based care if their complex support needs cannot be met and are at risk of institutionalisation. The Pathways to Community Living Initiative (PCLI) aims to address barriers to community living. This study evaluated the PCLI from the perspective of service users and family members. METHODS: Evaluation questions were explored in semi-structured interviews. Transcripts were coded inductively and deductively. This article adheres to relevant EQUATOR standards for qualitative research and reporting. RESULTS: There were 37 interviews with 27 service users and 12 family members. Factors associated with positive experiences of transition from hospital included detailed planning, personalised care, and staged transitions which alleviated concerns around safety, support, and coping. Community living provided opportunities to exercise greater choice and control in everyday life and, for some, to reconnect with family. Poor physical health and social isolation were noted as potential risks. CONCLUSIONS: Participants regarded community living as preferable to hospital settings, and highly valued their freedom. They reported that clinical, aged care and disability supports helped them. Additional support may be required to improve physical health and social connectedness, and families appear to have unmet needs for psychosocial support.
Subject(s)
Disabled Persons , Mental Disorders , Humans , Aged , Family/psychology , Mental Disorders/therapy , Hospitals , Qualitative ResearchABSTRACT
OBJECTIVE: The Pathways to Community Living Initiative (PCLI) aims to reform mental health care for people with severe and persistent mental illness (SPMI) and complex needs. This study reports independent evaluation findings on transitions from hospital and practice change in mental health services. METHODS: Data for this mixed-methods evaluation were obtained from administrative collections and semi-structured interviews with PCLI program managers, teams and executive leads; aged care managers; and leaders in inpatient, community and older people's mental health services. RESULTS: Between July 2015 and December 2020, 674 participants (67% of those eligible for the PCLI) were transitioned from hospital to community. Of those transitioned, 21 required subsequent long-stay admissions. The PCLI introduced resources, clearly defined processes, and state-wide networks to guide changes in practice which are becoming embedded in the operations and governance of mental health services across New South Wales. CONCLUSIONS: Severe and persistent mental illness and complex needs can be managed in community settings with highly individualised planning and care, supported by specialised clinical teams in partnership with mental health, aged care and disability services. Evaluation findings highlight the importance of continued investment in rehabilitation psychiatry.
Subject(s)
Community Mental Health Services , Mental Disorders , Mental Health Services , Humans , Aged , Mental Disorders/rehabilitation , Mental Health , New South Wales , Hospitalization , Chronic DiseaseABSTRACT
INTRODUCTION: Performance on the certifying examinations such as the American Board of Internal Medicine Certification Exam (ABIM-CE) is of great interest to residents and their residency programs. Identification of factors associated with certification exam result may allow residency programs to recognize and intervene for residents at risk of failing. Despite this, residency programs have few evidence-based predictors of certification exam outcome. The change to pass-or-fail score reporting of the USA Medical Licensing Exam (USMLE) Step 1 removes one such predictor. MATERIALS AND METHODS: We performed a retrospective study of residents from a medium-sized internal medicine residency program who graduated from 1998 through 2017. We used univariate tests of associations between ABIM-CE result and various demographic and scholastic factors. RESULTS: Of 166 graduates, 14 (8.4%) failed the ABIM-CE on the first attempt. Failing the first attempt of the ABIM-CE was associated with older median age on entering residency (29 vs 27 years; P = 0.01); lower percentile rank on the Internal Medicine In-Training Examination (IM-ITE) in each of the first, second, and third years of training (P < 0.001 for all); and lower scores on the USMLE Steps 1, 2 Clinical Knowledge, and 3 (P < 0.05 for all). No association was seen between a variety of other scholastic or demographic factors and first-attempt ABIM-CE result. DISCUSSION: Although USMLE step 1 has changed to a pass-or-fail reporting structure, there are still other characteristics that allow residency programs to identify residents at risk of ABIM-CE first time failure and who may benefit from intervention.
Subject(s)
Internal Medicine , Internship and Residency , Humans , Adult , Retrospective Studies , Certification , Inservice TrainingABSTRACT
The coronavirus disease (COVID-19) pandemic significantly accelerated the growth of telehealth services within the Veterans Health Administration (VHA), as the use of video conferencing to meet with Veterans in their homes increased tenfold in a 3-month period. A substantial portion of telehealth in VHA has traditionally comprised mental health services, and both the scope and volume of such services were significantly broadened in response to COVID-19 to allow for social distancing. The current article is a review of this mobilization from the framework of the People, Process, Technology, and Information model, with a particular highlight on the critical operational partnership between individual facilities providing care and the governing VHA program offices. Lessons learned and future goals for the sustainment and integration of telemental health services are also discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Subject(s)
COVID-19 , Mental Health Services , Telemedicine , Veterans , Humans , United States , United States Department of Veterans Affairs , Veterans/psychologyABSTRACT
This study explored parenting styles and values internalization. Perceived parenting styles were measured in Grade 7 (n = 749) and Grade 12 (n = 468), and values were measured in Grade 12 (n = 271) and one year postschool (n = 291). We measured three aspects of valuing: priority (extrinsic, intrinsic importance); regulation (controlled, autonomous); and successful enactment of values (success). Mothers' authoritative parenting in Grade 7 predicted increased importance and autonomous regulation of values one year postschool. Fathers' authoritative parenting in Grade 7 predicted decreased importance of extrinsic values. Fathers' permissive parenting in Grade 7 predicted decreased importance of intrinsic values. Authoritarian parenting in Grade 12 predicted more controlled values regulation postschool, particularly for extrinsic values. Parenting in early and late adolescence predicts values internalization in emerging adulthood.
Subject(s)
Adolescent Development/physiology , Father-Child Relations , Mother-Child Relations , Parenting/psychology , Social Values , Adolescent , Female , Humans , Longitudinal Studies , Male , Surveys and QuestionnairesABSTRACT
Background: Bereavement support is an integral part of palliative care. However, audits of Australian palliative care services have consistently identified bereavement care as one of the highest priorities for improvement. Objective: We assessed equity of access to bereavement support across Australian palliative care services by using survey data to compare services according to location (metropolitan vs. regional). We also evaluated changes in bereavement support over the last decade by comparing findings to results of a previous Australian study. Design, Setting, and Participants: A national, cross-sectional online survey of Australian palliative care services conducted from August to September 2017. Main Outcome Measures: Services' self-reported provision of bereavement support. Results: One hundred and eighty services (84%) responded. Of these, 91% provided bereavement support. Most offered support to all bereaved persons connected to the service. More than 80% of services provided a wide range of support types. Metropolitan services were more likely than regional services to offer specialist bereavement interventions. The staff most involved in coordinating and delivering bereavement support were social workers, nurses (particularly in regional areas), and bereavement coordinators/counselors (particularly in metropolitan areas). Resource limitations presented barriers to provision of bereavement support. Conclusions: Across Australia, in principle, access to bereavement support through palliative care services remains largely equitable. Nevertheless, observed variations in the type of professional delivering care and the level of support indicate that a more consistent approach is required. An increase in the range of supports available compared with a decade ago signifies a more comprehensive approach to bereavement support by many Australian palliative care services.
Subject(s)
Bereavement , Delivery of Health Care/organization & administration , Family/psychology , Health Services Accessibility/statistics & numerical data , Palliative Care/organization & administration , Quality Improvement/statistics & numerical data , Social Support , Adult , Aged , Aged, 80 and over , Australia , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
PURPOSE: The purpose of this study was to develop prioritised indicators to measure cancer patient experience and thus guide quality improvement in the delivery of patient care. METHODS: A Delphi study, consisting of two surveys and three workshops, was employed to gather expert opinions on the most important indicators to measure. Survey participants were 149 health professionals, academics/technical experts and consumers. The first survey was based on a literature review which identified 105 elements of care within 14 domains of patient experience. These were rated on a 7-point Likert scale, with '1' representing high importance. Elements with mean ratings between 1.0 and 2.0 were retained for the second survey. The 43 least-important elements were omitted, four elements were revised and nine new elements added. Consensus was defined as at least 70% of participants rating an element '1' or '2'. Multivariate and cluster analyses were used to develop 20 draft indicators, which were presented to 51 experts to refine and prioritise at the three workshops. RESULTS: All elements in the second survey were rated '1' or '2' by 81% of participants. Workshop participants agreed strongly on the four most important indicators: coordinated care, access to care, timeliness of the first treatment, and communication. Other indicators considered highly important were follow-up care for survivors; timeliness of diagnosis; information relating to side effects, pain and medication; comprehensibility of information provided to patients; and needs assessment. CONCLUSIONS: Experts identified priorities with a high level of consensus, providing a rigorous foundation for developing prioritised indicators of quality in cancer patient experience.
Subject(s)
Neoplasms/therapy , Quality Indicators, Health Care/standards , Adult , Communication , Consensus , Delphi Technique , Expert Testimony , Female , Health Services Accessibility , Humans , Male , Patient Satisfaction , Quality Improvement , Surveys and QuestionnairesABSTRACT
QUESTION: Can primary contact physiotherapists reduce waiting and treatment times and facilitate faster discharge in Australian emergency departments? DESIGN: Data on patients treated by primary contact physiotherapists were collected prospectively and compared with historical and concurrent cohorts of patients treated by other clinicians, using diagnosis and urgency. PARTICIPANTS: Twenty-nine primary contact physiotherapists, working at 10 sites, treated a total of 14 452 patients with musculoskeletal conditions in triage categories 3, 4 and 5. OUTCOME MEASURES: Data were analysed for two time periods: baseline (historical control) and implementation (12 to 15 months). A concurrent control cohort within the implementation period was selected using diagnosis (ICD-10-AM) and urgency of treatment (triage category). Waiting time, treatment time, and time to discharge from the emergency department were compared across periods and between cohorts. RESULTS: Significant differences were found in waiting and treatment times. On average, patients treated by primary contact physiotherapists waited 31minutes less than those treated by other practitioners and had an average treatment time of 108minutes compared with 148minutes. Overall, 93% of patients treated by primary contact physiotherapists and 75% treated by other practitioners were discharged from the emergency department within a 4-hour time period. To address concerns that these results could be due to other differences between cohorts, multiple regression models were used and the results were still significantly in favour of the primary contact physiotherapists. CONCLUSION: A primary contact physiotherapist model in hospital emergency departments can reduce waiting and treatment times for patients with musculoskeletal presentations, resulting in better performance in achieving discharge within the 4-hour national target. [Bird S, Thompson C, Williams KE (2016) Primary contact physiotherapy services reduce waiting and treatment times for patients presenting with musculoskeletal conditions in Australian emergency departments: an observational study.Journal of Physiotherapy62: 209-214].
Subject(s)
Emergency Service, Hospital , Musculoskeletal Diseases/therapy , Patient Care Team , Patient Satisfaction , Physical Therapy Specialty , Adult , Australia , Female , Humans , Male , Middle Aged , Primary Health Care , Time-to-TreatmentABSTRACT
Clinical video teleconferencing (CVT) is a treatment delivery modality that can be used to provide services to clinical populations that experience barriers to accessing mental health care. Recently, home-based CVT (HBCVT) has been developed in order to deliver treatment via CVT to patients in their homes. A number of clinical considerations, including the appropriate clinical population and individual patient factors, need to be taken into account when delivering CVT. Particular challenges can exist when setting up the home environment for HBCVT. Concerns about maintaining patient privacy while living in shared spaces, ensuring adequate CVT technology in the patient's home, and conducting risk management remotely are important to consider when delivering treatment via CVT. Since treatments delivered via CVT are often conducted across state lines, novel ethical and legal issues such as privacy laws, licensing of providers, prescribing practices, and insurance reimbursements need to be addressed when conducting services via these modalities. Future research on HBCVT will provide researchers and clinicians with information regarding which patients are most appropriate for treatment delivered via this modality and help further develop evidence for the cost-effectiveness of CVT and HBCVT clinical practice guidelines.
Subject(s)
Home Care Services , Mental Disorders/therapy , Physician-Patient Relations , Telemedicine/methods , Videoconferencing , Health Services Accessibility , Humans , Internet , PsychiatryABSTRACT
Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. Twenty percentage of patients treated with surgery and radiotherapy for ductal carcinoma in situ (DCIS) of the breast recur and our previous data show that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of focal adhesion kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples, we demonstrate that CSC-enriched populations are relatively radioresistant and possess high FAK activity. Immunohistochemical studies of active FAK in DCIS tissue show high expression was associated with a shorter median time to recurrence. Treatment with a FAK inhibitor or FAK siRNA in nonadherent and three-dimensional matrigel culture reduced mammosphere formation, and potentiated the effect of 2 Gy irradiation. Moreover, inhibition of FAK in vitro and in vivo decreased self-renewal capacity, levels of Wnt3a and B-Catenin revealing a novel FAK-Wnt axis regulating DCIS stem cell activity. Overall, these data establish that the FAK-Wnt axis is a promising target to eradicate self-renewal capacity and progression of human breast cancers.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Focal Adhesion Kinase 1/metabolism , Neoplastic Stem Cells , Radiation Tolerance/radiation effects , Wnt Signaling Pathway/radiation effects , Animals , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/enzymology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Cell Line, Tumor , Female , Focal Adhesion Kinase 1/antagonists & inhibitors , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Mice , Mice, Nude , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/enzymology , Neoplastic Stem Cells/pathology , RNA, Small Interfering/pharmacology , Radiation Tolerance/drug effects , Wnt3A Protein/metabolism , beta Catenin/metabolismABSTRACT
Invasive fungal infections are a major cause of morbidity and mortality in allogeneic stem cell transplant recipients. They can occasionally involve the tracheobronchial tree with serious clinical consequences. Tracheobronchial involvement is often an unexpected finding during diagnostic bronchoscopy. Herein, we report a case of pseudomembranous tracheobronchitis caused by Rhizopus sp. in an allogeneic stem cell transplant recipient.
Subject(s)
Bronchitis/microbiology , Immunocompromised Host , Mucormycosis/immunology , Stem Cell Transplantation/adverse effects , Tracheitis/microbiology , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Biopsy , Bronchitis/immunology , Bronchitis/pathology , Bronchoscopy , Fatal Outcome , Graft vs Host Disease/complications , Graft vs Host Disease/drug therapy , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Mucormycosis/drug therapy , Mucormycosis/pathology , Nausea/etiology , Respiratory Insufficiency/microbiology , Rhizopus/isolation & purification , Tracheitis/immunology , Tracheitis/pathology , Transplantation, HomologousABSTRACT
Breast-conserving surgery for ductal carcinoma in situ (DCIS) is often combined with irradiation, reducing recurrence rates to 20% within 10 years; however, there is no change in overall survival. Evidence in the invasive breast indicates that breast cancer stem cells (CSCs) are radiotherapy-resistant and are capable of re-initiating a tumor recurrence; hence, targeting CSCs in high risk DCIS patient may improve survival. HER2 is overexpressed in 20% of DCIS and is known to be highly active in breast CSCs; we therefore investigated the effect of Lapatinib on DCIS CSC activity using 2 in vitro culture systems. Two DCIS cell lines DCIS.com (HER2 normal) and SUM225 (HER2 overexpressed) as well as DCIS cells from patient samples (n = 18) were cultured as mammospheres to assess CSC activity and in differentiated 3D-matrigel culture to determine effects within the non-CSCs. Mammosphere formation was reduced regardless of HER2 status, although this was more marked within the HER2-positive samples. When grown as differentiated DCIS acini in 3D-matrigel culture, Lapatinib only reduced acini size in the HER2-positive samples via decreased proliferation. Further investigation revealed lapatinib did not reduce self-renewal activity in the CSC population, but their proliferation was decreased regardless of HER2 status. In conclusion we show Lapatinib can reduce DCIS CSC activity, suggesting that the use of Lapatinib in high-risk DCIS patients has the potential to reduce recurrence and the progression of DCIS to invasive disease.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Cell Proliferation/drug effects , Neoplastic Stem Cells/drug effects , Quinazolines/pharmacology , Breast Neoplasms/metabolism , Carcinoma, Intraductal, Noninfiltrating/metabolism , Cell Line, Tumor , Female , Humans , In Vitro Techniques , Lapatinib , Neoplastic Stem Cells/cytology , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
Parenting behaviors have been linked to children's self regulation, but it is less clear how they relate to adolescent psychological flexibility. Psychological flexibility is a broad construct that describes an individual's ability to respond appropriately to environmental demands and internal experiences in the service of their goals. We examined the longitudinal relationships between perceived parenting style and psychological flexibility among students at five Australian schools (N= 749) over 6 years, beginning in Grade 7 (50.3% female, mean age 12.39 years). Parenting style was measured in Grades 7 and 12, and psychological flexibility from Grade 9 through 12. Psychological flexibility decreased, on average, with age. Multi-level modelling indicated that authoritarian parenting (low warmth, high control) in Grade 7 predicted later (low) psychological flexibility. Moreover, increases in authoritarian parenting and decreases in authoritative parenting (high warmth and control) were associated with adolescent psychological flexibility across the high school years. Change in parenting predicted future psychological flexibility but did not predict change over time. Structural Equation Modelling revealed that adolescent psychological flexibility in Grade 9 predicted later decreases in authoritarian and increases in authoritative parenting. We discuss the implications of these findings for understanding how parenting changes and the consequences of such change for the development of psychological flexibility.
Subject(s)
Adolescent Behavior/psychology , Authoritarianism , Parent-Child Relations , Parenting/psychology , Permissiveness , Adolescent , Australia/epidemiology , Conflict, Psychological , Female , Humans , Male , Personality Development , Psychology, Adolescent , Resilience, Psychological , Social Support , Socioeconomic FactorsABSTRACT
Varenicline tartrate (Chantix®/Champix®) is a selective partial agonist of the α(4)ß(2) nicotinic acetylcholine receptor and is approved as an aid to smoking cessation. The usual oral dosage in adults is 1 mg twice daily for 12 weeks, with an initial titration week. Several clinical pharmacology studies have characterized the pharmacokinetics of varenicline in adult smokers aged 18-55 years, elderly smokers and nonsmokers aged ≥ 65 years, adolescent smokers aged 12-17 years and subjects with impaired renal function. Varenicline exhibits linear pharmacokinetics following single- and multiple-dose administration of up to 3 mg/day. After oral administration absorption is virtually complete and systemic availability is high. Oral bioavailability is not affected by food or time-of-day dosing; maximum plasma drug concentrations typically occur within 3-4 hours after dosing. Protein binding of varenicline is low (≤ 20%) and independent of age and renal function. Varenicline is almost exclusively excreted unchanged in urine, primarily through glomerular filtration, with some component of active tubular secretion via human organic cation transporter, hOCT-2. Varenicline does not undergo significant metabolism and is not metabolized by hepatic microsomal cytochrome P450 (CYP) enzymes. Consistent with an elimination half-life of â¼24 hours, steady-state conditions are reached within 4 days of repeat dosing. There are no remarkable differences between smokers and nonsmokers in metabolism or excretion of varenicline. In vitro, varenicline does not inhibit nor induce the activity of the major CYP enzymes. No clinically meaningful pharmacokinetic drug interactions are observed when varenicline is coadministered with the narrow therapeutic index drugs warfarin or digoxin, the smoking cessation therapies bupropion or transdermal nicotine, and the renally secreted drugs cimetidine or metformin. An integrated model-based analysis of varenicline pharmacokinetics across several studies in adult smokers further showed that renal function was the clinically important factor leading to interindividual variability in systemic exposure to varenicline. Although no dose adjustment is required for subjects with mild to moderate renal impairment, a dose reduction to 1 mg/day is indicated for subjects with severe renal insufficiency. After accounting for renal function, there was no apparent effect of age, sex or race on varenicline pharmacokinetics. Varenicline pharmacokinetics in adolescents were generally comparable to those in adults; the bodyweight effect, which resulted in greater exposure in individuals of smaller body size (weighing ≤ 55 kg), was adequately offset by administration of half the dose recommended in adults. (It is, however, important to note that varenicline is currently not approved for use in smokers aged under 18 years). Exposure-response analyses relating individual-specific drug exposure to clinical responses consistently showed that the end-of-treatment abstinence rate in adult smokers increased linearly with increasing varenicline exposure; the 1 mg twice-daily dose regimen was reliably associated with greater exposure and an increased probability of achieving a stable quit within 1 year from the start of treatment. Nausea was the single most frequently reported adverse event in varenicline clinical trials, with an incidence that was sex-related and increased with varenicline exposure. In all, the predictable pharmacokinetic properties and straightforward dispositional profile of varenicline simplify its use in clinical practice.
Subject(s)
Benzazepines/pharmacology , Nicotinic Agonists/pharmacology , Quinoxalines/pharmacology , Smoking Cessation/methods , Adolescent , Adult , Age Factors , Aged , Animals , Benzazepines/adverse effects , Benzazepines/pharmacokinetics , Biological Availability , Drug Interactions , Half-Life , Humans , Middle Aged , Nicotinic Agonists/adverse effects , Nicotinic Agonists/pharmacokinetics , Quinoxalines/adverse effects , Quinoxalines/pharmacokinetics , Varenicline , Young AdultSubject(s)
Benzazepines/adverse effects , Nausea/chemically induced , Poisoning/etiology , Quinoxalines/adverse effects , Serotonin Receptor Agonists/adverse effects , Vomiting/chemically induced , Adolescent , Benzazepines/blood , Drug Overdose , Humans , Nausea/complications , Poisoning/complications , Poisoning/prevention & control , Quinoxalines/blood , Receptors, Nicotinic/drug effects , Receptors, Serotonin, 5-HT3/drug effects , Serotonin Receptor Agonists/blood , Varenicline , Vomiting/complicationsABSTRACT
The pharmacological properties and pharmacokinetic profile of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline provide an advantageous combination of free brain levels and functional potencies at the target receptor that for a large part explain its efficacy as a smoking cessation aid. Since alpha4beta2 and other nAChR subtypes play important roles in mediating central processes that control reward, mood, cognition and attention, there is interest in examining the effects of selective nAChR ligands such as varenicline in preclinical animal models that assess these behaviors. Here we describe results from studies on varenicline's effects in animal models of addiction, depression, cognition and attention and discuss these in the context of recently published preclinical and preliminary clinical studies that collected data on varenicline's effects on mood, cognition and alcohol abuse disorder. Taken together, the preclinical and the limited clinical data show beneficial effects of varenicline, but further clinical studies are needed to evaluate whether the preclinical effects observed in animal models are translatable to the clinic.
Subject(s)
Affect/drug effects , Benzazepines/pharmacology , Cognition/drug effects , Nicotinic Agonists/pharmacology , Quinoxalines/pharmacology , Receptors, Nicotinic/physiology , Reward , Alcohol Drinking/drug therapy , Alcohol Drinking/psychology , Animals , Attention/drug effects , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Depression/drug therapy , Depression/psychology , Drug Partial Agonism , Hippocampus/drug effects , Hippocampus/physiology , Humans , Male , Mice , Mice, Inbred C57BL , Neurotransmitter Agents/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar , Recognition, Psychology/drug effects , Reflex, Startle/drug effects , Tobacco Use Disorder/drug therapy , Tobacco Use Disorder/psychology , VareniclineABSTRACT
OBJECTIVE: To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation. RESEARCH DESIGN AND METHODS: 320 healthy, motivated-to-quit smokers (> or =10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2-12: 0.5-2.0 mg/day). MAIN OUTCOME MEASURES: Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward. RESULTS: Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n=155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p<0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p<0.001), 24 (32.5 vs. 13.5%; p<0.001), and 52 (28.0 vs. 13.5%; p=0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations. CONCLUSIONS: A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation.
Subject(s)
Benzazepines/administration & dosage , Quinoxalines/administration & dosage , Smoking Cessation , Smoking/drug therapy , Adolescent , Adult , Aged , Benzazepines/adverse effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Placebos , Quinoxalines/adverse effects , Treatment Outcome , VareniclineABSTRACT
OBJECTIVES: To evaluate varenicline's efficacy for smoking cessation versus bupropion SR and placebo and to explore whether factors typically predictive of abstinence influence varenicline's efficacy versus placebo, as measured by the week 9-12 continuous abstinence rate (CAR9-12). METHODS: Smokers in 2 randomized, placebo-controlled trials received varenicline 1 mg BID (n=696), bupropion SR 150 mg BID (n=671), or placebo (n=685) for 12 weeks. Nontreatment followup lasted 40 weeks. RESULTS: CAR(9-12) was greater for varenicline (44.0%) versus bupropion SR (29.7%; P<0.0001) and placebo (17.7%; P<0.0001). CAR(9-12) for varenicline versus placebo was not affected by age, gender, or nicotine dependence level. CONCLUSIONS: Varenicline was more efficacious than bupropion SR or placebo. Varenicline's efficacy versus placebo was not influenced by factors predictive of abstinence.
Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Benzazepines/therapeutic use , Bupropion/therapeutic use , Quinoxalines/therapeutic use , Smoking Cessation/statistics & numerical data , Smoking Prevention , Smoking/epidemiology , Adolescent , Adult , Aged , Double-Blind Method , Follow-Up Studies , Humans , Middle Aged , Varenicline , Young AdultABSTRACT
BACKGROUND: Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young. OBJECTIVE: This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea. METHODS: A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan. Eligible subjects, smoking >or=10 cigarettes/d, received brief smoking-cessation counseling and were randomly assigned in a 1:1 ratio to varenicline 1 mg BID (titrated during the first week) or placebo. Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide