The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre-quit pharmacotherapies.

OBJECTIVES: In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation outcomes. The objective of the current study was to test the effects of the pre-quit use of varenicline and nicotine patch on smoking rate and satisfaction with smoking. METHODS: All participants were required to attend up to five study visit sections. Participants (n = 213) who were interested in quitting were randomised (open-label) to receive either pre-quit patch or varenicline (both treatments started 2 weeks prior to an assigned quit day, followed by 10 weeks post-quit) or standard patch (10 weeks starting from an assigned quit day). Participants used modified smartphones to monitor their smoking in real time for 4 weeks. RESULTS: Participants in the two pre-quit treatment groups reported significant reductions in both their satisfaction with smoking (p < 0.001) and smoking rate (p < 0.001) from baseline to the end of pre-quit period; participants in the standard patch group did not. The observed reduction of smoking rate was associated with the satisfaction with smoking (p < 0.01), although the mediation effect of satisfaction was small. CONCLUSIONS: Pre-quit treatment caused reductions in satisfaction with smoking and smoking rate. Satisfaction was associated with changes in smoking rate, but the relationship was weak. As such, monitoring reductions in satisfaction do not appear to be a viable method of evaluating responsiveness to treatment.

Examination of the mechanism of action of two pre-quit pharmacotherapies for smoking cessation.

BACKGROUND: There is substantial scope for improvement in the current arsenal of smoking cessation methods and techniques: even when front-line cessation treatments are utilized, smokers are still more likely to fail than to succeed. Studies testing the incremental benefit of using nicotine patch for 1-4 weeks prior to quitting have shown pre-quit nicotine patch use produces a robust incremental improvement over standard post-quit patch treatment. The primary objective of the current study is to test the mechanism of action of two pre-quit smoking cessation medications-varenicline and nicotine patch-in order to learn how best to optimize these pre-quit treatments. METHODS/DESIGN: The study is a three group, randomized, open-label controlled clinical trial. Participants (n = 216 interested quitters) will be randomized to receive standard patch treatment (10 weeks of patch starting from a designated quit day), pre-quit patch treatment (two weeks of patch treatment prior to a quit day, followed by 10 weeks post-quit treatment) or varenicline (starting two weeks prior to quit day followed by 10 weeks post-quit). Participants will use study-specific modified smart-phones to monitor their smoking, withdrawal symptoms, craving, mood and social situations in near real-time over four weeks; two weeks prior to an assigned quit date and two weeks after this date. Smoking and abstinence will be assessed at regular study visits and biochemically verified. DISCUSSION: Understanding how nicotine patches and varenicline influence abstinence may allow for better tailoring of these treatments to individual smokers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614000329662 (Registered: 27 March 2014).

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH METHODS: We searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually. MAIN RESULTS: A total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.

Diagnosis and early detection of COPD using spirometry.

The standard respiratory function test for case detection of chronic obstructive pulmonary disease (COPD) is spirometry. The criterion for diagnosis defined in guidelines is based on the FEV1/FVC ratio forced expiratory ratio (FER) and its severity is based on forced expiratory volume in one second (FEV1) from measurements obtained during maximal forced expiratory manoeuvres. Spirometry is a safe and practical procedure, and when conducted by a trained operator using a spirometer that provides quality feedback, the majority of patients can be coached to provide acceptable and repeatable results. This allows potentially wide application of testing to improve recognition and diagnosis of COPD, such as for case finding in primary care. However, COPD remains substantially under diagnosed in primary care and a major reason for this is underuse of spirometry. The presence of symptoms is not a reliable indicator of disease and diagnosis is often delayed until more severe airflow obstruction is present. Early diagnosis is worthwhile, as it allows risk factors for COPD such as smoking to be addressed promptly and treatment optimised. Paradoxically, investigation of the patho-physiology in COPD has shown that extensive small airway disease exists before it is detectable with conventional spirometric indices, and methods to detect airway disease earlier using the flow-volume curve are discussed.

Compliance with an EMA monitoring protocol and its relationship with participant and smoking characteristics.

INTRODUCTION: Arguably, the greatest advantage of ecological momentary assessment (EMA) studies is that data are collected repeatedly in real-time and real-world situations, which reduces recall and situational biases and thus improves the accuracy and validity of the data collected. However, the validity of EMA data is contingent upon compliance rates. If participant characteristics are related to missing data, analyses should control for these factors, or they should be targeted in EMA training sessions. This study evaluates the impact of demographic and smoking-related participant characteristics on compliance to an EMA smoking study protocol. METHODS: Prequit-day data were taken from the control arm of an ongoing randomized controlled trial of a smoking-cessation program. After training, 119 participants were asked to carry a mobile device with them at all times for ~6 days and to log every cigarette they smoked in addition to completing randomly scheduled assessments. Different types of compliance were assessed: the percentage of completed random prompts (signal-contingent compliance), the percentage of logged cigarettes per day compared to a timeline follow-back measure, and the correlation between logged cigarettes and a carbon monoxide assessment 2 hr later (both event-contingent compliance). RESULTS: Overall compliance rates were 78.48% for event-contingent and 72.17% for signal-contingent compliance. None of the demographic or smoking-related participant characteristics predicted signal-contingent compliance; however, female participants showed higher event-contingent compliance than male participants, and Caucasian participants showed higher event-contingent compliance than non-Caucasian participants. CONCLUSIONS: Compliance did not depend on smoking-related characteristics. EMA is a valid method for assessing smoking behavior in real-time and real-world settings.

Supporting health behaviour change in chronic obstructive pulmonary disease with telephone health-mentoring: insights from a qualitative study.

BACKGROUND: Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring. METHODS: Community nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change, using a framework of health behaviours; 'SNAPPS' Smoking, Nutrition, Alcohol, Physical activity, Psychosocial well-being, and Symptom management, through regular phone calls over 12 months. Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted. Interviews were analysed using iterative thematic and interpretative content approaches by two investigators. RESULTS: Of 90 participants allocated to health-mentoring, 65 (72%) were invited for interview at 12-month follow up. The 44 interviewees, 75% with moderate COPD, had a median of 13 mentor contacts over 12 months, range 5-20. Interviewed participants (n=44, 55% male, 43% current smokers, 75% moderate COPD) were representative of the total group with a mean age 65 years while 82% had at least one additional co-morbid chronic condition. Telephone delivery was highly acceptable and enabled good rapport. Participants rated 'being listened to by a caring health professional' as very valuable. Three participant groups were identified by attitude to health behaviour change: 14 (32%) actively making changes; 18 (41%) open to and making some changes and 12 (27%) more resistant to change. COPD severity or current smoking status was not related to group category. Mentoring increased awareness of COPD effects, helping develop and personalise behaviour change strategies, even by those not actively making changes. Physical activity was targeted by 43 (98%) participants and smoking by 14 (74%) current smokers with 21% reporting quitting. Motivation to maintain changes was increased by mentor support. CONCLUSIONS: Telephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care. Health behaviours targeted by this population, mostly with moderate disease, were mainly physical activity and smoking reduction or cessation. Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change. TRIAL REGISTRATION: ACTR12608000112368.

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these trials in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH STRATEGY: We searched the biomedical literature databases CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE and CINAHL from 1966 to April 2007. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed (cytological or histological) SCLC and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. MAIN RESULTS: A total of 29 trials involving 5530 patients were included in this systematic review. There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting, anaemia and thrombocytopenia toxicity. Three trials presented quality of life data but the data presented were not complete and therefore could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality of life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality of life assessment.

Barriers to the use of spirometry in general practice.

BACKGROUND: Guidelines advise chronic obstructive pulmonary disease (COPD) should be diagnosed and managed by using spirometry to demonstrate irreversible airflow limitation and monitor change in smokers and ex-smokers aged over 35 years. METHODS: A cross-sectional study of patients and their general practitioners investigating use of spirometry in COPD in two practices by lung function assessment, review of practice records, interviews and focus groups. RESULTS: Sixteen GPs, and 38 patients with a diagnosis of COPD participated. At diagnosis, although 72% had spirometry, this occurred in only 41% of 17 patients diagnosed by a GP; but in all 19 cases when a specialist was involved. Diagnosis often occurred late, despite all patients having previously recorded symptoms typical of COPD. General practitioners expressed a preference to diagnose COPD on clinical grounds. Although 58% of patients had recent spirometry for current management, only 32% were performed by their GP. There were organisational and technical barriers to spirometry and poor recognition of the essential role of spirometry in the diagnosis of COPD. DISCUSSION: There are a number of potentially reversible factors that hinder practice recommendations regarding the use of spirometry in general practice to diagnose and manage COPD.