The use of diagnostic complex robotic-assisted segmentectomy in the management of incidental and screen-detected pulmonary nodules.

OBJECTIVES: Robotic-assisted thoracoscopic surgery (RATS) facilitates complex pulmonary segmentectomy which offers one-stage diagnostic and therapeutic management of small pulmonary nodules. We aimed to explore the potential advantages of a faster, simplified pathway and earlier diagnosis against the disadvantages of unnecessary morbidity in benign cases. METHODS: In an observational study, patients with small, solitary pulmonary nodules deemed suspicious of malignancy by a multidisciplinary team were offered surgery without a pre or intraoperative biopsy. We report our initial experience with RATS complex segmentectomy (using >1 parenchymal staple line) to preserve as much functioning lung tissue as possible. RESULTS: Over a 4-year period, 245 RATS complex segmentectomies were performed; 140 right: 105 left. A median of 2 (1-4) segments was removed. There was no in-hospital mortality and no requirement for postoperative ventilation. Complications were reported in 63 (25.7%) cases, of which 36 (57.1%) were hospital-acquired pneumonia. A malignant diagnosis was found in 198 (81%) patients and a benign diagnosis in 47 (19%). The malignant diagnoses included: adenocarcinoma in 136, squamous carcinoma in 31 and carcinoid tumour in 15. The most frequent benign diagnosis was granulomatous inflammation in 18 cases. CONCLUSIONS: RATS complex segmentectomy offers a precise, safe and effective one-stop therapeutic biopsy in incidental and screen-detected pulmonary nodules.

Coronary artery bypass vs percutaneous coronary intervention in under 50s.

BACKGROUND: Young patients with coronary artery disease are undergoing percutaneous coronary intervention (PCI) primarily, with a view to deferring coronary artery bypass grafting (CABG). We investigated the validity of this approach, by comparing outcomes in patients ≤50 years undergoing CABG or PCI. METHODS: One hundred consecutive patients undergoing PCI and 100 undergoing CABG in 2004 were retrospectively studied to allow for 5 and 12 years follow-up. The two groups were compared for the primary endpoints of major adverse cardiac or cerebrovascular event (MACCE). RESULTS: Diabetes, peripheral vascular disease, and left ventricular ejection fraction <50% were higher in the CABG group. At 5 years, rates of myocardial infarction (MI) (9% vs 1%, P = .02), repeat revascularization (31% vs 7%, P < .01), and MACCE (34 vs 12, P < .01) were greater in the PCI vs the CABG group. Similarly, at 12 years, rates of MI (27.4% vs 19.4%, P = .19), repeat revascularization (41.1% vs 20.4%, P < .01), and MACCE (51 vs 40, P = .07) were greater in the PCI group. There were no differences in major outcomes in patients with 1 or 2VD, at 5 or 12 years. Rates of MI, revascularization, and MACCE were higher in patients with 3VD undergoing PCI (n = 21; MI, 47.6%; revascularization, 66.7%; and MACCE, 19 events) vs CABG (n = 78; MI, 19.2%; revascularization, 20.5%; and MACCE, 31 events); P < .01, for all end points. CONCLUSIONS: MACCE was lower in young patients undergoing CABG vs PCI at both 5 and 12 years follow-up, primarily as a consequence of patients with 3VD undergoing PCI having more MI and repeat revascularization. CABG should remain the preferred method of revascularization in young patients with 3VD.

The EuroSCORE: a neglected measure of medium-term survival following cardiac surgery.

OBJECTIVES: EuroSCORE is used to predict operative mortality following cardiac surgery. There are limited data to assess the ability of EuroSCORE to predict medium- to long-term survival. We aimed to test the ability of EuroSCORE to predict mid-term survival following cardiac surgery. METHODS: We analysed prospectively collected data from all patients undergoing cardiac surgery in an urban tertiary cardiac centre over a 6-year period. All-cause mortality following cardiac surgery was determined via Office of National Statistics data. Patients were grouped into all comers, coronary artery bypass graft (CABG), isolated aortic valve replacement (AVR), isolated mitral valve repair and replacement (MVR) and combined AVR/MVR and CABG. Each group was separated into EuroSCORE quartiles. Kaplan-Meier curves were used to calculate 6-year actuarial survival. Log-rank test was used to calculate the P-value. C-statistic discriminated the ability of the EuroSCORE to predict medium-term survival. RESULTS: A total of 9022 consecutive patients were identified. The mean age was 66.86 years, 73.7% were male. The cases were grouped according to their additive EuroSCORE into 0-5 (n = 5369), 6-10 (n = 3059), 11-15 (n = 506) and >15 (n = 93). Median follow-up was 2.92 years. The 6-year survival was 88.5, 71.8, 52.5 and 39.5%, respectively. The P-value for all operative categories was significant. The C-statistic was 0.68 (all comers), 0.72 for isolated MVR, 0.65 (isolated CABG), 0.62 (isolated AVR) and 0.69 (combined AVR/MVR and CABG). CONCLUSIONS: Additive EuroSCORE may be used to predict medium-term survival in patients undergoing cardiac surgery; increasing additive EuroSCORE resulting in significant decreases in survival. It is a good predictive tool for patients undergoing isolated MVR and a fair tool for patients undergoing the remaining operative procedures studied.

Increasing varenicline dose in smokers who do not respond to the standard dosage: a randomized clinical trial.

IMPORTANCE: Standard varenicline tartrate dosing was formulated to avoid adverse effects (primarily nausea), but some patients may be underdosed. To our knowledge, no evidence-based guidance exists for physicians considering increasing varenicline dose if there is no response to the standard dosage. OBJECTIVE: To determine whether increasing varenicline dose in patients showing no response to the standard dosage improves treatment efficacy. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind randomized placebo-controlled trial, 503 smokers attending a stop smoking clinic commenced varenicline use 3 weeks before their target quit date (TQD). Two hundred participants reporting no strong nausea, no clear reduction in smoking enjoyment, and less than 50% reduction in their baseline smoking on day 12 received additional tablets of varenicline or placebo. INTERVENTIONS: All participants began standard varenicline tartrate dosing, gradually increasing to 2 mg/d. Dose increases of twice-daily varenicline (0.5 mg) or placebo took place on days 12, 15, and 18 (up to a maximum of 5 mg/d). MAIN OUTCOMES AND MEASURES: Participants rated their smoking enjoyment during the prequit period and withdrawal symptoms weekly for the first 4 weeks after the TQD. Continuous validated abstinence rates were assessed at 1, 4, and 12 weeks after the TQD. RESULTS: The dose increase reduced smoking enjoyment during the prequit period, with mean (SD) ratings of 1.7 (0.8) for varenicline vs 2.1 (0.7) for placebo (P = .001). It had no effect on the mean (SD) frequency of urges to smoke at 1 week after the TQD, their strength, or the severity of withdrawal symptoms: these ratings for varenicline vs placebo were 2.7 (1.1) vs 2.6 (0.9) (P = .90), 2.6 (1.1) vs 2.8 (1.0) (P = .36), and 1.5 (0.4) vs 1.6 (0.5) (P = .30), respectively. The dose increase also had no effect on smoking cessation rates for varenicline vs placebo at 1 week (37 [37.0%] vs 48 [48.0%], P = .14), 4 weeks (51 [51.0%] vs 59 [59.0%], P = .32), and 12 weeks (26 [26.0%] vs 23 [23.0%], P = .61) after the TQD. There was significantly more nausea (P < .001) and vomiting (P < .001) reported in the varenicline arm than in the placebo arm. CONCLUSIONS AND RELEVANCE: Increasing varenicline dose in smokers with low response to the drug had no significant effect on tobacco withdrawal symptoms or smoking cessation. Physicians often consider increasing the medication dose if there is no response to the standard dosage. This approach may not work with varenicline. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206010.

Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial.

BACKGROUND: Nicotine replacement therapy (NRT) and varenicline are both effective in helping smokers quit. There is growing interest in combining the two treatments to improve treatment outcomes, but no experimental data exist on whether this is efficacious. This double-blind randomised controlled trial was designed to evaluate whether adding nicotine patches to varenicline improves withdrawal relief and short-term abstinence rates. METHODS: 117 participants seeking help to stop smoking were randomly allocated to varenicline plus placebo patch or varenicline plus nicotine patch (15 mg/16 hour). Varenicline use commenced one week prior to the target quit date (TQD), patch use started on the TQD. Ratings of urges to smoke and cigarette withdrawal symptoms were collected weekly over 4 weeks post-TQD. Medication use and smoking status were established at 1, 4 and 12 weeks. Participants lost to follow-up were included as continuing smokers. RESULTS: 92% of participants used both medications during the first week after the TQD. The combination treatment generated no increase in nausea or other adverse effects. It had no overall effect on urges to smoke or on other withdrawal symptoms. The combination treatment did not improve biochemically validated abstinence rates at 1 week and 4 weeks post-TQD (69% vs 59%, p=0.28 and 60% vs 59%, p=0.91, in the nicotine patch and placebo patch arm, respectively), or self reported abstinence rates at 12 weeks (36% vs. 29%, p=0.39, NS). CONCLUSIONS: The efficacy of varenicline was not enhanced by the addition of nicotine patches, although further trials would be useful to exclude the possibility of type II error. TRIAL REGISTRATION: Clinicaltrials.gov REGISTRATION NUMBER: NCT01184664.

Weight change during and after Ramadan fasting.

BACKGROUND: During Ramadan, observant Muslims fast from sunrise to sunset for a month. Knowing whether Ramadan fasting affects body weight has implications for health advice to the Muslim community, for understanding the effects of skipping meals on body weight, and for general weight management advice. METHODS: We compared body weight before and after the Ramadan fast and 1 month later in observant Muslims attending a Mosque in East London, UK. RESULTS: In 202 participants who provided weight at the beginning and the end of Ramadan, there was a small weight decrease (-0.84 kg, 95% CI = -0.6 to -1, P < 0.0001), with 46% of participants losing >1 kg. Participants who fasted throughout Ramadan lost significantly more weight (1 kg) than those who occasionally broke fast (0.3 kg, P = 0.013). In 87 participants who provided weight at the beginning and end of Ramadan and also 1 month later, all the lost weight was regained (+0.1 kg, 95% CI = 0.2-0.5, P = 0.504 compared with baseline). CONCLUSIONS: Observers of Ramadan lose on average about a kilogram of weight over 4 weeks, and the lost weight is quickly regained. Current weight management treatments generally assume that skipping meals leads to weight gain and advise against it. The finding suggests that further research is needed on the justification of the 'do not skip meals' advice.

Use of varenicline for 4 weeks before quitting smoking: decrease in ad lib smoking and increase in smoking cessation rates.

BACKGROUND: The use of varenicline tartrate alleviates postquit withdrawal discomfort, but it also seems to reduce the "reward" associated with smoking. The current treatment schedule, which commences 1 week before quitting, relies primarily on the first mechanism. We set out to determine whether increasing the prequit medication period renders cigarettes less satisfying and facilitates quitting. METHODS: One hundred one smokers attending a stop-smoking clinic in London, United Kingdom, were randomly allocated to receive varenicline for 4 weeks before the target quit date (TQD) or to receive placebo for 3 weeks before the TQD, followed by varenicline for 1 week before the TQD. In both groups, standard varenicline treatment was given for 3 months after the TQD. Measures included smoking satisfaction and smoke intake before quitting, urges to smoke and withdrawal discomfort after quitting, and sustained abstinence from the TQD to 3 months. RESULTS: Varenicline preloading reduced prequit enjoyment of smoking (P = .004) and smoke intake (P < .001), with 36.7% of participants reducing their cotinine concentrations by more than 50% (reducers). Varenicline preloading did not affect postquit withdrawal symptoms, but it increased 12-week abstinence rates (47.2% in the varenicline arm vs 20.8% in the placebo arm, P = .005). The effect was particularly strong among the reducers in the varenicline arm (66.7% in reducers vs 22.6% in nonreducers, P = .002). Varenicline preloading was well tolerated. CONCLUSIONS: Although several issues remain to be clarified, varenicline preloading can generate a substantial reduction in ad lib smoking and enhance 12-week quit rates. Current treatment schedules may lead to suboptimal treatment results. Trials with longer follow-up periods are needed to corroborate these findings. Trial Registration clinicaltrials.gov Identifier: NCT00789074.

Spontaneous combined lung and bowel hernia following an episode of acute bronchitis.

Spontaneous lung hernias are unusual conditions which usually follow attacks of excessive straining. Spontaneous bowel hernias are even rarer. Here, we present the first reported case of a combined spontaneous herniation of both the lung and bowel following an attack of acute bronchitis and coughing together with a description of surgical approach and repair.

Utility of 96-well plate aggregometry and measurement of thrombi adhesion to determine aspirin and clopidogrel effectiveness.

Aspirin and clopidogrel are key anti-thrombotic therapies. Results from platelet reactivity testing during therapy, have been shown to correlate with future events and would allow for the optimisation of therapy. However, there is little agreement among current tests and there remains a clear clinical need for a universal standardised test. It was the objective of this study to explore the potential of 96-well plate aggregometry as a definitive clinical test of platelet reactivity with respect to aspirin and clopidogrel. A small non-blinded trial of 16 healthy male volunteers assigned to seven days of aspirin (75mg/day) or clopidogrel (75mg/day) therapy. Blood was collected before and on day 7 of treatment. Platelet aggregation was measured using a 96-well plate based aggregation method, and thrombi adhesion measured by colourimetric assay. Platelet agonists used were ADP (0.1-30microM), arachidonic acid (0.03-1.3mM), collagen (0.1-30microg/ml), adrenaline (0.001-100microM), ristocetin (0.2-3mg/ml), TRAP6 amide (0.130microM) and U46619 (0.130microM). Concentration response curves were constructed to each agonist under the various conditions and used to extract data such as log EC(50), Hill slope, and area under the curve. These demonstrated low intra- and inter-assay variability and strong discrimination of drug effects. This study demonstrates the ability of the 96-well plate based aggregation and adhesion method to detect and differentiate between stable aspirin and clopidogrel treatment in healthy volunteers. Moreover, this assay marries the ability to test subjects or patients using a range of platelet agonists with more rapidity and ease than the current gold standard platelet assay, traditional light transmission aggregometry, making it a serious alternative assay for use in clinical settings.

Antiplatelet actions of statins and fibrates are mediated by PPARs.

OBJECTIVES: Statins and fibrates are hypolipidemic drugs which decrease cardiac events in individuals without raised levels of cholesterol. These drugs inhibit platelet function, but the mechanisms by which this pleiotropic effect is exerted are not known. METHODS AND RESULTS: We used a range of approaches to show statins inhibit human platelet activation in vitro while engaging PPARalpha and PPARgamma. The effects of simvastatin were prevented by the PPARgamma antagonist GW9662 or the PPARalpha antagonist GW6471. In a small-scale human study fluvastatin activated PPARalpha and PPARgamma in platelets and reduced aggregation in response to arachidonic acid ex vivo. The effects of fenofibrate were prevented by PPARalpha antagonism with GW6471. Fenofibrate increased bleeding time in wild-type, but not in PPARalpha-/- mice. The inhibitory effect of fenofibrate, but not simvastatin, on aggregation was prevented by deletion of PPARalpha in murine platelets. PKCalpha, which influences platelet activation, associated and immune-precipitated with PPARgamma in platelets stimulated with statins and with PPARalpha in platelets stimulated with fenofibrate. CONCLUSIONS: This study is the first to provide a unifying explanation of how fibrates and statins reduce thrombotic and cardiovascular risk. Our findings that PPARs associate with PKCalpha in platelets also provide a mechanism by which these effects are mediated.

Patients' views of the consent process for adult cardiac surgery: questionnaire survey.

OBJECTIVE: Consent for surgical procedures has assumed increasing importance in surgical practice in recent days especially following the public inquiry into paediatric cardiac surgery deaths at Bristol in the UK. This study examines patient perceptions and recollections following surgical consent as currently practised in a UK cardiac unit. METHODS: One hundred consecutive patients who underwent cardiac surgery in a London teaching hospital from January to February 2003 were studied. Patients completed questionnaires a day before their discharge from the hospital. RESULTS: The majority of patients (89/100) responded that the information given at consent had been adequate or more than adequate. The time spent on the consent process was thought to be adequate by 91 patients. Eleven patients felt the consent had been insensitive. Several patients (38/100) felt use of booklets in preference to verbal explanations would be less intimidating. For most patients (94/100) the operation and postoperative course met their expectations; although 12 patients experienced untold complications, only five felt that they should have been informed of the possibility of the complication. Although most patients were informed of the risk of death during consent, at time of discharge 43 had forgotten the figure that had been quoted. Regarding the influence of media and publicity, 19 patients said that media had influenced their expectations of the consent process, 59 would have liked to see hospital league tables while 26 would have liked to know the mortality figures for their surgeon prior to giving consent. CONCLUSIONS: Our study shows that patients undergoing cardiac surgery are largely satisfied with our improved consent procedures in the post-Bristol era. Use of booklets may be a useful adjunct to verbal consent as currently practised.