Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial. A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study. A prospective, randomized, controlled trial of an emergency department-based atrial fibrillation treatment strategy with low-molecular-weight heparin. Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy. Short-term effects of enhanced treatment for depression in primary care: results from a randomized controlled trial. Efficacy of adjuvant anterior left atrial ablation during intracardiac echocardiography-guided pulmonary vein antrum isolation for atrial fibrillation. A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Left atrial ablation versus biatrial ablation for persistent and permanent atrial fibrillation: a prospective and randomized study.
A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV. The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens. We assess an alternative accelerated clinical pathway approach to the management of patients with newly diagnosed or new-onset atrial fibrillation (AF).
                A prospective, randomized pilot study of 2 AF disease-management strategies was conducted at a single university hospital. A traditional approach of hospital admission versus an accelerated emergency department-based strategy with low-molecular-weight heparin and early cardioversion to sinus rhythm was assessed in a cohort of patients with uncomplicated AF. The primary end points were length of stay and total actual direct costs.
                Eighteen patients were randomized over a 15-month period. The accelerated treatment strategy in the ED resulted in a substantial decrease in length of stay (2.1+/-2.3 versus <1 day) and a favorable trend toward mean cost reduction ($1,706+/-$1,512 versus $879+/-$394; P =.15). The clinical outcomes (rate of sinus rhythm at discharge and follow-up and complications caused by AF) related to AF were similar in the 2 groups.
                A disease-management strategy for new, uncomplicated AF that uses an ED-outpatient treatment pathway results in a shorter length of stay at potentially lower cost. The results of this pilot study warrant further investigation. To compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections.
                A randomized controlled prospective nonblinded study was performed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty-seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily).
                Similar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients (P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations > or = MIC (CA 100%vs. IA 60% of patients) and/or > or = 5 x MIC (CA 100%vs. IA 55% of patients) were significantly better following continuous administration (P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients (P < 0.01).
                Although clinical cure rates were comparable, continuous cefotaxime administration led to significantly greater proportions of concentrations > MIC and > 5 x MIC compared with intermittent dosing. Continuous administration of cefotaxime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost-effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration. Depression is a highly prevalent, often recurring or persistent disorder. The majority of patients are initially seen and treated in primary care. Effective treatments are available, but possibilities for providing adequate follow-up care are often limited in this setting. This study assesses the effectiveness of primary-care-based enhanced treatment modalities on short-term patient outcomes.
                In a randomized controlled trial we evaluated a psycho-educational self-management intervention. We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder, assessed by a structured psychiatric interview. Patients were randomly assigned to: the Depression Recurrence Prevention (DRP) program (n=112); a combination of the DRP program with psychiatric consultation (PC+DRP, n=39); a combination with brief cognitive behavior therapy (CBT+DRP, n=44); and care as usual (CAU, n=72). Follow-up assessments were made at 3 months (response 90%) and 6 months (85%).
                Patient acceptance of enhanced care was good. The mean duration of the index episode was 11 weeks (S.D.=9.78) and similar in CAU and enhanced care. Recovery rate after 6 months was 67% overall; 17% of all participants remained depressed for the entire 6-month period.
                Enhanced care did not result in better short-term outcomes. We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program. Observed depression treatment rates in CAU were high. Recent data have shown that the septum and anterior left atrial (LA) wall may contain "rotor" sites required for AF maintenance. However, whether adding ablation of such sites to standard ICE-guided PVAI improves outcome is not well known.
                To determine if adjuvant anterior LA ablation during PVAI improves the cure rate of paroxysmal and permanent AF.
                One hundred AF patients (60 paroxysmal, 40 persistent/permanent) undergoing first-time PVAI were enrolled over three months to receive adjuvant anterior LA ablation (Group I). These patients were compared with 100 randomly selected, matched first-time PVAI controls from the preceding three months who did not receive adjuvant ablation (Group II). All 200 patients underwent ICE-guided PVAI during which all four PV antra and SVC were isolated. In group I, a decapolar lasso catheter was used to map the septum and anterior LA wall during AF (induced or spontaneous) for continuous high-frequency, fractionated electrograms (CFAE). Sites where CFAE were identified were ablated until the local EGM was eliminated. A complete anterior line of block was not a requisite endpoint. Patients were followed up for 12 months. Recurrence was assessed post-PVAI by symptoms, clinic visits, and Holter at 3, 6, and 12 months. Patients also wore rhythm transmitters for the first 3 months. Recurrence was any AF/AFL >1 min occurring >2 months post-PVAI.
                Patients (age 56 +/- 11 years, 37% female, EF 53%+/- 11%) did not differ in baseline characteristics between group I and II by design. Group I patients had longer procedure time (188 +/- 45 min vs 162 +/- 37 min) and RF duration (57 +/- 12 min vs 44 +/- 20 min) than group II (P < 0.05 for both). Overall recurrence occurred in 15/100 (15%) in group I and 20/100 (20%) in group II (P = 0.054). Success rates did not differ for paroxysmal patients between group I and II (87% vs 85%, respectively). However, for persistent/permanent patients, group I had a higher success rate compared with group II (82% vs 72%, P = 0.047).
                Adjuvant anterior LA ablation does not appear to impact procedural outcome in patients with paroxysmal AF but may offer benefit to patients with persistent/permanent AF. The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR) in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown.
                In this double-blind study, 161 subjects with persistent AF were randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62, short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52 weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%, P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%, P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31 to 2%, P=0.085). There was no difference in adverse event rate or quality of life scores between groups.
                Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion. Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV. More patients taking long-term amiodarone remained in SR at 52 weeks, but more had serious adverse effects requiring discontinuation of therapy. Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option. In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring.
                1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up. The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol.
                Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF. The aim of this study was to compare--in patients with persistent and permanent atrial fibrillation (AF)--the efficacy and safety of left atrial ablation with that of a biatrial approach.
                Left atrium-based catheter ablation of AF, although very effective in the paroxysmal form of the arrhythmia, has an insufficient efficacy in patients with persistent and permanent AF.
                Eighty highly symptomatic patients (age, 58.6 +/- 8.9 years) with persistent (n = 43) and permanent AF (n = 37), refractory to antiarrhythmic drugs, were randomized to two different ablation approaches guided by electroanatomical mapping. A procedure including circumferential pulmonary vein, mitral isthmus, and cavotricuspid isthmus ablation was performed in 41 cases (left atrial ablation group). In the remaining 39 patients (biatrial ablation group), the aforementioned approach was integrated by the following lesions in the right atrium: intercaval posterior line, intercaval septal line, and electrical disconnection of the superior vena cava.
                During follow-up (mean duration 14 +/- 5 months), AF recurred in 39% of patients in the left atrial ablation group and in 15% of patients in the biatrial ablation group (p = 0.022). Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up.
                In patients with persistent and permanent AF, circumferential pulmonary vein ablation, combined with linear lesions in the right atrium, is feasible, safe, and has a significantly higher success rate than left atrial and cavotricuspid ablation alone.
There is limited evidence to suggest that CA may be a better treatment option compared to medical therapies in the management of persistent AF. This review was also unable to recommend the best CA method.