Does reducing withdrawal severity mediate nicotine patch efficacy? A randomized clinical trial

Nicotine replacement therapy (NRT) repeatedly has been shown to improve smoking treatment outcome. The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal. The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal, collected by ecological momentary assessments administered on a palm-top computer. Smokers (N = 324) were randomized to receive either active high-dose (35 mg) 24-hr patches or placebo. Increases in positive affect and decreases in craving, negative affect, and attention disturbance severity were related to lower risk of lapsing. Although NRT treatment did significantly decrease withdrawal and craving severity, these reductions only partially accounted for NRT's impact on time to first lapse: The results from a mediation analysis showed that the hazard ratio for NRT, when controlling for withdrawal and craving severity, was only a third to a half lower than the uncontrolled hazard ratio for NRT alone. This suggests that other mechanisms for the effectiveness of NRT need to be examined.     

Can group interventions facilitate forgiveness of an ex-spouse? A randomized clinical trial

This study evaluated the effectiveness of 2 versions of an 8-session forgiveness group intervention for divorced individuals. Participants (randomized, n=192; analyzed, n=149) were randomly assigned to a secular forgiveness condition, a religious forgiveness condition, or a no-intervention comparison condition. Measures of forgiveness and mental health were obtained at pretest, posttest, and 6-week follow-up. Participants in both intervention conditions increased significantly more than comparison participants on self-reported forgiveness of an ex-spouse and understanding of forgiveness. Participants in the secular condition showed a greater decrease in depressive symptoms than comparison participants. Intrinsic religiousness did not moderate intervention effects.     

Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care

BACKGROUND: Patients frequently present with unexplained fatigue in primary care, but there have been few treatment trials in this context. We aimed to test cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients presenting to their family doctor with fatigue. Secondly, we described the outcome for a cohort of patients who presented to the same doctors with fatigue, who received standard care, plus a booklet. METHOD: This was a randomized trial, followed by a prospective cohort study. Twenty-two practices in SE England referred 144 patients aged 16 to 75 years with over 3 months of unexplained fatigue. Self-rated fatigue score, the hospital anxiety and depression rating scale, functional impairment, physical step-test performance and causal attributions were measured. In the trial six sessions of CBT or GET were randomly allocated. RESULTS: In the therapy groups the mean fatigue score decreased by 10 points (95% confidence interval (CI) = -25 to -15), with no significant difference between groups (mean difference = -1.3; CI = -3.9 to 1.3). Fewer patients attended for GET. At outcome one-half of patients had clinically important fatigue in both randomized groups, but patients in the group offered CBT were less anxious. Twenty-seven per cent of the patients met criteria for CFS at baseline. Only 25% of this subgroup recovered, compared to 60% of the subgroup that did not meet criteria for CFS. CONCLUSIONS: Short courses of GET were not superior to CBT for patients consulting with fatigue of over 3 months in primary care. CBT was easier 'to sell'. Low recovery in the CFS subgroup suggests that brief treatment is too short.     

Improved patient participation through advance care planning in nursing homes—A cluster randomized clinical trial

ObjectiveTo improve patient participation in advance care planning in nursing homes where most patients have some degree of cognitive impairment.MethodsThis was a pair-matched cluster randomized clinical trial with eight wards in eight Norwegian nursing homes. We randomized one ward from each of the matched pairs to the intervention group. We included all patients above 70. The primary outcome was prevalence of documented patient participation in end-of-life treatment conversations.The intervention included implementation support using a whole-ward approach where regular staff perform advance care planning and invite all patients and next of kin to participate.ResultsIn intervention group wards the patients participated more often in end-of-life treatment conversations (p < 0.001). Moreover, the patient’s preferences, hopes AND worries (p = 0,006) were more often documented, and concordance between provided TREATMENT and patient preferences (p = 0,037) and next of kin participation in advance care planning with the patient (p = 0,056) increased.ConclusionImproved patient participation – also when cognitively impaired - is achievable through advance care planning in nursing homes using a whole-ward approach.Practice implicationsPatients with cognitive impairment should be included in advance care planning supported by next of kin. A whole-ward approach may be used to implement advance care planning.Trial registrationISRCTN registry (ID ISRCTN69571462) – retrospectively registered.     

Can the randomized controlled trial literature generalize to nonrandomized patients?

To determine the extent to which published randomized controlled trials (RCTs) of psychotherapy can be generalized to a sample of outpatients, the authors matched information obtained from charts of patients who had been screened out of RCTs to inclusion and exclusion criteria from published RCT studies. Most of the patients in the sample who had primary diagnoses represented in the RCT literature were judged eligible for at least 1 RCT. However, many patients in the sample with substance use disorders or social anxiety disorder were not eligible for at least 2 RCTs. Common reasons that patients did not match with at least 2 published RCTs for psychotherapy included (a) patients were in partial remission, (b) patients failed to meet minimum severity or duration criteria, (c) patients were being treated with antidepressant medication, and (d) the disorder being studied was not primary (mostly for social anxiety patients). The implications of these findings for future research and clinical practice are discussed.     

Can extracellular fluid volume expansion in hemodialysis patients be safely reduced using the hemocontrol biofeedback algorithm? A randomized trial

Extracellular fluid volume (ECFV) expansion in hemodialysis patients is associated with increased mortality. Attempts to remove excess fluid often result in intradialytic hypotension (IDH). Blood volume monitoring has been used to aid selection of ultrafiltration rates and dialysate conductivity to minimize IDH. Automating ultrafiltration and dialysate conductivity using the Hemocontrol Biofeedback System (HBS) has reduced IDH in IDH-prone subjects. We undertook a randomized controlled trial to determine if the HBS could safely reduce ECFV in ECF-expanded subjects. Patients with ECFV >45% of total body water were randomized to receive hemodialysis by either HBS or best clinical practices for 6 months. The primary endpoint was change in ECFV; exploratory variables included frequency of IDH, interdialytic weight gain, and changes in serum Na. Treatment with HBS did not result in any change in ECFV, even after multivariable adjustment. The frequency of IDH was however significantly lower with HBS when compared with best clinical practices without differences in other variables.     

Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? results from a randomized clinical trial

PurposeFemale breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of primary surgical treatment. In this article, we report on the psychosocial impact of RGCT.MethodsNewly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits.ResultsBetween 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes.ConclusionsIn this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects.     

Curcumin improves treatment outcome of Takayasu arteritis patients by reducing TNF-α: a randomized placebo-controlled double-blind clinical trial

Tumor necrosis factor (TNF) inhibitors have been found to exhibit certain efficacy in treating refractory Takayasu arteritis (TA) in clinic despite severe adverse effects. The aim of this study is to investigate a natural anti-TNF compound, curcumin, its function, and its potential as treatment against TA. In total, 246 patients who were diagnosed of acute TA participated have completed this clinical trial. They were randomly assigned in either treatment group or control group, in which they were daily administered with curcumin or placebo accordingly for 4 weeks with weekly revisits for data collection. The treatment outcome consisted of a primary one defined using Birmingham Vascular Activity Score (BVAS) and a secondary one defined by laboratory results, e.g., C-reactive protein (CRP), TNF-α, and erythrocyte sedimentation rate (ESR). In this study, the primary and secondary treatment outcomes were found to be steadily attenuated in patients who received curcumin treatment, while showed no significant change in patients in placebo group. TNF-α was found to be significantly correlated with BVAS scores (γ ² = 0.81, p = 0.016), ESR (γ ² = 0.76, p = 0.037), and plasma levels of CRP (γ ² = 0.79, p = 0.041). The treatment outcome was greatly improved by curcumin administration probably due to its anti-TNF property.     

Efficacy of Papacarie® in reduction of residual bacteria in deciduous teeth: a randomized,controlled clinical trial

OBJECTIVES:

The aim of the present study was to analyze the efficacy of Papacarie® gel compared with the traditional method (low-speed bur) in reducing the counts of total bacteria, Lactobacillus, total Streptococcus and Streptococcus mutans group.

METHODS:

A randomized, controlled clinical trial with a split-mouth design was performed. The sample comprised 40 deciduous teeth in 20 children (10 males and 10 females) aged four to seven years. The teeth were randomly allocated to two groups: G1, or chemomechanical caries removal with Papacarie Duo®, and G2, or the removal of carious dentin tissue with a low-speed bur. Infected dentin was collected prior to the procedure, and the remaining dentin was collected immediately following the removal of the carious tissue. Initial and final counts of bacterial colonies were performed to determine whether there was a reduction in the number of colony-forming units (CFUs) of each microorganism studied. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01811420","term_id":"NCT01811420"}}NCT01811420.

RESULTS:

Reductions were found in the numbers of total bacteria, total Streptococcus and Streptococcus mutans group following either of the caries removal methods (p<0.05). A reduction was also noted in the number of Lactobacillus CFUs; however, this difference did not achieve statistical significance (p>0.05).

CONCLUSION:

Papacarie® is an excellent option for the minimally invasive removal of carious tissue, achieving significant reductions in total bacteria, total Streptococcus and S. mutans with the same effectiveness as the traditional caries removal method.     

Do different delivery systems of hormone therapy have different effects on psychological symptoms in surgically menopausal women? A randomized controlled trial

Objective

To compare the influence of different delivery forms of estrogen therapy on menopausal and psychological symptoms in surgically menopausal women.

Study design

Surgically menopausal women were assigned to a 1-year-therapy with oral conjugated estrogen 0.625 mg/day (n = 35), intranasal 300 μg/day estradiol hemihidrate (n = 33), percutaneous gel 1.5 mg/day estradiol hemihidrate (n = 32) or no treatment (control group, n = 32). Serum E₂ and FSH levels, Kupperman's Scale used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year-therapy.

Results

After 1 year, the greatest increase in E₂ was in the oral group, followed by the transdermal gel, and then the intranasal group (oral vs transdermal gel: p = 0.022: oral vs intranasal: p = 0.0001; transdermal gel vs intranasal: p = 0.0001). All treatment groups improved significantly in total Kupperman index score and HARS (p < 0.05) with no difference between the groups. With regard to HDRS, all treatment groups improved significantly (p < 0.05) with the greatest improvement in the oral group, and no difference between transdermal gel and intranasal groups (oral vs transdermal gel: p = 0.015; oral vs intranasal: p = 0.001; transdermal gel vs intranasal: p = 0.735). Control group scored worse in all tests after study (p < 0.05). All scores correlated significantly with post-treatment serum E₂ and FSH levels (p < 0.001).

Conclusion

Oral, intranasal and percutaneous gel estradiol therapies significantly improve menopausal and psychological symptoms in surgically menopausal women with oral route better than transdermal gel and intranasal modalities against depressive mood.     

Training auscultatory skills: computer simulated heart sounds or additional bedside training? A randomized trial on third-year medical students

Background  

The present study compares the value of additional use of computer simulated heart sounds, to conventional bedside auscultation training, on the cardiac auscultation skills of 3^rd year medical students at Oslo University Medical School.     

CMV in critically ill patients: pathogen or bystander?

Despite broad variability in study populations, methodologies for CMV detection, and analytic methods used, multiple studies have documented frequent CMV infection in non-immunocompromised adults with critical illness due to a variety of causes. Higher rates of CMV infection in studies of seropositive patients suggest that reactivation of latent infection rather than primary infection is the main mechanism in this setting. Risk factors for CMV reactivation (other than seropositivity) have not been clearly defined and there does not appear to be a consistent association with severity of illness. Furthermore, CMV reactivation in this setting has been associated with important adverse clinical outcomes, including increased duration of mechanical ventilation, longer length of stay and all-cause mortality. There are several biologically plausible mechanisms that could link CMV reactivation with adverse outcomes, including: direct lung injury (CMV pneumonia), amplification of inflammation systemically and within the lung, or predisposition to other nosocomial infections, but clinical data in the ICU setting are limited. Further observational studies are unlikely to significantly advance our understanding of the role of CMV in critically ill patients. Given the significant impact of critical illness, limited current therapeutic options, the availability of generally well-tolerated antiviral options for CMV, and the clinical data supporting a possible pathogenic role for CMV, there is a strong rationale for a randomised controlled trial of CMV prevention as a novel means of improving the outcomes of critically ill patients.     

HIV clinical trials in correctional settings: right or retrogression?

The right of incarcerated prison and jail inmates to health care is protected by the 8th and the 14th amendments of the Constitution, respectively. Does the right to health care include access to clinical trials? At the time of this writing, clinical trials have become part of the fabric of HIV/AIDS care, allowing patients to participate in studies of new and often lifesaving treatments. Participation in trials can also be dangerous, as illustrated by the recent death of a subject in a gene therapy trial. This danger is compounded by ethical dilemmas that can arise from the large amount of financial support for clinical trials (greater than 75%) that is derived from for-profit corporations. Indeed, clinical trials are the subject of grave concern on the part of the United States Government, which has recently taken steps to shore up human subject safeguards. Following a conference on the conduct of clinical trials in correctional settings, the Office for Human Research Protections suspended prison research conducted by 4 prestigious academic institutions.