Research reports on treatments for bipolar disorder: preliminary assessment of methodological quality

OBJECTIVE: To assess frequencies of types of publications about bipolar disorder (BD) and evaluate methodological quality of treatment studies. METHOD: We classified 100 randomly selected articles (1998-2002) from five psychiatric journals with highest impact ratings, by topic areas, and assessed methods employed in treatment studies. RESULTS: Topics ranked: treatment (41%; 37% on pharmacotherapy) > biology (31%) > psychopathology (14%) = miscellaneous (14%). Of treatment studies, only 19% of original articles were randomized, 15% were relatively large (n > or = 50) but non-randomized, 65% were small non-randomized, case-series or -reports, and 53% relied on baseline-to-endpoint contrasts without a control group. Patient dropout rates were > or =40% in 43% of prospective studies. Only two reports provided confidence intervals; one included a power analysis, and 53% included no references on study design or statistical methods. CONCLUSION: Even in highly respected journals, the typical methodological quality of recent reports on therapeutics for BD was unexpectedly limited, and psychopathology and psychotherapies were little studied.     

Adjunctive bright light in non-seasonal major depression: results from patient-reported symptom and well-being scales

OBJECTIVE: In this study, we tested the efficacy of bright light therapy as an adjunct to antidepressant treatment (sertraline) in patients with non-seasonal major depression. METHOD: In a randomized double-blind controlled trial, 102 patients were treated for 5 weeks with either white bright light (10.000 lx, 1 h/day) or red dim light (50 lx, 30 min/day). All patients received sertraline in a dosage of 50 mg daily. The self-assessment scales used were the Major Depression Inventory (MDI), the Psychological General Well-Being Scale (PGWB) and the Symptom Check List (SCL-90R). RESULTS: On all three questionnaires the score differences between baseline and endpoint were greatest in the bright light group. On the SCL-90R, the difference reached statistical significance. Results and effect sizes are compared with results from Danish national population studies applying PGWB and SCL-90R. CONCLUSION: The results advocate the use of bright light as an adjunct treatment of non-seasonal depression.     

A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is one of the commoner conditions seen in oral medicine clinics. Current treatments are palliative rather than curative. Numerous treatments have been tried but many have not been evaluated in randomized controlled trials (RCTs). OBJECTIVES: To review the effectiveness and safety of any therapy compared with placebo for the treatment of symptomatic OLP. METHODS: A systematic review of 11 RCTs, totalling 223 patients was done. The main outcome measures used were improvement of signs (erythema, reticulation, ulceration) and symptoms (pain, discomfort) usually after 8 weeks of therapy. RESULTS: Eleven interventions were grouped into four therapeutic classes (topical ciclosporins, topical or systemic retinoids, topical steroids and phototherapy) for comparison. No therapy was replicated exactly. Trials recording the same outcomes in each therapeutic class were pooled. The largest number of pooled trials was four. Small odds ratios with very wide confidence intervals indicating statistically significant but imprecisely known treatment benefits were seen in all but one trial. Only systemic agents were associated with treatment toxicities; all other side-effects were mild and mainly local. CONCLUSIONS: The results are tempered by the small study sizes, lack of replication, lack of standardized outcome measures and the very high likelihood of publication bias. Therefore this review provides only circumstantial evidence for the superiority of the assessed interventions over placebo for the palliation of symptomatic OLP. There is a need for larger placebo-controlled RCTs with carefully selected and standardized outcome measures.     

Controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) for multi-slice imaging.

In all current parallel imaging techniques, aliasing artifacts resulting from an undersampled acquisition are removed by means of a specialized image reconstruction algorithm. In this study a new approach termed "controlled aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) is presented. This technique modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure. This new parallel multi-slice technique is more efficient compared to other multi-slice parallel imaging concepts that use only a pure postprocessing approach. In this new approach, multiple slices of arbitrary thickness and distance are excited simultaneously with the use of multi-band radiofrequency (RF) pulses similar to Hadamard pulses. These data are then undersampled, yielding superimposed slices that appear shifted with respect to each other. The shift of the aliased slices is controlled by modulating the phase of the individual slices in the multi-band excitation pulse from echo to echo. We show that the reconstruction quality of the aliased slices is better using this shift. This may potentially allow one to use higher acceleration factors than are used in techniques without this excitation scheme. Additionally, slices that have essentially the same coil sensitivity profiles can be separated with this technique.     

Self-care intervention to reduce oral candidiasis recurrences in HIV-seropositive persons: a pilot study

OBJECTIVES: This single-blind randomized controlled pilot study evaluated the efficacy of a behavioral intervention program, PRO-SELF: Candidiasis, to reduce time to recurrence of oral candidiasis over 6 months in susceptible HIV-seropositive persons. The intervention involved instruction by dentists on improving oral hygiene, minimizing sugar intake, and self-diagnosing candidiasis. METHODS: Participants were adults with oral candidiasis responsive to antifungals who presented to the UCSF Stomatology Clinic between 1997 and 2000. At 2-3 weeks of follow-up visits, a dentist "examiner", masked to group assignment, quizzed participants as to the presence of candidiasis, and assessed candidiasis status. A second, unmasked dentist "instructor" then delivered the program to intervention participants. Participants recorded dietary and oral hygiene practices in 24-h recall diaries: intervention participants at each visit and controls at initial and final visits. RESULTS: At randomization, CD4+ cell counts (cells/mm(3)) were 298 +/- 188 among 18 intervention participants and 396 +/- 228 among 17 controls. The candidiasis recurrence rates at 6 months were 78% among intervention compared with 88% among control participants (hazard ratio 0.72; 95% CI 0.35-1.50). Performing oral hygiene after meals/snacks showed the largest relative improvement: intervention-control difference in proportion of meals/snacks affected was 24% (95% CI -1 to 48%). Self-diagnoses of candidiasis were inaccurate, possibly because of mild episodes. CONCLUSIONS: The results weakly indicate that regular instruction from healthcare professionals helps patients delay candidiasis recurrence by improving oral hygiene. Among HIV-seropositive persons, those with poor oral hygiene, and high-sugar diets are most likely to benefit.     

Locally delivered doxycycline improves the healing following non-surgical periodontal therapy in smokers

OBJECTIVE: The outcome of non-surgical periodontal therapy is known to be inferior in smokers compared to non-smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled-release doxycycline. METHODS: One hundred and three patients (42 smokers, 61 non-smokers), each having at least eight periodontal sites with PPD (probing pocket depth) > or =5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non-surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox trade mark ) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses). RESULTS: The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non-smokers (mean PPD 5.7-5.9 mm). The mean PPD reduction in the control group at 3-month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non-smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non-smokers, respectively. The mean CAL gain for smokers and non-smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect. CONCLUSION: Locally applied controlled-release doxycycline gel may partly counteract the negative effect of smoking on periodontal healing following non-surgical therapy.     

Effect of GBR and fixture installation on gingiva and bone levels at adjacent teeth

Guided bone regeneration (GBR) is frequently used in oral implantology. It is unclear to what extent GBR affects the periodontium of adjacent teeth. Therefore, the present study quantifies changes in the proximal gingiva and bone levels at these teeth in 30 patients. Staged surgery involved a standard GBR treatment, randomly using resorbable membranes with a bone substitute or non-resorbable membranes with or without a bone substitute, followed by fixture installation at 6 months and abutment connection a further 6 months later. The data were sampled at each surgery and analysed using MANOVA. Twelve months after GBR, there was on average a small but statistically significant amount of proximal gingival recession (0.75 mm) and bone resorption (0.34 mm) observed, of which 50% was the result of GBR surgery. No significant differences were found between the different GBR treatment modalities. It is concluded that GBR treatment may have a small negative effect on the levels of the free gingival margin and alveolar bone at adjacent teeth, which is in most patients not clinically relevant.     

Skin exposure during conventional phototherapy in preterm infants: A randomized controlled trial

OBJECTIVE: To assess the effect of reduced skin exposure in preterm infants receiving overhead phototherapy treatment on total serum bilirubin (TSB). METHODS: Randomized controlled trial. Preterm infants (>1500 g birthweight and < or = 36 weeks gestation) were randomized to being nursed either partially clothed with only disposable nappies and in posturally supported positions (n = 30) or naked without postural support (n = 29). Primary outcome was mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment (irradiance of 6 microW cm(-2)/nm at a wavelength of 425-475 nm). The incidence of rebound jaundice, number of infants continuing to receive phototherapy treatment at 24 h periods, parental stress, mother-infant interaction and mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment were examined. RESULTS: Mean TSB percentage change at 24 h of completed treatment for the partially clothed group was 15.4% (+/-18) and for the naked group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes were significantly affected by reduced skin exposure to overhead phototherapy treatment. CONCLUSION: Our results show no statistically significant difference in TSB level change using either nursing practice.     

High-frequency pulsed electromagnetic energy in tinnitus treatment

OBJECTIVES/HYPOTHESIS: Electromagnetic therapy has been used with reported success in multiple clinical settings, including the treatment of seizure disorders, brain edema, migraine headaches, revascularization of burn wounds, and diabetic ulcers. The purpose of the study was to investigate the effect of pulsed high-frequency electromagnetic therapy on chronic tinnitus. STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled pilot study was conducted to evaluate the effectiveness of high-frequency pulsed electromagnetic energy using the Diapulse device in the treatment of chronic tinnitus. Thirty-seven adult patients with chronic tinnitus of at least 6 months' duration were recruited and randomly assigned to either a treatment or a placebo group. METHODS: Patients received 30-minute treatments with the Diapulse device three times a week for 1 month. The unit was set to deliver electromagnetic energy at a frequency of 27.12 MHz at a repetition rate of 600 pulses per second. All subjects had pretreatment and post-treatment audiological testing, including tinnitus frequency and intensity matching. They responded to a tinnitus rating questionnaire and the Tinnitus Handicap Inventory before and after treatment. RESULTS: There was no significant change in the pretreatment and post-treatment audiometric thresholds in either group. There were no significant differences between the pretreatment and post-treatment Tinnitus Handicap Inventory scores or the tinnitus rating scores in either subject group (Student t test). No diagnosis-specific differences were identified. CONCLUSION: High-frequency pulsed electromagnetic energy (Diapulse) at the settings used in the study showed no role in the therapy of patients with chronic tinnitus.     

Effect of urinary versus recombinant follicle-stimulating hormone on platelet function and other hemostatic variables in controlled ovarian hyperstimulation

OBJECTIVE: To determine the effect of urinary versus recombinant FSH on platelet function and hemostatic variables in women undergoing controlled ovarian hyperstimulation cycles. DESIGN: Randomized clinical study. SETTING: Major university-based infertility and in vitro fertilization unit and hemostasis laboratory. PATIENT(S): Ten healthy women (in vitro study), and 24 women undergoing routine controlled ovarian hyperstimulation cycles (in vivo study), randomly assigned to receive either urinary (u-FSH) or recombinant gonadotropin (r-FSH). INTERVENTION(S): In vitro study: effect of preincubation of plasma with u-FSH or r-FSH, in the presence or absence of estradiol, on platelet function and coagulation parameters. In vivo study: Changes in platelet function and coagulation parameters after treatment with u-FSH or r-FSH during controlled ovarian hyperstimulation cycles. MAIN OUTCOME MEASURE(S): Platelet aggregation and ATP release, activated protein C resistance ratio, free protein S. RESULT(S): In vitro study: Platelet aggregation and ATP release were significantly inhibited by u-FSH relative to r-FSH in both the presence and absence of estradiol (P=.047). In vivo study: Platelet function was significantly inhibited after treatment with u-FSH (P=.05) but not with r-FSH. In both studies, small changes of minor clinical significance were noted in activated protein C resistance and free protein S levels. CONCLUSION(S): The different platelet response to u-FSH and r-FSH may have clinical implications in selected patients, especially those at risk of thromboembolic complications, in decisions regarding the appropriate medication for controlled ovarian hyperstimulation cycles.