Usual Clinical Practice Research Articles

Conducting research in everyday psychiatric settings: identifying the challenges to meaningful evaluation

A distinction is often made between research into the efficacy of a treatment, i.e. whether it can be shown to work under ideal conditions, and research into the effectiveness of a treatment, i.e. whether it can be shown to work within a routine health service or usual clinical practice. The purpose of this article is to use descriptive information collected from personnel on the implementation and evaluation of a psychological intervention as a way to highlight some of the challenges faced when conducting research within everyday clinical settings. A psychological intervention for low self-esteem was evaluated within a standard inpatient ward for dual diagnosis patients. Descriptive information was collected from interviews to identify the challenges encountered during the research process. A qualitative analysis of interview content was undertaken to identify the major themes. Personnel described a range of patient variables, staff characteristics and organizational factors that hindered the research process. A detailed account of these factors along with potential solutions that can facilitate research in clinical settings is provided. Conducting research within clinical settings requires considerable planning and monitoring throughout the whole research process. Particular attention should be given to the impact of patient characteristics, staff variables and organizational context when designing and implementing research protocols. The value of this type of research within everyday clinical settings has significant implications for improving patient treatment and outcomes across psychiatric services.

Rates of New or Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis

The rate of new or missed colorectal cancer (CRC) after colonoscopy and their risk factors in usual practice are unknown. Our objective was to evaluate the rate and risk factors in a population-based study. We analyzed data from the Canadian Institute for Health Information, the Ontario Health Insurance Program, and Ontario Cancer Registry for all patients (> or =20 years of age) with a new diagnosis of right-sided, transverse, splenic flexure/descending, rectal or sigmoid CRC in Ontario from April 1, 1997 to March 31, 2002, who had a colonoscopy within the 3 years before their diagnosis. Patients with new or missed cancers were those whose most recent colonoscopy was 6 to 36 months before diagnosis. We examined characteristics that might be risk factors for new or missed CRC. We identified a diagnosis of CRC in 3288 (right sided), 777 (transverse), 710 (splenic flexure/descending), and 7712 (rectal or sigmoid) patients. The rates of new or missed cancers were 5.9%, 5.5%, 2.1%, and 2.3%, respectively. Independent risk factors for these cancers in men and women were older age; diverticular disease; right-sided or transverse CRC; colonoscopy by an internist or family physician; and colonoscopy in an office. Because having an office colonoscopy and certain patient, procedure, and physician characteristics are independent risk factors for new or missed CRC, physicians must inform patients of the small risk (2% to 6%) of these cancers after colonoscopy. The influence of type of physician and setting on the accuracy of colonoscopy, potentially modifiable risk factors, warrants further study.

Initial Treatment of Severe Acute Psychosis with Fast Orally Disintegrating Risperidone Tablets

Although the use of atypical antipsychotics is the standard of care in the maintenance treatment of psychosis, most clinicians still rely on conventional neuroleptics to treat acutely agitated psychotic patients. The objective of this study was to evaluate the effectiveness and safety of a fast orally disintegrating tablet formulation of risperidone in the initial treatment of a large sample of very acutely ill psychotic patients. In this multi-center, prospective, open-label observational trial, 191 schizophrenic patients were treated upon admission to hospital with fast orally disintegrating risperidone tablets for up to seven days. Co-medication was per usual clinical practice and at physician's discretion. Psychopathology was rated at baseline, 2, 24 and 48 hours and 4 and 7 days after initiation of therapy. A mean PANSS total score of 114.3+/-23.4 at baseline reflected a severely exacerbated patient population. The PANSS total score was significantly reduced to 83.6+/-26.8 (p<0.0001) and the CGI from 5.6+/-0.7 to 4.5+/-1.1 (p<0.0001) after 7 days. The median time to calmness was 70 min and the associated PANSS item 4 (excitation) dropped two hours after the first intake of the study medication from 4.3+/-1.5 to 3.1+/-1.5 (p<0.0001). A total of 172 patients (90.1%) out of 191 completed the study. The median risperidone dose was 2 mg/d at the initiation of therapy and 4 mg/d after one week. Oral treatment of acutely exacerbated schizophrenic patients with fast orally disintegrating risperidone tablets, alone or in combination with benzodiazepines, was associated with a rapid onset of action and a significant and clinically relevant improvement of acute symptoms.

Impact of Febrile Neutropenia and Colony Stimulating Factor Use on Chemotherapy Delivery in Patients with Lymphoma: Results from the INC-EU Prospective Observational European Neutropenia Study.

New guidelines from 3 professional organisations (EORTC, ASCO and NCCN) highlight the importance of identifying patients at risk of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) and providing preventative therapy to avert infection-related consequences and impaired treatment delivery. This prospective observational study was conducted to assess the incidence and predictors of CIN, FN and reduced chemotherapy administration in routine practice in Western Europe. Lymphoma patients starting new chemotherapy regimens were enrolled from 34 centres in Belgium, France, Germany, Spain and the UK. Treatment was as per usual clinical practice, except for one additional blood count at cycle 1 neutrophil nadir. Of the total 305 patients, 65 (21%) had Hodgkin lymphoma (HL) and 240 (79%) had non-Hodgkin lymphoma (NHL). Mean age at diagnosis ± SD was 39 ± 17 years for HL and 63 ± 13 years for NHL. Ann Arbour stages were distributed, I 9%; II 52%; III 19%; IV 20% in the HL group. In the NHL group, stages were distributed I 18%; II 26%; III 16%; IV 40%. Chemotherapy regimens for HL patients were mainly ABVD-like (72%), BEACOPP-like (12%) and Stanford V (8%); regimens for NHL patients were 3-weekly CHOP-like (74%), followed by 2-weekly CHOP-like (17%), ACVBP-like (4%) and NHL other (5%). Primary colony stimulating factor (CSF) prophylaxis was used in 18% of HL and 28% of NHL patients; whereas 37% of HL and 29% of NHL patients received secondary CSF prophylaxis. Primary CSF use by regimen type was: ABVD-like 9%; BEACOPP-like 63%; Stanford V 20%; 3-weekly CHOP-like 12%; 2-weekly CHOP-like 76%; ACVBP-like 56%; and NHL other 67%. FN occurred in 15% (95% CI 8–27%) of HL and 22% (CI 17–28%) of NHL patients. FN occurrence was ≥ 20% for BEACOPP-like; Stanford V; 3-weekly CHOP-like; ACVBP-like; and NHL other regimens. Grade 4 CIN was observed in 40% (CI 28–53%) of HL and 54% (CI 47–60%) of NHL patients. Neutropenia-related hospitalisations were reported for 14% of HL and 18% of NHL patients. Mean relative chemotherapy dose intensity (RDI) ± SD compared to plan, taking into account non-administered cycles, was 88 ± 13% for HL and 86 ± 21% for NHL. Low RDI (≤ 85%) was observed in 31% and 32% of HL and NHL patients, respectively. Multivariate logistic regression confirmed first cycle FN and fewer cycles with CSF use as predictors of low RDI (table). In line with new guidelines for CSF support during myelosuppressive chemotherapy, routine European practice should be revised to include primary prophylaxis with CSF for regimens where an FN incidence of ≥ 20% was seen (e.g. 3-weekly CHOP), and where less than optimal RDI was attained. This study was supported by Amgen (Europe) GmbH.Predictors of RDI ≤ 85%Odds ratio (95% CI)Age (per additional 10 years of age)1.38 (1.13–1.70)ECOG performance status ≥ 22.39 (1.12–5.11)Type of chemotherapy regimen †:2-weekly CHOP-like2.04 (0.90–4.65)ACVBP-like9.48 (2.12–42.40)NHL other1.98 (0.56–6.91)ABVD-like2.71 (1.09–6.76)HL other3.19 (0.96–10.65)Cycles with CSF administration (per additional cycle with CSF)0.85 (0.76–0.96)Cycle 1 FN occurrence2.82 (1.16–6.86)† 3-weekly CHOP-like, reference category, p = 0.018 for this set of covariates.

Efectividad de la donación de sangre autóloga preoperatoria en prótesis total de rodilla

To assess the effectiveness in usual clinical practice of a preoperative autologous blood donation (PAD) program in total knee replacement (TKR). An observational study was carried out in which 127 patients undergoing TKR were followed from the pre-anaesthetic visit to hospital discharge. Number of patients transfused and number of autologous and homologous blood units transfused in the PAD group and in the control group were registered and compared. 73 patients (57.5% of the sample) entered in the PAD program, of which 18 (24.7%) received their own blood. Four patients in the PAD group (5.5%) also received one unit of homologous blood in comparison to 18.5% in the control group (p = 0.025). In the PAD group, 5.6% of patients who received antifibrinolytic treatment (n = 36) and 43.2% of those who did not (n = 37) were transfused (p < 0.001). Due to the low transfusion rate in TKR, especially when antifibrinolytic agents were administered, the use of PAD must be reconsidered in this indication.

Prise en compte clinique des différents toxiques dans les infertilités

This paper reviews the main toxics which are deleterious to fertility. Toxics are identified through in vitro, animal and clinical studies. The practitioner tries to assess whether a couple consulting for infertility has been exposed to such toxics. Some toxics are voluntarily taken: this is the case for tobacco, alcohol and other, maybe illegal, recreative drugs. Tobacco is the most frequently observed. The assessment of tobacco consumption and the implementation of weaning procedures have been studied in numerous papers: psychological, pharmacological and even immunotherapy-based approaches have been proposed. Alcohol abuse is even more difficult to assess: the border between acceptable convivial and excessive consumption is not clear-cut, except during pregnancy where there should be no alcohol consumption. This also holds for "recreative" drugs. It is usual clinical practice to register the medicine taken; some of these may be toxic for fertility. There is an ongoing work for listing these toxic drugs. Occupational life may also lead to exposure to toxics or be deleterious for fertility by imposing body constraints.

421: An Observational Study of Intramuscular Olanzapine Treatment in Acutely Agitated Patients with Bipolar I Disorder or Schizophrenia

The objective of this study was to evaluate intramuscular olanzapine treatment of acute agitation in usual clinical practice, allowing study of more severely agitated patients than in prospective, controlled clinical trials.

Using Innovative Simulation Modalities for Civilian-based, Chemical, Biological, Radiological, Nuclear, and Explosive Training in the Acute Management of Terrorist Victims: A Pilot Study

Chemical, biological, radiological, nuclear, and explosive (CBRNE) incidents are low frequency, high impact events that require specialized training outside of usual clinical practice. Educational modalities must recreate these clinical scenarios in order to provide realistic first responder/receiver training. High fidelity, mannequin-based (HFMB) simulation and video clinical vignettes were used to create a simulation-based CBRNE course directed at the recognition, triage, and resuscitation of contaminated victims. The course participants, who consisted of first responders and receivers, were evaluated using a 43-question pre- and post-test that employed 12 video clinical vignettes as scenarios for the test questions. The results of the pre-test were analyzed according to the various medical training backgrounds of the participants to identify differences in baseline performance. A Scheffe post-hoc test and an ANOVA were used to determine differences between the medical training backgrounds of the participants. For those participants who completed both the pre-course and post-course test, the results were compared using a paired Student's t-test. A total of 54 first responders/receivers including physicians, nurses, and paramedics completed the course. Pre-course and post-course test results are listed by learner category. For all participants who took the pre-course test (n = 67), the mean value of the test scores was 53.5 +/- 12.7%. For all participants who took the post-course test (n = 54), the mean value of the test scores was 78.3 +/-10.9%. The change in score for those who took both the pre- and post-test (n = 54) achieved statistical significance at all levels of learner. The results suggest that video clinical vignettes and HFMB simulation are effective methods of CBRNE training and evaluation. Future studies should be conducted to determine the educational and cost-effectiveness of the use of these modalities.

Immediate versus water-storage performance of Class V flowable composite restoratives

Objectives The aims of this investigation were to clarify the effects of 24 h water-storage and finishing time on mechanical properties and marginal adaptation to a Class V cavity of eight modern flowable resin-composites. Methods Eight flowable composites, plus two controls (one microfilled and one hybrid composite), were investigated with specimen sub-groups ( n = 10) for each property measured. The principal series of experiments was conducted in model Class V cavities with interfacial polishing either immediately (3 min) after setting or after 24 h water-storage. After the finishing procedure, each tooth was sectioned in a buccolingual direction through the center of the restoration, and the presence or absence of marginal-gaps was measured (and then summed for each cavity) at 14 points (each 0.5 mm apart) along the cavity restoration interface ( n = 10 per group; total points measured = 140). The shear bond-strengths to enamel and to dentin, and flexural strengths and moduli data were also measured at 3 min and after 24 h water-storage. Results For all flowable composites, polished immediately after setting, 14–30 summed gaps were observed (controls: 64 and 42). For specimens polished after 24 h, a significantly ( p < 0.05) reduced number of 8–17 summed gaps occurred for only 3 flowable composites; whereas for 5 flowable composites there were non-significantly-different ( p > 0.05) numbers (11–17) of summed gaps (controls: 28 and 22). After 24 h storage, shear bond-strengths to enamel and to dentin, flexural strengths and moduli increased highly significantly ( p < 0.001) for all materials, except Silux Plus. Significance A post-cure interval of 24 h resulted in enhanced mechanical and adhesive properties of flowable dental composites. In a minority of cases there was also a reduced incidence of marginal-gap formation. However the latter effect may be partly attributed to 24 h delayed polishing, even though such a delay is not usual clinical practice.

‘I've lost my husband, my house and I need a new knee … why should I smile?’: Action research evaluation of a group cognitive behavioural therapy program for older adults with depression

The current paper details an action research approach to developing and evaluating a group cognitive-behavioural therapy (CBT) program for older adults (65+ years) experiencing depression. This approach allowed the development of a novel program and for each component of the program to be evaluated and modified in an iterative, developmental fashion – a particularly important, ethically responsive feature when working with vulnerable populations. Formative and summative evaluations allowed the identification of beneficial, cohort-specific elements of an intervention without compromising individual wellbeing. A mixed methods data design was used to triangulate multiple and repeated quantitative and qualitative measures; in essence, a formalisation of usual clinical practice. The outcomes from the pilot study will be discussed in the context of a methodology that uniquely facilitates microanalytic research while maintaining therapeutic accountability, making replication and program accountability available to all clinicians.

Differences in time to positivity can affect the negative predictive value of blood cultures drawn through a central venous catheter

Sir: We have read with interest the contribution by Tanguy et al. [1] in Intensive Care Medicine reporting a negative predictive value of 98% for culture at 24 h of blood drawn through a catheter. The authors suggested that this could be used to rule out catheter-related infection in patients with central venous catheters (CVC) and sepsis of unknown origin. However, we think that some considerations must be noted in relation to the growth rate of micro-organisms. Clinical studies show variations in times to positivity of blood cultures between pathogens especially between bacteria and Candida spp. [2, 3, 4]. Weinstein et al. [2] observed that in usual clinical practice Enterobacteriaceae are positive in an average

Cancer screening trial to evaluate the efficacy of FDG-PET in healthy subjects: 2-year results of the Hamamatsu Medical Imaging Center study

1025 Background: Positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) is increasingly used for cancer screening in Japan. Although it is not rare that cancers at early stages are incidentally found on FDG-PET in usual clinical practice, it is still unknown whether FDG-PET is an effective tool for early detection of cancer and decrease of cancer death. To evaluate the efficacy of FDG-PET in cancer screening, we started a prospective study 2 years ago. Methods: From Aug 26 2003 to July 22 2004, 1197 healthy volunteers aged 35 years or older (46.7±7.7y.o.) participated in our cancer screening trial. They are supposed to undergo screening tests annually for 5 years and will be followed for years. The screening tests included whole-body FDG-PET, chest and abdominal CT, brain and pelvic MRI, tumor markers (CEA, CA19–9, SCC, PSA, CA125), and fecal occult blood test. From July 26 2004 to July 22 2005, 1158 subjects of the 1197 underwent the second screening a year after the first one. We made contact with 39 other subjects who skipped the second screening to check the occurrence of cancers. Results: In the 2-year period, primary cancers occurred in 19 subjects. Fifteen cancers (6 thyroid, 3 breast, 2 prostate, 3 lung, 1 ectopic thymus in thyroid grand) were detected on the first year and one (prostate) on the second year by the screening. Ten of the 16 were at stage I. Three subjects with negative findings at the screening developed gastric lymphoma, gastric cancer and malignant lymphoma of the kidney, respectively, within a year after the screening. FDG-PET was positive in 10 of 15 cancers (6 thyroid, 2 breast, 1 prostate and 1 ectopic thymus) on the first year. No PET positive cancer was found on the second year. Sensitivity of the screening tests as a whole and FDG-PET alone for the first year was 78.9% and 52.6%, respectively. Positive and negative predictive values and specificity of FDG-PET were 11.0% (10/91), 99.2% (1097/1106), and 93.1% (1097/1178), respectively. Conclusions: Cancer screening including FDG-PET showed reasonable accuracy and could detect a wide variety of cancers at early stages. This prospective study will clarify the details of efficacy and suitable interval of FDG-PET in cancer screening. No significant financial relationships to disclose.

Extended-release tramadol in the treatment of osteoarthritis:a multicenter, randomized, double-blind, placebo-controlled clinical trial

ABSTRACTObjective: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain.Methods: This 12‐week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity ≥ 40 on a 100‐mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.Main outcome measures: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity.Results: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall ( p ≤ 0.021) and for each dose ( p ≤ 0.050). However, the protocol-specified decision rule for the 3 co-primary endpoints was not satisfied because the overall comparison of subject global assessment of disease activity was not statistically significant ( p = 0.079). All doses of tramadol ER once daily were more effective than placebo ( p ≤ 0.050) for WOMAC Osteoarthritis Index joint stiffness subscale, WOMAC Osteoarthritis Index composite score, pain intensity of the index joint, and daily pain intensity scores. Tramadol ER 200 and 300 mg were significantly more effective than placebo ( p ≤ 0.050) for subject global assessment of disease activity and pain intensity of non-index joints. Adverse events (e.g., constipation, dizziness, nausea, somnolence, headache) occurred most often with tramadol ER 400 mg.Conclusions: Tramadol ER 100–300 mg once daily was associated with significant improvement in pain intensity and physical function, and was well tolerated, despite the use of a fixed-dose study design not reflective of usual clinical practice. Tramadol ER is a useful treatment option for patients with osteoarthritis pain.

Risk of Developing Colorectal Cancer Following a Negative Colonoscopy Examination

Limited evidence exists to guide the optimal frequency of repeat endoscopic examination for colorectal cancer screening after a negative colonoscopy. To determine the duration and magnitude of the risk of developing colorectal cancer following performance of a negative colonoscopy. Population-based retrospective analysis of individuals whose colonoscopy evaluations did not result in a diagnosis of colorectal neoplasia. Patients who had been evaluated between April 1, 1989, and December 31, 2003, were identified using Manitoba Health's physician billing claims database (N = 35 975). Standardized incidence ratios (SIRs) were calculated to compare colorectal cancer incidence in our cohort with colorectal cancer incidence in the provincial population. Stratified analysis was performed to determine the duration of the reduced risk. Patients with a history of colorectal cancer prior to the index colonoscopy, inflammatory bowel disease, resective colorectal surgery, and lower gastrointestinal endoscopy within the 5 years before the index colonoscopy were excluded. Cohort members were followed up from the time of the index colonoscopy until diagnosis of colorectal cancer, death, out-migration from Manitoba, or end of the study period on December 31, 2003. Incidence of colorectal cancer. A negative colonoscopy was associated with SIRs of 0.69 (95% confidence interval [CI], 0.59-0.81) at 6 months, 0.66 (95% CI, 0.56-0.78) at 1 year, 0.59 (95% CI, 0.48-0.72) at 2 years, 0.55 (95% CI, 0.41-0.73) at 5 years, and 0.28 (95% CI, 0.09-0.65) at 10 years. The proportion of colorectal cancer located in the right side of the colon was significantly higher in the colonoscopy cohort than the rate in the Manitoba population (47% vs 28%; P<.001). The risk of developing colorectal cancer remains decreased for more than 10 years following the performance of a negative colonoscopy. There is a need to improve the early detection rate of right-sided colorectal neoplasia in usual clinical practice.

IT-ESD Is Useful Technique for the Elderly Patients with Gastric Cancer

Background: Minimally invasive treatments, such as endoscopic mucosal resection (EMR), are now performed as usual clinical practice in Japan. Moreover, the introduction of various new devices, such as the insulation-tipped electrosurgical knife (IT-Knife), has expanded the indication of EMR for the treatment of early-stage gastric carcinoma, and it is called as endoscopic submucosal dissection using an IT-knife (IT-ESD). IT-ESD makes EMR possible to remove more wide lesion and en bloc resection. However, the safety of this strategy has not validated completely, particularly for elderly patients. In order to assess the availability and safety, especially for the elderly patients with gastric carcinoma, we evaluated efficacy of our expanded criteria compare to the standard criteria, and analyzed our results of IT-ESD retrospectively. Materials & Methods: All patients were undergoing for mucosal gastric carcinoma treated with IT-ESD in our expanded criteria. Our expanded criteria is 1. Mucosal invasive lesion, 2. Adenoma with severe atypia and differentiated carcinoma, 3. No ulceration, 4. Without limitation of tumor size. We retrospectively reviewed the records of 184 patients admitted to St. Marianna University School of Medicine Hospital with our criteria between April 2002 and November 2005. We analyzed our data in several factors, including resection rate, en bloc resection rate, recurrent rage, age, and background characteristics of the patients. We also assessed our expanded criteria compared to the standard one. Results: The number of 154 cases out of 184 (83.7%) were completely removed and 164 cases (87.0%) were en bloc resected with IT-ESD. Two cases were diagnosed to be recurrence by follow up endoscopic biopsy. One case was retried by IT-ESD and another was treated by laparoscopic gastrectomy. Complications, such as post operative bleeding and minimal perforation, occurred in 6%. IT-ESD could remove large lesions (over 20 mm) compare to the traditional EMR apparently. This cohort contained 119 cases (64.7%) of elderly (over 65 years old). There was no significant difference in resection rate and complication between elderly and others. Conclusion: IT-ESD might be safe and useful for treatment of larger tumor than the standard criteria. Moreover, IT-ESD may be useful technique for the elderly patients with gastric cancer.

Propuesta para un registro clínico de demencias

We outline a proposal for the structural and functional features needed to develop a registry of dementias which can be used to collect standardised information that is both reliable and valid concerning cases of dementia in the specialised health care centres within a particular geographical area. Due to the shortage of information about aspects concerning the impact of dementias on the health care system (in terms of the usage of resources and patterns of detection, referral, diagnosis and treatment in usual clinical practice in primary and secondary care), a sequential implementation of the registry is proposed so that it can be adapted to each health district or region. The first step is to identify the cases and sources of information; second, a system for collecting data must be developed that allows information to be gathered in a standardised manner while at the same time making it possible to work in close collaboration with the specialists who diagnose dementia; and, third, it must be set up with the logistics and staff needed to centralise all the functions and activities of the registry. Epidemiological surveillance is an essential instrument for planning, managing and distributing community health resources, for following up the natural history of chronic diseases and for assessing the impact of programmes of prevention. In this respect, and from a functional point of view, the proposed registry of dementias meets all the basic requirements of epidemiological surveillance.

Passive leg rising and pulse contour monitoring

Passive leg rising is proved to be a predictive tool of fluid challenge in the ventilated patient. Pulse contour analysis remains an innovative technique, so there are many dark sides to explore in usual clinical practice.

Effect of Clarithromycin on the Pharmacokinetics of Cabergoline in Healthy Controls and in Patients With Parkinson’s Disease

Cabergoline is used in the treatment of Parkinson's disease (PD). Clarithromycin is a potent inhibitor of CYP3A4 and P-glycoprotein and is often co-administered with cabergoline in usual clinical practice. We studied the effect of clarithromycin co-administration on the blood concentration of cabergoline in healthy male volunteers and in PD patients. Study 1: Ten healthy male volunteers were enrolled and were randomized to take a single oral dose of cabergoline (1 mg/day) for 6 days or a single oral dose of cabergoline plus clarithromycin (400 mg/day) for 6 days. Study 2: Seven PD patients receiving stable cabergoline doses were enrolled. They were evaluated for the plasma cabergoline concentration before and after the addition of clarithromycin 400 mg/day for 6 days, and again 1 month after discontinuation of clarithromycin. The dose and duration of clarithromycin were decided according to usual clinical practice. In healthy male volunteers, mean Cmax and AUC(0-10 h) of cabergoline increased to a similar degree during co-administration of clarithromycin. Mean plasma cabergoline concentration over 10 h post-dosing increased 2.6-fold with clarithromycin co-administration. In PD patients, plasma cabergoline concentration increased 1.7-fold during clarithromycin co-administration. Co-administration with clarithromycin may increase the blood concentration of cabergoline in healthy volunteers and in PD patients.

Reply: Hemorrhages during Escitalopram—Venlafaxine— Mirtazapine Combination Treatment of Depression

Dear Editor: The publication of Dr Benazzi's case report (1) is somewhat worrying. Although the report does not suggest that the treatment in this case is routine or normal practice, the concluding statement that clinicians should take care when combining several antidepressants that increase serotonin appears to condone the treatment outlined in the paper. Apart from the fact that all treatment algorithms for resistant depression recommend lithium augmentation prior to combined antidepressants, which in most cases come well down the list of strategies, given the limited evidence for this intervention, and putting aside the fact that, when recommended, the combination of antidepressants refers to 2 antidepressants, to add 2 antidepressants at once to an alreadyprescribed antidepressant is to court disaster. That nasal and rectal bleeding were the only consequences of this dangerous cocktail could be viewed as fortunate. What level of hemoglobin this patient bled down to is not revealed in the report, and it must be presumed that this was checked and was not of great concern. What is of concern is the risk that this report will encourage this sort of prescribing. References I. Benazzi F. Hemorrhages during escitalopram-venlafaxine-mirtazapine combination treatment of depression. Can J Psychiatry 2005;50:184. Andrew Al-Adwani, MRCPsych North Lincolnshire, UK Reply: Hemorrhages During Escitalopram-VenlafaxineMirtazapine Combination Treatment of Depression Dear Editor: I thank Dr Al-Adwani for his comments on the treatment of resistant depression, as the topic is a hot one. There are several guidelines on the treatment of depression, which should be distinguished as bipolar disorder I, bipolar disorder II, and major depressive (unipolar) disorder. Among these disorders, the treatment of bipolar II depression is the most understudied, even if bipolar II depression is at least as common as unipolar depression in nontertiary care outpatients (1,2). The several guidelines on the treatment of bipolar and unipolar depression follow different steps. What matters most is that these guidelines are the result of a consensus among academic experts, based on literature reviews and personal opinions, not on data from usual clinical practice. The result is that these guidelines are detached from real-world clinical practice (described as an irrelevant evidence base for clinical practice; 3). Even if we rely on the evidence we can find in the literature, this is of little help; at most it may guide the choice of a second antidepressant when the first one has failed. I have been in clinical practice for 21 years with the National Health Service as part-time consultant and with my private outpatient practice. In this latter setting (which is also the setting of most of my studies), I have thousands of visits yearly. Patients often come to see me after the failure of 1 or 2 antidepressants. …

Clinical Epilepsy: Adult

Clinical Epilepsy: Adult