Inadequate Symptom Control Research Articles

Modern Treatment for Gastroesophageal Reflux Disease

Context: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. Objective: To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD. Design, Setting, and Participants: The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions: Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation. Main Outcome Measure: Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method. Results: Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P Conclusion: This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years. Trial Registration: clinicaltrials.gov Identifier: NCT00251927

Neutropenia During Risperidone Treatment

Back to table of contents Previous article Next article LettersFull AccessNeutropenia During Risperidone TreatmentChih-Chieh Tseng, M.D.Chih-Chieh TsengSearch for more papers by this author, M.D.Published Online:1 Oct 2011https://doi.org/10.1176/jnp.23.4.jnpe19AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Neutropenia is defined as an abnormal absolute neutrophil count (ANC) value, containing fewer than 1,500 cells per mm3 in the peripheral blood. Neutropenia had resulted from a range of antipsychotics and mood stabilizers, most notably as a result of treatment with clozapine.1 Risperidone, an atypical antipsychotic, is widely used because of the tolerability, amelioration of negative symptoms, and reduced hematologic toxicity. We report the case of a patient who developed and was able to resolve neutropenia after administration of risperidone and then discontinuation.Case ReportA 55-year-old man had schizophrenia with acute exacerbation, without history of major surgery, hematologic disorder, or drug abuse. He was admitted for disorganized speech, auditory hallucinations, and persecutory delusions. Initial laboratory studies, including thyroid function test, and serum electrolyte, were within normal range. The white blood count (WBC) was 5,100 cells/mm3. Initially, quetiapine 1,200 mg was prescribed for 1 month. Because of inadequate control of symptoms and unacceptable sedative effect, quetiapine was tapered and stopped within 1 week, and risperidone 6 mg was added. One week later, all laboratory results were normal except the WBC and ANC. His WBC and ANC were 2,800 cells/mm3 and 1,400 cells/mm3, respectively, in the afternoon. Physical examination revealed no infectious signs. Risperidone-induced neutropenia was strongly suspected, and risperidone was tapered and stopped. Aripiprazole was cross-titrated to 15 mg per day for control of his psychotic symptoms. Two weeks later, the WBC was 4,600 cells/mm3, and the ANC was 3,420 cells/mm3; and 1 month later, the WBC was 8,200 cells/mm3, whereas the ANC was 5,000 cells/mm3.DiscussionThe incidence rates of risperidone-associated neutropenia were poorly established and seemed to be very low. It is usually reversible with dose reduction or medication discontinuation. The pathophysiology was controversial. The common hypothesis was decreased marrow production, increased peripheral destruction, or a combination of these. Risk factors include preexisting low WBC and a history of drug-induced neutropenia. In our patient, it developed after risperidone administration and resolved with discontinued. The clinical characteristics suggested that the underlying pathophysiology might be drug-related. Despite this case report of neutropenia in association with risperidone, a larger study would be required to evaluate the incidence of neutropenia with risperidone. Careful monitoring and initial hematological assessment should be considered when the patients have previously had neutropenia with other antipsychotic treatment, particularly clozapine. If such a side effect was suspected, dose reduction or medication discontinuation should considered. This is a particular concern because this complication could be easily missed if there is no mandatory white cell-count monitoring as there is with clozapine treatment.Dept. of Psychiatry Beitou Armed Forces Hospital Beitou District Taipei 112, Taiwane-mail: [email protected]com1. Copolov DL , Bell WR , Benson WJ , et al.: Clozapine treatment in Australia: a review of haematological monitoring. Med J Aust 1998; 168:495–497Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByRisperidone-Induced Neutropenia in a Schizophrenic Patient: A Case Report and Literature ReviewCase Reports in Psychiatry, Vol. 2021Frontiers in Endocrinology, Vol. 11Critical Reviews in Microbiology, Vol. 38, No. 3 Volume 23Issue 4 Fall 2011Pages E19-E19 Metrics PDF download History Published online 1 October 2011 Published in print 1 October 2011

Uterine Artery Embolization versus Myomectomy: Impact on Quality of Life—Results of the FUME (Fibroids of the Uterus: Myomectomy versus Embolization) Trial

This study was designed to compare quality of life (QoL) outcomes after uterine artery embolization (UAE) or myomectomy. Women with symptomatic fibroids diagnosed by ultrasound who wished to preserve their uterus were randomized to myomectomy (n=81) or UAE (n=82). Endpoints at 1 year were QoL measured by a validated questionnaire, hospital stay, rates of complications, and need for reintervention. UAE patients had shorter hospitalization (2 vs. 6 days, p<0.001). By 1 year postintervention, significant and equal improvements in QoL scores had occurred in both groups (myomectomy n=59; UAE n=61). There had been two (2.9%) major complications among UAE versus 6 (8%) among myomectomy patients (not significant). By 2 years, among UAE patients (n=57) there were eight (14.0%) reinterventions for inadequate symptom control compared with one (2.7%) among myomectomy patients (n=37). Half of the women who required hysterectomy had concomitant adenomyosis missed by US. UAE and myomectomy both result in significant and equal improvements in QoL. UAE allows a shorter hospital stay and fewer major complications but with a higher rate of reintervention.

Laparoscopic Antireflux Surgery vs Esomeprazole Treatment for Chronic GERD

Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD. The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation. Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method. Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%). This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years. clinicaltrials.gov Identifier: NCT00251927.

A single-blind cross over study investigating the efficacy of standard and controlled release levodopa in combination with entacapone in the treatment of end-of-dose effect in people with Parkinson’s disease

ObjectiveTo determine the efficacy of standard levodopa combined with controlled release levodopa and entacapone in controlling end-of-dose symptoms in Parkinson’s disease. MethodsA single-blind cross over design was used to compare the duration of action for three pharmacological combinations: standard levodopa (L/DDC); standard levodopa combined with entacapone (L/DDC/E); and standard levodopa combined with controlled release levodopa (CR) and entacapone (L/DDC/CR/E). Thirty two participants with wearing-off symptoms and inadequate symptom control with L/DDC/E had their optimum dose of L/DDC determined at base line. Entacapone was added to the optimal L/DDC dose and duration of action determined. Levodopa CR dosage was adjusted to match the optimal L/DDC dose for each participant. All participants were then trialed on L/DDC/CR/E and duration of response calculated. Timed Up and Go (TUG) times and magnitude of extra movements were recorded hourly throughout the day over several days to determine the optimum interval between doses for each combination. The UPDRS (Sections 2 and 3), PDQ39 and fatigue scale, the PDF-16, were recorded at base line and when dosage intervals had stabilized on L/DDC/CR/E. ResultsDuration of response was greatest with L/DDC/CR/E compared to L/DDC/E (p < 0.001) and number of daily doses were less on L/DDC/CR/E compared to L/DDC/E (p < 0.001). UPDRS, PDQ39 and fatigue scores also improved on L/DDC/CR/E compared to L/DDC (p < 0.001). Dyskinesia increased on L/DDC/CR/E (p = 0.001) however magnitude was mild. ConclusionCombining standard levodopa and levodopa CR preparations with entacapone is an additional treatment strategy to manage motor fluctuations in advanced PD.

Clinical Benefits of 7 Years of Treatment with Omalizumab in Severe Uncontrolled Asthmatics

Rationale. Severe asthma is characterized by inadequate symptom control and by high rate of inflammation despite high doses of steroids. Omalizumab, a recombinant humanized monoclonal anti-IgE, provides a new therapeutic strategy in severe allergic asthma. Aims. This study was aimed to assess whether long-term treatment with omalizumab improved clinical control in severe asthmatics. Methods. We investigated omalizumab effects on asthma outcomes evaluating seven severe allergic asthmatic patients who were treated for 7 years with add-on omalizumab. Number of exacerbations, use of antibiotics, additional asthma medications (systemic steroids, nebulized steroids and bronchodilators), and spirometry were analyzed before and after omalizumab treatment. Results. Omalizumab was well tolerated by all the studied patients. It improved FEV1 and FEV1/FVC ratio and reduced symptom score, asthma exacerbations, use of antibiotics, and use of nebulized steroids, bronchodilators, and oral corticosteroids. These effects were evident after 4 years of treatment and more pronounced after 7 years of treatment. Conclusions. This study underlines the utility of a long-term treatment with omalizumab to improve asthma clinical outcomes in severe asthmatics.

Managing patients with advanced cancer: the benefits of early referral for palliative care

Palliative care is becoming fundamental in the starting line-up of care choices.

Nurses' Psychosocial Barriers to Suicide Risk Management

Suicide remains a serious health care problem and a sentinel event tracked by The Joint Commission. Nurses are pivotal in evaluating risk and preventing suicide. Analysis of nurses' barriers to risk management may lead to interventions to improve management of suicidal patients. These data emerged from a random survey of 454 oncology nurses' attitudes, knowledge of suicide, and justifications for euthanasia. Instruments included a vignette of a suicidal patient and a suicide attitude questionnaire. Results. Psychological factors (emotions, unresolved grief, communication, and negative judgments about suicide) complicate the nurse's assessment and treatment of suicidal patients. Some nurses (n = 122) indicated that euthanasia was never justified and 11 were unsure of justifications and evaluated each case on its merits. Justifications for euthanasia included poor symptom control, poor quality of life, incurable illness or permanent disability, terminal illness, and terminal illness with inadequate symptom control or impending death, patient autonomy, and clinical organ death. The nurses indicated some confusion and misconceptions about definitions and examples of euthanasia, assisted suicide, and double effect. Strategies for interdisciplinary clinical intervention are suggested to identify and resolve these psychosocial barriers.

Anesthesia for patients undergoing transsternal thymectomy for juvenile myasthenia gravis

Background:Juvenile myasthenia gravis (JMG) is the rare form of myasthenia gravis presenting in childhood and adolescence. When medical management fails, thymectomy is offered for these patients. Complete resection of the thymus is best achieved through transsternal thymectomy. Anesthetic management of patients with JMG is challenging, particularly in regards to the goals of postoperative pain control, respiratory function, and extubation.Methods:We retrospectively reviewed the medical records of 13 patients, ranging in age from 6 to 22 years, who underwent transsternal thymectomy for JMG. Information on patient demographics, characteristics of their disease and treatment, anesthetic management, and postoperative course were collected.Results:All patients had undergone multiple treatment modalities and presented for surgery because of inadequate symptom control with medical management. As expected for a pediatric population, anesthesia induction was age dependent. 40% of the patients underwent an inhalation induction and 60% underwent an intravenous induction. Anesthesia was maintained with a low-dose inhalation agent in all patients, supplemented in 84% of patients with a remifentanil infusion, and in 69% of patients with an epidural infusion. Muscle relaxants were avoided in all patients. With this regimen, 92% of patients could be extubated successfully in the operating room.Conclusion:We found that avoidance of muscle relaxants and use of remifentanil with a low-dose hypnotic agent provided a stable intraoperative course, facilitated rapid emergence, and allowed early extubation in patients with JMG undergoing transsternal thymectomy. Epidural analgesia reduced the need for intra- and postoperative intravenous opioids and did not have an adverse effect on respiratory strength.

Pharmacotherapy for treatment-resistant schizophrenia

Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine.

Inadequate symptom control in advanced cancer patients across Europe

PurposeThe purpose of this study is to examine the adequacy of treatment for constipation, nausea, depression and poor sleep and the factors associated with inadequate symptom control in cancer patients receiving opioids.MethodsPatients receiving strong opioids for cancer pain were recruited from 17 centres in 11 European countries. By using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30, 1,938 patients reported their symptoms at four-point scales. Health care providers assessed symptoms at corresponding four-point scales and registered use of medications, demographic and disease-related variables. Symptomatic treatment was scored as 1 if not administered during the past 24 h and as 2 if administered. Adequacy of treatment was evaluated by subtracting the patients’ symptom score from the treatment score. Negative scores, caused by either no treatment or ineffective treatment of a symptom, were interpreted as inadequate treatment.ResultsApproximately 60% of patients with constipation, depression or poor sleep and 45% of nauseated patients were inadequately treated. Numbers of inadequately treated patients varied between countries. In general, underestimation of symptom intensity by health care providers (p < 0.001), low performance status (p < 0.05) and recent initiation of opioids (p < 0.05) increased the risk of inadequate treatment. The subset of demographic- and disease-related factors associated with inadequate treatment varied between the symptoms investigated.ConclusionsInadequate treatment, either no treatment or ineffective treatment, was frequent in cancer patients. There were subgroups of patients at particular risk for inadequate treatment, which might need additional attention from health care providers for achievement of adequate symptom control.

Efficacy of combined topiramate/thioctic acid therapy in migraine prophylaxis

Migraine cannot be cured and the aim, shared with the patient, is to minimise the impact of the illness on the patient’s life and lifestyle. The aim of prophylaxis is to reduce the number of migraine attacks. Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms. The efficacy and safety of topiramate 50mg/d and thioctic acid (α-lipoic acid) 300mg/d either as monotherapy or in combination were investigated as migraine prophylactic agents. Forty secondary school migraineur girls were enrolled in the study. The study was conducted in two phases, a prospective baseline phase and 1-month treatment phase. Combined topiramate/thioctic acid therapy was more effective than either topiramate or thioctic acid monotherapy as a migraine-preventive treatment. Combined topiramate/thioctic acid therapy decreased the mean monthly migraine frequency from 5.86±1.2 to 2.6±0.98 (p⩽0.05), topiramate (50mg/d) from 5.71±1.4 to 4.75±1.5 and thioctic acid (300mg/d) from 5.68±1.6 to 5.22±1.8. Reduction in mean monthly migraine days was also significantly greater in the group receiving combined topiramate/thioctic acid (from 12.32±1.85 to 5.74±1.1) compared to those receiving either topiramate 50mg/d (from 12.7±1.34 to 11.85±1.35) or thioctic acid 300mg/d (from 12.5±1.72 to 11.65±1.44). The responder rate (% of patients showing ⩾50% reduction in monthly migraine frequency) was 85% in patients receiving combined topiramate/thioctic acid therapy compared to 30% and 20% in patients receiving either topiramate or thioctic acid, respectively. The incidence of adverse events was higher in patients receiving topiramate (50mg/d) monotherapy. The most common adverse events were nausea, fatigue, paraesthesia and taste perversion. We conclude that combined topiramate/thioctic acid therapy is more effective and better tolerated than topiramate monotherapy. The combination has lower monthly medication costs compared to the traditionally used topiramate 100mg monotherapy.

Pisa Syndrome During Amisulpride Treatment

Back to table of contents Previous article Next article LETTERFull AccessPisa Syndrome During Amisulpride TreatmentTien-Chun Li M.D.Hsiu-Wen Chiu R.N.Hung-Hui Liu M.D.,Tien-Chun Li M.D.Search for more papers by this authorHsiu-Wen Chiu R.N.Search for more papers by this authorHung-Hui Liu M.D.Search for more papers by this author,Published Online:1 Jul 2010https://doi.org/10.1176/jnp.2010.22.3.352.e27AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Pisa syndrome, a movement disorder characterized by tonic, sustained lateral flexion with slight posterior rotation of the trunk, was first reported in 1972. 1 It appeared mainly subsequent to typical antipsychotics. Rare cases have been recently reported with atypical antipsychotics, cholinesterase inhibitors, and valproic acid. 2 Amisulpride, an atypical antipsychotic, induced fewer movement disorders. To our knowledge, there have been no reports of amisulpride-induced Pisa syndrome in the literature. This report presents a case of amisulpride induced Pisa syndrome. Case ReportA 26-year-old man was diagnosed with schizophrenia 5 years ago without history of major operations, neurological disorders, or drug abuse. Initial laboratory studies, including thyroid function test and serum electrolyte, were within normal ranges. He had been treated with risperidone, 6 mg/day, for the previous 6 months. He was admitted for disorganized speech, auditory hallucination, and persecutory delusions. On the first day, risperidone, 6 mg/day, was prescribed. The risperidone was tapered and stopped within 2 days for inadequate control of symptoms, whereas amisulpride, 800 mg/day, and valproic acid, 1,000 mg/day, were added on the second day. Two weeks later, he was observed walking with a tilt toward the left. Valproic acid levels were normal, and a physical examination revealed sustained tonic flexion of the trunk to the left side with slight backward rotation. No neurological deficits or mental status changes were noted. The differential diagnosis of catatonic presentation was ruled out. Trihexyphenidyl, 15 mg/day, was prescribed for acute dystonia. Diphenylhydramine, 100 mg/day, was also prescribed, but the symptoms did not improve after 1 week. Pisa syndrome was highly suspected, and amisulpride was tapered and stopped. Quetiapine was cross titrated to 800 mg/day to control his psychotic symptoms. The symptoms gradually resolved within 12 days.Discussion The incidence rates of Pisa syndrome were poorly established and seemed to be low. In 1991, a study by Yassa et al. 3 reported a rate of 8.3%. Similarly, a German study showed a lower rate of 0.037% in 2000. 4 It occurred mostly during the first month of treatment and responded to the discontinuation of antipsychotics. 5 In our case, it developed after 2 weeks of amisulpride administration and resolved with dose reduction. Risk factors were female gender, old age, organic brain disorder, and typical antipsychotics. 4 Our patient was a young man without organic brain disorder. The clinical characteristics suggested that the underlying pathophysiology might be drug-related. The pathophysiology was controversial. The common hypothesis was dopaminergic-cholinergic imbalance, an excess of cholinergic neurotransmission, and a decrease of dopaminergic neurotransmission. 6 Different antipsychotics had varying degrees of cholinergic and dopamine antagonistic effects. In our case, tapering off risperidone and switching to amisulpride resulted in this imbalance. Thus, switching of antipsychotics should be performed gradually, especially when the former antipsychotic has potent effects. The most effective treatment was either reduction or discontinuation of current medications. Delayed treatment may harm the rehabilitation of patients. Early detection of these symptoms would improve the patient’s quality of life even more. Department of Psychiatry, Beitou Armed Forces Hospital, Taipei, Taiwan

A physiological approach to modernize the management of cancer chemotherapy-induced gastrointestinal toxicity

Gastrointestinal toxicity during chemotherapy is frequent. Symptomatic therapies for gastrointestinal toxicity, which do not address the underlying cause, may result in inadequate symptom control. With advances in curative treatment regimens, it becomes more important to minimize treatment toxicity which otherwise may compromise optimal chemotherapy and the chance of cure. For decades, oncologists have concentrated on delineating the pathological processes, which occur within the gastrointestinal tract during chemotherapy treatment. However, pathological change does not in itself cause symptoms. Symptoms only arise when physiological functions are altered. In immunosuppressed patients, it is a priority to exclude infection as a cause for symptoms. In the presence of diarrhoea, the best investigative paradigm for this is stool culture, upper gastrointestinal endoscopy with duodenal biopsies and duodenal aspirate combined with flexible sigmoidoscopy and left colonic biopsies. Once infection has been excluded, although large studies have not been performed, case series repeatedly suggest that gastrointestinal symptoms arising during cancer chemotherapy can often be cured if newly acquired, gastrointestinal physiological deficits are identified. Although many physiological changes induced by chemotherapy may be relatively transient and settle weeks or months after the end of treatment, during chemotherapy, their manifestations can be protean and severe. A systematic failure to research the frequency with which physiological causes of the symptoms are amenable to treatment has denied many patients' logical therapies for their chemotherapy-induced symptoms, and as a result, it is likely that symptomatic treatments are frequently suboptimal.

Extensive elevation of creatine kinase with generic clozapine, but not with Leponex

Mr. M., a 27-year-old man, was hospitalized due to an exacerbation of his paranoid schizophrenia persisting for 8 years. Laboratory tests, a magnetic resonance imaging scan and an electroencephalogram revealed no indication of an organic cause of his recurrent psychotic symptoms. When the patient was earlier treated with several atypical as well as typical antipsychotics, either inadequate symptom control, or multiple adverse effects such as severe sleepiness, extrapyramidal motor side effects and sexual dysfunction were observed. Therefore we decided to treat him with clozapine. At that point, all laboratory results including creatine kinase (CK) (47 U/l) werewithin the normal range. After 5 days of upwardly titrating the dose of a generic manufactured clozapine to 50 mg, an increase of CK up to 1219 U/l was noted in a routine blood test. The patient did not receive concomitant medication. The increasing CK was not related to trauma or excessive muscle activity. Another blood sample taken 24 h later showed that the CK had risen further to 2763 U/l. Therefore, we stopped the generic clozapine at 50 mg. Despite discontinuation of the treatment with generic clozapine, CK levels continued to increase up to 3644 U/l within the next 2 days. To prevent acute kidney failure, treatment with sodium-chloride infusions 4 l/daywas instituted. The CK tapered off to normal levels over the next 6 days. This was the first time the patient had developed CK elevation while receiving antipsychotic treatment. Suspecting that the increase of CK was due to the generic clozapine and considering the patient's chronicity and earlier resistance to treatment, we decided to start antipsychotic treatment again with clozapine, but this time using Leponex. After upward titration of Leponex to a maximum of 300 mg/day, daily blood samples showed the CK levels to be within normal range. Studies have been examining the differences between Leponex and generic clozapine since the Leponex patent was extended in 1998. Concerning side effects, generic clozapine was not associated with an increase in reported adverse effects compared with Leponex in general. However, several studies showed differences in bioequivalence and interchangeability between Leponex and generic clozapine. Furthermore, it has been reported that these differences in bioequivalence might have consequences for the pharmacokinetic profile that result in a higher maximum plasma concentration leading to increased or emergent adverse effects. CK elevations related to clozapine treatment have been reported several times before. To our knowledge this is the first case in which an adverse effect associated with generic clozapine disappeared after changing the treatment to Leponex. We therefore suggest that due to certain risk factors, such as genetic variety or enzyme dysfunctions, differences in bioequivalence and interchangeability occur. These differences might lead to an individual tolerability and adverse effect profile. If CK elevation is observed during clinical monitoring in treatment with generic clozapine, switching to Leponex treatment might be a satisfactory choice.

Arterielle Embolisation von Lebermetastasen neuroendokriner Tumoren

Neuroendocrine tumors are slowly growing neoplasms and 75% of patients already present with hepatic metastases at the time of diagnosis. Size and growth of liver metastases is of prognostic value. Due to arterial vascularization of metastases, transarterial embolization (TAE) is a suitable procedure, which can also be combined with chemotherapeutic agents. Indications for embolization or chemoembolization (TACE) are growth of liver metastases or inadequate symptom control. The majority of patients show clinical improvement and partial remission can be achieved in 50% of cases with 5-year survival rates of 50-60%. Response rates, survival or complications are not dependent on the embolization technique (TAE or TACE). Embolization is usually performed in several sessions depending on individual tumor stage and disease progression. Embolization is a cost-effective procedure and is included in the treatment algorithm of international guidelines. Therefore, evaluation of new embolization therapies must be evaluated in randomized controlled studies.

Invited Commentary

Thoracic sympathectomy is an appropriate treatment for properly selected patients with hyperhidrosis who have undergone failed conservative measures. In general the results and satisfaction after video-assisted thoracic sympathectomy are excellent for patients with palmar or palmar and axillary symptoms combined, but there is a subset who will be dissatisfied mainly due to severe compensatory sweating. Other reasons for dissatisfaction outside of complications would be inadequate control of symptoms or symptom recurrence. Despite the extreme variations in description of results and the multitude of different surgical techniques, there is a growing impression that limiting the number of sympathetic levels interrupted and avoiding, if possible, the interruption of the T2 ganglion may help reduce the incidence of severe compensatory sweating [1Li X. Yuan-Rong T. Lin M. Lai F.C. Chen J.F. Dai Z.J. Endoscopic thoracic sympathectomy for palmar hyperhidrosis: a randomized control trial comparing T3 and T2-4 ablation.Ann Thorac Surg. 2008; 85: 1747-1752Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. The problem is that previously reported attempts to minimize the surgical approach have been associated with an increased incidence of recurrence or inadequate control of symptoms [2Lee D.Y. Kim D.H. Paik H.C. Selective division of T3 rami communicantes (T3 ramicotomy) in the treatment of palmar hyperhidrosis.Ann Thorac Surg. 2004; 78: 1052-1055Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar]. There is a stunning variation in reported results in the literature; part of this may be due to variability in the sympathetic chain, but clearly a large portion of this discordance is due to nonstandard descriptions of anatomy, techniques, and results. In this manuscript Li and colleagues [3Li X. Tu Y.-R. Lin M. Lai F.-C. Chen J.-F. Miao H.-W. Minimizing endoscopic thoracic sympathectomy for primary palmar hyperhidrosis: guided by palmar skin temperature and laser Doppler blood flow.Ann Thorac Surg. 2009; 87: 427-431Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] have postulated that a patient's surgery could be individualized to recognize possible anatomic variation by using intraoperative testing. Their use of skin temperature and Doppler blood flow changes to gauge adequacy of response, although somewhat arbitrary, is a commendable effort to try to use some “science” when making treatment decisions. By limiting the extent of sympathectomy, their goal was to minimize the risk for severe compensatory sweating, but still interrupt the sympathetic chain sufficiently to achieve an adequate clinical response. The goal of procedural efficacy for palmar symptoms seems to have been achieved at 1 year, but there still was an 8% dissatisfaction rate. Their reported data does not clearly define the reasons for this nor does it identify by extent of surgery the severe compensatory sweating that developed in 6% of patients. It is imperative that clinicians treating patients with hyperhidrosis come to an understanding as to descriptions of disease severity, treatment response, surgical techniques, and follow-up so that we can use the experience of a number of investigators to better understand how to advise and treat patients with severe hyperhidrosis. Organizations such as our thoracic societies and the International Society of Sympathetic Surgery (ISSS) can help encourage these efforts. Minimizing Endoscopic Thoracic Sympathectomy for Primary Palmar Hyperhidrosis: Guided by Palmar Skin Temperature and Laser Doppler Blood FlowThe Annals of Thoracic SurgeryVol. 87Issue 2PreviewLimiting the extent of sympathectomy in palmar hyperhidrosis was recently recognized as an effective method to minimize the incidence and severity of troublesome compensatory sweating. However, the levels at which transection should be performed remain controversial. In this study, we proposed that the level of ablation varies and should be adjusted for each individual patient. Guided by palmar skin temperature and laser Doppler blood flow, we try to find the correct target level in each case. Full-Text PDF

Asthma control during pregnancy and the risk of preterm delivery or impaired fetal growth

Concerns regarding potential harmful effect of medications on fetuses often result in inadequate treatment of asthma in pregnancy, whereas risks posed by poorly controlled maternal asthma are often underestimated. To evaluate the effect of maternal asthma on preterm delivery and fetal growth. Study participants were individuals enrolled in the Organization of Teratology Information Specialists Asthma Medications in Pregnancy Study between February 1, 1998, and December 31, 2003. Pregnant women with physician-diagnosed asthma (n = 719) evaluated their asthma control repeatedly during pregnancy based on symptom frequency and interference with daily activities and sleep and reported hospitalizations and unscheduled clinic visits for asthma exacerbations. The incidence of preterm delivery, the incidence of intrauterine growth restriction, and mean birth weight were evaluated relative to asthma symptom control and exacerbation measures. The incidence of preterm delivery was significantly higher among patients with inadequate asthma symptom control during the first part of pregnancy (11.4%) compared with patients with adequate asthma control (6.3%; P = .02). Similarly, patients who were hospitalized for asthma during pregnancy had a higher incidence of preterm delivery (16.4%) compared with asthmatic women without a history of hospitalization (7.6%; P = .02). The effect seemed independent from use of systemic corticosteroids and other covariates. Neither the incidence of intrauterine growth restriction nor mean birth weight varied by any measures of asthma symptom control or exacerbations. This study demonstrates a substantial risk for preterm delivery posed by poorly controlled maternal asthma and provides additional evidence regarding the importance of adequate treatment of asthma in pregnancy to maintain optimal asthma control.

Refractory Idiopathic Urge Urinary Incontinence and Botulinum A Injection

We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence. This institutional review board approved, multicenter registered trial randomized women with refractory urge incontinence, detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio. Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence. The primary outcome measure was time to failure, as evidenced by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection, or changes in treatment (initiation or increase) at any time after injection. Safety data, including increased post-void residual volume, defined as more than 200 ml irrespective of symptoms, was obtained at specified time points. Approximately 60% of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement. The median duration of their responses was 373 days, significantly longer than the 62 days or less for placebo (p <0.0001). In the botulinum toxin A group increased post-void residual urine (12 of 28 women or 43%) and urinary tract infection in those with increased post-void residual urine (9 of 12 or 75%) exceeded expected ranges. Further injections were stopped after 43 patients were randomized, including 28 to botulinum toxin A and 15 to placebo. Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder. However, a transient post-void residual urine increase was experienced in 43% of patients. Botulinum toxin A for idiopathic overactive bladder is still under investigation.

Uterine-Artery Embolization versus Surgery for Symptomatic Uterine Fibroids

The efficacy and safety of uterine-artery embolization, as compared with standard surgical methods, for the treatment of symptomatic uterine fibroids remain uncertain. We conducted a randomized trial comparing uterine-artery embolization and surgery in women with symptomatic uterine fibroids. The primary outcome was quality of life at 1 year of follow-up, as measured by the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36). Patients were randomly assigned in a 2:1 ratio to undergo either uterine-artery embolization or surgery, with 106 patients undergoing embolization and 51 undergoing surgery (43 hysterectomies and 8 myomectomies). There were no significant differences between groups in any of the eight components of the SF-36 scores at 1 year. The embolization group had a shorter median duration of hospitalization than the surgical group (1 day vs. 5 days, P<0.001) and a shorter time before returning to work (P<0.001). At 1 year, symptom scores were better in the surgical group (P=0.03). During the first year of follow-up, there were 13 major adverse events in the embolization group (12%) and 10 in the surgical group (20%) (P=0.22), mostly related to the intervention. Ten patients in the embolization group (9%) required repeated embolization or hysterectomy for inadequate symptom control. After the first year of follow-up, 14 women in the embolization group (13%) required hospitalization, 3 of them for major adverse events and 11 for reintervention for treatment failure. In women with symptomatic fibroids, the faster recovery after embolization must be weighed against the need for further treatment in a minority of patients. (ISRCTN.org number, ISRCTN23023665 [controlled-trials.com].)