Exploring the use of internal and externalcontrols for assessing microarray technical performance

Background

Anthroposophic medicine is a physician-provided complementary therapy system involving counselling, artistic and physical therapies, and special medications. The purpose of this analysis was to identify predictors of symptom improvement in patients receiving anthroposophic treatment for chronic diseases.

Methods

913 adult outpatients from Germany participated in a prospective cohort study. Patients were starting anthroposophic treatment for mental (30.4% of patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%), genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic indications. Stepwise multiple linear regression analysis was performed with the improvement of Symptom Score (patients' assessment, 0: not present, 10: worst possible) after 6 and 12 months as dependent variables. 61 independent variables pertaining to socio-demographics, life style, disease status, co-morbidity, health status (SF-36), depression, and therapy factors were analysed.

Results

Compared to baseline, Symptom Score improved by average 2.53 points (95% confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement after six months was baseline Symptom Score, which alone accounted for 25% of the variance (total model 32%). Improvement after six months was also positively predicted by better physical function, better general health, shorter disease duration, higher education level, a diagnosis of respiratory disorders, and by a higher therapy goal documented by the physician at baseline; and negatively predicted by the number of physiotherapy sessions in the pre-study year and by a diagnosis of genitourinary disorders. Seven of these nine variables (not the two diagnoses) also predicted improvement after 12 months. When repeating the 0-6 month analysis on two random subsamples of the original sample, three variables (baseline Symptom Score, physical function, general health) remained significant predictors in both analyses, and three further variables (education level, respiratory disorders, therapy goal) were significant in one analysis.

Conclusion

In adult outpatients receiving anthroposophic treatment for chronic diseases, symptom improvement after 6 and 12 months was predicted by baseline symptoms, health status, disease duration, education, and therapy goal. Other variables were not associated with the outcome. This secondary predictor analysis of data from a pre-post study does not allow for causal conclusions; the results are hypothesis generating and need verification in subsequent studies.     

Improvement in bronchial hyper-responsiveness in patients with moderate asthma after treatment with a hypnotic technique: a randomised controlled trial.

A prospective, randomised, single blind, and controlled trial of a hypnotic technique was undertaken in 39 adults with mild to moderate asthma graded for low and high susceptibility to hypnosis. After a six week course of hypnotherapy 12 patients with a high susceptibility score showed a 74.9% improvement (p less than 0.01) in the degree of bronchial hyper-responsiveness to a standardised methacholine challenge test. Daily home recordings of symptoms improved by 41% (p less than 0.01), peak expiratory flow rates improved by 5.5% (p less than 0.01), and use of bronchodilators decreased by 26.2% (p less than 0.05). The improvement in bronchial hyper-reactivity occurred without a change in subjective appreciation of the degree of bronchoconstriction. A control group 17 patients and 10 patients undergoing treatment with low susceptibility to hypnosis had no change in either bronchial hyper-responsiveness or any of the symptoms recorded at home. This study shows the efficacy of a hypnotic technique in adult asthmatics who are moderately to highly susceptible to hypnosis.     

Micturition and the mind: psychological factors in the aetiology and treatment of urinary symptoms in women.

The mental state of 211 women attending a urodynamic clinic was assessed using questionnaires. Patients with genuine stress incontinence had scores comparable with other patients with longstanding physical complaints. Patients with sensory urgency were more anxious than those with genuine stress incontinence. Patients with detrusor instability were as anxious as patients with sensory urgency and in addition had higher scores on the hysteria scale. A subset of patients (roughly a quarter of the total) was identified, comprising members of all three diagnostic groups, for whom urinary symptoms rendered life intolerable. These patients were as anxious, depressed, and phobic as psychiatric inpatients, emphasising the serious psychological morbidity experienced by patients with urinary symptoms. Fifty patients with detrusor instability or sensory urgency entered a randomised trial comparing psychotherapy, bladder drill, and propantheline. The psychotherapy group significantly improved on measures of urgency, incontinence, and nocturia, though not on frequency. Bladder training was an effective treatment for frequency and patients became less anxious and depressed. There was a modest improvement in frequency of micturition in patients given propantheline. Frequency may be a learnt disorder which responds to the direct symptom oriented approach of bladder training. Patients with urgency and nocturia predominating might derive more benefit from psychotherapy.     

Compliance therapy in psychotic patients: randomised controlled trial.

OBJECTIVE--To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later. DESIGN--Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes. SETTING--Acute psychiatric admissions ward serving an inner London catchment area. SUBJECTS--47 patients with psychosis. MAIN OUTCOME MEASURES--Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self-rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later. RESULTS--25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)). CONCLUSIONS--Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced.     

A therapeutic alternative for tension headache in children: treatment and 1-year follow-up results

Ten young subjects, ranging in age from 12 to 15 years, suffering from tension headache were treated by electromyographic biofeedback (EMG-BFB) twice a week for 12 sessions. The Pain Total Index (PTI) was recorded every month from the beginning to the end of the treatment. At the end of the treatment the PTI decreased significantly in all our patients and, at the same time, the muscular tension values also decreased. This result supports the hypothesis of a correlation between clinical symptom and muscular tension level. We saw our patients for follow-up sessions, and the clinical improvement was confirmed to 1 year from the completion of the treatment; however, the muscular tension values were increased with respect to the last-session values.     

A therapeutic alternative for tension headache in children: Treatment and 1-year follow-up results

Ten young subjects, ranging in age from 12 to 15 years, suffering from tension headache were treated by electromyographic biofeedback (EMG-BFB) twice a week for 12 sessions. The Pain Total Index (PTI) was recorded every month from the beginning to the end of the treatment. At the end of the treatment the PTI decreased significantly in all our patients and, at the same time, the muscular tension values also decreased. This result supports the hypothesis of a correlation between clinical symptom and muscular tension level. We saw our patients for follow-up sessions, and the clinical improvement was confirmed to 1 year from the completion of the treatment; however, the muscular tension values were increased with respect to the last-session values.     

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.     

Hypnosis for Asthma—a Controlled Trial: A Report to the Research Committee of the British Tuberculosis Association*

An investigation of hypnosis in asthma was made among patients aged 10 to 60 years with paroxysmal attacks of wheezing or tight chest capable of relief by bronchodilators. One group of patients was given hypnosis monthly and used autohypnosis daily for one year. Comparisons were made with a control group prescribed a specially devised set of breathing exercises aimed at progressive relaxation. Treatment was randomly allocated and patients were treated by physicians in nine centres. Results were assessed by daily diary recordings of wheezing and the use of bronchodilators, and by monthly recordings of F.E.V.₁ and vital capacity. At the end of the year independent clinical assessments were made by physicians unaware of the patients'' treatment.There were 252 patients (127 hypnosis and 125 controls) accepted for analysis, but a number of them did not continue the prescribed treatment for the whole year: 28 hypnosis and 22 control patients failed to co-operate, left the district, or had family problems; one hypnosis and one control patient died. Seven hypnosis and 17 control patients were withdrawn as treatment failures, the difference between the two groups being statistically significant.As judged by analyses based on the daily “score” of wheezing recorded in patients'' diaries, by the number of times bronchodilators were used, and by independent clinical assessors, both treatment groups showed some improvement Among men the assessments of wheezing score and use of bronchodilators showed similar improvement in the two treatment groups; among women, however, those treated by hypnosis showed improvement similar to that observed in the men, but those given breathing exercises made much less progress, the difference between the two treatment groups reaching statistical significance. Changes in F.E.V.₁ and V.C. between the control and hypnosis groups were closely similar.Independent clinical assessors considered the asthma to be “much better” in 59% of the hypnosis group and in 43% of the control group, the difference being significant There was little difference between the sexes. Physicians with previous experience of hypnosis obtained significantly better results than did those without such experience.     

Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory destrusor overactivity

Type A neurotoxin of Clostridium botulinum was purified by a simple procedure using a lactose gel column. This procedure was previously reported for type B neurotoxin. Hemagglutinin-positive toxins (19S and 16S) were bound to the column under acid conditions, and the neurotoxin alone was dissociated from these hemagglutinin-positive toxins by changing the pH of the column to an alkaline condition. The toxicity of this purified toxin preparation was retained for at least 1 year at -30 degrees C by supplementing it with either 0.1% albumin or 0.05% albumin plus 1% trehalose. This preparation was used to treat 18 patients with urinary incontinence caused by refractory idiopathic and neurogenic detrusor overactivity; 16 of the patients showed excellent improvement. Improvements started within 1 week after injection in most cases and lasted 3-12 months [corrected]     

The Effects of Hypnotherapy on Homosexuality

Fifteen homosexuals were treated with hypnosis. The patients were selected from a general psychiatric practice and had a long history of confirmed homosexual behaviour and showed no evidence of organic or psychotic illness. The type of hypnotic induction attempted in all cases is described. In those where a satisfactory depth of hypnotic trance was achieved a change in sexual orientation was suggested to the patient.Before therapy, each patient was assessed using the Kinsey scale. Results were evaluated in terms of the patient''s subsequent behaviour and his subjective feelings. Of the 15 patients, three showed no improvement, four showed a mild improvement and eight showed a marked improvement. There was a significant correlation between the depth of hypnosis achieved and the therapeutic outcome. Those patients who reached a deep level of hypnotic trance were most likely to show a marked improvement. There were no significant correlations with other factors such as degree of homosexuality as measured on the Kinsey scale and the patient''s marital status.Treatment of homosexuals with hypnosis may produce more satisfactory results than those obtainable by other means. The best results are likely to be achieved in patients who are good hypnotic subjects.     

Arthroscopic surgery compared with supervised exercises in patients with rotator cuff disease (stage II impingement syndrome)

OBJECTIVE--To compare the effectiveness of arthroscopic surgery, a supervised exercise regimen, and placebo soft laser treatment in patients with rotator cuff disease (stage II impingement syndrome). DESIGN--Randomised clinical trial. SETTING--Hospital departments of orthopaedics and of physical medicine and rehabilitation. PATIENTS--125 patients aged 18-66 who had had rotator cuff disease for at least three months and whose condition was resistant to treatment. INTERVENTIONS--Arthroscopic subacromial decompression performed by two experienced surgeons; exercise regimen over three to six months supervised by one experienced physiotherapist; or 12 sessions of detuned soft laser treatment over six weeks. MAIN OUTCOME MEASURES--Change in the overall Neer shoulder score (pain during previous week and blinded evaluation of function and range of movement by one clinician) after six months. RESULTS--No differences were found between the three groups in duration of sick leave and daily intake of analgesics. After six months the difference in improvement in overall Neer score between surgery and supervised exercises was 4.0 (95% confidence interval -2 to 11) and 2.0 (-1.4 to 5.4) after adjustment for sex. The condition improved significantly compared with placebo in both groups given the active treatments. Treatment costs were higher for those given surgery (720 pounds v 390 pounds). CONCLUSIONS--Surgery or a supervised exercise regimen significantly, and equally, improved rotator cuff disease compared with placebo.     

Efectos de un programa de intervención neuropsicológica basado en mindfulness sobre la enfermedad de Alzheimer: ensayo clínico aleatorizado a doble ciego

Introduction

The purpose of this research was to assess effects of a mindfulness based neuropsychological intervention on the clinical course of Alzheimer's disease.

Material and method

A two year randomized and double blind clinical trial was conducted on 127 probable Alzheimer's disease patients, according to NINCDS-ADRDA scale. Patients were grouped into three experimental groups (cognitive stimulation, progressive muscular relaxation, and mindfulness) plus a control group. All participants were receiving donepezil. Cognitive skills were assessed with CAMCOG and MMSE, functional area with RDRS-2, and NPI was used for psychopathology screening. Three treatment sessions per week were carried out for two years, and follow up measurements were taken every six months.

Results

The global cognitive function, functionality and behavioral disorders measurements indicated that patients from the experimental group based on mindfulness were stable during the two years, while patients from the control group, as well as the other experimental groups, showed a mild but significant worsening of their mental capacities.

Conclusion

The mindfulness based neuropsychological program showed better cognitive and functional stability, as well as significant improvement in the psychopathological condition of mild to moderate Alzheimer’ patients. These results support the idea that a mindfulness based intervention can produce a clinically relevant improvement in the treatment of dementia. More research is needed to confirm these data.     

Short and Long Term Outcome of Bilateral Pallidal Stimulation in Chorea-Acanthocytosis

Background

Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS.

Methods

Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months).

Results

Motor severity, assessed by the Unified Huntington’s Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery.

Conclusion

This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.     

Effect of prenalterol on orthostatic hypotension in the Shy-Drager syndrome.

Treatment of idiopathic orthostatic hypotension is often unsatisfactory. A patient with the Shy-Drager syndrome, in which the most important symptom is orthostatic hypotension, was treated with prenalterol, initially 30 mg six times daily. The dosage was reduced to 30 mg four times daily because of the development of complex ventricular premature beats. Orthostatic symptoms were reduced and standing blood pressure increased. Fludrocortisone 0.5 mg a day was added to treatment with further improvement. This clinical effect was maintained throughout 12 months of follow up, during which the treatment was continued unchanged. Prenalterol was effective in reducing orthostatic symptoms in this patient. Further studies in patients with a similar haemodynamic pattern are indicated.     

Stress reduction treatment of severe recurrent genital herpes virus

Four individuals with high-frequency recurrences of genital herpes virus of at least 2 years' duration were treated with two behavioral stress-reduction treatments. Subjects were given 10 weekly sessions of frontalis EMG biofeedback (2 subjects) or progressive muscle relaxation treatment (2 subjects). Presession and postsession frontalis EMG measures were recorded for all subjects across treatment. Outcome was measured by daily and weekly symptom charting mailed in weekly over 6 months, or by telephone interview after 6 months. Results demonstrated substantial improvement in reported symptoms with both treatments. Relaxation treatment resulted in a 66% and 100% reduction in frequency of recurrences. Frontalis EMG biofeedback resulted in a 72% and 7% reduction in frequency of recurrences. Follow-up at 1-year posttreatment showed that treatment effects were maintained by one subject, partially maintained by two, and reversed in one subject. The need for controlled investigation is emphasized.     

Prognosis of new and worsening angina pectoris.

The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated.     

Percutaneous cryoablation of pulmonary metastases from colorectal cancer

Objective

To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer.

Methods

The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months.

Results

The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8% and 59%, respectively. The 3-years local progression free intervals of tumors ≤15 mm in diameter was 79.8% and that of tumors >15 mm was 28.6% (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively.

Conclusion

The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression free interval was satisfactory at least for tumors that were ≤15 mm in diameter.     

The natural course of gold nephropathy: long term study of 21 patients.

To clarify the natural course of gold nephropathy and thereby facilitate its clinical management 21 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular sodium aurothiomalate were studied in detail throughout their renal illnesses. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 60 months (range 16-130 months). Ten patients developed proteinuria after six months'' treatment, 15 after 12 months, and 18 after 24 months. When treatment was stopped the proteinuria reached a median peak of 2.1 g/day (range 0.7-30.7 g/day) at two months (range 1-13 months) before resolving spontaneously, in eight patients by six months, in 13 by 12 months, and in 18 by 24 months. All patients were free of proteinuria by 39 months, the median duration being 11 months. The median first and last measurements of creatinine clearance showed no significant change (77 ml/minute and 59 ml/minute, respectively), and no patient died from or needed treatment for renal failure. HLA-B8 or DR3 alloantigens, or both, were identified in seven patients. Renal biopsy specimens showed membranous glomerulonephritis in 15 patients, a minimal change nephropathy in two, mesangial electron dense deposits in two, and no appreciable glomerular changes in two. In these 21 patients the proteinuria of gold nephropathy resolved completely when treatment was withdrawn. Renal function did not deteriorate, corticosteroids were unnecessary, and several different renal lesions were seen.     

Effects of Self‐Conditioning Techniques (Self‐Hypnosis) in Promoting Weight Loss in Patients with Severe Obesity: A Randomized Controlled Trial

Objective

The usefulness of the rapid‐induction techniques of hypnosis as an adjunctive weight‐loss treatment has not been defined. This randomized controlled trial evaluated whether self‐conditioning techniques (self‐hypnosis) added to lifestyle interventions contributed to weight loss (primary outcome), changes in metabolic and inflammatory variables, and quality of life (QoL) improvement (secondary outcomes) in severe obesity.

Methods

Individuals (with BMI = 35‐50 kg/m²) without organic or psychiatric comorbidity were randomly assigned to the intervention (n = 60) or control arm (n = 60). All received exercise and behavioral recommendations and individualized diets. The intervention consisted of three hypnosis sessions, during which self‐hypnosis was taught to increase self‐control before eating. Diet, exercise, satiety, QoL, anthropometric measurements, and blood variables were collected and measured at enrollment and at 1 year (trial end).

Results

A similar weight loss was observed in the intervention (?6.5 kg) and control (?5.6 kg) arms (β = ?0.45; 95% CI: ?3.78 to 2.88; P = 0.79). However, habitual hypnosis users lost more weight (?9.6 kg; β = ?10.2; 95% CI: ?14.2 to ?6.18; P < 0.001) and greatly reduced their caloric intake (?682.5 kcal; β = ?643.6; 95% CI: ?1064.0 to ?223.2; P = 0.005) in linear regression models. At trial end, the intervention arm showed lower C‐reactive protein values (β = ?2.55; 95% CI: ?3.80 to ?1.31; P < 0.001), higher satiety (β = 19.2; 95% CI: 7.71‐30.6; P = 0.001), and better QoL (β = 0.09; 95% CI: 0.02‐0.16; P = 0.01).

Conclusions

Self‐hypnosis was not associated with differences in weight change but was associated with improved satiety, QoL, and inflammation. Indeed, habitual hypnosis users showed a greater weight loss.

     

Stress reduction treatment of severe recurrent genital herpes virus

Four individuals with high-frequency recurrences of genital herpes virus of at least 2 years' duration were treated with two behavioral stress-reduction treatments. Subjects were given 10 weekly sessions of frontalis EMG biofeedback (2 subjects) or progressive muscle relaxation treatment (2 subjects). Presession and postsession frontalis EMG measures were recorded for all subjects across treatment. Outcome was measured by daily and weekly symptom charting mailed in weekly over 6 months, or by telephone interview after 6 months. Results demonstrated substantial improvement in reported symptoms with both treatments. Relaxation treatment resulted in a 66% and 100% reduction in frequency of recurrences. Frontalis EMG biofeedback resulted in a 72% and 7% reduction in frequency of recurrences. Follow-up at 1-year posttreatment showed that treatment effects were maintained by one subject, partially maintained by two, and reversed in one subject. The need for controlled investigation is emphasized.The authors thank Stephen Ritz for his contribution to this study.