Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial.

Aim: Study aim was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. Methods: In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. Primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed. Results: Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs. Conclusions: Study results showed that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

Sequential somatic mutations upon secondary anti-HER2 treatment resistance in metastatic ERBB2S310F mutated extramammary Paget's disease.

Metastatic extramammary Paget's disease is a rare adenocarcinoma with poor prognosis. Several reports of human epidermal growth factor receptor 2 alterations point to its pathogenic role in the disease. However, the occurrence of treatment resistance to anti-HER2 therapy demand the need for further knowledge. We report of a patient with metastatic penoscrotal extramammary Paget's disease, with an ERBB2S310F mutation, in which near complete response was achieved upon treatment with trastuzumab and carboplatin. However, after 10 cycles of trastuzumab and carboplatin, widespread metastasis re-occurred. Analysis of a newly developing metastasis revealed additional genomic alterations including ERBB3A232V and PIK3CAG106V point mutations as well as MET and CDK6 amplification, providing a potential mechanism of acquired treatment resistance. Therefore, ERBB family inhibitor afatinib was initiated. Unfortunately, the patient succumbed to disease-related complications shortly after treatment initiation. This is the first report of ERBB2S310F mutated, metastatic extramammary Paget's disease with secondary resistance to trastuzumab / carboplatin, potentially due to additional acquired genomic alterations. This case contributes to the growing evidence of HER2 in the pathogenesis of metastatic extramammary Paget's disease and emphasizes the importance of repetitive, genomic analysis in rare diseases.

Swiss (German) Version of the Actinic Keratosis Quality of Life questionnaire.

BACKGROUND: Actinic keratosis (AK) is a sun-induced skin lesion that may progress to invasive squamous cell carcinoma of the skin. Recently, the Actinic Keratosis Quality of Life questionnaire (AKQoL) was designed for patients with AK in Denmark as a specific quality of life instrument for AK patients. OBJECTIVE: The objective of this study was to adapt the AKQoL for the German language region of Switzerland and to evaluate its psychometric properties (validity, reliability). METHODS: Translation and cultural adaptation of the questionnaire were assessed by using the technique of cognitive interviewing. During the translation process, 34 patients with AK from the Department of Dermatology, University Hospital Zurich, were interviewed in 3 sessions of cognitive interviewing. The translated questionnaire was then distributed together with the Dermatology Life Quality Index (DLQI) to a second group of 113 patients for validation and reliability testing. Within this group, we measured the internal consistency by the Cronbach coefficient α and Spearman correlation coefficient between the AKQoL and the DLQI. RESULTS: The problems encountered during the translation process led to changes in 5 categories as described by Epstein: stylistic changes, change in breadth, change in actual meaning, change in frequency and time frame, change in intensity. We found a Cronbach α of 0.82, an acceptable internal consistency. The Spearman correlation coefficient between total scores of AKQoL and DLQI was 0.57. CONCLUSION: We culturally adapted and validated a Swiss (German) version of the AKQoL questionnaire applicable for the population of a university center in Switzerland to measure and monitor the quality of life in patients with AK.

A non-interventional, observational study of a fixed combination of pepsin and amino acid hydrochloride in patients with functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder characterized by recurrent and diverse symptoms and pathophysiology that remains unexplained following routine clinical investigation. Enzynorm®f is a pharmaceutical preparation comprising fixed amounts of pepsin of biological origin and organically bound acid in the form of amino acid hydrochloride. It is traditionally used as a mild agent to support gastric function and to stimulate the stomach's proteolytic activities in FD. METHODS: In a non-interventional, observational, post-marketing surveillance study, patients with an established diagnosis of FD were treated with a fixed combination of pepsin and amino acid hydrochloride taken as tablets three times daily for 6 weeks. The primary objective of this study was to assess the change in symptoms using the validated Gastrointestinal Symptom Score (GIS©). Secondary objectives included patients' assessment of their gastrointestinal symptoms as well as treatment safety and tolerability. RESULTS: A total of 97 patients (mean age 58.4 ± 13.9 years; 63.2% females) were included in the study, with 72 data having GIS© score data at baseline and at 6 weeks, and 34 also at 3 weeks. The overall GIS© sum score decreased by 4.1 (p < 0.0001) from 11.6 (±4.8) at baseline to 7.4 (± 4.6) reflecting an improvement of clinical symptomatology after 6 weeks of treatment. In a subgroup of 70 patients who had FD meeting the Rome III criteria a GIS© score reduction of ≥50% was observed after 3 weeks treatment in 24% and in 30.8% after 6 weeks. Adverse events were mostly gastrointestinal in nature and consistent with the underlying disease; no unexpected adverse reactions were reported. Twenty-seven patients discontinued the study, mostly because of gastrointestinal symptoms. CONCLUSION: The results of this study support the efficacy of a fixed combination of pepsin and amino acid hydrochloride for the treatment of patients with FD and also suggest good to moderate treatment tolerability. These findings should be further explored in a randomised, placebo-controlled clinical trial. CLINICAL TRIAL REGISTRATION: This study has been retrospectively registered in the ClinicalTrials.gov registry, trial identifier NCT03076411 .

Ayurvedic versus conventional dietary and lifestyle counseling for mothers with burnout-syndrome: A randomized controlled pilot study including a qualitative evaluation.

OBJECTIVES: Ayurveda claims to be effective in the treatment of psychosomatic disorders by means of lifestyle and nutritional counseling. DESIGN: In a randomized controlled study mothers with burnout were randomized into two groups: Ayurvedic nutritional counseling (according to tradition), and conventional nutritional counseling (following the recommendations of a family doctor). Patients received five counseling sessions over twelve weeks. MAIN OUTCOME MEASURES: Outcomes included levels of burnout, quality of life, sleep, stress, depression/anxiety, and spirituality at three and six months. It also included a qualitative evaluation of the communication processes. RESULTS: We randomized thirty four patients; twenty three participants were included in the per protocol analysis. No significant differences were observed between the groups. However, significant and clinically relevant intra-group mean changes for the primary outcome burnout, and secondary outcomes sleep, stress, depression and mental health were only found in the Ayurveda group. The qualitative part of the study identified different conversational styles and counseling techniques between the two study groups. In conventional consultations questions tended to be category bound, while counseling-advice was predominantly admonitory. The Ayurvedic practitioner used open-ended interrogative forms, devices for displaying understanding, and positive re-evaluation more frequently, leading to an overall less asymmetrical interaction. CONCLUSIONS: We found positive effects for both groups, which however were more pronounced in the Ayurvedic group. The conversational and counseling techniques in the Ayurvedic group offered more opportunities for problem description by patients as well as patient-centered practice and resource-oriented recommendations by the physician. TRIAL REGISTRATION: NCT01797887.

Effectiveness of Ayurvedic Massage (Sahacharadi Taila) in Patients with Chronic Low Back Pain: A Randomized Controlled Trial.

OBJECTIVES: Ayurveda is one of the oldest comprehensive healthcare systems worldwide. Ayurvedic massage and physical therapy are frequently used to treat patients with chronic pain syndromes and disorders of the musculoskeletal system. This study aimed to evaluate the effectiveness of Ayurvedic massage in nonspecific chronic low back pain by means of a randomized clinical trial. DESIGN: Sixty-four patients (mean age, 54.8 years; 49 women and 15 men) with chronic low back pain who scored >40 mm on a 100-mm visual analogue scale (VAS) were randomly assigned to a 2-week massage group with 6 hours of Ayurvedic massage and external treatment (n = 32) or to a 2-week local thermal therapy group (n = 32). The study observation period was 4 weeks, consisting of a 2-week intervention phase followed by a 2-week follow-up phase. OUTCOME MEASURES: Primary outcome measure was the change of mean pain (VAS) from baseline to week 4. Secondary outcomes included pain-related bothersomeness, the Roland Disability Questionnaire, quality of life (Medical Outcomes Study 36-Item Short Form), the Hanover Functional Ability Questionnaire for measuring back pain-related disability, and psychological outcomes. Outcomes were assessed at baseline and after 2 and 4 weeks. RESULTS: Mean back pain (primary outcome) at week 2 was significantly reduced from 53.4 ± 18.5 to 21.6 ± 18.2 in the massage group and from 55.3 ± 12.9 to 41.8 ± 19.8 in the standard thermal therapy group (mean group difference, -18.7; 95% confidence interval, -28.7 to -8.7; p < 0.001). While beneficial effects on pain-related bothersomeness and psychological well-being were also apparent, the Ayurvedic intervention did not improve function or disability in the short-term observation period. Both programs were safe and well tolerated. CONCLUSIONS: Ayurvedic external treatment is effective for pain-relief in chronic low back pain in the short term. Further studies with longer observation periods are needed to evaluate the long-term effects of the Ayurvedic external treatment approach on function and disability.

Effectiveness of focused meditation for patients with chronic low back pain-A randomized controlled clinical trial.

OBJECTIVES: We aimed to evaluate the effectiveness of an 8-week meditation program (focused meditation) in patients with chronic low-back pain. DESIGN: A randomized clinical trial was conducted on 68 patients (55 years;75% female) with chronic low-back pain who scored >40mm on a 100mm Visual-Analogue-Scale. Subjects were allocated to an 8-week meditation program (focused meditation) with weekly 75min classes or to a self-care exercise program with a wait-list offer for meditation. Both groups were instructed to practice at home. Outcomes were assessed baseline and after 4 and 8 weeks. The primary outcome measure was the change in mean back pain at rest after 8 weeks. Secondary outcomes included function, pain-related bothersomeness, perceived stress, quality-of-life (QOL), and psychological outcomes. RESULTS: Twelve (meditation) and 4 (exercise) patients were lost to follow-up. The primary outcome, pain at rest after 8 weeks, was reduced from 59.3±13.9mm to 40.8±21.8mm with meditation vs. 52.9±11.8mm to 37.3±18.2mm with exercise (adjusted group difference: -1.4 (95%CI:11.6;8.8;p=n.s.) Perceived stress was significantly more reduced with meditation (p=0.011). No significant treatment effects were found for other secondary outcomes as pain-related bothersomeness, function, quality-of-life and psychological scores, although the meditation group consistently showed non-significant better improvements compared to the exercise group. CONCLUSIONS: Focused meditation and self-care exercise lead to comparable, symptomatic improvements in patients with chronic low back pain. Future studies should include longer-term follow-ups and develop guided meditation programs to support compliance.

Effectiveness of jyoti meditation for patients with chronic neck pain and psychological distress--a randomized controlled clinical trial.

UNLABELLED: Chronic neck pain is a common medical complaint partly mediated by psychosocial distress and having a high socioeconomic impact. There is preliminary evidence that stress reduction by meditation might be beneficial in chronic pain syndromes. We aimed to evaluate the effectiveness of an 8-week meditation program (jyoti meditation) in patients with chronic neck pain by means of a randomized clinical trial. Eighty-nine patients (aged 49.7 ± 10.5 years, 73 female) with chronic neck pain who scored >40 mm on a 100-mm visual analog scale and had concomitant increased perceived stress were randomized to an 8-week meditation program (jyoti meditation) with weekly 90-minute classes (n = 45) or to a home-based exercise program (n = 44) with a wait list offer for meditation. Both groups were instructed to practice at home. Outcomes were assessed at baseline and after 8 weeks. Primary outcome measure was change of mean pain at rest (visual analog scale score) from baseline to week 8. Secondary outcomes included pain at motion, functional disability, pain-related bothersomeness, perceived stress, quality of life, and psychological outcomes. Patients had neck pain for a mean of 11 years. Eighteen patients in the meditation group and 16 patients in the exercise group were lost to follow-up. Meditation training significantly reduced pain when compared to the exercise group after 8 weeks (reduction of 45.5 ± 23.3 mm to 21.6 ± 17.2 mm in the meditation group, and 43.8 ± 22.0 mm to 37.7 ± 21.5 mm in the exercise group; mean difference: 13.2 mm [95% confidence interval: 2.1, 24.4; P = .02]). Pain-related bothersomeness decreased more in the meditation group (group difference 11.0 mm [95% confidence interval: 1.0, 21.0; P = .03]). No significant treatment effects were found for pain at motion, psychological scores, and quality of life, although the meditation group showed nonsignificant greater improvements compared to the exercise group. In conclusion, meditation may support chronic pain patients in pain reduction and pain coping. Further well-designed studies including more active control comparisons and longer-term follow-up are warranted. PERSPECTIVE: This article presents the results of a randomized controlled trial on the clinical effects of an 8-week meditation program or self-care exercise in patients with chronic neck pain. Meditation reduced pain at rest but not disability and might be a useful treatment option for pain management of chronic neck pain.

Additive Complex Ayurvedic Treatment in Patients with Fibromyalgia Syndrome Compared to Conventional Standard Care Alone: A Nonrandomized Controlled Clinical Pilot Study (KAFA Trial).

Background. Fibromyalgia (FMS) is a challenging condition for health care systems worldwide. Only limited trial data is available for FMS for outcomes of complex treatment interventions of complementary and integrative (CIM) approaches. Methods. We conducted a controlled, nonrandomized feasibility study that compared outcomes in 21 patients treated with Ayurveda with those of 11 patients treated with a conventional approach at the end of a two-week inpatient hospital stay. Primary outcome was the impact of fibromyalgia on patients as assessed by the FIQ. Secondary outcomes included scores of pain intensity, pain perception, depression, anxiety, and quality of sleep. Follow-up assessments were done after 6 months. Results. At 2 weeks, there were comparable and significant improvements in the FIQ and for most of secondary outcomes in both groups with no significant in-between-group differences. The beneficial effects for both treatment groups were partly maintained for the main outcome and a number of secondary outcomes at the 6-month followup, again with no significant in-between-group differences. Discussion. The findings of this feasibility study suggest that Ayurvedic therapy is noninferior to conventional treatment in patients with severe FMS. Since Ayurveda was only used as add-on treatment, RCTs on Ayurveda alone are warranted to increase model validity. This trial is registered with NCT01389336.

In-Patient Treatment of Fibromyalgia: A Controlled Nonrandomized Comparison of Conventional Medicine versus Integrative Medicine including Fasting Therapy.

Fibromyalgia poses a challenge for therapy. Recent guidelines suggest that fibromyalgia should be treated within a multidisciplinary therapy approach. No data are available that evaluated multimodal treatment strategies of Integrative Medicine (IM). We conducted a controlled, nonrandomized pilot study that compared two inpatient treatment strategies, an IM approach that included fasting therapy and a conventional rheumatology (CM) approach. IM used fasting cure and Mind-Body-Medicine as specific methods. Of 48 included consecutive patients, 28 were treated with IM, 20 with CM. Primary outcome was change in the Fibromyalgia Impact Questionnaire (FIQ) score after the 2-week hospital stay. Secondary outcomes included scores of pain, depression, anxiety, and well being. Assessments were repeated after 12 weeks. At 2 weeks, there were significant improvements in the FIQ (P < 0.014) and for most of secondary outcomes for the IM group compared to the CM group. The beneficial effects for the IM approach were reduced after 12 weeks and no longer statistically significant with the exception of anxiety. Findings indicate that a multimodal IM treatment with fasting therapy might be superior to CM in the short term and not inferior in the mid term. Longer-term studies are warranted to assess the clinical impact of integrative multimodal treatment in fibromyalgia.

Yoga for chronic neck pain: a pilot randomized controlled clinical trial.

UNLABELLED: Yoga has been found effective in the treatment of chronic low back pain. We aimed to evaluate the effectiveness of Iyengar yoga in chronic neck pain by means of a randomized clinical trial. Seventy-seven patients (aged 47.9 ± 7.9, 67 female) with chronic neck pain who scored >40 mm on a 100-mm visual analog scale (VAS) were randomized to a 9-week Iyengar yoga program with weekly 90-minute classes (n = 38) or to a self-care/exercise program (n = 38). Patients were examined at baseline and after 4 and 10 weeks. The primary outcome measure was change of mean pain at rest (VAS) from baseline to week 10. Secondary outcomes included pain at motion, functional disability, quality of life (QOL), and psychological outcomes. Twelve patients in the yoga group and 11 patients in the self-care/exercise group were lost to follow-up, with higher study nonadherence in the self-care group (5 versus 10 patients). Mean pain at rest was reduced from 44.3 ± 20.1 to 13.0 ± 11.6 at week 10 by yoga and from 41.9 ± 21.9 to 34.4 ± 21.1 by self-care/exercise (group difference: -20.1, 95% confidence interval: -30.0, -10.1; P < .001). Pain at motion was reduced from 53.4 ± 18.5 to 22.4 ± 18.7 at week 10 by yoga and from 49.4 ± 22.8 to 39.9 ± 21.5 by self-care/exercise (group difference: -18.7, 95% confidence interval: -29.3, -8.1; P < .001). Significant treatment effects of yoga were also found for pain-related apprehension, disability, QOL, and psychological outcomes. Sensitivity analyses suggested minimal influence of dropout rates. Both programs were well tolerated. In this preliminary trial, yoga appears to be an effective treatment in chronic neck pain with possible additional effects on psychological well-being and QOL. The effectiveness of yoga in chronic neck pain should be further tested by comparative effectiveness studies with longer observation periods. PERSPECTIVE: This article presents the results of a randomized controlled trial on the clinical effects of a 9-week yoga program or self-care exercise in patients with chronic neck pain. Yoga led to superior pain relief and functional improvements and might be a useful treatment option for chronic neck pain.

Clay jojoba oil facial mask for lesioned skin and mild acne--results of a prospective, observational pilot study.

BACKGROUND: External application of clay facial masks is a cosmetic procedure generally used to reduce skin lesions and to improve overall skin condition. OBJECTIVE: Collecting pilot data about self-treatment with clay jojoba oil masks on participants with acne-prone, lesioned skin and acne. METHODS: Open, prospective, observational pilot study: Participants received written information, instructions, and questionnaires without direct contact with the study physician. For 6 weeks, they applied the masks 2-3 times per week. The primary outcome is the difference of skin lesions: baseline vs. after 6 weeks. RESULTS: 194 participants (192 female, 2 male, mean age (± SE) (32.3 ± 0.7 years) returned questionnaires and diaries. 133 of these participants returned complete and precise lesion counts (per-protocol (PP) collective). A 54% mean reduction in total lesion count was observed after 6 weeks of treatment with clay facial mask. Both inflammatory and non-inflammatory skin lesions were reduced significantly after treatment compared to baseline: Median counts (MC) of pustules per affected participant were reduced from 7.0 ± 0.9 to 3.0 ± 0.5 (mean individual reduction (MIR) = 49.4%), the MC of the papules from 3.5 ± 2.2 to 1.0 ± 0.4 (MIR = 57.3%), the MC of cysts from 2.0 ± 0.8 to 0.5 ± 0.4 (MIR = 68.6%) and the MC of comedones from 26.5 ± 6.3 to 16.0 ± 4.0 (MIR = 39.1%). DLQI-average score decreased from 5.0 ± 4.5 (mean ± SE) before to 2.1 ± 2.8 after treatment. CONCLUSIONS: The present study gives preliminary evidence that healing clay jojoba oil facial masks can be effective treatment for lesioned skin and mild acne vulgaris.