A prospective, double-blind, pilot, randomized, controlled trial of an "embodied" virtual reality intervention for adults with low back pain.

ABSTRACT: Adults with chronic low back pain, disability, moderate-to-severe pain, and high fear of movement and reinjury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a 3-arm, prospective, double-blind, pilot, randomized, controlled trial comparing DTxP with a sham placebo comparator and an open-label standard care. Participants were enrolled for 6 to 8 weeks, after which, the standard care control arm were rerandomized to receive either the DTxP or sham placebo. Forty-two participants completed assessments at baseline, immediately posttreatment (6-8 weeks), 9-week, and 5-month follow-up. We found that participants in the DTxP group reported greater reductions in fear of movement and better global impression of change when compared with sham placebo and standard care post treatment. No other group differences were noted at posttreatment or follow-up. When compared with baseline, participants in the DTxP group reported lower disability at 5-month follow-up, lower pain interference and fear of movement post treatment and follow-up, and lower pain intensity at posttreatment. The sham placebo group also reported lower disability and fear of movement at 5-month follow-up compared with baseline. Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo, which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences.

Inspiratory Flow Parameters Through Dry Powder Inhalers in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease (COPD): Device Resistance Does Not Limit Use in COPD.

INTRODUCTION: Achieving correct inhalation technique through an inhaler to ensure effective drug delivery is key to managing symptoms in patients with chronic obstructive pulmonary disease (COPD). However, many patients struggle to use their inhalers correctly, with the resultant reduction in therapeutic benefit. Consequently, appropriate inhaler choice is important to maximize clinical benefit. The primary objective of this study was to characterize inspiratory flow parameters across two Easyhaler® inhalers and the HandiHaler® inhaler in patients with COPD and healthy volunteers. METHODS: In this randomized, open-label, crossover study, subjects (100 patients with COPD; 100 healthy volunteers) were trained to perform inhalations of placebo powder via two variants of Easyhaler and placebo capsules via the HandiHaler inhalers. Subjects then performed three placebo inhalations through each inhaler in a random sequence. Inspiratory flow parameters were assessed, including peak inspiratory flow (PIF), for each inhaler. A parallel sub-study was conducted in patients with COPD from the main study to assess correct use of the inhalers, patient's preference, ability to learn to use the inhalers, and the feasibility of the In-Check Dial device to measure PIF values. RESULTS: Mean PIF rates and inspiratory volumes through the three inhalers were similar between patients with COPD and healthy volunteers, and all subjects achieved the 30 L/min PIF required for effective use of Easyhaler. Almost 70% of the 88 patients enrolled in the sub-study used the Easyhaler and HandiHaler inhalers without errors. The Easyhaler was preferred by 51% of patients, while 25% favored the HandiHaler. Teaching the use of both inhalers to almost 70% of patients was very easy. The In-Check Dial PIF values and those obtained via spirometry were strongly correlated (p<0.0001) for all three inhalers. CONCLUSION: The respiratory performance of patients with COPD does not appear to be a limiting factor in the use of Easyhaler.

Pharmacokinetics of Salmeterol and Fluticasone Propionate Delivered in Combination via Easyhaler and Diskus Dry Powder Inhalers in Healthy Subjects.

BACKGROUND: Easyhaler® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide® Diskus® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference. METHODS: Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 µg/inhalation strength) in fasting conditions. Blood samples were drawn before dosing and at frequent time points between 2 minutes and 34 hours after dosing for determination of drug concentrations. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration-time curve (Cmax) and area under the concentration-time curve from time zero to the last sample with quantifiable concentration (AUCt). For salmeterol, the primary variables for total systemic exposure were Cmax and AUCt and for lung deposition Cmax and AUC up to 30 minutes after study treatment administration (AUC30min). RESULTS: One of the Easyhaler test products met all the criteria for bioequivalence with the reference. The 96.7% confidence intervals (CIs) for the test/reference ratios of fluticasone propionate Cmax and AUCt were 0.9901-1.1336 and 0.9448-1.0542, respectively. Ninety percent CIs for salmeterol Cmax, AUC30min, and AUCt ratios were 1.0567-1.2012, 1.0989-1.2255, and 1.0769-1.1829, respectively. Median salmeterol time to maximum concentration (tmax) was 4.0 minutes. Median fluticasone propionate tmax was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9-10 hours for fluticasone propionate. CONCLUSIONS: Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.

Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study.

BACKGROUND: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. OBJECTIVE: To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. DESIGN, SETTING, AND PARTICIPANTS: From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n=47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). RESULTS AND LIMITATIONS: In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07-0.58; p=0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17-0.74; p=0.006) than those who had a BSI increase >20% during treatment. CONCLUSIONS: The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. PATIENT SUMMARY: An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer.

Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial.

BACKGROUND: ODM-201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate cancer cells through high-affinity binding to the AR and inhibition of AR nuclear translocation. This trial assessed ODM-201's safety, pharmacokinetics, and activity in men with metastatic castration-resistant prostate cancer. METHODS: The ARADES trial is an open-label phase 1-2 trial undertaken in 23 hospitals across Europe and USA with ongoing long-term follow-up. Men with progressive metastatic castration-resistant prostate cancer, who had castrate concentrations of testosterone and an Eastern Cooperative Oncology Group score of 0-1 were enrolled. In the phase 1 part of the trial, patients were given oral ODM-201 at a starting daily dose of 200 mg, which was increased to 400 mg, 600 mg, 1000 mg, 1400 mg, and 1800 mg. In phase 2, patients were randomly assigned centrally and stratified by previous chemotherapy and treatment with CPY17 inhibitors, to receive one of three daily doses of ODM-201 (200 mg, 400 mg, and 1400 mg). The primary endpoint in phase 1 was safety and tolerability, whereas in phase 2 it was the proportion of patients with a PSA response (50% or greater decrease in serum PSA) at week 12. All analyses included patients who had received at least one dose of ODM-201. This trial is registered with ClinicalTrials.gov, number NCT01317641, and NCT01429064 for the follow-up after 12 weeks. FINDINGS: We enrolled patients between April 5, 2011, and March 12, 2013. In phase 1, 24 patients were enrolled to six sequential cohorts of three to six patients and received a daily dose of ODM-201, 200-1800 mg. No dose-limiting toxic effects were reported and the maximum tolerated dose was not reached. In phase 1, three patients reported eight adverse events of grade 3 (fracture, muscle injury, laceration, paralytic ileus, pain, presyncope, urinary retention, and vomiting) and one patient had a grade 4 adverse event (lymphoedema). None of the grade 3-4 adverse events were deemed to be related to ODM-201. Of the phase 1 patients, the four who received 200 mg, seven who received 400 mg, and three who received 1400 mg entered the phase 2 part of the trial. In addition to these patients, 110 were randomly assigned to three groups: 200 mg (n=38), 400 mg (n=37), and 1400 mg (n=35). For these patients, the most common treatment-emergent adverse events were fatigue or asthenia (15 [12%] of 124 patients), hot flush (six [5%]), and decreased appetite (five [4%]). One patient (<1%) had a grade 3 treatment-emergent adverse event (fatigue); no patients had a treatment-emergent grade 4 adverse event. 38 patients who received 200 mg, 39 who received 400 mg, and 33 who received 1400 mg were assessable for PSA response at 12 weeks. 11 (29%) patients in the 200 mg group, 13 (33%) in the 400 mg group, and 11 (33%) in the 1400 mg group had a PSA response at 12 weeks. INTERPRETATION: Our results suggest that ODM-201 monotherapy in men with progressive metastatic castration-resistant prostate cancer provides disease suppression and that ODM-201 has a favourable safety profile. These findings support further investigation of clinical responses with ODM-201 in men with castration-resistant prostate cancer. FUNDING: Orion Corporation Orion Pharma, Endo Pharmaceuticals Inc.

Fever with rash in patients returning from popular tourist resort Phuket, Thailand: dengue--or measles?

We report three recent cases of measles in travelers to a popular vacation resort, Phuket, Thailand, two initially diagnosed clinically as dengue, one as drug reaction. In countries with no indigenous measles, clinicians may no longer recognize the disease. When left misdiagnosed, the patients continue to be potential transmitters.

[Rabies]. / Vesikauhu.

Rabies is a mammalian zoonosis caused by a virus belonging to the family of rhabdoviruses. In Finland, the risk of rabies is associated with imported animals and traveling. We describe the second case of human rabies diagnosed in Finland. Strong hydrophobia was present in the initial phase of the disease. The patient had encephalomyelitis, and he died 11 days after the onset of symptoms. Diagnosis was confirmed by RT-PCR using Saliva. Rabies infection leads invariably to death, but can. be prevented after the exposure with vaccine and immunoglobulin therapy.

[Traveler's diarrhea, the most common health problem of travelers]. / Turistiripuli, matkailijan yleisin vitsaus.

Bacteria cause 50 to 80% of travelers' diarrheic diseases. The most important pathogens include enterotoxigenic Escherichia coli (ETEC), campylobacteria, salmonellae and shigella. Diarrheic viruses cause 5 to 25% and protozoa less than 10% of travelers' diarrheas. Hand and food hygiene constitute the main preventive measures. Treatment of traveler's diarrhea is based on rehydration therapy and rest. Antimicrobial therapy is required only in cases with exceptionally severe symptoms.

Swimming and Campylobacter infections.

A matched case-control study was conducted to study risk factors for domestically acquired sporadic Campylobacter infections in Finland. Swimming in natural sources of water was a novel risk factor. Eating undercooked meat and drinking dug-well water were also independent risk factors for Campylobacter infection.

No increased risk of endometrial hyperplasia with fixed long-cycle oestrogen-progestogen therapy after five years.

OBJECTIVE: The aim of this study was to evaluate the long-term endometrial safety of long-cycle sequential oestrogen-progestogen hormone replacement therapy (HRT). STUDY DESIGN: A prospective, longitudinal, single group study was undertaken in postmenopausal women, aged 45-66 years, treated with up to 21 3-month cycles (five years) of sequential oestrogen-progestogen HRT. Treatment consisted of 70 days of 2 mg/day oestradiol valerate (E(2)V), followed by 14 days of E(2)V combined with 20 mg/day medroxyprogesterone acetate (MPA), followed by seven days placebo. Endometrial biopsies were assessed at baseline, at 12 months in women with an endometrial thickness >6 mm and in all participants at 24, 36, 48 and 60 months. Mammography was performed at baseline and at 24-month intervals thereafter. Adverse events were assessed throughout the study. RESULTS: Of 132 women enrolled, 94 completed five years of treatment (540 women years). Endometrial changes (oestrogen effect II) were apparent in most women from 24-60 months (95, 83.3% women at 24 months). One case of simple hyperplasia was found (at 60 months), and none of complex hyperplasia or endometrial cancer. The pattern and frequency of adverse events were consistent with other sequential oestrogen-progestogen HRT regimens. CONCLUSIONS: The incidence of hyperplasia over five years (0.19%, upper 95% CI 0.88) was well within the acceptable rates defined by the European Union Committee for Proprietary Medicinal Products (CPMP).

Microbial factors in spondyloarthropathies: insights from population studies.

Infections and genetics play a role in the development of reactive arthritis. The clinical manifestations and severity of the features depend on the triggering infections and the epidemiologic setting. Reports from hospital-based series show the lowest frequency of reactive arthritis, but often, patients have severe arthritis associated with a high frequency of HLA-B27. At the population level, reactive arthritis occur in 7 to 15% of the infected subjects. The disease is usually mild, affects small joints, can be polyarticular, often rapidly disappears, and has a low association with HLA-B27. There also seems to be a change in the spectrum of triggering infections. Reports of Yersinia arthritis are less common, whereas arthritis in association with Campylobacter or Salmonella infections seems to be increasing. The role of early antimicrobial chemotherapy for the prevention of reactive arthritis needs to be studied.

No increased risk of endometrial hyperplasia with fixed long-cycle hormone replacement therapy after two years.

The appropriate dose of progestogen during long-cycle hormone replacement is still under debate. We present preliminary two-year results from an open five-year clinical trial of 132 postmenopausal women. All subjects had long-cycle HRT consisting of 70 days 2 mg oestradiol valerate (E(2)V), followed by 14 days 2 mg E(2)V plus 20 mg medroxyprogesterone acetate, and a seven-day hormone-free period. No endometrial samples with hyperplasia or indicative of malignancy were found at 24 months.