A model-based approach to predict individual weight loss with semaglutide in people with overweight or obesity.

AIMS: To determine the relationship between exposure and weight-loss trajectories for the glucagon-like peptide-1 analogue semaglutide for weight management. MATERIALS AND METHODS: Data from one 52-week, phase 2, dose-ranging trial (once-daily subcutaneous semaglutide 0.05-0.4 mg) and two 68-week phase 3 trials (once-weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure-response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure-response model to predict 1-year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials. RESULTS: Based on population PK, exposure levels over time consistently explained the weight-loss trajectories across trials and dosing regimens. The exposure-response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction. CONCLUSION: An exposure-response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight-loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly.

A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity.

OBJECTIVE: To evaluate the efficacy of transcranially applied pulsed electromagnetic fields (PEMF) on functional impairments and symptom severity in multiple chemical sensitivity (MCS) patients. METHODS: The study was conducted as a nationwide trial in Denmark using a randomised, parallel-group, double-blind and placebo-controlled design. Sample size was estimated at 40 participants. Eligibility criteria were age 18-75 years and fulfilment of the MCS case criteria. Participants received either PEMF or placebo PEMF (no stimulation) applied transcranially for 6 weeks. The primary outcome was the Life Impact Scale (LIS) of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Secondary outcomes were the Symptom Severity Scale (SSS) and the Chemical Intolerance Scale of QEESI. RESULTS: A total of 39 participants were randomised to PEMF or placebo treatment. No significant difference was observed on QEESI LIS between groups with a mean change score of -5.9 in the PEMF group compared with -1.5 in the placebo group (p=0.35, effect size=-0.31). However, a significant decrease was detected on QEESI SSS within and between groups with a mean change score of -11.3 in the PEMF group compared with -3.2 in the placebo group (p=0.03, effect size=-0.60). CONCLUSION: PEMF treatment of 6 weeks showed no effect on functional impairments in MCS. However, a significant decrease in symptom severity was observed.

Two of three patients with multiple chemical sensitivity had less symptoms and secondary hyperalgesia after transcranially applied pulsed electromagnetic fields.

Background Multiple chemical sensitivity (MCS) is a chronic, disabling condition characterized by recurrent multisystem symptoms triggered by common airborne chemicals. Evidence points towards abnormal sensory processing in the central nervous system (CNS) as a likely pathophysiological mechanism. No effective treatment has yet been reported, but clinical observations suggest that as pulsed electromagnetic fields (PEMF) is a treatment for some CNS disorders (depression and chronic pain), it may also be a treatment modality for MCS. Methods In an open case study, the effects of PEMF were assessed in three MCS patients. All cases received 30 min daily treatment 5 days a week for 8 consecutive weeks. Symptoms and functional impairments related to MCS, depressive symptoms, and capsaicin-induced secondary punctate hyperalgesia were assessed at baseline and weekly until an 18-week follow-up. Results Two of the three cases showed considerable improvement on all measures of symptoms and functional impairments related to MCS in response to PEMF therapy. One case showed no improvement and during the treatment period was unexpectedly diagnosed with depression. Conclusion Our findings indicate potential benefits of PEMF therapy in MCS. Implication The therapeutic effect of PEMF in MCS needs to be investigated by a randomized placebo-controlled trial.

Transcranial pulsed electromagnetic fields for multiple chemical sensitivity: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. The symptoms may have severe impact on patients' lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes. METHODS/DESIGN: In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum, and quality of life. DISCUSSION: This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a documented effect on MCS, and in terms of healthcare there is very little to offer these patients. There is thus a great need for well-conducted randomized trials aimed at assessing possible treatment effects. A positive outcome will pave the way for improved healthcare and understanding of this very disabling and overlooked condition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01834781.

Chemical intolerance among hairdressers in Denmark.

OBJECTIVES: To investigate the prevalence and the severity of fragrance-related symptoms among hairdressers in Denmark compared with the Danish general population. Further, to characterize former hairdressers who are severely chemically intolerant to fragranced products in relation to sex, age and health- and work-related reasons for leaving the hairdressing profession. METHODS: The study population consisted of all hairdressers who graduated from the public vocational schools in Denmark during 1985 and 2007 (n = 7840) and a random sample of individuals from the Danish general population (n = 6000). Both populations received a postal questionnaire on symptoms from inhalation of fragranced products and the resultant behavioural consequences. All former hairdressers also answered additional questions on health- and work-related reasons for leaving the profession. RESULTS: No differences were found in the prevalence (OR = 1.0, CI = 0.89-1.14) or the severity (OR = 1.1, CI = 0.80-1.51) of symptoms from inhalation of fragranced products in hairdressers compared with the general population. Among hairdressers, however, experience of fragrance-related symptoms (OR = 1.2, CI = 1.01-1.31) and adjustments of social (OR = 1.8, CI = 1.12-2.80) and occupational conditions (OR = 2.8, CI = 1.84-4.25) were reported significantly more often by former hairdressers than current hairdressers. CONCLUSIONS: The prevalence and the severity of fragrance-related symptoms were similar in hairdressers and the general population. Former hairdressers were more affected by fragranced products than current hairdressers were. Although fragrance-related symptoms did not seem to be more frequent among hairdressers, the hairdressing profession might pose a problem for those who are chemically intolerant.

Multiple chemical sensitivity: on the scent of central sensitization.

BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor contributing to the clinical manifestations. PURPOSE: To use quantitative sensory testing (QST) to study central hyperexcitability and multiple aspects of central sensory processing in MCS patients without comorbid overlapping disorders and to compare the results with those among matched controls. METHODS: 15 MCS patients and 15 healthy matched controls underwent QST to assess the following aspects of pain: capsaicin-induced secondary punctate hyperalgesia, stimulus response function (SRF) to punctate mechanical stimuli before and after capsaicin injection, temporal summation to punctate stimuli post capsaicin injection, pressure pain thresholds, heat pain thresholds, tonic heat stimulation and conditioning pain modulation (CPM: formerly known as diffuse noxious inhibitory control or DNIC). RESULTS: The mean area of capsaicin-induced secondary punctate hyperalgesia was significantly larger in MCS patients than in controls at 5, 30 and 60 min post capsaicin injection (p=0.01). In addition MCS patients reported higher ratings in response to punctate mechanical stimuli assessed by SRF compared with controls (p<0.001). The CPM test induced significantly higher pain ratings in patients than in controls (p=0.002). We found no group differences in pressure pain and heat pain thresholds, temporal summation to punctate stimuli post capsaicin injection, capsaicin and tonic heat pain ratings or CPM effect. CONCLUSION: Increased capsaicin-induced secondary punctate hyperalgesia was demonstrated in MCS patients without comorbid, overlapping disorders, suggesting facilitated central sensitization in MCS.