A new study finds that rising placebo responses may play a part in the increasingly high failure rate for clinical trials of drugs, but the authors of the study say that the increase in placebo responses occurred only in trials conducted in the United States...

When yesterday's placebo is tomorrow's treatment

Fadel Zeidan
Nov 18, 2015; 35:15307-15325
BehavioralSystemsCognitive

Dopamine was long thought to play a part in the placebo effect for pain relief, but a new study is questioning its true role

La découverte d’un circuit cérébral impliqué dans l’effet antidouleur des placebos pourrait permettre le développement de traitements analgésiques.

Ogilvy UK Vice Chairman Rory Sutherland co-founded a behavioural science practice within the agency, which works with a consulting practice of psychology graduates who look for ‘unseen opportunities’ in consumer behaviour. At WIRED Health, Sutherland explores the psychological reasons why people do things and how perception and placebos can be used for a positive outcome. "It doesn't really matter why people do it so as long as they do," Sutherland points out. "There's a danger in activity which goes 'it's not enough for people to go and do the thing we want them to do, they have to do it for the right reason'. To be honest, I don't really mind if people buy an electric car because they think it's really cool." ABOUT WIRED HEALTH 600 innovators, scientists and business leaders gathered at The Francis Crick Institute in London, for WIRED Health on March 26, 2019. Discover some of the fascinating insights from speakers here: http://wired.uk/health-event ABOUT WIRED EVENTS WIRED events shine a spotlight on the innovators, inventors and entrepreneurs who are changing our world for the better. Explore this channel for videos showing on-stage talks, behind-the-scenes action, exclusive interviews and performances from our roster of events. Join us as we uncover the most relevant, up-and-coming trends and meet the people building the future. ABOUT WIRED WIRED brings you the future as it happens - the people, the trends, the big ideas that will change our lives. An award-winning printed monthly and online publication. WIRED is an agenda-setting magazine offering brain food on a wide range of topics, from science, technology and business to pop-culture and politics. CONNECT WITH WIRED Events: http://wired.uk/events Subscribe for Events Information: http://wired.uk/signup Web: http://bit.ly/VideoWired Twitter: http://bit.ly/TwitterWired Facebook: http://bit.ly/FacebookWired Instagram: http://bit.ly/InstagramWired Magazine: http://bit.ly/MagazineWired Newsletter: http://bit.ly/NewslettersWired

There are a lot of factors that help to regulate our overall health and wellness. If we are content in our lives and relationships, we are more likely to be healthy. If we exercise and eat well, we reap the benefits in our mind and body. Also, as recent studies by Ted Kaptchuck and others show,...

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

Ted Kaptchuk, professor of medicine at Harvard Medical school - and leading placebo researcher, has just published an analysis on bmj.com describing the effect of open label placebo - placebos that patient's know are placebos, but still seem to have some clinical effect. Ted joins us to speculate about what's going on in the body, what this means...

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

Robert R. Henry
Mar 1, 2015; 38:412-419
Evolving Tactics With Inhibition of Sodium-Glucose Cotransporters

Hans-Ulrich Häring
Jun 1, 2014; 37:1650-1659
Emerging Technologies and Therapeutics

Khalid A. Jadoon
Oct 1, 2016; 39:1777-1786
Emerging Technologies and Therapeutics

Vanita R. Aroda
Sep 1, 2019; 42:1724-1732
Emerging Therapies: Drugs and Regimens

OBJECTIVE

Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone.

OBJECTIVE

To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

In Eliot Spitzer's sex scandal and tragicomic downfall, the question that bugged many people did not have to do with ethics or politics, but whether Spitzer got a raw deal.

Fabrizio Benedetti
Nov 9, 2005; 25:10390-10402
Symposia and Mini-Symposia

Dimenhydrinate, an antihistaminic agent, is a widely used drug in Canada and Europe. It limits stimulation of the vomiting center via the vestibular system. Multiple studies have shown its effectiveness in the treatment of vertigo and postoperative nausea and vomiting.

Dimenhydrinate, when given orally, did not significantly decrease the frequency of vomiting in children with acute gastroenteritis compared with placebo. The reported adverse effect proportions were similar for the dimenhydrinate and placebo groups. (Read the full article)

Omega-3 fatty acids (O3FA) are commonly used as complementary treatments in pediatric psychiatric disorders, including Tourette’s disorder (TD), and are well known to have anti-inflammatory properties. However, no studies to date have examined the effects of O3FA on pediatric TD.

This is the first double-blind, placebo-controlled clinical trial of O3FA in pediatric TD. The results indicate that O3FA supplementation may be beneficial in the reduction of tic-related impairment for some children and adolescents with TD, but not tics per se. (Read the full article)

Children with obstructive sleep apnea (OSA) are usually treated by surgical removal of their upper airway lymphadenoid tissue. Recently, medications were offered to patients with nonsevere OSA. Montelukast, for this indication, had never been studied in a randomized controlled manner.

Montelukast effectively reduced polysomnographic findings, symptoms, and the size of the adenoidal tissue in children with nonsevere OSA. The findings support the potential of a leukotriene modifier as a novel, safe, noninvasive alternative for children with mild to moderate OSA. (Read the full article)

Honey is recommended as a cough medication by the World Health Organization. To date, the efficacy of this treatment has been shown in 2 studies: one tested only buckwheat honey and the other study was not blinded.

In a randomized controlled trial, we compared 3 types of honey versus placebo as a treatment of upper respiratory tract infection–associated cough. These types of honey were superior to placebo in alleviating cough. (Read the full article)

Stressful events adversely affect the immune system, particularly the natural killer (NK) cells. Infants in the NICUs are exposed to stressful stimuli. The effect of massage therapy on the immune system of preterm infants has not been investigated.

This randomized placebo-controlled study found daily massage performed in stable preterm infants for a minimum of 5 days was associated with an increase in NK cell cytotoxicity despite lower absolute NK cell numbers compared with controls. (Read the full article)

Preterm infants in the NICU receive the greatest number of transfusions of any patient population. The administration of the long-acting erythropoiesis stimulating agent (ESA) darbepoetin to reduce or eliminate transfusions in preterm infants has not been evaluated.

Infants receiving ESAs received half the number of transfusions and were exposed to approximately half the donors compared with the placebo group. More than half of the ESA recipients (59% darbepoetin recipients, 52% erythropoietin recipients) remained untransfused during their hospitalization. (Read the full article)

Although a number of randomized controlled trials of erythropoietin administration to preterm infants have been performed, few studies have reported 2-year or longer neurodevelopmental outcomes, and no studies have evaluated neurodevelopmental outcomes of infants randomized to receive Darbepoetin.

This is the first prospectively designed study to evaluate the neurocognitive outcomes of preterm infants randomized to receive Darbepoetin or erythropoietin compared with placebo. Infants in the ESA groups had significantly higher cognitive scores compared with the placebo group. (Read the full article)

Strictly-defined pediatric bipolar I disorder (BP-I) is a serious condition. Although lithium is a benchmark treatment and has shown effectiveness in adults for decades, no definitive efficacy or long-term safety studies had been performed in pediatric patients with BP-I.

This study provides evidence to support the efficacy of lithium in the acute treatment of youths with BP-I who are currently in a manic or mixed state. Lithium had an adverse effect profile that was acceptable for most patients. (Read the full article)

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

T. Michael O'Shea
Jul 1, 1999; 104:15-21
ARTICLES

Title: Could Viagra, Cialis Work Largely by Placebo Effect?
Category: Health News
Created: 3/26/2020 12:00:00 AM
Last Editorial Review: 3/27/2020 12:00:00 AM

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 10⁸ CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 10⁹ CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 10⁸-CFU standard dose (n = 50) or a ≥2 x 10⁹-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

Governments have taken to announcing monetary compensation for victims' kin in cases of criminal acts as well, but it hardly masks their failure to impose the rule of law or bring about systemic improvements, says Harish Narasappa.

Interview with Gail Hayward, MA (Oxon) D.Phil MRCP MRCGP, author of Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults: A Randomized Clinical Trial