¿Influye la comunicación con el paciente sobre la kinesiofobia? Una revisión sistemática / Does patient communication influence kinesiophobia? A systematic review

El objetivo de la presente revisión sistemática consistió en determinar el efecto de la comunicación en el ámbito sanitario sobre la kinesiofobia. Para ello, se realizó una búsqueda bibliográfica en siete bases de datos entre noviembre de 2022 y febrero de 2023. La revisión se efectuó acorde a la declaración Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) y para el análisis de la calidad metodológica se utilizaron: la escala Physiotherapy Evidence Database (PEDro), los criterios de Van Tulder y el análisis del riesgo de sesgo de la Colaboración Cochrane. Se incluyeron un total de 13 artículos que presentaron una calidad metodológica media de 7,1 sobre 10. Se obtuvieron resultados significativos para al menos una variable (kinesiofobia, discapacidad o nivel de actividad física) en 12 trabajos. Existe evidencia sólida de que la comunicación puede influir sobre la kinesiofobia del sujeto. Es más probable que esta influencia ocurra en un sentido negativo o discapacitante, pero también puede actuar en sentido positivo disminuyendo la misma. (AU)

The aim of the present systematic review was to determine the effect of communication in the health care setting on kinesiophobia. To this end, a literature search was conducted in seven databases between November 2022 and February 2023. The review was carried out following the PRISMA statement and for the analysis of methodological quality we used: PEDro Scale, Van Tulder criteria and risk of bias analysis of the Cochrane Collaboration. A total of 13 articles were included with a mean methodological quality of 7.1 out of 10. Significant results were obtained for at least one variable (kinesiophobia, disability or level of physical activity) in 12 articles. There is strong evidence that communication can influence a subject's kinesiophobia. This influence is most likely to be in a negative or disabling sense, but it can also act in a positive sense by decreasing it. (AU)

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalised Anxiety.

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed as many patients do not respond to current agents or experience unwanted side-effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalised anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic 'lorazepam' or 'saline'. Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham 'lorazepam' reported significant positive expectations of reduced anxiety (p = 0.001) but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (p's > 0.350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function, or behaviour in line with a Bayesian predictive coding framework, attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

Which portion of physiotherapy treatments' effect is attributable to contextual effects in people with musculoskeletal pain?: A meta-analysis of randomised placebo-controlled trials.

OBJECTIVE: To quantify the proportion attributable to contextual effects of physical therapy interventions for musculoskeletal pain. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched Ovid, MEDLINE, EMBASE, CINAHL, Scopus, PEDro, Cochrane Controlled Trials Registry, and SPORTDiscus databases from inception to April 2023. STUDY SELECTION CRITERIA: Randomized placebo-controlled trials evaluating the effect of physical therapy interventions on musculoskeletal pain. DATA SYNTHESIS: Risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials (ROB 2.0). The proportion of physical therapy interventions effect that is explained by contextual effects was calculated, and a quantitative summary of the data from the studies was conducted using the random-effects inverse-variance model (Hartung-Knapp-Sidik-Jonkman method). RESULTS: Sixty-eight studies were included in the systematic review (participants: n=5,238), and 54 placebo-controlled trials informed our meta-analysis (participants: n=3,793). Physical therapy interventions included soft tissue techniques, mobilization, manipulation, taping, exercise therapy and dry needling. Placebo interventions included manual, non-manual interventions, or both. The proportion attributable to contextual effects of mobilization accounted for 88% of the immediate overall treatment effect for pain intensity (PCE=0.88, 95%CI 0.57-1.20). In exercise therapy, contextual effects accounted for 46% of the overall treatment effect for pain intensity (PCE=0.46, 95%CI 0.41-0.52). Contextual effects in manipulation excelled in short-term pain relief (PCE=0.81, 95%CI 0.62-1.01) and in mobilization in long-term effects (PCE=0.86, 95%CI 0.76-0.96). In taping, contextual effects accounted for 64% of disability improvement (PCE=0.64, 95%CI 0.48-0.80). CONCLUSION: The outcomes of physical therapy interventions for musculoskeletal pain were significantly influenced by contextual effects. Boosting contextual effects consciously to enhance therapeutic outcomes represents an ethical opportunity that could benefit patients.

The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.

Introduction: Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers' singular positive nonverbal behaviours (NBs) on pain reports. Methods: Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups. Results: There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation. Discussion: Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream. Conclusion: No NB of caregivers is more effective in reducing pain. Caregivers' NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.

Ecocebo: How the interaction between environment and drug effects may improve pharmacotherapy outcomes.

This narrative review describes the research on the effects of the association between environmental context and medications, suggesting the benefit of specific design interventions in adjunction to pharmacotherapy. The literature on Evidence-Based Design (EBD) studies and Neuro-Architecture show how contact with light, nature, and specific physical features of urban and interior architecture may enhance the effects of analgesic, anxiolytics, and antidepressant drugs. This interaction mirrors those already known between psychedelics, drugs of abuse, and setting. Considering that the physical feature of space is a component of the complex placebo configuration, the aim is to highlight those elements of built or natural space that may help to improve drug response in terms of efficacy, tolerability, safety, and compliance. Ecocebo, the integration of design approaches such as EBD and Neuro-Architecture may thus contribute to a more efficient, cost-sensitive, and sustainable pharmacotherapy.

Dravet syndrome seizure frequency and clustering: Placebo-treated patients in clinical trials.

OBJECTIVE: Dravet syndrome is a rare developmental epilepsy syndrome associated with severe, treatment-resistant seizures. Since seizures and seizure clusters are linked to morbidity, reduced quality of life, and premature mortality, a greater understanding of these outcomes could improve trial designs. This analysis explored seizure types, seizure clusters, and factors affecting seizure cluster variability in Dravet syndrome patients. METHODS: Pooled post-hoc analyses were performed on data from placebo-treated patients in GWPCARE 1B and GWPCARE 2 randomized controlled phase III trials comparing cannabidiol and placebo in Dravet syndrome patients aged 2-18 years. Multivariate stepwise analysis of covariance of log-transformed convulsive seizure cluster frequency was performed, body weight and body mass index z-scores were calculated, and incidence of adverse events was assessed. Data were summarized in three age groups. RESULTS: We analyzed 124 placebo-treated patients across both studies (2-5 years: n = 35; 6-12 years: n = 52; 13-18 years: n = 37). Generalized tonic-clonic seizures followed by myoclonic seizures were the most frequent seizure types. Mean and median convulsive seizure cluster frequency overall decreased between baseline and maintenance period but did not change significantly during the latter; variation in convulsive seizure cluster frequency was observed across age groups. Multivariate analysis suggested correlations between convulsive seizure cluster frequency and age (positive), and body mass index (BMI) (negative). INTERPRETATION: Post-hoc analyses suggested that potential relationships could exist between BMI, age and convulsive seizure cluster variation. Results suggested that seizure cluster frequency may be a valuable outcome in future trials. Further research is needed to confirm our findings.

Single-arm meta-analysis of drug response in placebo-controlled versus active-controlled antipsychotic drug trials in schizophrenia.

Antipsychotic drug efficacy may vary in placebo-controlled and active-controlled trials. The study aims to investigate the performance of antipsychotics in these two different study designs using single-arm meta-analysis. We included randomized controlled trials (RCTs) comparing second-generation antipsychotics with placebo or other antipsychotics from our previous systematic reviews and updated the results with the search on Cochrane Schizophrenia Group register until March 06, 2022. The outcomes were the differences in the change of overall, positive and negative symptoms of schizophrenia, and the difference in study discontinuation between placebo-controlled and head-to-head trials. Random-effects single-arm meta-analysis and subgroup test were conducted to examine the differences in each outcome. A total of 208 RCTs (n = 42,159) were included in the analysis. Of these, 85 trials with 17,056 participants were placebo-controlled, while the remaining were head-to-head trials. Antipsychotics in head-to-head trials demonstrated a significantly greater improvement in overall symptoms (MC -23.58; 95 % CI -25.33, -21.83) compared to antipsychotics in placebo-controlled trials (MC -16.74; 95 % CI -17.80, -15.69; p < 0.0001). Similar findings were observed for positive symptoms, negative symptoms, study discontinuation and sensitivity analyses. Notably, when assessing antipsychotics individually, the same antipsychotic consistently demonstrated superior performance in head-to-head trials compared to placebo-controlled trials. In conclusion, antipsychotics in head-to-head trials presented a considerable efficacy superiority compared to those in placebo-controlled trials. Moreover, the efficacy of the same antipsychotics varied depending on the study design. Future trials should carefully consider the methodology and employ strategies to mitigate the potential for overestimation or underestimation of treatment efficacy.

A methodological review of randomised n-of-1 trials.

BACKGROUND: n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions. METHODS: Databases and clinical trials registries were searched for articles including "n-of-1" in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables. RESULTS: We identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo controlled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient-reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions. CONCLUSIONS: n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies. TRIAL REGISTRATION: Not applicable.

Declaration of Helsinki: ethical norm in pursuit of common global goals.

The World Medical Association's Declaration of Helsinki is in the process of being revised. The following amendments are recommended to be incorporated in pursuit of the common goal of promoting health for all. 1. Data-driven research that facilitates broad informed consent and dynamic consent, assuring participant's rights, and the sharing of individual participant data (IPD) and research results to promote open science and generate social value. 2. Risk minimisation in a placebo-controlled study and post-trial access to the best-proven interventions for all who need them. 3. A future-oriented research framework for co-creation with all the relevant stakeholders.

Investigating the effects of dopamine on short- and long-latency afferent inhibition.

Short- and long-latency afferent inhibition (SAI and LAI respectively) are phenomenon whereby the motor evoked potential induced by transcranial magnetic stimulation (TMS) is inhibited by a sensory afferent volley consequent to nerve stimulation. It remains unclear whether dopamine participates in the genesis or modulation of SAI and LAI. The present study aimed to determine if SAI and LAI are modulated by levodopa (l-DOPA). In this placebo-controlled, double-anonymized study Apo-Levocarb (100 mg l-DOPA in combination with 25 mg carbidopa) and a placebo were administered to 32 adult males (mean age 24 ± 3 years) in two separate sessions. SAI and LAI were evoked by stimulating the median nerve and delivering single-pulse TMS over the motor hotspot corresponding to the first dorsal interosseous muscle of the right hand. SAI and LAI were quantified before and 1 h following ingestion of drug or placebo corresponding to the peak plasma concentration of Apo-Levocarb. The results indicate that Apo-Levocarb increases SAI and does not significantly alter LAI. These findings support literature demonstrating increased SAI following exogenous dopamine administration in neurodegenerative disorders. KEY POINTS: Short- and long-latency afferent inhibition (SAI and LAI respectively) are measures of corticospinal excitability evoked using transcranial magnetic stimulation. SAI and LAI are reduced in conditions such as Parkinson's disease which suggests dopamine may be involved in the mechanism of afferent inhibition. 125 mg of Apo-Levocarb (100 mg dopamine) increases SAI but not LAI. This study increases our understanding of the pharmacological mechanism of SAI and LAI.

Oral dydrogesterone for prevention of miscarriage in threatened miscarriage: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage. METHODS: A randomized, controlled trial study was conducted among pregnant Thai women at the gestational age of six to less than 20 weeks who visited King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand with threatened miscarriage from August 2021 to August 2022. These pregnant women were randomized to receive oral dydrogesterone 20 mg per day or placebo twice a day until one week after vaginal bleeding stopped or otherwise for a maximum of six weeks. RESULTS: A total of 100 pregnancies were recruited. Fifty of them were assigned to receive oral dydrogesterone and 50 were assigned to receive placebo. The rate of continuing pregnancy beyond 20 weeks of gestational age was 90.0% (45 out of 50 women) in the dydrogesterone group and 86.0% (43 out of 50 women) in the placebo group (p = 0.538). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Oral dydrogesterone 20 mg/day could not prevent miscarriages in women with threatened miscarriage.

Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs-a pilot study.

Introduction: Cannabinoids show great therapeutic potential, but their effect on anesthesia still remains unclear. Use of chronic recreational Cannabis in humans undergoing anesthetic procedures tends to require a higher dose when compared to non-users. On the other hand, studies on rodents and dogs have shown that cannabinoid agonists may potentiate certain anesthetics. This contrast of effects possibly occurs due to different time lengths of administration of different phytocannabinoids at different doses, and their distinct effects on the Endocannabinoid System, which is also affected by anesthetics such as propofol and isoflurane. Methods: Twenty-seven healthy male dogs, client-owned, ranging from 1 to 7 years, and from 5 to 35 kg were selected, mean weight 15.03±7.39 kg, with owners volunteering their animals to participate in the research performed in the Federal University of Santa Catarina (UFSC). Dogs were randomized into 3 groups. The Control Group (CON, n = 9), receiving only Extra Virgin Olive Oil, the same oil-base used in the treatment groups. Group 2 (G2, n = 9) received 2 mg/kg of total phytocannabinoids, and Group 3 (G3, n = 9) received 6 mg/kg of total phytocannabinoids. All groups received their treatments transmucosally, 75 min before their induction with propofol. Heart and respiratory rate, blood pressure, temperature and sedation were evaluated prior to, and at 30, 60, and 75 min after administration of the fsCBD-rich extract or Placebo extract. Preanesthetic medication protocol was also included across all treatment groups, 15 min before induction. Parametric data was analyzed with one-way ANOVA, followed by Student-Newman-Keuls (SNK) if significant statistical differences were found. Non-parametric data was analyzed using Friedman's test, followed by Dunn test for comparisons between all timepoints in the same group. Kruskal-Wallis followed by Dunn was utilized for between groups comparisons. Propofol dose necessary for induction was analyzed through One-way ANOVA followed by Tukey's Multiple Comparisons Test, using Instat by Graphpad, and differences were considered statistically significant when p < 0.05. Our analysis assessed if statistical significance was present between time points in the same group, and between groups in the same time points. Results: In our study, 6 mg/kg of total phytocannabinoids were able to reduce the dose of propofol necessary for induction by 23% when compared to the control group. The fsCBD-rich extract did not produce significant sedation within or between groups, although statistically significant differences in heart rate and systolic blood pressure were found. Discussion: Our findings indicate that phytocannabinoids could be an adjunct option in anesthesia, although further research is necessary to better confirm this data. Additionally, further research is needed to determine the best dosage, delivery method, time for administration, ideal molecular profile for desired effects, safety, drug-drug interactions, and transurgical effects.

Effects of vaginal progesterone and placebo on preterm birth and antenatal outcomes in women with singleton pregnancies and short cervix on ultrasound: a meta-analysis.

Background: Vaginal progesterone in preterm birth and adverse outcomes caused by cervical insufficiency remains controversial. To address it, the effect of vaginal progesterone on preterm delivery and perinatal outcome of single pregnancy women with short cervix (less than 25 mm) was systematically evaluated by meta-analysis. Methods: "Vaginal progesterone," "placebo," "ultrasound," "cervix," "singleton pregnancy," "preterm birth," and "antenatal outcomes" were entered to screen clinical studies PubMed, Embase, and the Chinese Biomedical Literature Database (CBM). The study population consisted of women with singleton pregnancies and a short cervix on ultrasound, and were assigned into the progesterone group (n = 1,368) and the placebo group (n = 1,373). Treatment began after the patient was diagnosed with short cervix until delivery. Neonatal survival rate, Neonatal Intensive Care Unit (NICU) admission rate, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), neonatal mortality, and birth weight <1,500 g were analyzed. Results: A total of 8 articles, totaling 2,741 study subjects, were enrolled. The progesterone group exhibited an obvious reduced rate of preterm birth at <34 weeks (OR = 0.67, 95% CI: 0.53∼0.84; Z = 3.53, P = 0.004), preterm birth at <32 weeks (OR = 0.46, 95% CI: 0.28∼0.77; Z = 2.99, P = 0.003), NICU admission rate (OR = 0.45, 95% CI: 0.30∼0.66; Z = 0.15, P < 0.0001), RDS rate (OR = 0.42, 95% CI: 0.28∼0.63; Z = 4.25, P < 0.0001), IVH incidence rate (OR = 0.40, 95% CI: 0.17∼0.95; Z = 2.08, P = 0.04), neonatal mortality (OR = 0.25, 95% CI: 0.13∼0.46; Z = 4.39, P < 0.0001), and proportion of neonates with birth weight < 1,500 g (OR = 0.45, 95% CI: 0.32∼0.64; Z = 4.50, P < 0.0001). Conclusion: Vaginal progesterone lowered the incidences of preterm birth and adverse pregnancy outcomes in women with singleton pregnancies and a short cervix.

Investigating the Relationship Between Cannabis Expectancies and Anxiety, Depression, and Pain Responses After Acute Flower and Edible Cannabis Use.

Objective: Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants' cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. Methods: Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. Results: Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. Conclusions: Cannabis users' expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.

Individualized homeopathic medicines in preventing the progression from pre-diabetes to diabetes: A double-blind, randomized, placebo-controlled, parallel-arm trial.

CONTEXT: Pre-diabetes is a significant public health problem worldwide. India has a very high rate of progression from pre-diabetes to diabetes, 75-78 per thousand persons per year. OBJECTIVE: To study the efficacy of individualized homeopathic medicinal products (HMPs) against placebos in preventing the progression from pre-diabetes to diabetes. DESIGN: Six-month, double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. SETTING: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India. PATIENTS: Sixty participants with pre-diabetes. INTERVENTIONS: Verum: HMPs plus yoga therapy (YT; n = 30); control: identical-looking placebos plus YT (n = 30). MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion of participants progressing from pre-diabetes to diabetes, measured after three and six months. Secondary outcomes comprised of fasting blood glucose (FBS), oral glucose tolerance test (OGTT), glycated hemoglobin percentage (HbA1c%), lipid profile, liver enzymes (alanine transaminase, aspartate transaminase), urea and creatinine, and Measure Yourself Medical Outcome Profile version 2 (MYMOP-2); all measured after 3 and 6 months. RESULTS: The proportion of participants converted from pre-diabetics to diabetics (n/N; n = diabetics, N = prediabetics) was significantly less in the verum group than control: HbA1C% (month 3: verum - 2/30 versus control - 11/30, p = 0.003; month 6: 3/30 vs. 2/30, p = 0.008), OGTT (month 3: 0/30 vs. 8/30, p = 0.015; month 6: 0/30 vs. 1/30, p = 0.008), but not according to FBS (month 3: 1/30 vs. 1/30, p = 0.779; month 6: 1/30 vs. 3/30, p = 0.469). Several secondary outcomes also revealed significant improvements in the verum group than in placebo: HbA1C% (p < 0.001), OGTT (p = 0.001), serum ALT (p = 0.031), creatinine (p = 0.012), and MYMOP-2 profile scores (p < 0.001). Sulphur, Bryonia alba, and Thuja occidentalis were the most frequently indicated medicines. Thus, HMPs outperformed placebos by successfully preventing the progression of pre-diabetes to diabetes. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2022/04/042,026; UTN: U1111-1277-0021.

Effects of a diverse prebiotic fibre supplement on HbA1c, insulin sensitivity, and inflammatory biomarkers in pre-diabetes: a pilot placebo-controlled randomised clinical trial.

Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid, and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (n = 33) and placebo (n = 33) interventions. Participants in the treatment arm consumed 20g per day of a diverse prebiotic fibre supplement and participants in the placebo arm consumed 2g per day of cellulose for 24 weeks. A total of 51 and 48 participants completed the week 16 and week 24 visits, respectively. The intervention was well-tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group, but only in participants with lower baseline HbA1c levels (<6% HbA1c) (P = 0.05; treatment -0.17 ± 0.27 vs. placebo 0.07 ± 0.29, mean ± SD). Within the whole cohort, we showed significant improvements in insulin sensitivity (P = 0.03; treatment 1.62 ± 5.79 v. placebo -0.77 ± 2.11), and C-reactive protein (P FWE = 0.03; treatment -2.02 ± 6.42 vs placebo 0.94 ± 2.28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.

Equivalence of single and standard doses of antenatal corticosteroids for late preterm neonatal outcomes: insights from a secondary analysis.

BACKGROUND: The recent paradigm shift of treating individuals at risk of late preterm birth with antenatal corticosteroids warrants an assessment of the effect of single dosage. OBJECTIVE: To compare outcomes of neonates born in the late preterm period (34.0-36.6 weeks) after a single dose of antenatal corticosteroids vs placebo. STUDY DESIGN: We performed a secondary analysis of the Antenatal Late Preterm Steroids trial. All individuals enrolled in the parent trial who received only a single dose of either antenatal corticosteroids or placebo and delivered within 24 hours were included. Primary outcome was a composite of respiratory support at 72 hours, including continuous positive airway pressure or high-flow nasal cannula ≥2 hours, oxygen with an inspired fraction of ≥30% for ≥4 hours, or mechanical ventilation. RESULTS: Of the 2831 individuals in the parent trial, 1083 (38.3%) met inclusion criteria; of them, 539 (49.8%) received a single dose of antenatal corticosteroids and 544 (50.2%) a single placebo dose. The placebo and antenatal corticosteroids groups had similar demographic and clinical characteristics. There was no difference in the rate of the primary respiratory outcome (adjusted risk ratio, 1.12; 95% confidence interval, 0.85-1.47) or in the rate of respiratory distress syndrome (adjusted risk ratio, 1.47; 95% confidence interval, 0.95-2.26) between those who received a single antenatal corticosteroids dose and placebo. An exploratory stratification by randomization-to-delivery intervals of 12-hour increments also showed no association with lower primary respiratory outcome rates. CONCLUSION: In individuals with late preterm birth pregnancies who received antenatal corticosteroids and delivered before a second dose, there were no differences in neonatal respiratory morbidities compared with placebo. However, this study is not powered to detect treatment efficacy.

Hymenoptera Venom Immunotherapy Meets Factitious Disorder.

Factitious disorder on self is a psychiatric disorder in which individuals fabricate or induce signs or symptoms of a disease. Factitious anaphylaxis, with symptoms suggestive of a life-threatening allergic reaction, is extremely rare. Several cases of factitious disorder reactions during allergen immunotherapy for airborne allergens have been reported. We report the case of a young female patient who presented factitious anaphylaxis during venom immunotherapy to vespid venom extract. Symptoms of stridor, dyspnea, coughing and loss of consciousness were observed during the built-up phase of venom immunotherapy, mimicking allergic reactions to the venom extracts. Diagnosis of factitious disorder prompted the discontinuation of venom immunotherapy.

Open-label placebos enhance test performance and reduce anxiety in learner drivers: a randomized controlled trial.

Passing the driving school test can be very challenging, especially in big cities, where up to 52% of all students fail this test. Consequently, many learner drivers experience stress and anxiety. For some learner drivers these feelings can be extreme and negatively affect the performance in the driving test. Different strategies to face anxiety and stress are known, including, for example, psychological or pharmacological approaches and even placebo pills. Recent intriguing findings have also demonstrated that placebos without deception, so-called open-label placebos, successfully reduce anxiety. Here we aimed to test effects of this novel treatment for learner drivers. We investigated whether open-label placebos affect test performance and feelings of anxiety in learner drivers. Sixty-eight healthy participants (mean age 21.94 years, 26 females) were randomized into two groups. The open-label placebo group received placebo pills two weeks before the driving test (two pills each day). The control group received no treatment. Results revealed that the open-label placebo group experienced significantly less anxiety than the control group before the test (measured with the State-Trait-Anxiety-Inventory, STAI-S, and the German Test Anxiety Inventory, PAF). Moreover, in the open-label placebo group less learner drivers failed the driving test (29.41% vs. 52.95%). The results suggest that open-label placebos may provide an ethical unproblematic way to experience less anxiety and might also enhance the probability to pass the driving test. We discuss possible mechanisms of open-label placebos and limitations of our findings.

Comparing the efficacy of fluconazole and cryotherapy Versus cryotherapy alone on treating cutaneous leishmaniasis: a triple-blind randomized clinical trial.

OBJECTIVE: Cutaneous Leishmaniasis (CL) is one of the highly prevalent endemic diseases in the Middle East. The disease is a complex skin infection imposing a heavy burden on many developing countries. This study aimed to evaluate the impact of adding oral fluconazole to topical cryotherapy on the treatment efficacy and time to achieve complete recovery of CL lesions. METHOD: This triple-blind randomized clinical trial included 52 participants with CL. Participants were allocated to receive either weekly cryotherapy with liquid nitrogen and oral fluconazole at a dose of 6 mg/kg daily at a maximum of 400 mg for 6 weeks as the interventional arm or weekly cryotherapy with liquid nitrogen plus the placebo for the same period of 6 weeks as the control arm. RESULTS: Fifty-two eligible participants enrolled the study, with a CL lesion count of 1 to 8 (mean 1.96), and served as the interventional (n = 28) and control (n = 24) arms. The trend of the mean surface area of the lesions was significantly decreasing in both arms (P < 0.001), with no statistically significant difference between arms (P = 0.133) or all assessed time point pairwise comparisons (P > 0.05). There was no significant difference between the treatment arms in terms of the end-point recovery status (P = 0.491) or the frequency of post-treatment secretion (P = 0.437). No adverse effect was observed. CONCLUSION: Despite a slightly higher reduction in the lesion surface in the cryotherapy and fluconazole treatment arm, the addition of fluconazole did not provide statistically significant therapeutic value to cryotherapy in the treatment of CL. However, with adjustment for the initial lesion size, the efficacy of the regimen in the interventional arm was more pronounced, though it was still insignificant.