Poor Evidence Research Articles

Trends of blood pressure and heart rate in normal pregnancies: a systematic review and meta-analysis

BackgroundCurrent reference ranges for blood pressure and heart rate throughout pregnancy have a poor evidence base.MethodsThis is a systematic review and meta-analysis. We included studies measuring blood pressure or heart rate from healthy pregnant women within defined gestational periods of 16 weeks or less. We analysed systolic blood pressure, diastolic blood pressure and heart rate by gestational age. We assessed effects of measurement year and method.ResultsWe included 39 studies undertaken in 1967–2017, containing 124,349 systolic measurements from 36,239 women, 124,291 diastolic measurements from 36,181 women and 10,948 heart rate measurements from 8317 women. Mean (95% CI) systolic blood pressure was lowest at 10 weeks gestation, 110.4 (108.5, 112.3) mmHg, rising to 116.0 (113.6, 118.4) mmHg at 40 weeks, mean (95% CI) change 5.6 (4.0, 7.2) mmHg. Mean (95% CI) diastolic blood pressure was lowest at 21 weeks gestation, 65.9 (64.2, 67.7) mmHg; rising to 72.8 (71.0, 74.6) mmHg at 40 weeks, mean (95% CI) change 6.9 (6.2, 7.5) mmHg. Mean (95% CI) heart rate rose from 79.3 (75.5, 83.1) beats/min at 10 weeks to 86.9 (82.2, 91.6) beats/min at 40 weeks gestation, mean (95% CI) change 7.6 (1.8, 13.4) beats/min. Studies using manual measurement reported higher diastolic blood pressures than studies using automated measurement, mean (95 CI) difference 4.9 (0.8, 8.9) mmHg. Diastolic blood pressure increased by 0.26 (95% CI 0.10–0.43) mmHg/year. Including only higher-quality studies had little effect on findings, with heterogeneity remaining high (I2 statistic > 50%).ConclusionsSignificant gestational blood pressure and heart rate changes occur that should be taken into account when assessing pregnant women. Commonly taught substantial decreases in blood pressure mid-pregnancy were not seen and heart rate increases were lower than previously thought. Manual and automated blood pressure measurement cannot be used interchangeably. Increases in diastolic blood pressure over the last half-century and differences between published studies show contemporary data are required to define current normal ranges.Study registrationPROSPERO CRD42014009673

Irritable bowel syndrome: how can symptoms and quality of life be improved with diet?

This article aims to review the current scientific evidence of dietary approaches to control the symptoms of irritable bowel syndrome (IBS). In the last decade, there was an important evolution in the study of the low fermentable oligo, di, mono-saccharides and polyols (FODMAP) diet (LFD). Current scientific evidence suggests a significant efficacy in the overall control of symptoms. LFD seems to be effective in improving quality of life. Recent studies suggest that LFD is effective and nutritionally well tolerated also in the long term, and longer adherence may contribute to greater effectiveness in improving depression. There is insufficient scientific evidence for the recommendation of gluten exclusion in IBS therapy, and some authors still suggest that the efficacy of this approach results from the limited ingestion of fructans. There is a promising efficacy of pre, pro, and symbiotic supplements, but there is no consensus on the most appropriate and effective strains in each case. Given the poor evidence and the pathophysiological variability of IBS, the interest of each therapeutic option should be always evaluated individually. Nevertheless, LFD is currently the dietary approach with a higher degree of scientific evidence.

Sport supplement use in Brazilian cyclists: Where is the information coming from?

Sport supplement use in Brazilian cyclists: Where is the information coming from?

The use of urethral bulking injections in post‐prostatectomy stress urinary incontinence: A narrative review of the literature

Post-prostatectomy stress urinary incontinence (PPI) is a common condition with significant impact on patient quality of life. With rising numbers of prostatectomies performed, recognition of incontinence during survivorship care is growing. With increasing hesitance of the use of suburethral mesh in females, urethral bulking injections in this patient population as a minimally invasive alternative to surgery are evaluated. This review aims to evaluate the existing evidence base for urethral bulking therapy in PPI and provide a summary of its efficacy, durability, and side-effect profile. A literature search of Medline/Pubmed and Cochrane databases was conducted to identify publications reporting the clinical outcomes of urethral bulking injections in patients with PPI, up to and including October 1st, 2018. Case reports, letters and reviews were excluded. We identified 25 studies that fit our inclusion criteria, comprised of one RCT, two large retrospective cohort studies, and 22 case series. The success rates reported varying widely from 13%-100% with reports of symptomatic control deterioration. Complication rates remain low. This review highlighted a poor performance using the more historic bulking agents (BA), and the lack of strong evidence with the more novel BA in PPI and discussed challenges regarding optimal patient selection and techniques. There exists poor clinical evidence base concerning the use of urethral bulking in PPI with few high-level studies and a significant lack of consistency between studies. Further study in this area is required to evaluate the role of BA in this patient population.

Salvage arthrodesis for failed first metatarsophalangeal joint arthroplasty: A network meta-analysis

BackgroundWe aim to provide an evidence-based literature review of salvage arthrodesis for failed first metatarsophalangeal joint arthroplasty with a network meta-analysis. MethodsA search of PubMed, Embase and Cochrane databases was conducted in December 2016 which identified 12 relevant articles out of 340 articles assessing the efficacy of salvage arthrodesis for failed joint arthroplasty of the first metatarsophalangeal joint. The 12 studies were assigned a level of evidence (I–V) and interventions were graded a level of recommendation (A–C, I) in support of or against the treatment modality. ResultsThere is fair evidence (grade B) to support salvage arthrodesis with structural bone graft. There is poor evidence (grade C) for salvage arthrodesis without bone graft. There was no good evidence (grade A) to recommend either intervention. Meta-analysis showed that salvage arthrodesis resulted in improved functional outcome over time. ConclusionsSalvage arthrodesis showed good bone union rates and patient satisfaction.Level of Clinical Evidence: III – Systematic Review of Level III studies.

The impact of surgical therapies for inflammatory bowel disease on female fertility.

The impact of surgical therapies for inflammatory bowel disease on female fertility.

Comprehensive analysis of the HIV/AIDS policy-making process in Iran

BackgroundA huge number of people living with HIV/AIDS lives in developing countries. Thus, strengthening health systems in these countries is a prerequisite for improving disease prevention and care. After three decades of HIV/AIDS policy-making in Iran, conducting a comprehensive analysis on the policy process seems to be essential. In the present study, we aimed to analyse the HIV/AIDS policy-making process in Iran from 1986 to 2016.MethodsThis was a theory-based, multi-method and retrospective study. Interviewing of key informants and review of policy documents were concurrently conducted to identify and include further key informants (39 participants) and documents in the study. Framework analysis was used to analyse data.ResultsThe mean age of participants working in HIV/AIDS policy-making was of 48 years and participants had a mean of 14 years of working experience. Findings were categorized as contextual factors, content of HIV/AIDS policies, actors involved in the policy process, and evidence use in the policy process. Contextual effective factors on the HIV/AIDS policy-making process were categorized into five major themes, namely situational factors, structural-managerial factors, socioeconomic factors, political and legal factors, and international factors. The HIV/AIDS phenomenon in Iran was identified to be deeply rooted in the culture and traditions of society. The HIV/AIDS policy content has, recently, been crystallized in the national strategic plans and harm reduction policies of the country. The policy process has been conducted with a solely governmental top-down approach and is now suffering from poor evidence and lack of sufficient consideration of contextual factors.ConclusionsThere is a great need for change in the approach of government towards the issue and to increase the participation of non-governmental sectors and civil society in the policy process.

Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases.

A proportion of patients with fibrosing interstitial lung diseases (ILDs) develop a progressive phenotype characterised by decline in lung function, worsening quality of life and early mortality. Other than idiopathic pulmonary fibrosis (IPF), there are no approved drugs for fibrosing ILDs and a poor evidence base to support current treatments. Fibrosing ILDs with a progressive phenotype show commonalities in clinical behaviour and in the pathogenic mechanisms that drive disease worsening. Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD). In vitro data demonstrate that nintedanib inhibits several steps in the initiation and progression of lung fibrosis, including the release of pro-inflammatory and pro-fibrotic mediators, migration and differentiation of fibrocytes and fibroblasts, and deposition of extracellular matrix. Nintedanib also inhibits the proliferation of vascular cells. Studies in animal models with features of fibrosing ILDs such as IPF, SSc-ILD, rheumatoid arthritis-ILD, hypersensitivity pneumonitis and silicosis demonstrate that nintedanib has anti-fibrotic activity irrespective of the trigger for the lung pathology. This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis. A trial of nintedanib in patients with progressive fibrosing ILDs other than IPF (INBUILD) will report results in 2019.

Twice upon a time: The progression of canine visceral leishmaniasis in an Argentinean city.

Canine Visceral Leishmaniasis (CVL) prevalence, spatial distribution and associated factors were assessed in four locations in Iguazú department in 2014 and in Puerto Iguazú city again in 2018. The city areas were divided into a grid of 400x400m cells. All cells were sampled in 2014 and a random subsampling was developed in 2018. In each cell, five dogs clustered in a ‘critical scenario’ (prone to have vectors) were sampled. A rapid immunochromatographic dipstick was used to detect antibodies against Leishmania infantum, confirming by lymph node smears observation and PCR. For Puerto Iguazú, Generalized Linear Models (GLMs) were constructed considering environmental, dog and clinical variables. Pearson's Chi square and Fisher's exact tests were employed to evaluate the association between CVL, dog clinical signs and infestation with other parasites. Cartographic outputs were made and Moran's I indices were calculated as spatial autocorrelation indicators. CVL prevalence rates were 26.18% in 2014 and 17.50% in 2018. No associations were established in environmental models, but dog age and repellent use were significant when running 2014 dog models. Clinical models showed significant associations between seropositive dogs and ophthalmological, dermal signs and onychogryphosis in 2014. In 2018, only adenomegaly was associated. The results of global Moran´s I were not significant but regarding local analysis, six sites in 2014 and one in 2018 presented autocorrelation with neighboring sites. The decrease in CVL prevalence may be associated to transmission stabilization, which could explain the lack of associations with dog-related variables. Further, spatial distribution of CVL is a poor evidence for design of transmission control measures but could be important in case of intensive parasite circulation or when the first autochthonous cases appear. For control success, sensitivity of diagnostic methods, political will and adequate material resources remain critical. Modeling of multiple variables will be required to identify factors that drive disease stabilization/destabilization.

Dexmedetomidine Attenuates Lung Injury in Obstructive Jaundice Rats Through PI3K/Akt/HIF-1α Signaling Pathway

Obstructive jaundice (OJ) could seriously affect the biochemical and immune functions in the body. Up to now, there are still poor evidences about the role of dexmedetomidine in OJ. Male Wistar rats were divided into four groups: Sham operation group (Sham group, n=10), obstructive jaundice group (OJ group, n=10), OJ+dexmedetomidine group (D group, n=10), OJ+ dexmedetomidine+LY294002 group (DL group, n=10). The expressions of phospho-Akt(p-Akt), HIF-1α(hypoxia inducible factor-1α), Akt mRNA, HIF-1αmRNA, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in different groups were evaluated. The lung injury score was decreased in OJ group compared with that in DL group. The expression of the HIF-1α protein, p-Akt protein, Akt mRNA, and HIF-1α mRNA in OJ group were significantly increased (p <0.05) (vs. S group). Meanwhile, these protein molecular were significantly higher in the D group than that in OJ group (p <0.05). However, the mRNA expressions of these molecular in OJ group were significantly lower than that in D group (p <0.05). The concentrations of IL-6 and TNF-α in OJ group and D group was significantly up-regulated compared with that in S group (p<0.05). Meanwhile, IL-6 and TNF-α concentrations were significantly up-regulated in DL group compared with that in group D (p <0.05). The concentrations of IL-6 and TNF-α were significantly decreased in the D group and DL group compared with that in OJ group (p <0.05). Dexmedetomidine can attenuate lung injury in obstructive jaundice rats through PI3K/Akt/HIF-1α signaling pathway. Meanwhile, dexmedetomidine can reduce the concentrations of IL-6 and TNF-α in obstructive jaundice rats.

CHALLENGES IN TREATING HEMODIALYSIS-DEPENDENT PATIENTS WITH ACUTE MYOCARDIAL INFARCTION. A СLINICAL CASE

The clinical case reports a personalized expert approach to the management of a patient with myocardial infarction receiving programmed hemodialysis. The challenges facing by cardiologists with antiplatelet therapy, statin therapy, betablockers and renin-angiotensin-aldosterone system blockers as basic therapy have been discussed. The experience of performing coronary angiography with a limited dosage of the contrast agent followed by the stenting in the patient intolerant to unfractionated heparin is presented The complexity of post-puncture hemostasis before dialysis is highlighted. A particular attention has been paid to the existing difficulties in selecting rational loading doses of antiplatelet agents for these patients due to poor evidences on the elimination of clopidogrel metabolites from the blood flow.

Prescription Of analgesia in Emergency Medicine (POEM): a multicentre observational survey of pain relief in patients presenting with an isolated limb fracture and/or dislocation.

Acute pain is one of the most commonly cited reasons for attendance to the emergency department (ED), and the Royal College of Emergency Medicine (RCEM) Best Practice Guideline (2014) acknowledged that the current management of acute pain in UK EDs is inadequate and has a poor evidence base. The Prescription Of analgesia in Emergency Medicine (POEM) survey is a cross-sectional observational survey of consecutive patients presenting to 12 National Health Service (NHS) EDs with limb fracture and/or dislocation in England and Scotland and was carried out between 2015 and 2017. The primary outcome was to assess the adequacy of pain management in the ED against the recommendations in the RCEM Best Practice Guidelines. In all, 8346 patients were identified as attending the ED with a limb fracture and/or dislocation but adherence to RCEM guidelines could only be evaluated for the 4160 (49.8%) patients with a recorded pain score. Of these, 2409/4160 (57.9%) patients received appropriate pain relief, but only 1347 patients were also assessed within 20 minutes of their arrival in the ED. Therefore, according to the RCEM guidelines, only 16.1% (1347/8346) of all patients were assessed and had satisfactory pain management in the ED. The POEM survey has identified that pain relief for patients with an isolated limb fracture remains inadequate when strictly compared to the RCEM Best Practice Guidelines. However, we have found that some patients receive analgesia despite having no pain score recorded, while other analgesic modalities are provided that are not currently encompassed by the Best Practice Guidelines. Future iterations of these guidelines may wish to encompass the breadth of available modalities of pain relief and the whole patient journey. In addition, more work is needed to improve timely and repeated assessment of pain and its recording, which has been better achieved in some EDs than others.

P.043 Cannabis treatment in children with epilepsy: practices and attitudes of neurologists in Canada

Background: Cannabis has been shown to be an effective therapy for epilepsy in children with Dravet and Lennox-Gastaut syndrome. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about pediatric neurologists’ attitudes towards it. Methods: A 26-item online survey was distributed to 148 pediatric neurologists across Canada. Results: 56/148 neurologists responded and reported that over 600 children with epilepsy are currently taking cannabinoids. 34% of neurologists authorized cannabis to children, 38% referred children for authorization, and 29% did not authorize or refer their patients. Of those neurologists who referred, 76% referred to a community-based non-neurologist. The majority of physicians authorized cannabis to patients with Dravet syndrome (68%) and Lennox-Gastaut syndrome (64%). Cannabis was never authorized as a first-line treatment. 54% of neurologists stated that their patients were taking CBD alone, despite this option not being available in Canada. All physicians reported having at least one hesitation regarding cannabis, the most common ones being poor evidence (66%), poor quality control (52%), and cost (50%). Conclusions: The majority of Canadian pediatric neurologists use cannabis as a treatment for epilepsy in children. However, there appear to be knowledge gaps and hesitations.

Functional Brain Networks Underlying Evidence Integration and Delusions in Schizophrenia.

Integrating evidence that contradicts a belief is a fundamental aspect of belief revision and is closely linked to delusions in schizophrenia. In a previous functional magnetic resonance imaging (fMRI) study on healthy individuals, we identified functional brain networks underlying evidence integration as visual attention network (VsAN; dorsal anterior cingulate cortex, insula, occipital regions), default-mode network (DMN), and cognitive evaluation network (CEN; orbitofrontal cortex, inferior frontal gyrus, parietal cortex). In the current clinical fMRI study, we compared network-based activity during evidence integration between healthy controls (n = 41), nondelusional (n = 37), and delusional (n = 33) patients with schizophrenia, and related this activity to cognitive processing involved in evidence integration measured outside the scanner. Task-induced coordinated activation was measured using group-constrained principal component analysis for fMRI. Increased VsAN activation, reduced DMN deactivation, and reduced CEN activation were observed for schizophrenia, with this pattern being most pronounced for the delusional group. Importantly, poor evidence integration comprehensively measured outside the scanner was significantly associated with increased VsAN activation and reduced DMN deactivation when processing confirmatory evidence, and with reduced CEN activation when processing disconfirmatory evidence. This is the first comprehensive study of the functional brain networks associated with evidence integration in schizophrenia and highlights how an imbalance of functional brain networks responding to confirmatory and disconfirmatory evidence may underlie delusions in schizophrenia.

A systematic review of the psychometric properties of the cross-cultural adaptations and translations of the Prolapse Quality of Life (P-QoL) questionnaire.

Due to linguistic and cultural differences, there is a need to test the psychometrics of the translated versions of any patient-reported outcome measures. We investigated the psychometric properties of the Prolapse Quality of Life (P-QoL) questionnaire for non-English-speaking populations by conducting a systematic review of studies that examined the psychometric properties of non-English versions. We searched PubMed, Latin American and Caribbean Health Science Information Center (LILACS), and Science Direct databases for articles published in English up to February 2018. Methodological quality and quality of psychometric properties were assessed by two independent reviewers using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and validated quality assessment criteria. The two assessments were combined to produce the best level of evidence per language/translation. Sixteen articles in 13 languages were retrieved. Most (n = 9; 56.3%) were not rigorously translated or reported, and there was poor evidence for structural validity. Internal consistency was reported in all studies, and all studies had good methodological quality. There was fair evidence for construct and good to fair for criterion validity. Evidence for responsiveness was good, although this was evaluated only in three studies. There is limited evidence supporting the psychometric robustness of the original validation and translated versions of P-QoL. Cross-cultural adaptations are insufficient. Given this variability, the individual psychometrics of a translation must be considered prior to use. Responsiveness, measurement error, and cutoff values should also be assessed to increase the clinical utility and psychometric robustness of the translated versions.

Esophageal Compliance Quantifies Epithelial Remodeling in Pediatric Patients With Eosinophilic Esophagitis.

The management of eosinophilic esophagitis (EoE) relies on the severity of esophageal eosinophilia, yet there is poor evidence of its prediction of esophageal fibrotic remodeling and subsequent complications such as dysphagia, food impactions, or strictures. Functional luminal imaging planimetry (FLIP) has had limited use in pediatric patients to evaluate esophageal tissue mechanics. We aimed to standardize the FLIP technique and to measure esophageal compliance in children with EoE in comparison to controls. Subjects were enrolled into a prospective observational study and had FLIP performed at the time of endoscopy. We calculated esophageal distensibility and compliance for the total and segmental esophagus independently (ie, proximal, middle, and distal esophageal segments). We evaluated esophageal biopsies for eosinophilia and epithelial remodeling, calculated endoscopy scores, and documented patient symptoms. We enrolled 11 EoE and 12 controls subjects, aged 5 to 18 years old. While EoE subjects had lower esophageal compliance (P = 0.004) than controls, the difference in distensibility did not reach significance (P = 0.151). Epithelial remodeling severity was more strongly correlated with compliance than with distensibility. Epithelial remodeling scores ≥2 had a significant association with lower compliance both segmentally and in the entire esophagus (P = 0.029), but not with distensibility. Compliance measures were more sensitive in detecting subjects with remodeling score ≥2 than distensibility (79% vs 64%). Compliance is a more sensitive measure of esophageal epithelial remodeling in children compared to distensibility, and a more appropriate measure of esophageal tissue mechanics. Standardized placement of the FLIP catheter is important to accurately assess esophageal compliance.

Outcome of total hip and knee arthroplasty in HIV-infected patients: A systematic review.

Significant advances in the treatment of Human Immunodeficiency Virus (HIV) have occurred in recent times, with life expectancy now approaching the normal population. Therefore, patients with HIV will increasingly be undergoing joint replacement in the future, however concerns remain regarding the complications and outcome in this patient cohort. The aim was to assess the outcome of total hip and knee arthroplasty in HIV-infected patients. A systematic search of the literature using MOOSE reporting guidelines was performed to assess the outcome of hip and knee arthroplasty in HIV-infected patients. The primary outcome was infection. Secondary outcome was all-cause revision. The search yielded 552 results, of which 19 met the inclusion criteria, comprising 5.819.412 joint replacements. The overall quality of the studies was poor with significant heterogeneity between the studies. Infection and revision appeared to be more likely to occur in HIV positive patients compared to HIV negative patients. A subgroup analysis of four studies revealed a risk ratio of 3.31 and 2.25 for increase in infection and revision respectively in HIV positive patients. This systematic review and meta-analysis demonstrates an increased risk of infection and revision in HIV infected patients undergoing total hip and knee arthroplasty. However, these findings are based on poor quality evidence in a limited number of studies and need to be interpreted with caution. Further research should concentrate on large, well-designed, prospective studies, that control for co-morbidities and employ standardised outcome measures to allow for direct comparison.

Perspective: Variation in Guideline Implementation and Adherence Regarding Severe Traumatic Brain Injury Treatment: A CENTER-TBI Survey Study in Europe

Since 1990, the so-called “Brain Decade” was an exciting and promising period for the comprehension and tentative of treatment of the head trauma in order to improve the outcome of those devastating pathology.After several research and pre-clinical and clinical results a lot of protocols started with the concepts of brain autoregulation, brain perfusion, and neural rescue. Brain monitoring, also with the multimodal approach, transcranial Doppler, hypothermia, and neurosurgical techniques for brain decompression were also again updated.In 1992, the Lund protocol (LP) was the first guide published in Europe, for treatment of severe traumatic brain injury (s-TBi) (Grande, 2017). It was a theoretical approach in the field of brain pathophysiology. The main idea was on the way of cerebral perfusion pressure, fluid therapy, ventilation, sedation, nutrition, the use of vasopressors, and osmotherapy. The treatment is standardized, strictly applied with less need for individualization of the patient. Alternative European guidelines were published a few years later and were mainly based on meta-analytic approaches from clinical outcome studies. When introduced, they differed extensively from the LP. We still lack any large randomized outcome study comparing the European guidelines with other guidelines including the LP. From our point of view, there is poor evidence in favor of any of the guidelines used today. Despite the LP has not been changed since its introduction some components of the alternative guidelines have been proposed. As part of the “lucky Generation” of Neuroscientists, witnesses of the brain care evolution changing paradigms and evidence-based medicine era, in this chapter, we analyze and discuss the contents, results, and adherence of the current European protocols for head trauma.

A multi-national validity analysis of the self-perceived communication competence scale

ABSTRACTThe self-perceived communication competence (SPCC) measure has been used in over 50 published studies since 2000. McCroskey and McCroskey (1988. Self-report as an approach to measuring communication competence. Communication Research Reports, 5, 108–113. doi: 10.1080/08824098809359810) developed the measure to be used within the US college/university classroom. Despite its intended use, the measure is frequently used outside of the US and outside of the college/university setting without tests of measurement invariance. In fact, only four studies have performed tests of internal consistency on the measure since 2000, and each has found poor fit. Therefore, the purpose of this study was to assess the utility of the measure outside of its intended population. The measure was utilized to survey respondents from 12 countries and failed to yield acceptable fit statistics in all samples, showing poor evidence of construct validity.

Does Sex/Gender Play a Role in Placebo and Nocebo Effects? Conflicting Evidence From Clinical Trials and Experimental Studies.

Sex has been speculated to be a predictor of the placebo and nocebo effect for many years, but whether this holds true or not has rarely been investigated. We utilized a placebo literature database on various aspects of the genuine placebo/nocebo response. In 2015, we had extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine). These meta-analyses were screened for whether sex/gender differences had been noted to contribute to the placebo/nocebo effect: in only 3 such analyses female sex was associated with a higher placebo effect, indicating poor evidence for a contribution of sex to it in RCTs. This was updated with another set of meta-analyses for the current review, but did not change the overall conclusion. The same holds true for 18 meta-analyses investigating adverse event (nocebo) reporting in RCT in the placebo arm of trials. We also screened our database for papers referring to sex/gender and the placebo effect in experimental studies, and identified 28 papers reporting 29 experiments. Their results can be summarized as follows: (a) Despite higher sensitivity of pain in females, placebo analgesia is easier to elicit in males; (b) It appears that conditioning is effective specifically eliciting nocebo effects; (c) Conditioning works specifically well to elicit placebo and nocebo effects in females and with nausea; (d) Verbal suggestions are not sufficient to induce analgesia in women, but work in men. These results will be discussed with respect to the question why nausea and pain may be prone to be responsive to sex/gender differences, while other symptoms are less. Lastly, we will discuss the apparent discrepancy between RCT with low relevance of sex, and higher relevance of sex in specific experimental settings. We argue that the placebo response is predominantly the result of a conditioning (learning) response in females, while in males it predominantly may be generated via (verbal) manipulating of expectancies. In RCT therefore, the net outcome of the intervention may be the same despite different mechanisms generating the placebo effect between the sexes, while in experimental work when both pathways are separated and explicitly explored, such differences may surface.