Is Positive Communication Sufficient to Modulate Procedural Pain and Anxiety in the Emergency Department? A Randomized Controlled Trial.

OBJECTIVE: Research suggests that therapeutic communication could enhance patient comfort during medical procedures. Few studies have been conducted in clinical settings, with adequate blinding. Our hypothesis was that a positive message could lead to analgesia and anxiolysis, and that this effect would be enhanced by an empathetic interaction with the nurse performing the procedure, compared with an audio-taped message. This study aimed to modulate the contents and delivery vector of a message regarding peripheral intravenous catheter (PIC) placement in the emergency department (ED). METHODS: This study was a 2 + 2 randomized controlled trial registered on ClinicalTrials.gov (NCT03502655). A positive versus standard message was delivered through audio tape (double-blind) in the first phase ( N = 131) and through the nurse placing the catheter (single-blind) in the second phase ( N = 120). RESULTS: By design, low practitioner empathic behavior was observed in the first phase (median, 1 of 5 points). In the second phase, higher empathic behavior was observed in the positive than in the standard message (median, 2 versus 3, p < .001). Contrary to our hypothesis, the intervention did not affect pain or anxiety reports due to PIC placement in either phase (all p values > .2). CONCLUSIONS: The positive communication intervention did not impact pain or anxiety reports after PIC. There might have been a floor effect, with low PIC pain ratings in a context of moderate pain due to the presenting condition. Hence, such a therapeutic communication intervention might not be sufficient to modulate a mild procedural pain in the ED.

Analgesic and Anxiolytic Effects of Virtual Reality During Minor Procedures in an Emergency Department: A Randomized Controlled Study.

STUDY OBJECTIVE: We aimed to assess the analgesic and anxiolytic efficacy of distraction, a nonpharmacologic intervention provided by 3-dimensional (3D) virtual reality (VR) compared with that provided by 2-dimensional (2D) VR during minor emergency department (ED) procedures. METHODS: This randomized controlled study conducted in the ED of a teaching hospital included patients aged more than or equal to 18 years undergoing minor procedures. The patients watched the same computer-generated VR world either in 3D in a head-mounted display (intervention) or in 2D on a laptop screen (control). Our main outcomes were pain and anxiety during the procedure, assessed on a 100-mm visual analog scale. Secondary outcomes included the impression of telepresence in the computer-generated world assessed using the Igroup Presence Questionnaire, and the prevalence and intensity of cybersickness measured on a 100-mm visual analog scale. RESULTS: The final analysis included 117 patients. The differences in median procedural pain and anxiety levels between the 2D and 3D VR groups were not significant: -3 mm (95% confidence interval [CI] -14 to 8) and -4 mm (95% CI -15 to 3), respectively; the difference in telepresence was 2.0 point (95% CI 0 to 2.0), and the proportion difference of cybersickness was -4% (95% CI -22 to 14), with an intensity difference of -5 mm (95% CI -9 to 3). CONCLUSION: During minor procedures in adult patients in the ED, distraction by viewing a 3D virtual world in a head-mounted VR display did not result in lower average levels of procedural pain and anxiety than that by 2D viewing on a screen despite a higher sense of telepresence. There were no significant differences in the prevalence and intensity of cybersickness between the 2 groups.

Determinants of drug expenditure in the Swiss healthcare market in 2006.

BACKGROUND: Several measures are in force in Switzerland to control the cost of drugs, but are not effective enough. There are many determinants influencing these expenditures, related to treatments, markets, physicians, patients and regions, but their impact on costs is not clear. METHODS: We applied a Bayesian multilevel model with five levels to adjust for patients, drugs' market, and physicians 'characteristics, treatment type, and district (i.e. Swiss canton). We used data of the Swiss drugs' market in 2006, offering real choices for doctors and patients (multiple products for similar active substances), with a neutral position of pharmacists (no financial incentives). RESULTS: Variance partitioning of yearly drugs' cost per insured showed that market level (delivered substance) contributed to 76% of the variance, treatment level (delivered product) to 20%, whereas patients' and physicians' levels accounted for only 2% each, without significant differences between Swiss cantons. After adjusting for covariables at each level, the model explained about 51% of the variation at the market and 20% at the treatment levels. We found that older but substitutable drugs, generics, larger size of the market and physician's specialty were associated with lower expenditure, whereas drugs requiring a physician's prescription, the number of prescribers per patient, patient' age, male gender, and comorbidities increased expenditure. Our results show that for a specific medication the yearly cost of recently released drugs was 36 CHF higher than for similar and substitutable drugs introduced 15 years earlier, corresponding to one third of the average annual treatment cost observed in our dataset. Competition did not seem to be effective to reduce expenditure on the drug market. CONCLUSION: The main finding of this study is that recentness of drugs was associated with an increase in drug expenditure in 2006, even after adjustment for all non-controllable determinants. Further research is recommended to confirm those results with updated data.

Width of margins in phyllodes tumors of the breast: the controversy drags on?-a systematic review and meta-analysis.

PURPOSE: Phyllodes tumors (PT) of the breast are rare fibroepithelial neoplasms. Information is controversial in the literature regarding to the optimal surgical management. Most studies suggested margins of at least 10 mm while some recent studies suggested narrower margins without an increased risk of local recurrences (LR) and distant metastases (DM). The objective of this systematic review was to identify and compare studies that assessed these different practices. METHODS: A systematic review was performed through five databases up to April 2019. Studies exploring the association between the width of margins, subtypes of PT, and the LR and DM rates were considered for inclusion. A statistical model for analyzing sparse data and rare events was used. RESULTS: Thirteen studies met eligibility criteria and were selected. Considering a threshold of 10 mm (margins < 10 vs margins ≥ 10 mm), the 5-year incidence rate of LR was estimated to be 5.22 vs. 3.63 (diff. -1.59) per 100 person-years for benign PT, 9.60 vs. 7.33 (diff. -2.27) for borderline PT, and 28.58 vs. 21.84 (diff. -6.74) for malignant PT. For DM, it was estimated to be 0.88 vs. 0.86 (diff. -0.02) for benign PT, 1.61 vs. 1.74 (diff. 0.13) for borderline PT, and 4.80 vs 5.18 (diff. 0.38) for malignant PT. The data for a threshold of 1 mm were not sufficient to draw any conclusions. CONCLUSION: Irrespective of tumor grade, we found that DM was a rarer event than LR. Malignant PT had the highest incidence rate of LR and DM. This meta-analysis found a clear association between width of margins and LR rates. Whatever the tumor grade, surgical margins ≥ 10 mm guaranteed a lower risk of LR than margins < 10 mm. On the other hand, the width of margin did not influence the apparition of DM.

Interscalene brachial plexus block for surgical repair of clavicle fracture: a matched case-controlled study.

BACKGROUND: Innervation of the clavicle is complex and debated, with scarce data on the analgesic and clinical impact of regional anaesthesia after surgical repair of clavicle fracture. METHODS: In order to assess the analgesic efficiency of an interscalene brachial plexus block (ISB) for surgical repair of clavicle fracture, 50 consecutive patients scheduled for surgical fixation of middle/lateral clavicle fracture under general anaesthesia with ISB were prospectively enrolled. This cohort was compared to a historical control of 76 retrospective patients without regional block. The primary outcome was total intravenous morphine equivalent consumption at 2 postoperative hours. To assess the ISB impact, both an overall cohort analysis and a case-matched analysis with each ISB-treated patient matched to a Non-ISB-treated patient was performed. Matching employed a 1-to-1, nearest-neighbour approach using the Mahalanobis metric. RESULTS: In the overall cohort, patients with ISB had significantly lower i.v. morphine equivalent consumption at 2 postoperative hours (0.7 mg (95% CI 0.1 to 1.2) versus controls 8.8 mg (95% CI 7.1 to 10.4); P <  0.0001). These results persisted after case-matching the cohorts (mean difference for the primary outcome: 8.3 mg (95% CI 6.5 to 10.0); P <  0.001). CONCLUSIONS: ISB provides effective analgesia after surgical fixation of middle and lateral clavicle fracture. These results should help physicians in establishing an analgesic strategy for this type of surgery. Further research is needed to identify the optimal regional technique for medial third clavicle fractures and the clinically relevant contributions of the cervical and brachial plexus. TRIAL REGISTRATION: Clinicaltrials.gov - NCT02565342, October 1st 2015.

Fetal Anthropometric Features: A Postmortem Study of Fetuses After the Termination of Pregnancy for Psychosocial Reasons Between 12 and 20 Gestational Weeks.

INTRODUCTION: Reference ranges in fetal postmortem anthropometric data derive from heterogeneous studies and rely on data obtained after intrauterine fetal death and abortion, which may introduce bias in the reported fetal growth parameters. We report anthropometric findings in fetuses with the least variation due to cause of death or developmental anomalies. METHODS: We analyzed fetuses after the termination of pregnancy for psychosocial reasons. The external measurements, X-ray dimensions, and body and organ weights were recorded as well as the placenta weight. A thorough and standardized postmortem analysis allowed the design of 2 different groups. Group 1 was composed of fetuses (1) born to mothers with no relevant obstetrical history, (2) no X-ray anomaly, (3) no abnormal autopsy findings, and (4) unremarkable placenta histology. An anomaly in any of these 4 entities moved the fetuses to Group 2. For reference ranges and graph construction, a well-designed statistical methodology was applied. RESULTS: A total of 335 fetuses were analyzed during an 11-year period. Group 1 comprised 232 fetuses aged 12 to 20 gestational weeks, whereas 103 fetuses were considered in Group 2. Comparison between the 2 groups showed almost no differences. Only the Group 1 results were submitted to statistical analysis, and reference ranges and graphs were constructed. CONCLUSIONS: To the best of our knowledge, we provide in this study the first anthropometric references established from almost normal fetuses, albeit for a limited fetal timeframe.

Fascia iliaca block in the emergency department for hip fracture: a randomized, controlled, double-blind trial.

BACKGROUND: Hip fracture causes moderate to severe pain and while fascia iliaca block has been reported to provide analgesic benefit, most previous trials were unblinded, with subsequent high risks of performance, selection and detection biases. In this randomized, control double-blind trial, we tested the hypothesis that a fascia iliaca block provides effective analgesia for patients suffering from hip fracture. METHODS: Thirty ASA I-III hip fracture patients over 70 years old, who received prehospital morphine, were randomized to receive either a fascia iliaca block using 30 ml of bupivacaine 0.5% with epinephrine 1:200,000 or a sham injection with normal saline. The fascia iliaca block was administered by emergency medicine physicians trained to perform an anatomic landmark-based technique. The primary outcome was the comparison between groups of the longitudinal pain score profiles at rest over the first 45 min following the procedure (numeric rating scale, 0-10). Secondary outcomes included the longitudinal pain score profiles on movement and the comparison over 4 h, 8 h, 12 h, and 24 h after the procedure, along with cumulative intravenous morphine consumption at 24 h. RESULTS: At baseline, the fascia iliaca group had a lower mean pain score than the sham injection group, both at rest (difference = - 0.9, 95%CI [- 2.4, 0.5]) and on movement (difference = - 0.9, 95%CI [- 2.7; 0.9]). These differences remained 45 min after the procedure and the two longitudinal pain score profiles were parallel both for patients at rest and on movement (test of parallelism for patients at rest p = 0.53 and on movement p = 0.45). The same parallel change in pain scores over time was observed over 24 h of follow-up (test of parallelism for patients at rest p = 0.82 and on movement p = 0.12). These results were confirmed after adjustment for gender, ASA score, and cumulative sums of intravenous morphine received pre-procedure and during-follow-up. In addition, there was no difference between the two groups in total cumulative intravenous morphine consumption at 24 h. CONCLUSION: Fascia iliaca block following anatomic landmarks may not provide supplementary analgesia for patients suffering from hip fracture, when low pain scores are reported after prehospital morphine. Additional larger trials will help reach definitive conclusion. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov - NCT02433548 . The study was registered retrospectively.

Meta-analysis of rare events under the assumption of a homogeneous treatment effect.

We studied the performance of several meta-analysis methods in rare event settings, when the treatment effect is assumed to be homogeneous and baseline prevalences are either homogeneous or heterogeneous. We conducted extensive simulations that included the three most common effect sizes with count data: the odds ratio, the relative risk, and the risk difference. We investigated several important scenarios by varying the level of rareness, the value of the trials' arms unbalance, and the size of the treatment effect. We found that the Mantel-Haenszel method and the Binomial regression model provided the best results across all the scenarios investigated. The Peto method performed satisfactorily only when the true effect size was not too large and the degree of unbalance moderate. Inverse variance was the least reliable method. The use of a continuity correction factor slightly improved the performance of the inverse variance method but deteriorated that of the Peto and Mantel-Haenszel methods. A method based on median unbiased estimators of the probabilities provided similar results to those obtained when using the inverse variance method with a continuity correction. Therefore, when the treatment effect can be assumed to be homogeneous and for either homogeneous or heterogeneous baseline prevalences, we highly recommend using the Mantel-Haenszel method without continuity correction (for all the effect sizes) or the Binomial regression model (for the odds ratio only) to meta-analyze the data.

Use of oscillometric devices in atrial fibrillation: a comparison of three devices and invasive blood pressure measurement.

BACKGROUND: The use of automated (oscillometric) blood pressure (BP) devices is not validated in atrial fibrillation (AF) patients. OBJECTIVES: To assess the reliability of three oscillometric BP devices, and the agreement with invasive arterial blood pressure(IBP) in AF patients. METHODS: 48 AF patients with randomized sequences of 10 consecutive BP measurements with two pairs of devices: (1) OmronR7™(wrist) and OmronHEM907™(arm); (2) OmronR7™ and Microlife WatchBPhome(arm). Reliability and agreement of each device were assessed by the intra-class correlation coefficient (ICC) for the continuous BP measurements and Bland & Altman methodology, respectively. In 10 additional AF patients, 10 consecutive measurements with IBP and OmronHEM907™, and IBP and Microlife WatchBPhome were performed. RESULTS: The OmronR7™ was not able to obtain any BP Readings. Arm devices presented better ICC for systolicBP(SBP) than for diastolicBP(DBP) (Omron HEM907™:0.94 [0.90; 0.97] vs. 0.77 [0.67; 0.89]; Microlife WatchBPhome:0.92 [0.88; 0.96] vs.0.79 [0.69; 0.89]).The correlation coefficient between Microlife WatchBPhome and IBP computed using the average of repeated measurements from two to ten measurements improved up to the third and remained stable afterwards. The agreement between IBP and SBP, and IBP and DBP, was moderate as illustrated by a wide limit of agreement [-24; 26](SBP) and [-15;17](DBP) for Microlife WatchBPHome, respectively and [-30; 13](SBP) and [-7; 15](DBP) for OmronHEM907. CONCLUSIONS: BP measurement using the two arm oscillometric devices achieved a high reliability for SBP. The agreement between IBP and arm devices was low but using the average of three consecutive measurements improved the results substantially.

Determinants of new drugs prescription in the Swiss healthcare market.

BACKGROUND: Drug markets are very complex and, while many new drugs are registered each year, little is known about what drives the prescription of these new drugs. This study attempts to lift the veil from this important subject by analyzing simultaneously the impact of several variables on the prescription of novelty. METHODS: Data provided by four Swiss sickness funds were analyzed. These data included information about more than 470,000 insured, notably their drug intake. Outcome variable that captured novelty was the age of the drug prescribed. The overall variance in novelty was partitioned across five levels (substitutable drug market, patient, physician, region, and prescription) and the influence of several variables measured at each of these levels was assessed using a non-hierarchical multilevel model estimated by Bayesian Markov Chain Monte Carlo methods. RESULTS: More than 92% of the variation in novelty was explained at the substitutable drug market-level and at the prescription-level. Newer drugs were prescribed in markets that were costlier, less concentrated, included more insured, provided more drugs and included more active substances. Over-the-counter drugs were on average 12.5 years older while generic drugs were more than 15 years older than non-generics. Regional disparities in terms of age of prescribed drugs could reach 2.8 years. CONCLUSIONS: Regulation of the demand has low impact, with little variation explained at the patient-level and physician-level. In contrary, the market structure (e.g. end of patent with generic apparition, concurrence among producers) had a strong contribution to the variation of drugs ages.

Performance of Predictive Equations Specifically Developed to Estimate Resting Energy Expenditure in Ventilated Critically Ill Children.

OBJECTIVE: To determine, based on indirect calorimetry measurements, the biases of predictive equations specifically developed recently for estimating resting energy expenditure (REE) in ventilated critically ill children, or developed for healthy populations but used in critically ill children. STUDY DESIGN: A secondary analysis study was performed using our data on REE measured in a previous prospective study on protein and energy needs in pediatric intensive care unit. We included 75 ventilated critically ill children (median age, 21 months) in whom 407 indirect calorimetry measurements were performed. Fifteen predictive equations were used to estimate REE: the equations of White, Meyer, Mehta, Schofield, Henry, the World Health Organization, Fleisch, and Harris-Benedict and the tables of Talbot. Their differential and proportional biases (with 95% CIs) were computed and the bias plotted in graphs. The Bland-Altman method was also used. RESULTS: Most equations underestimated and overestimated REE between 200 and 1000 kcal/day. The equations of Mehta, Schofield, and Henry and the tables of Talbot had a bias ≤10%, but the 95% CI was large and contained values by far beyond ±10% for low REE values. Other specific equations for critically ill children had even wider biases. CONCLUSIONS: In ventilated critically ill children, none of the predictive equations tested met the performance criteria for the entire range of REE between 200 and 1000 kcal/day. Even the equations with the smallest bias may entail a risk of underfeeding or overfeeding, especially in the youngest children. Indirect calorimetry measurement must be preferred.

Higher occurrence of nausea and vomiting after total hip arthroplasty using general versus spinal anesthesia: an observational study.

BACKGROUND: Under the assumption that postoperative nausea and vomiting (PONV) may occur after total hip arthroplasty (THA) regardless of the anesthetic technique used, it is not clear whether general (GA) or spinal (SA) anesthesia has higher causal effect on this occurrence. Conflicting results have been reported. METHODS: In this observational study, we selected all elective THA interventions performed in adults between 1999 and 2008 in a Swiss orthopedic clinic under general or spinal anesthesia. To assess the effect of anesthesia type on the occurrence of PONV, we used the propensity score and matching methods, which allowed us to emulate the design and results of an RCT. RESULTS: Among 3922 procedures, 1984 (51 %) patients underwent GA, of which 4.1 % experienced PONV, and 1938 underwent SA, of which 3.5 % experienced PONV. We found that the average treatment effect on the treated, i.e. the effect of anesthesia type for a sample of individuals that actually received spinal anesthesia compared to individuals who received GA, was ATET = 2.00 % [95 % CI, 0.78-3.19 %], which translated into an OR = 1.97 [95 % CI 1.35; 2.87]. CONCLUSION: This suggests that the type of anesthesia is not neutral regarding PONV, general anesthesia being more strongly associated with PONV than spinal anesthesia in orthopedic surgery.

The effect of patient, provider and financing regulations on the intensity of ambulatory physical therapy episodes: a multilevel analysis based on routinely available data.

BACKGROUND: Many studies have found considerable variations in the resource intensity of physical therapy episodes. Although they have identified several patient- and provider-related factors, few studies have examined their relative explanatory power. We sought to quantify the contribution of patients and providers to these differences and examine how effective Swiss regulations are (nine-session ceiling per prescription and bonus for first treatments). METHODS: Our sample consisted of 87,866 first physical therapy episodes performed by 3,365 physiotherapists based on referrals by 6,131 physicians. We modeled the number of visits per episode using a multilevel log linear regression with crossed random effects for physiotherapists and physicians and with fixed effects for cantons. The three-level explanatory variables were patient, physiotherapist and physician characteristics. RESULTS: The median number of sessions was nine (interquartile range 6-13). Physical therapy use increased with age, women, higher health care costs, lower deductibles, surgery and specific conditions. Use rose with the share of nine-session episodes among physiotherapists or physicians, but fell with the share of new treatments. Geographical area had no influence. Most of the variance was explained at the patient level, but the available factors explained only 4% thereof. Physiotherapists and physicians explained only 6% and 5% respectively of the variance, although the available factors explained most of this variance. Regulations were the most powerful factors. CONCLUSION: Against the backdrop of abundant physical therapy supply, Swiss financial regulations did not restrict utilization. Given that patient-related factors explained most of the variance, this group should be subject to closer scrutiny. Moreover, further research is needed on the determinants of patient demand.

Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS: ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS: One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS: Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Reproducibility of diabetes quality of care indicators as reported by patients and physicians.

INTRODUCTION: Self-report of diabetes care has moderate validity and is prone to under- and over-reporting. We assessed reproducibility of a range of processes and outcomes of diabetes care as reported by patients and physicians. METHODS: In a Swiss community-based survey, patients with diabetes and physicians independently reported past 12 months processes of care (HbA1c, lipids, microalbuminuria, blood pressure, weight, foot and eye examinations) and last measured values of HbA1c, height, weight and blood pressure. For dichotomous variables, we assessed reliability by Cohen's kappa and agreement by uniform kappa. For continuous measures, we used Lin's concordance correlation coefficient and limits of agreement, respectively. RESULTS: Mean age of the 210 patients was 65 years; 40% were women, and 51% had diabetes for >10 years. Agreement was good for recommended processes of care such as blood pressure (uniform kappa = 0.94), HbA1c (0.93), weight (0.88) and lipid (0.78), but lower for microalbuminuria, foot and eye examinations (all <0.50). Cohen's kappa values were all low (<0.25). Comparisons of reported continuous variables showed large limits of agreement for height (±6 cm) and weight (8-10 kg) despite high concordance correlation coefficients (0.93 and 0.97). Concordance correlation coefficients were smaller for HbA1c (0.72) and blood pressure (0.5-0.6), with large limits of agreement (±2% and ±25 mmHg). CONCLUSION: While agreement of routine processes of care was good, agreement was less satisfactory for microalbuminuria, foot and eye examinations. Reports of continuous outcomes yielded good reliability but too wide limits of agreement. Quality of care evaluation relying on self-report only should be made cautiously.

Diagnostic accuracy of carotid plaque instability by noninvasive imaging: a systematic review and meta-analysis.

AIMS: There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. METHODS AND RESULTS: Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CONCLUSION: CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. REGISTRATION: PROSPERO ID CRD42022329690.

A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial.

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference -46.4%, 95% confidence interval (CI) -57.6 to -35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. Clinicaltrials.gov Identifier: NCT05144763.

Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days.

Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure.

Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR ß-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤ 80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤ 9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.

Use of clinical tolerance limits for assessing agreement.

In this study, we have further extended the methodology proposed, first, by Lin et al. (2002) and, later, extended by Stevens et al. (2017, 2018), on the coverage probability/probability of agreement, by relaxing the strong parametric assumptions regarding the distribution of the latent trait and developing inference methods allowing to compute both pointwise and simultaneous confidence bands. The methodology requires repeated measurements by at least one of the two measurement methods and accommodates heteroscedastic measurement errors. It performs often very well even when one has only one measurement by one of the two measurement methods and at least five repeated measurements from the other. It circumvents some of the deficiencies of the Bland & Altman limits of agreement method and provides a more direct assessment of the agreement level.