Explore the vast range of titles available.

Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect. Participants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI <25), overweight (BMI >25 and <30) or clinically obese (BMI ≥30) from Littoral regions of Cameroon will be evaluated for their parasitological, immunological, metabolic and biochemical profile before and after treatment of their parasitic infections. Anthropomorphic measurements and a detailed questionnaire will complement our analysis. The investigation will assess blood immune cell populations, serum adipokines and cytokines that could be influenced by the parasite infection and/or metabolic diseases. Further, parameters like blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR), circulating lipids and circulating makers of liver function will be monitored. Parameters will be assessed before treatment, 12 and 18 months after treatment. The focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases. doi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1.

The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4-6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. ClinicalTrials.gov #06010453.

Novel drugs or drug combinations that kill or permanently sterilize adult worms would be very helpful for treatment and elimination of onchocerciasis. In absence of a reliable biomarker for viable adult worms, histopathological assessment of worms within onchocercal nodules is a standard method to determine macrofilaricidal activity. The goal of the present study was to determine the agreement between two independent experts in the analysis of nodule sections and to assess the value of digital imaging as a means of standardizing the analysis. Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously examined by microscopy, and included additional immunostains for endobacteria. These slides were digitalized, read by the two assessors and results were compared with original microscopy results. The degree of agreement between assessors varied for different parameters. Agreement for female worm counts in nodules was approximately 80%, while agreement regarding female worm viability was 98%. There were no major differences observed between results obtained by microscopy or digital images. Good agreement for important parameters was also observed for the nodules of the quality panel. Nodule analysis by experienced microscopists was reproducible with regard to important parameters such as identification of living female worms or detection of normal embryogenesis. Assessments varied more for other parameters, and we recommend continued use of two independent readers for detailed analyzes. Analysis of scanned images provided similar results to direct microscopy. This facilitates training and comparison of nodule findings by readers in different locations. Analysis of high quality digital images that can be viewed remotely should improve the quality and availability of nodule assessments that are primary endpoints for onchocerciasis clinical trials.

To develop and validate a pragmatic risk screening score for postoperative delirium (POD) based on routine preoperative data. Prospective observational monocentric trial. Preoperative data and POD assessment were collected from cardiac and non-cardiac surgical patients at a German university hospital. Data-driven modelling approaches (step-wise vs. component-wise gradient boosting on complete and restricted predictor set) were compared to predictor selection by experts (investigators vs. external Delphi survey). Inpatients (≥60 years) scheduled for elective surgery lasting more than 60 min. POD was assessed daily during first five postoperative or post-sedation days with confusion assessment method for intensive and standard care unit (CAM-ICU/CAM), 4 ‘A's test (4AT) and Delirium Observation Screening (DOS) scale. From 1023 enrolled patients, 978 completed observations were separated in development (n = 600; POD incidence 22.2%) and validation (n = 378; POD incidence 25.7%) cohorts. Data-driven approaches generated models containing laboratory values, surgical discipline and several items on cognitive and quality of life assessment, which are time consuming to collect. Boosting on complete predictor set yielded the highest bootstrapped prediction accuracy (AUC 0.767) by selecting 12 predictors, with substantial dependence on cardiac surgery. Investigators selected via univariate comparison age, ASA and NYHA classification, surgical risk as well as ´serial subtraction´ and ´sentence repetition´ of the Montreal Cognitive Assessment (MoCA) to enable rapid collection of their risk score for preoperative screening. This investigator model provided slightly lower bootstrapped prediction accuracy (AUC 0.746) but proved to have robust results on validation cohort (AUC 0.725) irrespective of surgical discipline. Simplification of the investigator model by scaling and rounding of regression coefficients into the PROPDESC score achieved a comparable precision on the validation cohort (AUC 0.729). The PROPDESC score showed promising performance on a separate validation cohort in predicting POD based on routine preoperative data. Suitability for universal screening needs to be shown in a large external validation. •PROPDESC score was developed for preoperative screening of POD risk.•Different modelling approaches with statistical and clinical input were investigated.•Prediction model development aimed to provide a pragmatic screening tool.•PROPDESC score predicts POD risk based on preoperative rapidly available parameters.•PROPDESC score provides POD prediction in various surgical disciplines.

Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839.

Study objectiveTo develop and validate a pragmatic risk screening score for postoperative delirium (POD) based on routine preoperative data.DesignProspective observational monocentric trial.SettingPreoperative data and POD assessment were collected from cardiac and non-cardiac surgical patients at a German university hospital. Data-driven modelling approaches (step-wise vs. component-wise gradient boosting on complete and restricted predictor set) were compared to predictor selection by experts (investigators vs. external Delphi survey).PatientsInpatients (≥60 years) scheduled for elective surgery lasting more than 60 min.MeasurementsPOD was assessed daily during first five postoperative or post-sedation days with confusion assessment method for intensive and standard care unit (CAM-ICU/CAM), 4 ‘A's test (4AT) and Delirium Observation Screening (DOS) scale.Main resultsFrom 1023 enrolled patients, 978 completed observations were separated in development (n = 600; POD incidence 22.2%) and validation (n = 378; POD incidence 25.7%) cohorts. Data-driven approaches generated models containing laboratory values, surgical discipline and several items on cognitive and quality of life assessment, which are time consuming to collect. Boosting on complete predictor set yielded the highest bootstrapped prediction accuracy (AUC 0.767) by selecting 12 predictors, with substantial dependence on cardiac surgery. Investigators selected via univariate comparison age, ASA and NYHA classification, surgical risk as well as ´serial subtraction´ and ´sentence repetition´ of the Montreal Cognitive Assessment (MoCA) to enable rapid collection of their risk score for preoperative screening. This investigator model provided slightly lower bootstrapped prediction accuracy (AUC 0.746) but proved to have robust results on validation cohort (AUC 0.725) irrespective of surgical discipline. Simplification of the investigator model by scaling and rounding of regression coefficients into the PROPDESC score achieved a comparable precision on the validation cohort (AUC 0.729).ConclusionsThe PROPDESC score showed promising performance on a separate validation cohort in predicting POD based on routine preoperative data. Suitability for universal screening needs to be shown in a large external validation.