Grading system to assess clinical performance of closed-loop glucose control

Closed-loop control of the glucose concentration in type 1 diabetes has been the subject of extensive research over the last 3 decades. Building on the recent progress in continuous glucose sensing techniques, several prototypes of a closed-loop system have been developed. To complement existing measures of glucose control, we designed a grading system specifically designed to provide clinical assessment of closed-loop systems including that of glucose controllers. The system introduces six grades, A-F, describing the level of control and the therapeutic intervention during outside-meal and postprandial conditions. Grades A and B represent excellent and good glucose control, respectively, without the need for a corrective therapeutic action. Grade C represents suboptimal control with a recommendation for a corrective action. Grade D represents poor control requiring a corrective action. Grades E and F represent very poor and life-threatening control, respectively, with a need for an immediate corrective action or requiring external assistance. The outcome of grading is the quantification of time spent in each grade. The grading system is exemplified using data obtained with a model predictive controller within an in silico simulation environment. We conclude that the grading system provides suitable means to assess efficacy and safety of glucose controllers complementing existing measures of glucose control.     

Fecal Steroid 21-Dehydroxylase, a Potential Marker for Colorectal Cancer

Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone. Tetrahydrodeoxycorticosterone, in contrast to pregnanolone, is carcinogenic for hamster embryonic cells (HECT test). In patients with recently diagnosed, untreated sigmoidal or rectal cancer the fecal concentration of 21-dehydroxylating organisms is reduced by more than 99% as compared with age-matched controls. The lack of fecal 21-dehydroxylating organisms, therefore, is a potential marker for the disorder. The role of steroid 21-dehydroxylase in the pathogenesis of colorectal cancer is unknown.     

From 1901 to 2022, how far are we from truly understanding the pathogenesis of age-related dementia?

GeroScience - From the first described AD case in 1901 to the current year 2022, understanding the pathogenesis of Alzheimer’s disease (AD) and dementia has undergone a long and tortuous...     

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis

High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes.     

Implementing Adolescent Screening,Brief Intervention,and Referral to Treatment (SBIRT) Education in a Pediatric Residency Curriculum

Background: Screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care for adolescents as well as adults. In an effort to promote universal SBIRT, the Substance Abuse and Mental Health Services Administration awarded funding to residency programs to develop and implement SBIRT education and training. Our project focused on creating scientifically based, developmentally appropriate strategies and teaching materials for the adolescent age range. This paper describes curriculum development and implementation and presents evaluation data. Methods: Pediatric and child psychiatry residents were trained. The training consisted of 4 activities: (1) case-based teaching modules, (2) role-play of motivational interviewing and brief interventions, (3) mock interviews with trained adolescents, and (4) supervised “hands-on” screening and brief interventions. Main outcome measures included trainee satisfaction, and SBIRT knowledge, perceived self-efficacy, and self- and observer report of use of the SBIRT algorithm. Results: Among 150 total participants completing the SBIRT training modules, nearly all (92.3%) were satisfied/very satisfied with the training modules. Knowledge accuracy immediately post training was high, but declined significantly by the end of the first residency year, with little change across subsequent years of residency. Confidence ratings also declined over time. Use of the SBIRT algorithm during the Adolescent Medicine rotation was high according to trainee self- and faculty observer report. Conclusions: We found evidence of training satisfaction, increased confidence in talking to adolescents about substance use, and widespread use of recommended practices immediately following training. Use of a highly structured algorithm to guide practice, and simple, highly structured brief interventions was a successful training approach, as residents self-reported accurate use of the SBIRT algorithm immediately after training. Knowledge and self-confidence declined over time. It is possible that “booster” sessions and ongoing opportunities to review materials could help residents retain knowledge and skills.     

Spontaneous daily variability of atrial sensitivity. A study with an implanted DDD pacemaker

BACKGROUND: Spontaneous variations in the chronic stimulation threshold were widely investigated in the last few years and formed the basis of the safety margin concept of stimulation energy. The dynamic variability of sensitivity, particularly in the atrium, is less studied and, in the literature, contrasting data are present about the actual entity of these variations. A 2:1 safety margin is still recommended by many authors, although some papers reported that this value was inadequate to guarantee a correct sensing function. AIM OF THE STUDY: We evaluated daily variability of atrial sensitivity (AS) in patients implanted with the Cosmos 3 DDD cardiac pacemaker, with a special algorithm that continuously measures the minimum-maximum sensitivity values in atrium or in the ventricle during a 12-h sampling period. MATERIALS AND METHODS: 34 patients, 20 males and 14 females, with a mean age of 72+/-5 years, were implanted with a Cosmos 3 DDD pacemaker (PM). The indication to implant a PM was sick sinus syndrome in 21 patients and a high degree of AV block in 13 patients. Atrial bipolar leads were always employed. At 1, 2, 3 and 6 months after the implant, we analyzed the minimum-maximum values of atrial sensitivity for the last 12-h. This analysis was performed in the late afternoon. RESULTS: The mean AS varied more than threefold, from a mean minimum of 0.68 to a mean maximum value of 2.19 mV at 1 month, from 0.68 to 2.21 mV at 2 months, from 0.69 to 2.19 mV at 3 months and from 0.67 to 2.17 mV at 6 months, without significant differences among the four follow-up controls. In seven patients, there was a fourfold variation, while the variation was fivefold in five patients. CONCLUSION: In conclusion, from our data, we can confirm that atrial sensitivity may vary widely during the day and, consequently, we recommend that a 3:1 safety margin should be programmed and the recommended 2:1 ratio should be abandoned. Moreover, at implant, particular attention should be paid to obtaining the best atrial signal amplitude, at least threefold higher than the highest sensitivity value available in the implanted PM. To achieve this goal and to obviate to the oversensing phenomena, bipolar leads are preferable to unipolar leads.     

Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans

Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture and in medicine, and also for antiestrogen therapy, e.g., for breast cancer treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol 14alpha-demethylase), and estrogen biosynthesis reduction is due to azole inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is usually an unwanted side effect and may cause endocrine disruption. A fluorimetric assay based on human recombinant CYP19 enzyme with dibenzylfluorescein as a substrate was used to compare the inhibitory potency of 22 azole compounds. Dose responses were established and duplicate datasets were analyzed with a nonlinear mixed-effects model with cumulative normal distribution for the logarithm of concentration. IC50 values (50% inhibitory concentration) of 13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047 microM. The potency of seven human drugs spanned more than 7000-fold, starting from 0.019 microM. Most potent fungicides included prochloraz, flusilazole, and imazalil, and most potent medicinal antifungals were bifonazole, miconazole, and clotrimazole. These in vitro data indicate that the top-ranking azoles used as antifungal agents or drugs are as potent inhibitors of aromatase as are antiestrogen therapeutics used to treat breast cancer. These putative effects of azole agents and drugs on steroid biosynthesis and sex hormone balance should be considered when used in human subjects and also in wildlife exposed to azole fungicides used in agriculture.     

The role of diabetes mellitus on the formation of severe odontogenic abscesses—a retrospective study

Objectives

To analyze the correlation of diabetes mellitus and hyperglycemia with severe odontogenic abscesses.

Materials and methods

Records of all patients in the Department of Oral and Maxillofacial Surgery of the Medical Center of the Johannes Gutenberg-University who underwent inpatient treatment for severe odontogenic abscesses between 2010 and 2016 were evaluated retrospectively regarding diabetes anamnesis, maximum and fasting blood sugar count, and duration until discharge. In order to compare the numbers to a general maxillofacial group, all patients who received inpatient treatment in 2013 for any diagnosis other than an abscess of the head and neck region were analyzed as well, and the numbers were correlated.

Results

In total, 977 abscess patients were found in the analyzed period. 7.0% of the patients had a known diagnosis of diabetes mellitus type II and 0.6% of type I. Correlation with the general group showed that abscesses were significantly more likely in diabetics as well as patients with abnormal maximum and fasting blood sugar counts. These patients also needed significantly longer inpatient treatment.

Conclusions

Diabetics and patients with abnormal glucose tolerance show significantly higher numbers of severe odontogenic abscesses and might therefore benefit from earlier escalation of antibiotic medication.

Clinical relevance

Severe odontogenic abscesses are one of the most frequent diagnoses in maxillofacial practice. Adjusting the therapeutic approach for diabetics or patients with abnormal blood sugar counts might help to prevent the development of abscesses.