Effect Of Preventive Treatment Research Articles

Preventive treatment effects on brain structures and functions in patients with chronic migraine: A multimodel magnetic resonance imaging study.

Patients with chronic migraine (CM) often exhibit structural and functional alterations in pain-matrix regions, but it remains unclear how preventive treatment affects these changes. Therefore, this study aimed to investigate the structural and functional changes in pain-matrix regions in CM patients after 6-month treatment. A total of 24 patients with CM and 15 healthy controls were recruited for this study. Patients were divided into responder group (N = 9) and non-responder group (N = 15). After completing the Migraine Disability Assessment (MIDAS) questionnaire, all patients underwent whole-brain high-resolution T1-weighted images, diffusion-weighted imaging, and resting-state functional magnetic resonance imaging at baseline and 6-month follow-up. Whole brain gray matter volume and white matter diffusion indices were analyzed using voxel-based analysis. Structural and functional connectivity analyses were performed to understand brain changes in patients after 6-month preventive treatment. The responder group exhibited significantly higher MIDAS scores than the non-responder group at baseline, but no significant difference between the two groups at follow-up. No significant interval change was noted in gray matter volume, white matter diffusion indices, and structural connectivity in CM patients after 6-month treatment. Nonetheless, the functional connectivity was significantly increased between occipital, temporal lobes and cerebellum, and was significantly decreased between parietal and temporal lobes after 6-month preventive treatment. We concluded that resting-state functional connectivity was suitable for investigating the preventive treatment effect on CM patients.

The significance of preventive treatment for tuberculosis infection in children

Objective: to evaluate the value of tuberculosis preventive treatment (PTT) in children with tuberculosis infection. Material and methods. As part of a continuous study, a cohort of 200 children from 1 to 17 years old taken for clinical observation in group VI A (positive test result with the recombinant tuberculosis allergen [ATR]) was analyzed. All children underwent additional examination methods to exclude the local form of tuberculosis: physical examination, laboratory clinical and biochemical tests of blood and urine, multislice computed tomography of the chest organs and, according to clinical recommendations, PTT was proposed, which the parents of 65 children refused. Study groups: 1 — those with no family contact with a patient with tuberculosis (ТВ) (n=70): 2 — those with contact with a patient with ТВ (n=65), in group 3 included children whose parents refused PTT, despite the presence of indications (n=65), incl. 14 children were from Tl lesions. Children group 1 and 2 received PTT. Control over the PTT was carried out on the "Yandex.Teleconference". Results. As a result of comparison of the three groups, reliable data were obtained on the effectiveness of PTT according to the criteria of preventing the disease and reducing the results of the ATR test. A significantly high percentage of sick children in group 3 was established, compared with children from group 1 (p=0.008; x2=18.6). When assessing the dynamics of the results of immunodiagnostic tests in children of the group 1 who received PTT, a decrease in the test with ATR was significantly more often observed compared to children without PTT(p=0.001; x2=17.2). It is worth noting that children had satisfactory tolerability of the drugs; no adverse events were observed in patients with daily video recording. Conclusion. A conclusion was made about the need for preventive work with parents of children who refused preventive treatment to increase their level of adherence, the need to evaluate the effectiveness of PTT courses using primary and additional criteria, including the importance of controlled PTT.

Influence of an iron dextran injection in various diseases on hematological blood parameters, including serum ferritin, neonatal dairy calves

BackgroundFeeding milk substitutes with low iron content or whole milk without iron supplementation is considered a major factor in developing iron-deficiency anemia in neonatal dairy calves. Young calves are often supplemented with iron dextran injections on the first day of life to prevent anemia. However, the effects of preventive treatment and the presence of disease on serum iron (Fe) concentrations, serum ferritin levels, and hematological blood parameters during the early neonatal stages have not been examined in detail. Therefore, we examined and evaluated the effects of iron dextran injections and health status on the development of hematocrit (Ht), red blood cells (RBC), hemoglobin concentration (Hb), erythrocyte indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration), Fe, and serum ferritin concentrations in dairy calves within the first 10 days of life. The suitability of serum ferritin as a reliable indicator of anemia in very young calves was evaluated by correlating ferritin concentrations with known laboratory diagnostic parameters of anemia.ResultsIron supplementation significantly increased Fe levels (P = 0.048) but did not affect serum ferritin levels in neonatal calves. Fe concentrations were significantly lower in diseased than healthy calves (P = 0.0417). Iron supplementation significantly affected the health status, as observed in Ht (Ptreat=0.0057; Phealth=0.0097), RBC (Ptreat=0.0342; Phealth=0.0243), and Hb (Ptreat=0.0170; Phealth=0.0168). Serum ferritin levels did not significantly correlate with Fe levels. Both groups showed marked differences in ferritin levels, with the highest levels measured on day 2. Fe concentrations showed weak negative correlations with Hb and Ht levels on day 3 (ρ=-0.45; P = 0.0034 and ρ=-0.045; P = 0.0032, respectively). RBC count showed strong positive correlations with Hb and Ht levels (ρ = 0.91 and ρ = 0.93; P < 0.001).ConclusionIron dextran injections increased Fe concentrations but reduced Ht level, RBC count, and Hb level. The presence of diseases led to a reduction in Fe and higher values of Ht, RBC, and Hb in moderate disease than in severe disease. Due to physiological fluctuations during the first 3 days of life, serum ferritin level seems unuseful for evaluating iron storage before day 4 of life.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury.

Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury.

Comparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals.

Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies. Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D. Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study. For each metabolic measure, t-Values from t tests for detecting a treatment effect were compared with chi-square values from proportional hazards regression for predicting T1D. Participants in the teplizumab prevention trial and participants in the Pathway to Prevention study selected with the same inclusion criteria used for the teplizumab trial were studied. Six-month changes in glucose-based endpoints predicted diabetes better than C-peptide-based endpoints, yet the latter were better at detecting a teplizumab effect. Combined measures of glucose and C-peptide were more balanced than measures of glucose alone or C-peptide alone for predicting diabetes and detecting a teplizumab effect. The capacity of a metabolic endpoint to detect a treatment effect does not necessarily correspond to its accuracy for predicting T1D. However, combined glucose and C-peptide endpoints appear to be effective for both predicting diabetes and detecting a response to immunotherapy. These findings suggest that combined glucose and C-peptide endpoints should be incorporated into the design of future T1D prevention trials.

Experience of Fixed-Dose Combinations of Anti-Tuberculosis Drugs for Preventive Treatment in Children

The objective: to evaluate the effectiveness and safety of preventive treatment with fixed-dose combination of anti-tuberculosis drugs (FDCs) in children from groups at high risk of developing tuberculosis.Subjects and Methods. Effectiveness of preventive treatment was analyzed in 318 children from groups at high risk of developing tuberculosis. Also, we studied the possibility of successful completion of the full course of treatment using FDCs and preventive treatment regimens containing at least two single drugs. Inclusion criteria were as follows: the child at high risk of developing tuberculosis; no clinical and radiological signs of active tuberculosis; lack of information about the resistance to first-line drugs at the suspected source of infection; and negative HIV status. A group of children (172 people) underwent preventive treatment using FDCs, of them 126 patients received FDCs containing isoniazid 150 mg + pyrazinamide 500 mg + pyridoxine hydrochloride 15 mg, and 46 patients received FDCs containing isoniazid 150 mg + ethambutol 400 mg + pyridoxine hydrochloride 15 mg. The comparison group (CG) included 146 children who received preventive treatment with single drugs: 111 children received isoniazid and pyrazinamide, and 35 children received isoniazid and ethambutol.Results. When assessing the safety and effectiveness, no statistically significant differences were found when using FDCs and single-drug regimens. 91.9% of children receiving FDCs and 86.3% of children receiving single-drug regimens successfully completed the full course of treatment. When taking FDCs, there was a tendency to lower incidence of adverse events. With the FDC (isoniazid 150 mg + pyrazinamide 500 mg + pyridoxine hydrochloride 15 mg), the proportion of adverse events did not exceed 4.0%. There were no adverse events with the FDC (isoniazid 150 mg + ethambutol 400 mg + pyridoxine hydrochloride 15 mg).Conclusion. Preventive treatment of children with tuberculosis infection with FDC is a modern and effective technology.

Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings.

To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10-14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.

The effectiveness of preventive use of partially hydrolyzed dietary fibers of cyamopsis tetrahedral (OptiFibre®) in patients with benign prostatic hyperplasia and chronic functional constipation

Anatomical proximity of the prostate gland and colon, common innervation, blood and lymph circulation create prerequisites for the involvement of the intestine in the pathological process in prostate diseases.&#x0D; Aim To evaluate the effectiveness of preventive treatment of chronic constipation (CC) with the use of partially hydrolyzed dietary fibers of cyamopsis tetrahedral (OptiFiber®) in patients with benign prostatic hyperplasia (BPH) who are shown to have a prostate tour and its effect on the course of the postoperative period.&#x0D; Materials and methods. We examined 60 patients with BPH who were referred for surgical treatment (transurethral resection of the prostate), who had chronic functional constipation. By random sampling, the patients were divided into two groups of 30 people. In group 1, standard preparation for surgical treatment was carried out for 1 month. In group 2, patients, in combination with standard preparation for surgical treatment, took partially hydrolyzed dietary fibers of cyamopsis tetrahedral (OptiFiber®) with food for the first 3 days – 1 sachet (5 g) per day, from the 4th to the 6th day – 2 sachets per day. From day 7, patients in group 2 were divided into two subgroups. In subgroup 2a, patients whose bowel function returned to normal continued taking the drug at a dose of 2 sachets per day. Those patients in whom the effect of restoring the regularity of bowel function was not satisfactory, took 3 sachets a day from the 7th day and were assigned to subgroup 2b. In the preoperative period, patients were examined on the 1st day (visit 1), 15th day (visit 2) and 30th day (visit 3) of observation. The average number of acts of defecation during the previous week, the severity and dynamics of clinical manifestations of constipation were evaluated on the basis of the Patient Assessment of Constipation Symptoms (PAC-SYM questionnaire), according to the totality of symptoms in points, as well as for each criterion separately. Evaluation of the effectiveness of treatment in the postoperative period was carried out on the basis of dynamic observation for 5–7 days.&#x0D; Results. Initially, all patients in the two groups had signs characteristic of BPH and chronic functional constipation, the groups were homogeneous. According to the results obtained in group 1 for 30 days of follow-up before surgery, none of the studied parameters significantly changed (p0.05). In group 2, after 15 days of follow-up, a significant (p0.05) positive dynamics was revealed for all the studied indicators, both in comparison with group 1 and in comparison with the results obtained at visit 1. By visit 3, despite the absence of statistically significant dynamics in the indicators of both group 1 and group 2, in comparison with visit 2, significant (p0.05) differences remained between the groups. During the study, subgroup 2a included 19 patients who took 2 sachets of OptiFiber® per day, and subgroup 2b included 11 men who took 3 sachets per day from the 7th day of observation. Restoration of intestinal motility in patients taking dietary fiber occurred at an earlier time, while the differences were also statistically significant (p0.05). In group 1, 14 cases of early postoperative complications were registered, and in group 2–9 cases, which is 35.7% less. The number of cases of antibiotic-associated diarrhea in group 1 was 3, while in group 2 there was 1 such case, which is 66.7% less. When analyzing the results obtained, there were no significant differences in the studied parameters in the postoperative period between subgroups 2a and 2b. All 30 (100%) patients of group 2 gave a positive review of partially hydrolyzed dietary fibers of cyamopsis tetrahedral (OptiFiber®), and plan to continue taking them after completing participation in the study.&#x0D; Conclusion. Thus, according to the results of the study, we consider it appropriate to use partially hydrolyzed dietary fibers of cyamopsis tetrahedral (OptiFiber®) in the treatment of CC in patients with BPH who are shown to have a prostate tour as a means to effectively eliminate the manifestations of CC, improve the results of surgical treatment and improve the quality of life of this category of patients.

Computer Statistics Modeling of Medical Process

Computer statistical modeling plays a huge role in medicine for making an accurate diagnosis and, on its basis, choosing the right method of treatment, predicting the outcome of the disease, and evaluating the effectiveness of the chosen treatment tactics. Computer-statistical modeling of the course of the disease on the example of oncology, carried out by the author on the basis of a scientific-statistical SSP package adapted to medical data (rewritten in the Turbo Basic programming language), included all the main elements of computer statistical data processing underlying computer statistical modeling with regard to communication, based on the creation of computer-aided medical-statistical models of the disease, to actively participate in the effective treatment of patients in clinical practice. Effective participation in the treatment of cancer patients was carried out through the implementation of the developed computer-statistical models of the tactics of individual planning of the examination of the patient, individualized prognosis of the course of the disease, which determine the possibility of an individual approach to observation and postoperative treatment of the patient. The paper presents the results of computer-statistical data processing using the SSP scientific-statistical software package, which became the basis of the development of a computer-statistical model of accurate interpolation prediction of the timing of the appearance of metastases in cancer patients after surgical treatment, and of evaluation of the effectiveness of preventive treatment for the appearance of metastases after surgery.

Prevalence and Risk Factors of Enteral Feeding Intolerance in Critically Ill Patients and the Effectiveness of Preventive Treatments: A Prospective Study.

Feeding intolerance (FI) is a prevalent cause of enteral nutrition (EN) disruption. Factors that can prevent FI are poorly described. To determine the prevalence and risk factors associated with FI in critically ill patients and the effectiveness of preventive treatments. This prospective observational study included critically ill patients admitted to the ICU of a general hospital who received EN through a nasogastric or nasointestinal tube from March 2020 to October 2021. Independent sample t-test, repeated measurement analysis of variance, and multivariate analysis were used to explore independent risk factors and the efficacy of preventive treatments. The study included 200 critically ill patients (mean age: 59.1 ± 17.8 years), of whom 131 were male. Most patients (58.50%) developed FI after a median EN duration of 2 days. The independent risk factors for FI were fasting for >3 days, high APACHE II score, and acute gastrointestinal injury (AGI) grade I before EN (P < 0.05). During EN, whole protein was found to be an independent preventive treatment that significantly decreased FI (P < 0.05), while before EN, early use of enema and gastric motility drugs in patients with abdominal distention/constipation significantly decreased FI (for both, P < 0.05). The preventive treatment group had significantly higher intake of the nutrient solution and significantly shorter invasive mechanical ventilation duration than the without preventive treatment group (for both, P < 0.05). In ICU patients receiving nasogastric or nasointestinal tube feeding, FI was frequent, occurred early, and was more frequent in patients with fasting >3 days, a high APACHE II score, and an AGI grade before EN. Preventive treatments can reduce FI prevalence and result in patients consuming more nutrient solutions and having shorter invasive mechanical ventilation duration. ChiCTR-DOD-16008532.

Bronchitis, COPD, and pneumonia after viral endemic of patients with leprosy on Sorok Island in South Korea

Viral respiratory diseases (VRDs) cause lung inflammation and inflammatory cytokine production. We study whether dapsone is responsible for its observed preventive treatment effects of the sustained viral RNA interferon response. Around 2008 and 2012, Korea’s Dementia Management Act stipulated drastic changes in the administration of dementia medication by medical staff. Participants were randomized and we compared leprosy patients with VRDs after prescribing dapsone as a standard treatment from 2005 to 2019. Significance was evaluated based on the dapsone-prescribed (+) subgroup and the dapsone-unprescribed (−) subgroup of the VRD diagnosed (+) and VRD undiagnosed (−) subgroup. We analyzed VRD ( +)/(− with dapsone (+)/(−) group and used a T-test, and designed the equation of acetylation with dapsone and acetylcholine (AA) equation. The 6394 VRD participants who received the dapsone intervention compared to the 3255 VRD participants in the control group demonstrated at T2 VRD (+) dapsone (−) (mean (M) = 224.80, SD = 97.50): T3 VRD (−) dapsone (+) (M = 110.87, SD = 103.80), proving that VRD is low when dapsone is taken and high when it is not taken. The t value is 3.10, and the p value is 0.004395 (significant at p < 0.05). After an increase in VRDs peaked in 2009, bronchitis, COPD, and pneumonia surged in 2013. The AA equation was strongly negatively correlated with the prevalence of bronchitis and chronic obstructive pulmonary disease (COPD): with bronchitis, r(15) = −0.823189, p = 0.005519, and with COPD, r(15) = −0.8161, p = 0.000207 (significant at p < 0.05). Dapsone treated both bronchitis and COPD. This study provides theoretical clinical data to limit acetylcholine excess during the VRD pandemic for bronchitis, COPD, and pneumonia.

LACTOFERRIN – A ROLE IN THE PROTECTIVE FUNCTIONS IN ADOLESCENTS WITH LATENT TUBERCULOSIS INFECTION

When evaluating the role of lactoferrin to improve the effectiveness of preventive treatment of latent tuberculosis infection in adolescents, it was found that the prescriptions of Lactoferrin imun + Colostrum contributed to a significantly more pronounced decrease in the frequency of hyperergic reactions in test with tuberculosis recombinant allergen (from 51.3% to 12.5% in the main group, from 50.7 % to 33.3% in the comparison group, p &lt; 0.05), a decrease in the average size of the papule (from 17.6 mm to 8.2 mm in the main group and from 17.1 to 14.5 mm in the comparison group, p &lt; 0.05). In patients of the main group, the restoration of free radical oxidation and antioxidant protection indicators to the level of healthy donors was established, while in the comparison group, the intensity of blood plasma chemiluminescence and the activity of myeloperoxidase in neutrophils remained elevated, while the activity of catalase and superoxidedismutase remained reduced. The level of lactoferrin during treatment in the main group increased to normal values (740 ng/ml, 95%CI 702.2-777.8), and in the control group remained reduced (440 ng/ml, 95%CI 411.5-478.5), p &lt; 0.05. At the same time, the continuing level of positive reactions to tuberculosis recombinant allergen (Diaskintest®) against the background of normalization of the lactoferrin level indicates the high diagnostic capabilities of Diaskintest® to detect LTBI in adolescents

Prognostic impact of coronary artery calcifications in patients with newly diagnosed prostate cancer

Abstract Background Patients diagnosed with prostate cancer (PCa) are known to be at increased risk of cardiovascular events. Because of the ageing population and better cancer treatment, the number of these patients is increasing. A prostate-specific membrane antigen positron emission tomography (PSMA-PET) is guideline recommended as part of the diagnostic workup. This scan includes a non-ECG-gated computed tomography (CT) of the thorax, allowing assessment of coronary artery calcifications (CAC). It is not well-established, whether estimation of CAC based on this CT scan can identify patients with increased risk of major adverse cardiac events (MACE) and thus possibly improve therapy and prognosis. Purpose This study aims to assess CAC and evaluate whether high calcium scores predict the risk of MACE in patients newly diagnosed with PCa. Methods We identified 634 consecutive patients diagnosed with PCa and undergoing PSMA-PET from 2016 to 2019 in an area of 300.000 residents. In total, 63 patients were excluded due to prior revascularization. The remaining 571 patients (mean age 69.9±6.7 years) were included. Patients were followed until June 2021 or until an event occurred (mean follow-up 962±372 days). We used a standard cardiac CT software to assess CAC. Information on MACE defined as all-cause mortality, stroke and myocardial infarction were obtained from electronic patient files. We divided patients into five groups based on their coronary artery calcium score (CACS): 0–10, 11–99, 100–399, 400–999, and + 1000. Cox regression analysis was used to compute the hazard ratios (HR) for MACE with CACS 0–10 as reference while adjusting for age, hypertension diabetes, and treatment with aspirin and statins. Results We found a significantly increasing risk of MACE with increasing CACS after adjustment for risk factors. For CACS 100–399 (n=136): HR 2.10 (95% CI: 0.98–4.51, p=0.056), for CACS 400–999 (n=79): HR of 2.99 (95% CI: 1.35–6.59, p=0.007) and for CACS +1000 (n=150): HR 3.06 (95% CI: 1.37–6.85, p=0.006) (Figure 1). Cardiovascular disease prevention treatment with statins and aspirin was 53% and 16% in patients with CACS 400–999 and 52% and 19% in patients with CACS + 1000. Conclusion In patients with PCa, estimating coronary calcium score based on non-ECG-gated CT scans, which are performed as part of the diagnostic workup, predicts the occurrence of MACE. In the patient group with the highest CAC, a four-year event rate of 24% was found. In combination with the finding of infrequent use of statin and aspirin, this emphasizes the possibility of early detection of high CAC in patients with PCa and illustrates the potential for more extensive use of preventive treatment. Future studies should investigate the effect of preventive treatment being initiated in patients with PCa and high CAC. Funding Acknowledgement Type of funding sources: None.

Pigment dispersion syndrome and pigmentary glaucoma: overview and racial disparities.

Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are two stages within the same ophthalmic disease spectrum, which are known to be affected by race. The prevalence of PDS is underestimated, largely due to its minor clinical symptoms. Although the prevalence of PG is low, the visual impairment associated with PG is extremely severe. The prevalence of PDS-PG is four or more times higher in Caucasians than in Blacks or Asians, and the "classic" PDS in Caucasians has long been used as a benchmark diagnostic criterion. Following extensive research focused on African Americans and Asians, the standard for diagnosing PDS-PG was refined. At the same time, the pathogenesis of PDS is not the same in different races. Hence, the effectiveness of preventive treatment and the need for treatment may not be equivalent in different races. The rate of conversion of PDS to PG is nearly 1/3 in Caucasians and higher in blacks and Asians, requiring more aggressive treatment and monitoring. We systematically searched a PubMed database from inception to March 2022 to provide an overview of research progress in various aspects of PDS-PG. Specifically, this paper considers the effects of race on disease prevalence, clinical manifestation, diagnostic criteria, disease mechanism, hereditary traits, treatment, and prevention to provide an accurate and comprehensive guide for the diagnosis and treatment of PDS-PG in various races.

Comparative effectiveness of preventive treatment with dimethyl fumarate-loaded solid lipid nanoparticles and oral dimethyl fumarate in a mouse model of multiple sclerosis

BackgroundOrally administered dimethyl fumarate (DMF) presents gastrointestinal adverse effects, such as pain and diarrhea, in addition to flushing and lymphopenia. ObjectiveSolid lipid nanoparticles (SLNs) with DMF were developed for subcutaneous administration. MethodsDMF-incorporated SLNs and free DMF were tested in mice induced with experimental autoimmune encephalomyelitis (EAE). ResultsPreventive treatment of free or incorporated DMF were able to reduce the EAE clinical scores, increase the weight of the animals, reduce the lesion area (demyelination and infiltration), reduce microglial fluorescence intensity and reduce the number of microglial cells and astrocytes, when compared to untreated EAE animals. Groups that received DMF had reduced numbers of T cells, B cells and natural killer (NK) cells in the blood, when compared to the non-induced group. ConclusionsDMF incorporated in SLNs was as effective as free DMF in reducing the clinical scores of the animals, but with reduced administrations when given subcutaneously. In addition, SLN-DMF preventive treatment partially prevented a reduction in the percentages of T and B cells, in the blood, when compared to preventive treatment with free DMF (oral), which suggests reduction of lymphopenia.

COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial

ObjectivesThis study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups.MethodsWe conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests.ResultsWe detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27).ConclusionOur findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat/high-fructose diet in rats.

Objective(s):To investigate the protective and preventive treatment effects of Eucommia ulmoides leaves on a rat model of high-fat and high-fructose diet (HFFD) induced hyperuricemia and renal injury.Materials and Methods:Network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of E. ulmoides leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform to collect E. ulmoides leaf flavonoid and iridoid components. Swiss Target Prediction, Similarity ensemble approach (SEA), GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database were used to obtain core targets, and the Search Tool for Recurring Instances of Neighbouring Genes (STRING) protein database was used as core target for gene ontology enrichment Set and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was applied to predict the pathways regulating the metabolism of uric acid. The selected targets and targeting efficacy were validated using a rat model of hyperuricemia and renal injury induced by a high-fat and high-fructose diet.Results:A total of 32 chemical components with effective targets, which regulated the PI3K-AKT pathway and endocrine resistance, were collected. Molecular docking results showed that iridoids and flavonoids are bound to proteins related to inflammation and uric acid metabolism. In addition, it was verified via animal experiments that an E. ulmoides leaf extract ameliorated hyperuricemia, renal injury, and inflammation, which are closely related to the targets Interleukin- 6 (IL-6), Tumor necrosis factor-α (TNF-α), Toll-Like Receptor 4 (TLR4), and Glucose transporter 9 (GLUT9). Conclusion: E. ulmoides leaf flavonoids and iridoids ameliorate hyperuricemia and uric-acid–induced inflammation through a multi-component, multi-target, and multi-pathway mechanism, which provides a theoretical basis for the development of therapeutics from E. ulmoides leaf components.

Beneficial effects of a preventive treatment with anethole trithione on pulmonary hypertension

Pulmonary hypertension (PH) is a multifactorial disease characterized by pulmonary arteries (PA) and right ventricular (RV) alterations. Mitochondria dysfunction and associated reactive oxygen species production were shown to contribute to these phenomena. OP2 Drugs start-up demonstrated that anethole trithione (ATT), the active ingredient of its principal lead OP2113, specifically inhibits mitochondrial ROS production from complex I. In this context, this study aims to assess the effects of ATT on PH set-up. By using osmotic mini-pump, influence of a preventive treatment with ATT or its vehicle was tested on PH development in male rats exposed to three weeks of chronic hypoxia (CH - 10 % O2). PA and cardiac PH hallmarks (remodelling, fibrosis and hemodynamic parameters) were assessed. Contraction and intracellular calcium signal of isolated cardiomyocytes from RV were simultaneously measured by IonOptix system. We quantified cardiac mitochondrial mass by measuring VDAC1 expression by western blotting. The effect of preventive or acute treatment with ATT on PA reactivity was measured by isometric tension. In rats with PH, preventive treatment with ATT reduced PA remodelling and RV systolic pressure, whereas RV hypertrophy and fibrosis seemed not to be affected. However, this preventive treatment abolished the decrease of both speed of cardiomyocytes contraction and VDAC1 expression induced by CH. Preventive and acute treatment with ATT reversed PA hyperreactivity to 5-HT in rats with PH. Acute ATT treatment triggered a sustained relaxation of preconstricted PA in both control and PH conditions. L-NAME (eNOS inhibitor) and CHAPS (non-denaturing detergent used to remove endothelium) did not affect the acute effect of ATT on PA contraction and relaxation whereas glibenclamide (KATP channel inhibitor) attenuated ATT induced relaxation. Y27632 (a ROCK inhibitor) and ATT induced additive reduction of 5-HT contraction. Altogether, these results highlighted the benefit of an ATT preventive treatment on PA reactivity and remodelling as well as RV cardiac function suggesting a potential therapeutic interest of ATT in PH set-up. Whereas ATT effect on reactivity seemed to be endothelium and ROCK-independent, KATP channel was partly involved in ATT-induced relaxation.

Preventive treatment with fish oil facilitates the antidepressant-like effect of antidepressant drugs in type-1 diabetes mellitus rats: Implication of serotonergic system

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment – FO plus antidepressants (FLX or IMI – both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.