Preventive Regimens Research Articles

Transition of radical, preventive and presumptive treatment regimens for malaria in China: a\xa0systematic review

BackgroundGlobally, malaria is still a major public health challenge. Drug-based treatment is the primary intervention in malaria control and elimination. However, optimal use of mass or targeted treatments remains unclear. A variety of radical, preventive and presumptive treatment regimens have been administrated in China and a systematic review was conducted to evaluate effectiveness, and discuss experiences, limitations, and lessons learnt in relation to the use of these regimens.MethodsThe search for information includes both paper documents, such as books, malaria control annals and guidelines for malaria prevention and treatment, as well as three computer-based databases in Chinese (CNKI, WanFangdata and Xueshu.baidu) and two databases in English (PubMed and Google Scholar), to identify original articles and reports associated with drug administration for malaria in China.ResultsStarting from hyperendemicity to elimination of malaria in China, a large number of radical, preventive and presumptive treatment regimens had been tried. Those effective regimens were scaled up for malaria control and elimination programmes in China. Between 1949 and 1959, presumptive treatment with available anti-malarial drugs was given to people with enlarged spleens and those who had symptoms suggestive of malaria within the last 6 months. Between 1960 and 1999, mass drug administration (MDA) was given for preventive and radical treatment. Between 2000 and 2009, the approach was more targeted, and drugs were administed only to prevent malaria infection in those at high risk of exposure and those who needed radical treatment for suspected malaria. Presumptive therapy was only given to febrile patients. From 2010, the malaria programme changed into elimination phase, radical treatment changed to target individuals with confirmed either Plasmodium vivax or Plasmodium ovale within the last year. Preventive treatment was given to those who will travel to other endemic countries. Presumptive treatment was normally not given during this elimination phase. All cases of suspected were confirmed by either microscopy or rapid diagnosis tests for malaria antigens before drugs were administered. The engagement of the broader community ensured high coverage of these drug-based interventions, and the directly-observed therapy improved patient safety during drug administration.ConclusionA large number of radical, preventive and presumptive treatment regimens for malaria had been tried in China with reported success, but the impact of drug-based interventions has been difficult to quantify because they are just a part of an integrated malaria control strategy. The historical experiences of China suggest that intervention trials should be done by the local health facilities with community involvement, and a local decision is made according to their own trial results.

Применение интерферона альфа-2b для профилактики новой коронавирусной инфекции у медицинских работников

Novel coronavirus infection (COVID-19) caused by SARS-CoV-2 has some specific clinical and immunopathogenic properties. SARS-CoV-2 is a single-stranded RNA virus that belongs to the Coronaviridae family, the Betacoronavirus genus. COVID-19 can be asymptomatic, the most common clinical manifestation of this disease is viral pneumonia. The development of acute respiratory distress syndrome is noted in less than 5% of cases. The entry gates of this virus are the epithelium of the upper respiratory tract and epithelial cells (epitheliocytes) of the gastrointestinal tract. When the virus enters the human respiratory tract, mucociliary clearance is inhibited and epithelial cells die, allowing the virus to enter the peripheral blood with subsequent damage to target organs (lungs, digestive tract, heart, kidneys). An important pathogenic characteristic of SARS-CoV-2 infection, especially with severe disease, is an excessive immune system response with massive release of cytokines, which causes acute respiratory distress syndrome. Clinical and experimental studies have shown that SARS-CoV-2 can be significantly more sensitive to type I interferons (IFN-I), than other coronaviruses. IFN-I deficiency is thought to play a key role in the pathogenesis of COVID-19, and several studies have shown that delayed IFN-I signaling is associated with sustained viral replication and serious complications. The use of interferon-based medicines (IFN-I) for the treatment and prevention of COVID-19 appears to be quite important to study attentively. This paper presents an original regimen of recombinant interferon alpha-2b-based medicine (Grippferon®, nasal drops and spray) for the medication-assisted post-exposure prevention of COVID-19 in healthcare specialists, working in the pediatric infectious disease hospital. The effectiveness and safety of this medication regimen for the COVID-19 prevention was shown. Key words: medication-assisted prevention, COVID-19, post-exposure protection of healthcare workers, recombinant interferon alpha-2b, Grippferon

Oral manifestation and dental treatment of pediatric patient with beta-mannosidosis: A case report

β-mannosidosis is a rare autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of β-mannosidase. Clinical presentation includes intellectual deficits, hearing loss, and recurrent respiratory infections. This report describes the dental treatment and follow-up dental care of a child with β-mannosidosis. The patient presented to the dental clinic at the age of 6 years with a localized swelling of his lower posterior teeth. Sickle cell disease and physical and mental developmental delays were noted. Clinical examination revealed a flattened nasal bridge, large head, short neck, open bite, gingival overgrowth, macroglossia, enlarged pulp chambers, and poor oral hygiene. Surgical treatment under general anesthesia included extractions, pulp therapy, and restorations. Four years later, the child returned with generalized gingival inflammation and new carious lesions. Periodontal and restorative treatment was provided, and a preventive dental regimen was established. Mannosidosis cases require complex dental procedures, consultations, and prompt follow-up.

Childhood trauma and cardiometabolic risk in severe mental disorders: The mediating role of cognitive control.

Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics. Participants with schizophrenia and bipolar spectrum disorders (N=819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes' PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group. Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p=0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference. The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

Comparison of colloid preloading and continuous infusion of norepinephrine versus crystalloid co-loading and continuous infusion of norepinephrine in the prevention of maternal hypotension

Background and goal of study: Spinal anesthesia for cesarean section can be frequently complicated by hypotension, with untoward effects for both the mother and fetus. Recently, norepinephrine has been shown to be effective in maintaining blood pressure in obstetric patients. Another technique widely used to prevent hypotension is fluid administration. Current evidence suggests that the combination of fluid administration and vasoconstrictive medications should be the main strategy for prevention and management of hypotension. The aim of this randomized study was to investigate the combination of a norepinephrine infusion and colloid preloading versus the combination of a norepinephrine infusion and crystalloid co-loading for the prevention of maternal hypotension during elective cesarean section under combined spinal-epidural anaesthesia Materials and methods: One hundred parturients were randomized to receive either 6% hydroxyethyl starch 130/0.4 5 mL/kg before spinal anesthesia (colloid preload) or Ringer’s Lactate solution 10 mL/kg starting with intrathecal injection (crystalloid co-load). Both groups were also administered norepinephrine 4 μg/min, starting simultaneously with the administration of the subarachnoid solution. The primary outcome was the incidence of maternal hypotension (SBP <80% of baseline). The incidence of severe hypotension (SAP <80 mmHg), total dose of ephedrine administered as well as maternal side-effects and the acid-base status and Apgar score of the neonate were also recorded Results: There were no significant differences in the incidence of hypotension (13.7% vs. 16.3%, P = 0.933 or severe hypotension (0% vs. 4%, P = 0.238) between colloid preload and crystalloid co-load groups, respectively. The median [range] ephedrine dose was 0 [0–15] mg in the colloid preload group and 0 [0–10] mg in the crystalloid co-load group (P = 0.807). There were no significant differences in maternal side-effects or neonatal outcomes between groups Conclusion: The incidence of hypotension during elective cesarean section is low and comparable when a norepinephrine infusion is used in combination with either colloid preload or crystalloid co-load, with perhaps a marginal superiority of colloid preload in the prevention of severe hypotension. It appears that the optimal regimen for prevention of maternal hypotension is a combination of fluids and a prophylactic vasopressor like norepinephrine.

Estimation of Flouride Concentration in Drinking Water Sources of Bhilai, Chattisgarh

Background: Fluoride has always been considered as a “double edged sword”. The optimum and judicious use of fluoride has resulted in caries protection whereas injudicious use has resulted in chronic fluoride toxicity, which manifests as dental and skeletal fluoride. Dental fluorosis occurring due to drinking water with high concentration of fluoride is a common public health problem in India. Hence the present study was designed with an aim to estimate fluoride concentration in drinking water source of the people from Bhilai, Chattisgarh. Aim: To estimate fluoride concentration in drinking water source of the people from Bhilai, Chattisgarh. Material and Methods: Eight different samples of ground water was collected from bhiali, Chattisgarh, which is divided into four different areas: kurud (north), Maroda (south), Charoda (east), Nehrunagar (west); all these samples were tested by HI-96759-11 portable photometre and the fluoride concentration was determined. All the data obtained was then further subjected to statistical analysis and a conclusion was inferred regarding the fluoride concentration of drinking water source of the people of Bhilai, Chattisgarh which is essential for an effective fluoride regimen for prevention of dental caries in children. Result: Highest fluoride concentration in Bhilai is found to be 0.52 ± .056 ppm and the lowest being 0.31 ± .148 ppm. So, the fluoride concentration of the ground water in Bhilai is found to be in the range of 0.3-o.6 ppm. Thus, it does not possess any chance to cause dental fluorosis in the people of Bhilai. However, a fluoride supplementation of 0.25mg/day for 3-6yrs children and 0.50mg/day for 6-16yrs children can be done to enhance the prevention of dental caries in the children residing in Bhilai, Chattisgarh.

Blockade of High-Fat Diet Proteomic Phenotypes Using Exercise as Prevention or Treatment

AbstractThe increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the overconsumption of a high-fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regimen for animals on either a HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and downregulation of SERPINA1E and complement factor D (CFD; adipsin). Some of these changes were significantly reverted using exercise as a preventative measure but not as a treatment regimen. To determine if either the intensity or duration of exercise influenced the outcome, we compared high-intensity interval training and endurance running. Endurance running slightly outperformed high-intensity interval training exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the HFD, including SERPINA7, apolipoprotein E, SERPINA1E, and CFD. Finally, we compared the changes induced by overconsumption of a HFD with previous data from mice fed on an isocaloric high-saturated fatty acid or polyunsaturated fatty acid diet. This identified several common changes, including not only increased apolipoprotein C-II and apolipoprotein E but also highlighted changes specific for overconsumption of a HFD (fructose-bisphosphate aldolase B, SERPINA7, and CFD), saturated fatty acid–based diets (SERPINA1E), or polyunsaturated fatty acid–based diets (haptoglobin). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by HFD consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

Methods for Caries Prevention in Children Reported by Dentists from a Brazilian Community

Objective: To describe the dental practice patterns related to caries prevention in children aged 6-18 years and associated factors . Material and Methods: Dentists (n=162) from Araraquara, Brazil, completed two paper questionnaires: (1) one about characteristics of their practice and their patient population; and (2) a translated version of the “Assessment of Caries Diagnosis and Caries Treatment” Questionnaire from the National Dental Practice-Based Research Network. Regression analyses were used for data analysis (p<0.05). Results: Dentists reported using in-office fluoride (IOF) and dental sealants (DS) in 74.2% and 45.1% of their pediatric patients, respectively. Regression analysis showed that female dentists (p=0.035 for DS; p=0.044 for IOF; p=0.011 for non-prescription fluoride rinse), those with advanced degrees (p=0.032 for prescription of fluoride), those who graduated from a private dental school (p=0.018 for chlorhexidine rinse), those who provided caries prevention regimens (p<0.001 for DS; p=0.004 for IOF; p=0.013 for non-prescription fluoride rinse), those with a greater percentage of patients interested in a caries prevention regimen (p=0.007 for non-prescription fluoride rinse), those working in a private practice model (p=0.047 for prescription of fluoride) were more likely to recommend some type of preventive methods to their pediatric patients . Conclusion: Dentists reported recommending IOF to most of their pediatric patients. Certain dentists’, practices’, and patients’ characteristics were associated to some caries prevention regimens recommended by dentists.

Efficacy and Safety of Adding Olanzapine to the Standard Preventive Regimen for Chemotherapy-induced Nausea and Vomiting in Children: A Randomized Double-blind Controlled Trial.

This study aimed to assess the additive value of olanzapine to a combination of ondansetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. A total of 40 patients between 4 to 18 years of age were enrolled in this randomized clinical trial. Both groups received a combination of ondansetron and dexamethasone, and 0.14 mg/kg olanzapine or matched placebo were administered for olanzapine and control groups, respectively. The primary end points were complete response and lack of nausea as far as three days after chemotherapy evaluated by the Common Terminology Criteria for Adverse Effects (CTCAE) v5.0 and the Multinational Association of Supportive Care in Cancer (MASCC) Anti-emesis Tool (MAT). Side effects of olanzapine were also analyzed. In patients receiving the standard regimen of ondansetron and dexamethasone, nausea was observed in 10.5% and 21% of patients according to MAT and CTCAE scales, respectively. In the olanzapine group, 37.5% (MAT scale) and 31.3% (CTCAE scale) of patients developed nausea. Complete response was observed in 84% (MAT scale) and 94.7% (CTCAE scale) of patients in the placebo group receiving ondansetron and dexamethasone. In comparison, it was observed in 87.5% (MAT scale) and 81.25% (CTCAE scale) for patients allocated to the olanzapine group. Neither acute nor delayed CINV was statistically different between placebo and olanzapine groups. The frequency of adverse effects was higher in the olanzapine group. Adding olanzapine to the standard regimen of CINV prophylaxis was only unhelpful in pediatric patients receiving moderately emetogenic chemotherapy but also associated with a higher rate of minor side effects.

Fallout Following Unproven Prophylactic Use of Exogenous Vitamin D for COVID-19

The ongoing COVID-19 (Coronavirus Disease of 2019) pandemic has devastated the human race socially, psychologically, mentally, medically, and economically. It has greatly impacted both developed and developing societies. No region of the earth has been spared of the adverse consequences of the disease. To date, the treatment of the disease has remained ill-defined. Additionally, there are no standard preventive regimens for the disease except for non-pharmacologic interventions and vaccinations. However, several unproven preventive medications are awash in social media including the use of chloroquine, Zinc, Ivermectin, Vitamin D, and so many others as prophylactic agents for COVID-19. This has led to the unregulated/unsupervised self-induced consumption of these unproven medications that may be deleterious to health if taken in excess. Herein is a case of a 24-year-old undergraduate who self-medicated with a high dosage of exogenous Vitamin D for unproven COVID-19 prophylaxis for 2 months. He developed Vitamin D Toxicity (VDT) and manifested with varying clinical (dehydration, hypertension, acute abdomen) and metabolic (hypercalcemia, hypokalemia, alkalosis, hyperphosphatemia, hypoparathyroidism, hypercalciuria, and crystalluria) consequences all related to VDT. However, hypercalcemia was the initiating metabolic disorder for all the clinical and the other metabolic derangements. He was admitted, managed accordingly, and discharged home in good clinical condition. Regulations and public health enlightenment of these unproven medications, including Vitamin D, for COVID-19 prophylaxis, should be prioritized to stem the deleterious effect of these agents. These measures will limit the current pandemic to a viral pandemic rather than a pandemic of drug misuse and overdose.

Genetic diversity of the Plasmodium falciparum GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase genes reveals new insights into sulfadoxine-pyrimethamine antimalarial drug resistance.

Plasmodium falciparum parasites resistant to antimalarial treatments have hindered malaria disease control. Sulfadoxine-pyrimethamine (SP) was used globally as a first-line treatment for malaria after wide-spread resistance to chloroquine emerged and, although replaced by artemisinin combinations, is currently used as intermittent preventive treatment of malaria in pregnancy and in young children as part of seasonal malaria chemoprophylaxis in sub-Saharan Africa. The emergence of SP-resistant parasites has been predominantly driven by cumulative build-up of mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, but additional amplifications in the folate pathway rate-limiting pfgch1 gene and promoter, have recently been described. However, the genetic make-up and prevalence of those amplifications is not fully understood. We analyse the whole genome sequence data of 4,134 P. falciparum isolates across 29 malaria endemic countries, and reveal that the pfgch1 gene and promoter amplifications have at least ten different forms, occurring collectively in 23% and 34% in Southeast Asian and African isolates, respectively. Amplifications are more likely to be present in isolates with a greater accumulation of pfdhfr and pfdhps substitutions (median of 1 additional mutations; P<0.00001), and there was evidence that the frequency of pfgch1 variants may be increasing in some African populations, presumably under the pressure of SP for chemoprophylaxis and anti-folate containing antibiotics used for the treatment of bacterial infections. The selection of P. falciparum with pfgch1 amplifications may enhance the fitness of parasites with pfdhfr and pfdhps substitutions, potentially threatening the efficacy of this regimen for prevention of malaria in vulnerable groups. Our work describes new pfgch1 amplifications that can be used to inform the surveillance of SP drug resistance, its prophylactic use, and future experimental work to understand functional mechanisms.

Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure.

Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models. Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats. Seventy-five mice underwent a prevention treatment strategy with a KE comprised of hexanoyl-hexyl-3-hydroxybutyrate KE (KE-1) diet, and 77 rats were treated in either a prevention or treatment regimen using a commercially available β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG; KE-2) diet. The KE-1 diet in mice elevated β-hydroxybutyrate levels during nocturnal feeding, whereas the KE-2 diet in rats induced ketonemia throughout a 24-hour period. The KE-1 diet preventive strategy attenuated development of left ventricular dysfunction and remodeling post-transverse aortic constriction/MI (left ventricular ejection fraction±SD, 36±8 in vehicle versus 45±11 in KE-1; P=0.016). The KE-2 diet therapeutic approach also attenuated left ventricular dysfunction and remodeling post-MI (left ventricular ejection fraction, 41±11 in MI-vehicle versus 61±7 in MI-KE-2; P<0.001). In addition, ventricular weight, cardiomyocyte cross-sectional area, and the expression of ANP (atrial natriuretic peptide) were significantly attenuated in the KE-2-treated MI group. However, treatment with KE-2 did not influence cardiac fibrosis post-MI. The myocardial expression of the ketone transporter and 2 ketolytic enzymes was significantly increased in rats fed KE-2 diet along with normalization of myocardial ATP levels to sham values. Chronic oral supplementation with KE was effective in both prevention and treatment of heart failure in 2 preclinical animal models. In addition, our results indicate that treatment with KE reprogrammed the expression of genes involved in ketone body utilization and normalized myocardial ATP production following MI, consistent with provision of an auxiliary fuel. These findings provide rationale for the assessment of KEs as a treatment for patients with heart failure.

The protective function of invariant natural killer T cells in the relapse of experimental autoimmune uveoretinitis

Experimental autoimmune uveoretinitis (EAU) in mice provides a useful platform to study the pathogenesis and experimental therapeutics of human uveitis. One often used EAU model employs C57BL/6 (B6) mice sensitized with a peptide residue having 1 to 20 amino acids of human interphotoreceptor retinoid binding protein (hIRBP1-20). The model using the B6 background has permitted a liberal use of genetically engineered strains and has provided insights for understanding uveoretinitis. However, this is usually acute/monophasic and does not represent human uveoretinitis that is characterized as a chronic/recurrent disease. Several chronic/recurrent EAU models have been developed; of these, we employed administration of staphylococcal enterotoxin B (SEB) for relapse in the present study, and found that recurrence was induced at day 24 after primary immunization, which is thought to be the convalescent phase. We reported the activation of invariant natural killer T (iNKT)-cells upon primary immunization of the EAU model mice with the ligand RCAI-56, which was found to mitigate the disease in our previous study. Here, we first attempted to ameliorate EAU in the relapse model using a preventive regimen by activating iNKT cells at the same time relapse induction (day 24) or in a regimen after 3 days of relapse induction (day 27). The preventive as well as post-inductive regimens were successful in reducing histopathological scores by inhibiting the Ag-specific Th17-biased response. Collectively, activation of iNKT cells may be useful to mitigate the relapse response of EAU induced with SEB.

STRENGTHENING AND STABILIZATION EXERCISES IN PREVENTION OF SHOULDER INJURIES

The shoulder joint is the most flexible joint in the human body which experiences high loads during certain sport activities involving overhead motion. Overhead athletes experience rapid shoulder elevation, abduction and external rotation during the movement and rapid deceleration after the movement, making them susceptible to shoulder injuries. Due to the extreme ranges of motion, overhead athletes tend to develop increased external rotation, combined with decreased range of internal rotation, emphasizing the need for balanced shoulder care program in the training process to prevent such occurrences. The aim of the research paper was to develop training regimen for injury prevention and shoulder maintenance that can be incorporated in daily training activities of the athletes in order to decrease the occurrence of injuries. Three part training program was designed consisting of specific warm up, strengthening and stabilization exercises and stretching exercises. The aim of the specific warm up was to prepare the shoulder for the training loads, mimicking the overhead movements and stimulating the stabilization in the joint. Strengthening and stabilization exercises aimed to strengthen external rotators in the shoulder and improve the stabilization of the shoulder joint by targeting specific muscles such as serratus anterior. The focus of stretching exercises was to stretch internal rotation muscles, which experience high loads in the overhead athlete's training. An effective training program that can be performed with minimal equipment and in a short time frame was designed to enable its simple incorporation into the daily training of overhead athletes.

Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90

AbstractTrial ALL-BFM 90 was designed to improve outcome in patients with childhood acute lymphoblastic leukemia (ALL) by using a reduced treatment regimen. Patients were stratified into a standard-risk group (SRG), a medium-risk group (MRG), both defined by adequate early treatment response; and a high-risk group (HRG), defined by inadequate response to the cytoreductive prednisone prephase, induction failure, or Philadelphia-chromosome–positive ALL. Four treatment modifications were evaluated: dose intensification in induction by a more rapid drug sequence; administration of l-asparaginase during consolidation therapy in the MRG (randomized); enforced consolidation by rotational elements in the HRG; and reduction in the dose of anthracyclines and use of only 12-Gy preventive cranial radiotherapy in the MRG and HRG, with the aim of avoiding toxicity. Among all 2178 patients (≤ 18 years of age), the 6-year event-free survival (EFS) rate (± SE) was 78% ± 1%, with a median observation time of 4.8 years. EFS was 85% ± 2% in the SRG (n = 636) and 82% ± 1% in the MRG (n = 1299). l-asparaginase did not improve outcome in the MRG: the event-free interval was 83% ± 2% withl-asparaginase (n = 528) and 81% ± 2% without it (n = 557). Because there were more systemic relapses in the HRG (n = 243), EFS was 34% ± 3%, an outcome inferior to that in the HRG in a previous trial, ALL-BFM 86, in which EFS was 47% ± 5% (P = .04). The rates of isolated central nervous system relapse in the MRG and HRG were 0.8% and 1.6%, respectively; thus, the 12-Gy preventive cranial radiotherapy regimen apparently provided sufficient central nervous system prophylaxis. The overall improvement over the results in ALL-BFM 86 (6-year EFS, 72%; P = .001) was based on fewer recurrences among patients in the MRG with B-cell-precursor ALL, indicating an advantage of more condensed induction therapy. In multivariate analysis, inadequate in vivo response emerged as the strongest adverse prognostic variable.

Cost of Delivering 12-Dose Isoniazid and Rifapentine Versus 6 Months of Isoniazid for Tuberculosis Infection in a High-Burden Setting.

BackgroundSuccessful delivery and completion of tuberculosis preventive treatment are necessary for tuberculosis elimination. Shorter preventive treatment regimens currently have higher medication costs, but patients spend less time in care and are more likely to complete treatment. It is unknown how economic costs of successful delivery differ between longer and shorter regimens in high-tuberculosis-burden settings.MethodsWe developed survey instruments to collect costs from program and patient sources, considering costs incurred from when household contacts first entered the health system. We compared the cost per completed course of preventive treatment with either 6 months of daily isoniazid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network tuberculosis program in Karachi, Pakistan, between October 2016 and February 2018.ResultsDuring this period, 459 individuals initiated 6H and 643 initiated 3HP; 39% and 61% completed treatment, respectively. Considering costs to both the program and care recipients, the cost per completed course was 394 US dollars (USD) for 6H and 333 USD for 3HP. Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP to 290 USD. Under varying assumptions about drug prices and costs incurred by care recipients, the cost per completed course was lower for 3HP in all scenarios, and the largest cost drivers were the salaries of clinical staff.ConclusionsIn a high-burden setting, the cost of successful delivery of 3HP was lower than that of 6H, driven by higher completion.

Clinical features of recurrent Mycoplasma pneumoniae-induced rash and mucositis.

The characteristics of patients experiencing recurrent Mycoplasma pneumoniae-induced rash and mucositis (MIRM) are not well understood. We aimed to characterize patients with recurrent disease by comparing the demographics, skin and mucosal involvement, seasonality, and treatment to those with single episodes (isolated MIRM). This retrospective case series screened all patients seen by our dermatology inpatient consult service from September 2014 to March 2020. Cases were selected based on laboratory and clinical criteria that confirmed a diagnosis of MIRM. We identified 13 patients with MIRM: 5 who experienced recurrence (38%) and 8 with isolated, single episodes without recurrence. Mean age was 13.6years for initial episodes in the recurrent patients compared to 11.7 in patients with isolated episodes. All 5 recurrent MIRM patients were male (compared with 75% of isolated MIRM patients) and predominantly Black (60%, compared with 25%). Most episodes overall (isolated and recurrent) occurred from the months of October to February. Recurrences after initial MIRM episode had less severe skin and mucosal findings, often involving only one mucous membrane, less frequent need for hospital admission, and shorter duration of hospital stay. Prophylactic treatments and treatments beyond supportive care were of unclear value. Some characteristics of MIRM differ between patients with recurrent and isolated disease. Clinicians should be aware of the potential for recurrence, which occurred in 38% of our cohort. Although recurrences after initial MIRM episode tended to be less severe, there is still potential for prolonged hospitalizations with recurrent episodes. More evidence is needed regarding effective preventive and treatment regimens in patients with recurrent MIRM.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.

Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. The NMA included 24 studies evaluating 14 regimens in 11321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin+lactated Ringer's solution, followed by diclofenac+nitrate and indomethacin+normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.

The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) cause significant morbidity and premature mortality among Australian Aboriginal and Torres Strait Islander peoples. RHDAustralia has produced a fully updated clinical guideline in response to new knowledge gained since the 2012 edition. The guideline aligns with major international ARF and RHD practice guidelines from the American Heart Association and World Heart Federation to ensure best practice. The GRADE system was used to assess the quality and strength of evidence where appropriate. The 2020 Australian guideline details best practice care for people with or at risk of ARF and RHD. It provides up-to-date guidance on primordial, primary and secondary prevention, diagnosis and management, preconception and perinatal management of women with RHD, culturally safe practice, provision of a trained and supported Aboriginal and Torres Strait Islander workforce, disease burden, RHD screening, control programs and new technologies. Key changes include updating of ARF and RHD diagnostic criteria; change in secondary prophylaxis duration; improved pain management for intramuscular injections; and changes to antibiotic regimens for primary prevention. Other changes include an emphasis on provision of culturally appropriate care; updated burden of disease data using linked register and hospitalisations data; primordial prevention strategies to reduce streptococcal infection addressing household overcrowding and personal hygiene; recommendations for population-based echocardiographic screening for RHD in select populations; expanded management guidance for women with RHD or ARF to cover contraception, antenatal, delivery and postnatal care, and to stratify pregnancy risks according to RHD severity; and a priority classification system for presence and severity of RHD to align with appropriate timing of follow-up.

МОРФОФУНКЦИОНАЛЬНЫЕ НАРУШЕНИЯ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА И ИХ ПРОФИЛАКТИКА У ДЕТЕЙ С ЗАБОЛЕВАНИЯМИ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА, НАХОДЯЩИХСЯ НА ОРТОДОНТИЧЕСКОМ ЛЕЧЕНИИ

Subject. At present, diseases of the gastrointestinal tract, with a high frequency in children aged 9―14 years, are accompanied by lesions of the oral mucosa. These conditions are aggravated with orthodontic treatment. Therefore, the development of a scheme for the prevention of complications in children with gastrointestinal diseases undergoing orthodontic treatment is an urgent task of modern dentistry.&#x0D; Purpose ― to consider the problem of the state of the oral cavity and the cytological characteristics of the mucous membrane in children with gastrointestinal diseases, physiological occlusion and malocclusion undergoing orthodontic treatment, to investigate the dynamics of inflammatory processes of the jaw mucosa under the bases of removable orthodontic appliances.&#x0D; Methodology. The study involved 60 children aged 7―15 years. The cytomorphometric method was used.&#x0D; Results. The results of the study showed the possibility of using the cytomorphometric method for diagnosing and evaluating the effectiveness of the use of various prevention programs and medicines during orthodontic treatment. Cytomorphometry revealed significant differences in the effectiveness of the proposed prophylaxis scheme in children, contributed to the improvement of cytogram parameters and normalization of the inflammatory-destructive index, however, complete recovery of all cytomorphological parameters in patients undergoing orthodontic treatment did not occur.&#x0D; Conclusions. To improve the level of oral hygiene for children undergoing orthodontic treatment, it is necessary to use not only therapeutic and prophylactic toothpastes, but also an additional amount of prophylaxis. Children with gastrointestinal tract diseases and malocclusion who are undergoing orthodontic treatment are recommended to include Lizobact drugs in the periodontal disease prevention regimen, however, the use of these drugs alone is not enough to completely eliminate the inflammatory process.