Improving immune reconstitution while preventing graft-versus-host disease in allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies or inherited disorders. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevent the development of graft-versus-host disease (GVHD). However, the consequence of these nonspecific approaches is a long-lasting immunodeficiency associated with increased disease relapse, graft rejection, and reactivation of viral infections. Donor lymphocyte infusion, to treat leukemic relapse after allogeneic HSCT, can cause severe GVHD. Several strategies are being optimized to specifically inactivate anti-host T cells while preserving antileukemic or antimicrobial immunocompetence, based on ex vivo or in vivo elimination of anti-host T cells or on the modulation of their anti-host activity.     

Fluoridation cessation and oral health equity: a 7-year post-cessation study of Grade 2 schoolchildren in Alberta,Canada

ObjectiveCommunity water fluoridation, because of its universal scope and passive mechanism of uptake, is one component of a multifaceted approach to promoting equity in dental health. The objective of this study was to examine social inequities in children’s dental health in the Canadian cities of Calgary (fluoridation cessation in 2011) and Edmonton (still fluoridated).MethodsWe analyzed data from surveys of population-based samples of Grade 2 (approx. age 7) children in Calgary in 2009/2010 (pre-cessation; n=557) and in both Calgary and Edmonton in 2013/2014 (Calgary, n=3230; Edmonton, n=2304) and 2018/2019 (Calgary, n=2649; Edmonton, n=2600) (post-cessation). We estimated associations between several socioeconomic indicators and dental caries indicators (i.e., dental caries experience [deft, DMFT] and untreated decay in two or more teeth [untreated decay]) using zero-inflated Poisson, binary logistic regression, and the concentration index of inequality. We compared those associations over time (between survey waves) and between cities at post-cessation.ResultsPersistent social inequities in deft and untreated decay were evident; for example, having no dental insurance was significantly associated with higher odds of untreated decay across city and survey wave. In most (but not all) cases, differences between cities and survey waves were consistent with an adverse effect of fluoridation cessation on dental health inequities. For example, the association between no dental insurance and higher odds of untreated decay in Calgary was greater in 2018/2019 (later post-cessation) than in 2009/2010 (pre-cessation; odds ratio [OR] for comparison of coefficients = 1.89 [1.36–2.63], p<0.001) and 2013/2014 (early post-cessation; OR for comparison of coefficients = 1.67 [1.22–2.28], p=0.001); that same association in 2018/2019 was greater in Calgary (fluoridation cessation) than in Edmonton (still fluoridated) (OR for comparison of coefficients = 1.44 [1.03–2.02], p=0.033).ConclusionSocial inequities in dental caries were present in both Calgary and Edmonton. Those inequities tended to be worse in Calgary where fluoridation was ceased. Our findings may be relevant to other settings where income inequality is high, dental services are costly, and dental public health infrastructure is limited.     

Observational Cohort Study of Evolving Epidemiologic,Clinical, and Virologic Features of Monkeypox in Southern France

We enrolled 136 patients with laboratory-confirmed monkeypox during June 4–August 31, 2022, at the University Hospital Institute Méditerranée Infection in Marseille, France. The median patient age was 36 years (interquartile range 31–42 years). Of 136 patients, 125 (92%) were men who have sex with men, 15 (11%) reported previous smallpox vaccinations, and 21 (15.5%) were HIV-positive. The most frequent lesion locations were the genitals (68 patients, 53%), perianal region (65 patients, 49%), and oral/perioral area (22 patients, 17%). Lesion locations largely corresponded with the route of contamination. Most (68%) patients had isolated anal, genital, or oral lesions when they were first seen, including 56 (61%) who had >1 positive site without a visible lesion. Concurrent sexually transmitted infections were diagnosed in 19 (15%) patients, and 7 patients (5%) were asymptomatic. We recommend vaccination campaigns, intensified testing for sexually transmitted infections, and increased contact tracing to control the ongoing monkeypox outbreak.     

Feature Selection Based on Modified Bio-inspired Atomic Orbital Search Using Arithmetic Optimization and Opposite-Based Learning

Feature selection (FS) has the largest influence on the performance of machine learning methods. FS can remove the irrelevant and redundancy features from the data while preserving the same quality of increasing it. However, the traditional FS methods are time-consuming and can be stuck in local optima. So, the metaheuristic (MH) techniques are used to avoid these limitations since they have several operators that explore and exploit the search domain better than traditional methods. Besides these behaviors of MH, we present an improved atomic orbital search (IAOS) algorithm using a global search strategy that uses the operators of arithmetic optimization algorithm (AOA), which has proven a good exploration ability to provide a promising candidate solution. The opposite-based learning (OBL) is applied to enhance the initial population, which leads to enhancing the convergence rate towards the optimal solution. In addition, a dynamic photon rate is used to enhance the balance between exploration and exploitation. Finally, the sequential backward selection (SBS) is used as a local search strategy to improve the best solution, and this leads to obtaining a set of relevant features that increase the classification accuracy. To evaluate the performance of the presented IAOS-SBS as an FS method, a set of twenty UCI datasets is used; also, it is compared with other well-known FS methods. The results show the superiority of IAOS-SBS among the performance measures. Finally, it is concluded that IAOS-SBS can select fewer features with achieving high classification accuracy for most of the datasets utilized in the study. This indicates the use of OBL and SBS leads to enhancing the original AOS.

     

Community Health Worker Interventions to Improve Glycemic Control in People with Diabetes: A Systematic Review and Meta-Analysis

OBJECTIVES

We set out to review the efficacy of Community Health Worker (CHW) interventions to improve glycemia in people with diabetes.

METHODS

Data sources included the Cochrane Central Register of Controlled Trials, Medline, clinicaltrials.gov, Google Scholar, and reference lists of previous publications. We reviewed randomized controlled trials (RCTs) that assessed the efficacy of CHW interventions, as compared to usual care, to lower hemoglobin A1c (A1c). Two investigators independently reviewed the RCTs and assessed their quality. Only RCTs with a follow-up of at least 12 months were meta-analyzed. A random effects model was used to estimate, from unadjusted within-group mean reductions, the standardized mean difference (SMD) in A1c achieved by the CHW intervention, beyond usual care.

RESULTS

Thirteen RCTs were included in the narrative review, and nine of them, which had at least 12 months of follow-up, were included in the meta-analysis. Publication bias could not be ruled-out due to the small number of trials. Outcome heterogeneity was moderate (I²= 37 %). The SMD in A1c (95 % confidence interval) was 0.21 (0.11-0.32). Meta-regression showed an association between higher baseline A1c and a larger effect size.

CONCLUSIONS

CHW interventions showed a modest reduction in A1c compared to usual care. A1c reduction was larger in studies with higher mean baseline A1c. Caution is warranted, given the small number of studies.     

Biphenotypic plasma cell myeloma: two cases of plasma cell neoplasm with a coexpression of kappa and lambda light chains

Plasma cell neoplasm (PCM) is a medullary and extra medullary proliferation of clonal plasma cells that occurs due to accidental translocation of proto-oncogenes into immunoglobulin (Ig) gene loci. While the majority of plasma cell neoplasms are monoclonal, up to 2% of the PCMs [1] considered being biclonal based on electrophoretic analysis, characterized by secretion of paraprotein with two distinct heavy chains or light chains are possible and present unique diagnostic challenges. Methods: Traditionally protein electrophoresis has been used to diagnose, characterize, and monitor progression of plasma cell neoplasm. To characterize neoplastic plasma cells, in our institution, other ancillary studies, including in situ hybridization, flow cytometric analyses of plasma cell surface markers and cytoplasmic immunoglobulins with DNA ploidy, are also utilized routinely. Results: We present two cases of plasma cell myeloma in which the neoplastic plasma cells shows production of cytoplasmic kappa and lambda light chain, with secretion of free lambda light chain only. Co-expression of kappa and lambda light chain by the same neoplastic plasma cells is a rare but reported phenomenon. Conclusions: Our study indicates that serum electrophoresis alone could mischaracterize biphenotypic myeloma as monotypic plasma cell myelomas in the absence of additional testing methods.     

Cost-effectiveness analysis of medical intervention in patients with early detected of Diabetic Nephropathy in a tertiary care hospital in Bangladesh

The economic burden resulting from Diabetic Nephropathy (DN) consumes a major portion of resources allocated for health-care services. Cost-effectiveness of various interventions on DN and its complications have relatively been well explored in developed countries, but these are almost absent in developing countries. The present study was undertaken to assess the cost-effectiveness of medical intervention in patients with DN. Two hundred patients with DN, with at least 1 yr of follow-up, were purposively selected from BIRDEM (tertiary diabetes care hospital) of Bangladesh. Of them 100 were late in detection (Serum Creatinine ≥4.0 mmom/l, Late detected DN or Late detected diabetic nephropathy) and 100 were detected early (Serum Creatinine <4.0 mmom/l, early detected DN or early detected diabetic nephropathy). The degree and extent of complications like cardiopathy, peripheral neuropathy, retinopathy and vasculopathy, treatment outcome, clinical effectiveness of interventions and direct, indirect and incremental cost of complications were calculated. Comparison was made between the groups. Cost included drugs, hospitalizations, diagnostics and visits. A total of 200 patients were considered for an average of 365 days, amounting to 651 person years of observation in total. The mean ± SD fasting serum glucose of the groups was 9.36 ± 0.40 mmol/l and 4.78 ± 0.38 mmol/l, total cholesterol was 206.50 ± 42.60 and 104.20 ± 35.50 mg/dl, HbA1c was 9.80 ± 0.50% and 5.70 ± 0.38%, TG was 163.76 ± 99.46 and 155.67 ± 94.84 mg/dl and serum creatinine was 0.89 ± 0.03 and 4.90 ± 1.17 mmol/l in Late detected diabetic nephropathy and early detected diabetic nephropathy respectively. About 19% patients in Late detected diabetic nephropathy and 36% in early detected diabetic nephropathy were free of diabetic complications other than DN. In Late detected diabetic nephropathy, 32% had one complication, 29% had two and 20% had more than two complications. On the other hand, in early detected diabetic nephropathy the corresponding values were 48%, 10% and 6% respectively. The most frequent complication was cardiopathy, which affected 33% patients in Late detected diabetic nephropathy and 27% in early detected diabetic nephropathy, followed by peripheral neuropathy 21% and 18%, retinopathy 17% and 13%, and vasculopathy 10% and 6% respectively. The average annual cost of care was US$ 27,954 (direct US$ 16,983 and indirect US$ 10,971), with an average US$ 140 per patient. Among the average annual cost Late detected diabetic nephropathy consumed US$ 19,837 (US$ 198 per patient) and early detected diabetic nephropathy US$ 8117 (US$ 81 per patient). 48% (US$ 13,473) of costs were attributable to drugs for both groups of which US$ 10,817 (80%) was for Late detected diabetic nephropathy and US$ 2656 (20%) for early detected diabetic nephropathy, 31% (US$ 8739) to hospitalizations of which US$ 5211 (60%) for Late detected diabetic nephropathy and 3528 (40%) for early detected diabetic nephropathy. In case of diagnostics and visits the corresponding values were US$ 2136 (60%) and 1419 (40%) and US$ 1673 (76%) and 514 (24%) for Late detected diabetic nephropathy and early detected diabetic nephropathy respectively. The annual medical costs increased with the number of complications from US$ 1320–2296 and to 3989 in Late detected diabetic nephropathy with one, two and more than two complications (other than DN) which is increasing at a rapid rate and US$ 917–1556 and to 2372 in early detected diabetic nephropathy respectively, increasing at a diminishing marginal rate. The regression equation showed that medical cost is significantly related to complications tested in both univariate (P < 0.0001) and multiple linear regression analyses (R² = 0.52; F = 82.3, P < 0.0001). Proper management with regular screening substantially reduces the expenditure related to care of patients with Diabetic Nephropathy and related complications even in a developing country. Strategies aimed at preventing Diabetic Nephropathy and early detection of the onset of nephropathy complication will reduce medical costs in a substantial way.     

Association between antibiotic use and changes in susceptibility patterns of Pseudomonas aeruginosa in an intensive care burn unit: a 5-year study, 2000-2004

This study aimed to evaluate the relationship between antimicrobial resistance in Pseudomonas aeruginosa and annual antibiotic use in a burn unit.From 1 January 2000 to 31 December 2004, 203 non-repetitive strains of Ps. aeruginosa were recovered from various clinical specimens. Antimicrobial susceptibility testing was performed using the disc diffusion method, and susceptibility data were interpreted according to break points recommended by the French Society of Microbiology. The antibiotic consumption for imipenem, ceftazidime, cefotaxime, piperacillin-tazobactam, ofloxacin, ciprofloxacin, gentamicin and amikacin was calculated with antimicrobial density. The relationship between antibiotic use and the resistance of Ps. aeruginosa was analysed.The consumption of ceftazidime and amikacin showed no association with resistance. A statistically significant relationship was observed between increasing use of ciprofloxacin and the incidence of resistant Ps. aeruginosa to this antibiotic (rs = 0.89, p = 0.05), and a significant correlation between ciprofloxacin consumption and resistance to imipenem was noted (rs = 0.89, p = 0.043). Restricted use of ciprofloxacin during 2003 and 2004 was followed by a significant decrease of resistance in Ps. aeruginosa. Our report illustrates the major role of ciprofloxacin in the emergence of resistant Ps. aeruginosa.