Ancillary Treatments Research Articles

Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.

COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few. Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children. We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports. The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives. COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.

Effect of probiotics on quality of life for patients with cancer undergoing immunotherapy.

e24148 Background: Probiotics are crucial in oncology for enhancing gut health, boosting immune response, potentially improving immunotherapy efficacy, and reducing side effects of cancer treatments. Research links a healthy gut microbiome with better immunotherapy outcomes, however, more studies in this area are required to validate this hypothesis. Methods: Oncological patients at Hospital Ángeles Puebla's Comprehensive Cancer Center undergoing immunotherapy were invited to participate and provided their consent to receive a daily probiotic and prebiotic mix (including Lactobacillus rhamnosus, Bifidobacterium longum, Pediococcus pentosaceus, and others) for three months. Their health was closely monitored, and quality of life assessed using the EORTC-QLQ-C30 questionnaire at the start, day 45, and day 90. A Kruskal-Wallis H-test was conducted to correlate the EORTC-QLQ-C30 scores with their diagnosis, clinical stage, presence of comorbidities, and use of ancillary treatments, as well as a Spearman's test to associate these scores with their age. Results: 22 patients were included. Average age was 64.5 years, with 77% being male and 23% female. 68.18% were in stage IV, 4.55% in stage III, 18.18% in stage II, and 9.09% in stage I. Comorbidities included: diabetes in 31.82%, hypertension in 40.91%, and other diseases in 22.73%. Treatment regimens involved 81.81% receiving Anti-PD-L1 and 18.18% receiving Anti-PD-1. Additionally, 40.91% were on corticosteroids and another 40.91% on proton pump inhibitors as ancillary treatments. Median follow-up was 3.13 months, during which 23% of the patients experienced adverse events. Of these, 9.09% were grade 4 according to the CTCAE v.5, and 13.63% were grade 1. Significant differences were found between patients with hepatocellular carcinoma versus renal carcinoma in the overall score on day 1 (KW: 4.47, p-value: 0.0344), with no differences in the rest of the scores. Significant differences were also identified between patients with advanced-stage versus early or locally advanced-stage cancer in terms of pain (KWS: 4.091, p-value: 0.043), dyspnea (KWS: 4.355, p-value: 0.037), loss of appetite (KWS: 4.091, p-value: 0.043), constipation (KWS: 3.971, p-value: 0.046), and diarrhea (KWS: 4.355, p-value: 0.037). A negative correlation was found between age and social functioning (Spearman: -0.73, p-value: 0.03), as well as with the presence of pain (Spearman: -0.73, p-value: 0.04). Conclusions: In this study, we observed a decrease in symptoms and an increase in functionality and overall quality of life scores among the patients. This suggests that patients undergoing active immunotherapy treatment may benefit from the use of probiotics and prebiotics as an ancillary treatment. However, further extended studies with larger populations are necessary to corroborate our findings.

Recurrence rate and management after endoscopic papillectomy in a tertiary referral center

Background and study aimsEndoscopic papillectomy (EP) is considered a safe procedure for ampullary lesions. Few data are available on management of residual and recurrent adenomas. The aims of the present study were to evaluate long-term recurrence rate, median time-to-recurrence after EP and treatment of both residual and recurrent adenomas. Patients and methodsConsecutive patients who underwent EP of major and minor papilla at our endoscopy center between 2011 and 2022 were enrolled. Residual adenoma was defined as the endoscopic evidence of adenomatous tissue after EP. Recurrent adenoma was defined as the presence of adenomatous tissue after the first endoscopic follow-up and complete adenoma resection. Results95 patients satisfied the inclusion criteria. Pathology after resection showed adenoma with low-grade dysplasia (LGD) in 52 patients, high-grade dysplasia (HGD) in 25 patients, adenocarcinoma in 6 patients, NET in 4 patients and not-neoplastic duodenal mucosa in 8 patients. Adverse events occurred in 25 % of patients. The median follow-up after EP was 22.5 months. Local residual was observed in 27 patients (28,4 %) and recurrence after the endoscopic retreatments occurred in 11 patients (11,6 %). Furthermore, recurrence occurred in 16 of 68 patients with adenoma-free after a first endoscopic follow-up and 9 patients developed at least a second recurrence. All the recurrences but one were endoscopically treated. ConclusionsEP and its ancillary treatments for residual and recurrent adenomas is an effective treatment for ampullary tumors. Long-term surveillance demonstrates that recurrences can be mainly treated endoscopically.

Retrospective Long-Term Evaluation of Miltefosine-Allopurinol Treatment in Canine Leishmaniosis.

Miltefosine-Allopurinol (MIL-AL) combination is reported to be one of the most effective treatments for canine leishmaniosis, thanks to its oral administration and MIL-documented low impact on renal function. However, MIL-AL is considered a second-choice treatment when compared to meglumine-antimoniate-allopurinol combination, mainly due to the risk of earlier relapses. The aim of this study was to evaluate the efficacy of the MIL-AL protocol during a long-term follow-up with an average duration of nine years. Dogs were living in Southern Italy (Puglia, Italy) in an area considered endemic for Canine leishmaniosis (CanL). Inclusion criteria were clinical and/or clinicopathological signs consistent with CanL; positive result to Leishmania quantitative ELISA; and negativity to the most frequent canine vector-borne infections. All dogs received 2 mg/kg MIL for 28 days, and 10 mg/kg AL, BID, for a period varying between 2 and 12 months. Ancillary treatments were allowed according to the clinical condition of the dog. A total clinical score and a total clinicopathological score were calculated at each time point by attributing one point to each sign or alteration present and then by adding all points. Improvement after each treatment was defined by the reduction of at least 50% of the total score. A survival analysis (Kaplan-Meier curve) was performed for quantifying the probability of the events occurring during the study follow-up. The following events were considered: decreased and negative ELISA results; improvement/recovery of the clinical and clinicopathological alterations; and relapse of leishmaniasis. One hundred seventy-three dogs (75f and 98m) were retrospectively included in the study by examining their clinical records since the first diagnosis of CanL. One hundred forty-three (83%) dogs were under five years of age. The mean duration of the follow-up period was 5.4 (±1.1) years with a minimum of 3.2 years and a maximum of 9 years. All dogs received a first treatment of MIL-AL at inclusion; then, during the follow-up course, 30 dogs required a second treatment, 2 dogs required a third treatment and 1 dog required a fourth and a fifth treatment. The mean time interval between the first and the second treatment was 27.2 (±18.3) months. After the first treatment, all dogs had decreased ELISA levels, in an average interval of 2.6 (±1.6) months. One hundred seventy dogs (98%) experienced a clinical improvement (mean time 3.0 ± 4.9 months); 152 (88%) dogs were considered clinically recovered after a mean time of 16.7 ± 13.5 months. A similar trend was observed for clinicopathological alterations; interestingly, proteinuria decreased in most dogs (p < 0.0001-Chi-square for trends). Thirty dogs experienced relapses, the earliest after 4.8 months. The mean time without relapse was 90.4 (±2.5) months. In relapsed dogs, the mean time for clinical improvement after the second treatment was 8.6 (±12.6) months, whereas it was 11.0 (±15.4) months for clinicopathological alterations. Five dogs had limited gastrointestinal side effects associated with MIL treatment. The present study confirms that the MIL-AL protocol can be considered one of the most effective treatments for CanL therapy, mainly for its capacity to provide a long-time clinical improvement in a large majority of treated dogs. As reported in the literature, the clinical stabilization of dogs does not occur immediately after treatment, probably due to the particular pharmacokinetic properties of MIL. The efficacy of MIL-AL decreases in dogs that need more than one treatment, suggesting the necessity to alternate anti-Leishmania drugs for the treatment of relapses. Side effects were transient and slight, even in dogs that required several treatments.

The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant Enterolobium contortisiliquum; A Case of Two Soul Mates Meeting.

Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from Crotalus durissus terrificus total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity. A Kunitz-like EcTI inhibitor protein with a molecular mass of 20 kDa was isolated from Enterolobium contortisiliquum and showed high trypsin inhibition. Thus, the objective of this work is to verify the possible inhibition of the pharmacological activities of Cdtsp-2 by the Kutinz-type inhibitor EcTI. To isolate Cdtsp-2 from total C. d. terrificus venom, we used three-step chromatographic HPLC. Using the mice paw edema model, we observed an edematogenic effect, myotoxicity and hepatotoxicity caused by Cdtsp-2. In vitro and in vivo experiments showed that the alterations in hemostasis caused by Cdtsp-2 are crucial for the development of marked hepatotoxicity and that EcTI significantly inhibits the enzymatic and pharmacological activities of Cdtsp-2. Kunitz-like inhibitor may be a viable alternative for the development of ancillary treatments against the biological activities of venoms.

Can we predict the ancillary treatments after extracorporeal shockwave lithotripsy for renal and upper ureteral stones?

To quantify the predictors for the ancillary treatments after extracorporeal shock wave lithotripsy (SWL) for renal and upper ureteral stones. From January 2014 to January 2017, patients undergoing SWL using an electromagnetic lithotripter machine (Compact Delta; Dornier MedTech GmbH, Wessling, Germany) for renal and upper ureteral stones ≤ 20 mm were retrospectively reviewed. All patients underwent CT urography prior to SWL. The cohort was subdivided into three groups according to stone attenuation values in Hounsfield Units (HU). Group I; HU < 500 (n = 20), group II; HU 500-1000 (n = 51) and group III; HU ≥ 1000 (n = 180). The parameters included for multivariate analysis were stone size, location, multiplicity, stone attenuation value, number of shocks and stone clearance rate by 3 months. The ancillary treatments were ureteroscopy (URS), ureteral stenting and hospital readmission for pain or fever. A total of 251 patients were included in the study. The overall SWL success rate was 92.4%. Mean stone size was 10.9 ± 2.1, 11.6 ± 3 and 11.4 ± 3.6 mm and mean stone attenuation values were 364 ± 125, 811 ± 154 and 1285 ± 171 HU for groups I, II and III respectively. The stone clearance rates by 3 months were 96%, 92% and 88.4% for groups I, II and III respectively. On subgroup analysis, group III required ancillary treatments in 70% of patients whereas group I, II, did not require any ancillary treatments. On multivariate analysis, stone multiplicity, stone location (lower calyceal stones) and HU were independent significant predictors for the need for ancillary treatments after SWL (p values < 0.05). Patients with stone attenuation value (HU) > 1000, multiple stones and/or lower calyceal stones have higher risk to necessitate ancillary treatments after SWL. These patients would likely benefit from upfront endoscopic lithotripsy for treating symptomatic renal or upper ureteral stones.

The future of paediatric acute respiratory distress syndrome

Heterogeneity is a familiar concept to paediatric intensive care physicians, because patients, pathologies, and treatments vary both within the paediatric intensive care unit (PICU) and within a given disease process. Paediatric acute respiratory distress syndrome (ARDS) typifies this problem. Children with ARDS vary in terms of age (and therefore lung development), underlying cause (pneumonia, sepsis, or trauma), pre-existing comorbid conditions, and baseline immunological state. There is not one pathway by which ARDS occurs or manifests, as indicated by the identification of hyperinflammatory and hypoinflammatory subtypes in adults and children. 1 Calfee CS Delucchi KL Sinha P et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018; 6: 691-698 Google Scholar , 2 Dahmer MK Yang G Zhang M et al. Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis. Lancet Respir Med. 2022; 10: 289-297 Google Scholar Furthermore, treatments probably differ in their effectiveness, with interventions that are beneficial in some patients but harmful in others, leading to a null population average treatment effect. 3 Prescott HC Calfee CS Thompson BT Angus DC Liu VX Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med. 2016; 194: 147-155 Google Scholar Thus, important questions need to be addressed to improve the management and outcomes of paediatric ARDS. In a Series paper in The Lancet Respiratory Medicine, 4 Kneyber MCJ Khemani RG Bhalla A et al. Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome. Lancet Respir Med. 2022; (published online Dec 22.)https://doi.org/10.1016/S2213-2600(22)00483-0 Google Scholar Martin Kneyber and colleagues—a multinational group of paediatric ARDS experts—provide a welcome summary of where we are now as a field, and what tools are available to address challenges for the next generation of paediatric ARDS trials. Two key questions need to be considered to improve the management and outcomes of paediatric ARDS. First, can we improve outcomes by identifying mechanisms or pathways to target therapeutically within specific subgroups? And second, can this be done through a nuanced approach rather than through the use of blunt, pleiotropic instruments? Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndromePaediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Full-Text PDF

Multimodal Management of Fecal Incontinence Focused on Sphincteroplasty: Long-Term Outcomes from a Single Center Case Series.

The management of patients with fecal incontinence and an external anal sphincter (EAS) defect remains controversial. A retrospective series of overlapping anal sphincteroplasties performed between 1985–2013 from a single center, supplemented by selective puborectalis plication and internal anal sphincter repair is presented. Patients were clinically followed along with anorectal manometry, continence scoring (Cleveland Clinic Incontinence Score—CCS) and patient satisfaction scales. Patients with a suboptimal outcome were managed with combinations of biofeedback therapy (BFT), peripheral tibial nerve stimulation (PTNS), sacral nerve stimulation (SNS) or repeat sphincteroplasty. There were 120 anterior sphincter repairs with 90 (75%) levatorplasties and 84 (70%) IAS repairs. Over a median follow-up of 120 months (IQR 60–173.7 months) there were significant improvements in the recorded CCIS values (90.8% with a preoperative CCIS > 15 vs. 2.5% postoperatively; p < 0.001). There were 42 patients who required ancillary treatment with four repeat sphincteroplasties, 35 patients undergoing biofeedback therapy, 10 patients treated with PTNS and three managed with SNS implants with an ultimate good functional outcome in 92.9% of cases. No difference was noted in ultimate functional outcome between those treated with sphincteroplasty alone compared with those who needed ancillary treatments (97.1% vs. 85.7%, respectively). Overall, 93.3% considered the outcome as either good or excellent. Long-term functional outcomes of an overlapping sphincteroplasty are good. If the initial outcome is suboptimal, response to ancillary treatments remains good and patients are not compromised by a first-up uncomplicated sphincter repair.

Ancillary treatment referrals and visits after breast cancer surgery in a sociodemographically diverse population.

1533 Background: Ancillary therapies by rehabilitative, palliative, and survivorship specialists mitigate breast cancer surgery's physical and emotional effects. Existing data suggest that patients from disadvantaged backgrounds may be less likely to receive such care. We investigated provider referrals and patient visits at a high-volume urban cancer center to identify associated sociodemographic factors and characterize which populations may not be maximally benefiting from ancillary services. Methods: Data was culled from electronic health records of surgically-treated breast cancer patients at Yale-New Haven Health System between 2010-2017. Post-operative provider referrals to Physical/Occupational Therapy, Palliative Medicine, and Survivorship Program were evaluated for associations with demographic and disease variables in univariable and multivariable logistic regression analyses. Patient utilization of referrals, defined as attending at least one consultation, were analysed similarly. Results: Among 5,496 patients identified, 2,288 (41.6%) were referred for ancillary treatments and 1,572 (28.6%) attended at least one consultation. Provider referrals were highest among patients of Hispanic and Black ancestry (57.5% and 54.9%, respectively), no health insurance (57.6%), lowest percentage high school degree for zip code (50.5%), and lowest median income for zip code (50.7%). These associations remained significant in multivariable analysis [all p&lt;0.050]. In contrast, referral utilization was greatest among patients with private insurance (70.7%), highest percentage high school degree (72.8%), and highest median household income (72.2%), in addition to Hispanic ethnicity (73.5%). In multivariable analysis, highest median household income (OR 1.45, p = 0.019) and Hispanic ethnicity (OR 1.50, p = 0.048) remained associated. Conclusions: In a large urban health system serving a diverse population, traditional markers of poor healthcare access were positively associated with provider referral for ancillary services after breast cancer surgery. However, referral did not translate to utilization, suggesting that access remains a critical barrier to therapies that target post-operative morbidity and elevate quality of life.[Table: see text]

The use of Patient-Led Goal Setting in the Intervention of Chronic Low Back Pain in Adults: A Narrative Review

Chronic low back pain (cLBP) impacts millions of adults annually. Several nonsurgical interventions are recommended for treating this condition, however, limited literature exists regarding the impactpatient-led goals may have on outcomes in the treatment of cLBP. The purpose of this narrative reviewis to identify gaps and synthesize literature examining the associations of patient-led goals combined with care for cLBP. A total of12 studies were reviewedand findings were synthesized. Patient-led goal setting may serve as an effective intervention for adults with cLBP. Current outcome measures may not align with patient-led goals. Further investigationis required to understand patient-led goals with ancillary treatments and specific age groups, such as adults over age65.

Cerebrospinal fluid cytokine, chemokine, and SARS-CoV-2 antibody profiles in children with neuropsychiatric symptoms associated with COVID-19

BackgroundNeuropsychiatric symptoms and CSF cytokine, chemokine, and SARS-COV-2 antibody profiles are unknown in pediatric patients with COVID-19 or multisystem inflammatory syndrome (MIS-C), (NP-COVID-19). MethodsChildren at a single pediatric institution quaternary referral center with laboratory-confirmed COVID-19 or MIS-C and neuropsychiatric symptoms were included in this retrospective case series. Clinical symptoms, ancillary testing data, treatments and outcomes are described. Multiplexed electrochemiluminescence assays for cytokines, chemokines and SARS-CoV-2 antibodies were tested in the CSF NP-COVID-19 patients compared to five controls and were analyzed using the Student's t-test. ResultsThree of five NP-COVID-19 patients had psychiatric symptoms, and two patients had encephalopathy and seizures. All patients had full or near resolution of neuropsychiatric symptoms by discharge. One patient received intravenous steroids for treatment for psychiatric symptoms; 3/5 other patients received immunotherapy for MIS-C, including IVIG, high-dose steroids, anakinra, and tocilizumab. Pro-inflammatory chemokines, including MIG, MPC, MIP-1β, and TARC were significantly elevated in NP-COVID-19 patients compared to controls. Two of five patients had elevated CSF neurofilament light chain. CSF SARS-CoV-2 antibody titers to the full-length spike, receptor binding domain and N-terminal domain were significantly elevated. SARS-CoV-2 antibody titers strongly correlated with pro-inflammatory chemokines/cytokines, including IL-1β, IL-2, IL-8, TNF-α, and IFN-γ (P≤0.05 for all). ConclusionsA spectrum of neuropsychiatric clinical manifestations can occur in children with SARS-CoV-2 infection. CSF pro-inflammatory chemokines and SARS-CoV-2 antibodies may serve as biomarkers of SARS-CoV-2 mediated NP-COVID-19. Additional study is required to understand the pathophysiologic mechanisms of neuroinflammation in children with COVID-19 and MIS-C.

Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Italian Society of Pediatrics

BackgroundItaly was the first Western country to be hit by the SARS-CoV-2 epidemic. There is now mounting evidence that a minority of children infected with SARS-CoV2 may experience a severe multisystem inflammatory syndrome, called Multisystem inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C). To date no universally agreed approach is available for this disease.Main bodyas Italy is now facing a second hity of COVID-19 cases, we fear a recrudescence of MIS-C cases. We have, therefore, decided to prepare a report that will help clinicians to face this novel and challenging disease. We propose a diagnostic algorithm, to help case definition and guide work-up, and a therapeutic approach. MIS-C should be promptly recognized, based on the presence of systemic inflammation and specific organ involvement. Early treatment is crucial, and it will be based on the combined use of corticosteroids, high-dose immunoglobulins and anti-cytokine treatments, depending on the severity of the disease. Ancillary treatments (such as. aspirin and thrombo-profilaxis) will be also discussed.Conclusionswe propose a document that will help physicians to diagnose and treat MIS-C patients. Given the level of evidence available and the methodology used, this document should not be interpreted as a guideline; the final decision about the optimal management should still be taken by the caring physician, on an individual basis.

A More Severe Non-melanoma Skin Cancer Phenotype Is Seen in Patients with Inflammatory Bowel Disease on Tumor Necrosis Factor-α Antagonists

Limited data suggest that non-melanoma skin cancer (NMSC) risk is higher in patients with inflammatory bowel disease (IBD) particularly in those on a tumor necrosis factor-α antagonist (TNF antagonist). It remains unknown whether TNF antagonist exposure alters the clinical course of NMSC in patients with IBD or if this therapy should be discontinued. To assess the impact of TNF antagonist exposure on NMSC severity, recurrence and need for ancillary treatments. Patients with IBD seen at London Health Sciences Centre, London, Canada were assessed for a history of NMSC and pre-diagnosis TNF antagonist exposure. NMSC severity (low risk and high risk), ancillary NMSC therapies, including chemo or radiotherapy, and changes to IBD therapy were assessed. Eleven of 472 patients with IBD reviewed were diagnosed with NMSC. Sixty-four percent (7/11) were on a TNF antagonist at the time of NMSC diagnosis. All patients with TNF antagonist exposure, (7/7) presented with a high-risk lesion based on National Comprehensive Cancer Network (NCCN) clinical practice guidelines. The incidence of positive margins was 42.9% (3/7) and 14.3% (1/7) required ancillary therapy. No metastatic disease was seen. TNF antagonist therapy was discontinued in a single patient due to NMSC diagnosis. Recurrent NMSC lesions were not seen in any of the TNF antagonist exposed patients. In this case series, TNF antagonist exposure may be associated with a severe NMSC clinical course. Larger studies are needed to confirm whether TNF antagonist discontinuation should be considered in the setting of NMSC diagnosis in IBD.

Kawasaki Disease and Clinical Outcome Disparities Among Black Children

ObjectiveTo determine whether Black children with Kawasaki disease exhibit disparities in prevalence, sequelae, and response to intravenous gamma globulin (IVIG) treatment.Study designInternational Classification of Diseases codes were used to identify children with Kawasaki disease admitted to a tertiary center in the southeastern US. Subjects diagnosed and treated according to American Heart Association criteria were included. Demographic, laboratory, clinical, and echocardiographic data from the electronic medical record (2000-2015) were compared between Blacks and Whites.ResultsData from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment, or coronary artery (CA) abnormalities during hospitalization were observed. Blacks showed lower IVIG response rates than Whites for patients administered IVIG within 10 days of fever onset (86.6% vs 95.6%; P = .007). Blacks received more ancillary drugs (9.6% vs 2.6%; P = .003), and endured longer hospitalizations (mean, 5 ± 3.9 days vs 3.4 ± 2.2 days; P = .001). Blacks presented with higher C-reactive protein level and erythrocyte sedimentation rate and lower hemoglobin, albumin, and sodium levels. Blacks had a higher proportion of persistent CA abnormalities than Whites at second follow-up echocardiogram (14.5% vs 6.3%; P = .03), and at third follow-up echocardiogram (21.2% vs 6.9%; P = .01).ConclusionsCompared with White children, Black children with Kawasaki disease had higher IVIG refractory prevalence, more severe inflammation, more ancillary treatments, and longer hospitalizations. Despite no racial differences in time to diagnosis or initial treatment, there was greater CA abnormality persistence among Black children at follow-up.

The Design of Early-Stage Plant Breeding Trials Using Genetic Relatedness

The use of appropriate statistical methods has a key role in improving the accuracy of selection decisions in a plant breeding program. This is particularly important in the early stages of testing in which selections are based on data from a limited number of field trials that include large numbers of breeding lines with minimal replication. The method of analysis currently recommended for early-stage trials in Australia involves a linear mixed model that includes genetic relatedness via ancestral information: non-genetic effects that reflect the experimental design and a residual model that accommodates spatial dependence. Such analyses have been widely accepted as they have been found to produce accurate predictions of both additive and total genetic effects, the latter providing the basis for selection decisions. In this paper, we present the results of a case study of 34 early-stage trials to demonstrate this type of analysis and to reinforce the importance of including information on genetic relatedness. In addition to the application of a superior method of analysis, it is also critical to ensure the use of sound experimental designs. Recently, model-based designs have become popular in Australian plant breeding programs. Within this paradigm, the design search would ideally be based on a linear mixed model that matches, as closely as possible, the model used for analysis. Therefore, in this paper, we propose the use of models for design generation that include information on genetic relatedness and also include non-genetic and residual models based on the analysis of historic data for individual breeding programs. At present, the most commonly used design generation model omits genetic relatedness information and uses non-genetic and residual models that are supplied as default models in the associated software packages. The major reasons for this are that preexisting software is unacceptably slow for designs incorporating genetic relatedness and the accuracy gains resulting from the use of genetic relatedness have not been quantified. Both of these issues are addressed in the current paper. An updating scheme for calculating the optimality criterion in the design search is presented and is shown to afford prodigious computational savings. An in silico study that compares three types of design function across a range of ancillary treatments shows the gains in accuracy for the prediction of total genetic effects (and thence selection) achieved from model-based designs using genetic relatedness and program specific non-genetic and residual models.Supplementary materials accompanying this paper appear online.

Optimal management of large proximal ureteral stones (>10mm): A systematic review and meta-analysis of 12 randomized controlled trials.

To develop an evidence base to guide clinicians treating adults with large proximal ureteral stones (LPUS) greater than 10mm. A systematic search of PubMed, EMBASE, and Cochrane Library was conducted to identify randomized controlled trials (RCT) concerning different LPUS management techniques including laparoscopic ureterolithotomy (LU), percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URL) up until March 2020. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement when searching and determining inclusion. All included articles were quality assessed and the data analyses were conducted with Review Manager (5.3). 12 RCTs involving 1416 patients met our eligibility criteria and were analyzed. Of these participants, 44.6% (n=632) underwent URL, 25.5% (n=361) PCNL, and 29.9% (n=423) LU. Pooled analysis revealed that URL had a significantly lower stone-free rate (SFR) compared to PCNL and LU (both with p<0.05). URL had a significantly higher ureteral injury rate compared to LU (Relative risk (RR)=5.27, 95% confidence interval (CI) 1.52 to 18.22, p=0.009) and PCNL (RR=4.11, 95% CI 1.03 to 16.34, p=0.04). However, no significant differences were found between PCNL and LU in terms of SFR or overall complications, both with p>0.05. URL initially costs less than PCNL (Weighted mean difference (WMD) -597.35US$, 95% CI -823.10 to -371.60, p<0.00001), but being less effective creates greater demand for repeat or ancillary treatments compared to LU (RR 15.65, 95% CI 2.11-116.12, p=0.007) and PCNL (RR 8.86; 95% CI 3.19-24.60; p<0.00001). Both PCNL and LU appear more effective and safer than URL for LPUS; although, LU has higher risk of urine leakage and is more likely incur trauma which requires additional support. However, caution must be taken because this recommendation is based upon a very limited number of clinical studies, and even fewer comparing flexible ureteroscopic technologies. Further prospective real-world studies or RCTs comparing flexible URL, LU and PCNL are required, as well as an in depth analysis of the hidden costs involved in unsuccessful URL treatments.

Incidence of snakebites in Can Tho Municipality, Mekong Delta, South Vietnam-Evaluation of the responsible snake species and treatment of snakebite envenoming.

Data on incidence of snakebites and the responsible snake species are largely missing in Vietnam and comprehensive national guidelines for management of snakebite envenoming are not yet available. They are needed to estimate the scope of this health problem, to assess the demand for snake antivenom and to ensure the best possible treatment for snakebite victims. A cross-sectional community-based survey was conducted from January to April 2018. Multistage cluster sampling was applied and snakebite incidence in Can Tho municipality, excluding two central districts of Can Tho city, was calculated at 48 (95%-confidence interval (CI): 20.5-99.8) snakebites per 100,000 person-years. Seven snakebite victims found during the survey reported 3 bites from green pit vipers and 4 bites from non-venomous snakes. In 2017 two treatment centres for snakebite envenoming in Can Tho city, the Military Hospital 121 and the Paediatric Hospital, received 520 admissions of snakebite victims. Two hundred sixty-seven came from Can Tho Municipality and 253 from neighbouring provinces. According to these data, the incidence of snakebites for Can Tho municipality was calculated at 21 (95%-CI: 18.5-23.7) snakebites per 100,000 person-years. Incidence was 14 (95%-CI: 12-17) snakebites per 100,000 person years in those 7 districts of the municipality which were part of the community survey. Green pit vipers were responsible for 92% of snakebite envenoming. Antivenom, antibiotics and corticosteroids were administered to 405 (90%), 379 (84%), and 310 (69%) out of 450 patients, respectively. Incidence of snakebites in Can Tho Municipality is relatively low and green pit vipers are responsible for the vast majority of bites. Approximately one third of snakebite patients sought medical care in hospitals and although hospital data still underestimate the real incidence of snakebites, these statistics are valuable and can be obtained fast and inexpensively. Evaluation of patients' records indicates the need for development of guidelines for management of snakebite envenoming in Vietnam to ensure a rational use of antivenom and ancillary treatments.

Micro-dystrophin Gene Therapy Partially Enhances Exercise Capacity in Older Adult mdx Mice

Micro-dystrophin (μDys) gene therapeutics can improve striated muscle structure and function in different animal models of Duchenne muscular dystrophy. Most studies, however, used young mdx mice that lack a pronounced dystrophic phenotype, short treatment periods, and limited muscle function tests. We, therefore, determined the relative efficacy of two previously described μDys gene therapeutics (rAAV6:μDysH3 and rAAV6:μDys5) in 6-month-old mdx mice using a 6-month treatment regimen and forced exercise. Forelimb and hindlimb grip strength, metabolic rate (VO2 max), running efficiency (energy expenditure), and serum creatine kinase levels similarly improved in mdx mice treated with either vector. Both vectors produced nearly identical dose-responses in all assays. They also partially prevented the degenerative effects of repeated high-intensity exercise on muscle histology, although none of the metrics examined was restored to normal wild-type levels. Moreover, neither vector had any consistent effect on respiration while exercising. These data together suggest that, although μDys gene therapy can improve isolated and systemic muscle function, it may be only partially effective when dystrophinopathies are advanced or when muscle structure is significantly challenged, as with high-intensity exercise. This further suggests that restoring muscle function to near-normal levels will likely require ancillary or combinatorial treatments capable of enhancing muscle strength.

Burden-of-illness and cost-driving factors in Dravet syndrome patients and carers: A prospective, multicenter study from Germany.

Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. This study estimated cost, cost-driving factors and quality of life (QoL) in patients with Dravet syndrome and their caregivers in a prospective, multicenter study in Germany. A validated 3-12-month retrospective questionnaire and a prospective 3-month diary assessing clinical characteristics, QoL, and direct, indirect and out-of-pocket (OOP) costs were administered to caregivers of patients with DS throughout Germany. Caregivers of 93 patients (mean age 10.1 years, ±7.1, range 15 months-33.7 years) submitted questionnaires and 77 prospective diaries. The majority of patients (95%) experienced at least one seizure during the previous 12 months and 77% a status epilepticus (SE) at least once in their lives. Over 70% of patients had behavioural problems and delayed speech development and over 80% attention deficit symptoms and disturbance of motor skills and movement coordination. Patient QoL was lower than in the general population and 45% of caregivers had some form of depressive symptoms. Direct health care costs per three months were a mean of €6,043±€5,825 (median €4054, CI €4935-€7350) per patient. Inpatient costs formed the single most important cost category (28%, €1,702±€4,315), followed by care grade benefits (19%, €1,130±€805), anti-epileptic drug (AED) costs (15%, €892±€1,017) and ancillary treatments (9%, €559±€503). Total indirect costs were €4,399 ±€ 4,989 (median €0, CI €3466-€5551) in mothers and €391±€1,352 (median €0, CI €195-€841) in fathers. In univariate analysis seizure frequency, experience of SE, nursing care level and severe additional symptoms were found to be associated with total direct healthcare costs. Severe additional symptoms was the single independently significant explanatory factor in a multivariate analysis. This study over a period up to 15 months revealed substantial direct and indirect healthcare costs of DS in Germany and highlights the relatively low patient and caregiver QoL compared with the general population.

Dialectical Behavior Therapy in the Treatment of Borderline Personality Disorder

DBT is the first and the most studied CBT approach in the treatment of BPD. It is a modular manualized treatment program developed for suicidal women most of who were noticed to meet the criteria for borderline personality disorder. The theory behind DBT is called the biosocial theory. The theory suggests that biological factors such as being born with an emotionally vulnerable temperament and social or environmental factors play roles in the development of BPD. DBT attend to the balance of acceptance-based and change-based strategies. This is the “teeter-totter” on which the therapist rests. DBT consists of five modes of treatment, which are the individual therapy, skills training, telephone consultation, therapist consultation team and ancillary treatments. If we think CBT as a technology of change based on the techniques of field of learning, DBT is more like balancing change with acceptance. On the other hand, cognitive modification program applied in DBT is driven from CBT. DBT can be applied to various settings and populations successfully. The main advantage of DBT is its low drop-out rates. Even though more research should be conducted on its generalizability, it proved itself as one of the successful treatments since it has been widely used by therapists with different treatment approaches.