Proactive Treatment Research Articles

Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells.

In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence‐based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research. ANN NEUROL 2021;89:1226–1233

SNP rs12794714 of CYP2R1 is associated with serum vitamin D levels and recurrent spontaneous abortion (RSA): a case-control study.

Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. This case-control study enrolled 75 RSA patients and 83 controls. Serum VD and some cytokines were detected with LC-MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. The results revealed a significant correlation between the AG genotype of CYP2R1 rs12794714 and VD levels (OR 0.686; 95% CI 0.49-0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1 rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683-1023.265, 3.110-1138.367; p = 0.009, 0.007, respectively). Our results indicate that CYP2R1 rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1 rs12794714 is necessary to warrant proactive counseling and treatment against RSA.

Civilian gunshot wounds to the head: a case report, clinical management, and literature review

BackgroundCivilian gunshot wounds to the head refer to brain injury caused by projectiles such as gun projectiles and various fragments generated by explosives in a power launch or explosion. Gunshot wounds to the head are the deadliest of all gun injuries. According to literature statistics, the survival rate of patients with gunshot wounds to the head is only 9%. Due to the strict management of various types of firearms, they rarely occur, so the injury mechanism, injury and trauma analysis, clinical management, and surgical standards are almost entirely based on military experience, and there are few related reports, especially of the head, in which an individual suffered a fatal blow more than once in a short time. We report a case with a return to almost complete recovery despite the patient suffering two gunshot injuries to the head in a short period of time.Case presentationsWe present a case of a 53-year-old man who suffered two gunshot injuries to the head under unknown circumstances. On initial presentation, the patient had a Glasgow Coma Scale score of 6, was unable to communicate, and had loss of consciousness. The first bullet penetrated the right frontal area and finally reached the right occipital lobe. When the patient reflexively shielded his head with his hand, the second bullet passed through the patient’s right palm bone, entered the right frontotemporal area, and came to rest deep in the lateral sulcus. The patient had a cerebral hernia when he was admitted to the hospital and immediately entered the operating room for rescue after a computed tomography scan. After two foreign body removals and skull repair, the patient recovered completely.ConclusionsGunshot wounds to the head have a high mortality rate and usually require aggressive management. Evaluation of most gunshot injuries requires extremely fast imaging examination upon arrival at the hospital, followed by proactive treatment against infection, seizure, and increased intracranial pressure. Surgical intervention is usually necessary, and its key points include the timing, method, and scope of the operation.

Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort

Background: HIV-associated cryptococcal meningitis accounts for 15% of AIDS related deaths globally. In sub-Saharan Africa, acute mortality ranges from 24% to 100%. In addition to the mortality directly associated with cryptococcosis, patients with HIV-associated cryptococcal meningitis are at risk of a range of opportunistic infections (OIs) and hospital acquired nosocomial infections (HAIs). The attributable mortality associated with co-prevalent infections in cryptococcal meningitis has not been evaluated. Methods: As part of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial, consecutive HIV-positive adults with cryptococcal meningitis were randomised to one of five anti-fungal regimens and followed up until 10-weeks. We conducted a retrospective case note review of ACTA participants recruited from Queen Elizabeth Central Hospital in Blantyre, Malawi to describe the range and prevalence of OIs and HAIs diagnosed, and the attributable mortality associated with these infections. Results: We describe the prevalence of OIs and HAIs in 226 participants. Baseline median CD4 count was 29 cell/mm3, 57% (129/226) were on anti-retroviral therapy. 56% (127/226) had at least one co-prevalent infection during the 10-week study period. Data were collected for 187 co-prevalent infection episodes. Suspected blood stream infection was the commonest co-prevalent infection diagnosed (34/187, 18%), followed by community-acquired pneumonia (32/187, 17%), hospital-acquired pneumonia (13/187, 7%), pulmonary tuberculosis (12/187, 6%) and confirmed blood stream infections (10/187, 5%). All-cause mortality at 10-weeks was 35% (80/226), diagnosis of an OI or HAI increased the risk of death at 10 weeks by nearly 50% (HR 1.48, 95% CI 1.01-2.17, p=0.04). Conclusion: We demonstrate the high prevalence and broad range of OIs and HAIs occurring in patients with HIV-associated cryptococcal meningitis. These co-prevalent infections are associated with a significantly increased risk of death. Whether a protocolised approach to improve surveillance and proactive treatment of co-prevalent infections would improve cryptococcal meningitis outcomes warrants further investigation.

Calcipotriol/Betamethasone Dipropionate Foam Inhibits Th17 Cytokine Secretion and Improves Epidermal Barrier Markers in a Human Th17 Skin Inflammation Model.

IntroductionT-helper 17 (Th17) cytokines play a key role in the pathophysiology of psoriasis by driving inflammatory responses that lead to epidermal alterations. Markers of epidermal differentiation, including the proteins loricrin (LOR), filaggrin (FLG) and involucrin (IVL), are dysregulated in psoriatic skin. The fixed-dose combination of calcipotriol/betamethasone dipropionate (Cal/BD) foam and clobetasol propionate (CP) are widely used, effective topical treatments for psoriasis. In this study, we investigated the effects of Cal/BD foam and CP cream on Th17 cytokine secretion and epidermal differentiation using a human Th17 skin inflammation model (InflammaSkin®).MethodsThe fixed-dose combination Cal/BD foam and the CP cream were applied once and twice daily, respectively, onto the air-exposed epidermal surface of InflammaSkin cultures for 7 days. Th17 cytokine levels were measured in culture supernatants, and gene expression analysis and immunohistochemical staining for LOR, FLG and IVL were performed on the skin samples.ResultsTopical treatment with Cal/BD foam almost completely inhibited Th17 cytokine secretion and upregulated LOR and IVL expression, but not FLG expression, at the mRNA and protein levels. Topical treatment with CP cream significantly reduced Th17 cytokine levels, but to a lesser extent than Cal/BD foam, and did not improve expression of any of the epidermal differentiation markers.ConclusionCompared with CP treatment, the fixed-dose combination Cal/BD foam showed a greater suppression of Th17 cytokine secretion and improved epidermal differentiation, resulting in an overall higher degree of improvement of the skin. These results support our understanding of the mechanisms behind the clinical efficacy observed for Cal/BD foam and of its use for long-term proactive treatment of psoriasis vulgaris.

Computational Drug Repositioning Identifies Statins as Modifiers of Prognostic Genetic Expression Signatures and Metastatic Behavior in Melanoma

Despite advances in melanoma treatment, more than 70% of patients with distant metastasis die within 5 years. Proactive treatment of early melanoma to prevent metastasis could save lives and reduce overall healthcare costs. Currently, there are no treatments specifically designed to prevent early melanoma from progressing to metastasis. We used the Connectivity Map to conduct an in silico drug screen and identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) as a drug class that might prevent melanoma metastasis. To confirm the invitro effect of statins, RNA sequencing was completed on A375 cells after treatment with fluvastatin to describe changes in the melanoma transcriptome. Statins induced differential expression in genes associated with metastasis and are used in commercially available prognostic tests for melanoma metastasis. Finally, we completed a chart review of 475 patients with melanoma. Patients taking statins were less likely to have metastasis at the time of melanoma diagnosis in both univariate and multivariate analyses (24.7% taking statins vs. 37.6% not taking statins, absolute risk reduction= 12.9%, P= 0.038). These findings suggest that statins might be useful as a treatment to prevent melanoma metastasis. Prospective trials are required to verify our findings and to determine the mechanism of metastasis prevention.

Proactive tobacco treatment for veterans with posttraumatic stress disorder.

Individuals with posttraumatic stress disorder (PTSD) smoke at higher rates compared to the general population and experience significant barriers to initiating cessation treatment. Proactive outreach addresses these barriers by directly engaging with smokers and facilitating access to treatment. The objective of the present study was to evaluate a proactive outreach intervention for increasing rates of treatment utilization and abstinence among veteran smokers with and without PTSD. This is a secondary analysis of a randomized controlled trial conducted from 2013 to 2017 that demonstrated the effectiveness of proactive outreach among veterans using Veterans Affairs mental health care services. Electronic medical record data were used to identify participants with (n = 355) and without (n = 1,583) a diagnosis of PTSD. Logistic regressions modeled cessation treatment utilization (counseling, nicotine replacement therapy [NRT], and combination treatment) and abstinence (7-day point prevalence and 6-month prolonged at 6- and 12-month follow-ups) among participants randomized to proactive outreach versus usual care in the PTSD and non-PTSD subgroups, respectively. Compared to usual care, proactive outreach increased combined counseling and NRT utilization among participants with PTSD (odds ratio [OR] = 26.25, 95% confidence interval [3.43, 201.17]) and without PTSD (OR = 10.20, [5.21, 19.98]). Proactive outreach also increased 7-day point prevalence abstinence at 12 months among participants with PTSD (OR = 2.62, [1.16, 5.91]) and without PTSD (OR = 1.61, [1.11, 2.34]). Proactive outreach increased treatment utilization and abstinence among smokers with and without PTSD. Smokers with PTSD may need additional facilitation to initiate cessation treatment but are receptive when it is offered proactively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Systemic inflammatory syndrome in children during COVID-19 pandemic in Ceará state, northeastern Brazil: an observational study.

In this study, we report the occurrence of multisystemic inflammatory syndrome among 64 children (2 deaths) with recent severe acute respiratory syndrome-related coronavirus 2 (SARS-COV-2) infections in the northeast region of Brazil. The major clinical symptoms and signs reported were exanthema (60.9%), abdominal pain (56.3%), nausea and vomiting (46.9%), diarrhea (37.5%), and dyspnea (37.5%). Laboratory findings revealed that the levels of C-reactive protein (75.0%), hemoglobin (51.6%), D-dimer (48.4%), lymphocytes (43.8%), LDH (45.3%), AST (42.2%), ALT (51.6%), and ferritin (48.4%) were above the reference values for a given age and gender. The clinical findings were similar to those observed in Kawasaki disease, although it represents a separate entity, emphasizing the need for proactive surveillance and early treatment.

Early diagnosis of CYP17A1 compound heterozygous mutations in a 46, XY child with disorders of sexual development

17-Hydroxylase/17,20-lyase deficiency is a rare congenital disorder accounting for 1% of congenital adrenal hyperplasia. This disease is recessively expressed as autosomal inheritance through mutations in the CYP17A1 gene, leading to defective levels of glucocorticoids and sex hormones. Individuals with loss-of-function mutations usually present with phenotypic female genitalia, primary amenorrhea, or hypertension in puberty caused by excessive production of mineralocorticoids. In this report, we describe a girl with CYP17A1 mutations diagnosed even though the pathognomonic symptoms had not developed. Herein, we report a case of a 3-year-old girl who prenatally diagnosed as a 46, XY female. After birth, the baby had normal female-type external genitalia without symptoms. She underwent a gonadectomy at the age of 3 years. To explore the pathogenesis of her condition, her genomic data were reviewed for genes involved in disorders of sexual differentiation (DSDs) using high-throughput sequence data from a whole-exome study. Pathogenic variants causing frameshift mutation involving codon 329 of CYP17A1 and a concomitant missense mutation involving codon 358 of the same gene were detected, mutations which are likely to result in loss of function of the enzyme. Each mutation was inherited from each of the parents, both holding carrier status. In addition, her younger sister (46, XX) acquired those identical variants without any abnormal phenotypical traits. Loss-of-function mutations of CYP17A1 which may cause secondary hypertension are not commonly identified in early life because of the wide spectrum of clinical manifestations and various pathophysiologies, which manifest in different sexes. Affected cases usually present later in life with hypertension or primary amenorrhea. High-throughput sequencing is suggested in DSD cases as it may give a precise diagnosis, enabling a proactive treatment plan and prevention of sequelae that potentially occur in puberty.

Recurrence Factors following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

Background: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common and the prognosis of recurrent ICC is dismal. Objective: This study was designed to investigate the risk factors and prognosis after disease recurrence following curative-intent resection for ICC. Methods: Data of patients undergoing curative resection for ICC in a single institution were identified. Results: A total of 147 patients were included. With a median follow-up of 21 months, 101 patients (68.7%) experienced ICC recurrence. On multivariate analysis, rim-enhanced or hypovascular mass on late arterial phase of CT image (hazard ratio [HR] 3.893, 95% confidence interval [CI] 1.700-8.915; p = 0.0013 and HR 6.241, 95% CI 2.670-14.586, p < 0.001, respectively), macrovascular invasion (HR 0.518, 95% CI 0.280-0.960; p = 0.037), microvascular invasion (HR 1.813, 95% CI 1.134-2.900, p = 0.013), advanced T stage ( HR 1.801, 95% CI 1.105-2.934, p = 0.018), and Lymph node metastasis (HR 2.067, 95% CI 1.168-3.657, p = 0.013) were associated with recurrence of ICC following curative resection, independently. Median survival after recurrence was better among patients who tried any treatment modality (18.5 months) than patients who did not received treatment (5.0 months) [p < 0.001]. Conclusions: Several factors including preoperative vascularity of ICC on CT image are the independent risk factors for recurrence of ICC after curative resection. Proactive treatment for recurrent ICC can be helpful to prolong the survival length of patients with recurrent ICC.

How do we identify the crashing traumatic brain injury patient - the neurosurgeon's view.

To provide an overview on recent advances in the field of assessment and monitoring of patients with severe traumatic brain injury (sTBI) in neurocritical care from a neurosurgical point of view. In high-income countries, monitoring of patients with sTBI heavily relies on multimodal neurocritical parameters, nonetheless clinical assessment still has a solid role in decision-making. There are guidelines and consensus-based treatment algorithms that can be employed in both absence and presence of multimodal monitoring in the management of patients with sTBI. Additionally, novel dynamic monitoring options and machine learning-based prognostic models are introduced. Currently, the acute management and treatment of secondary injury/insults is focused on dealing with the objective evident pathology. An ongoing paradigm shift is emerging towards more proactive treatment of neuroworsening as soon as premonitory signs of deterioration are detected. Based on the current evidence, serial clinical assessment, neuroimaging, intracranial and cerebral perfusion pressure and brain tissue oxygen monitoring are key components of sTBI care. Clinical assessment has a crucial role in identifying the crashing patient with sTBI, especially from a neurosurgical standpoint. Multimodal monitoring and clinical assessment should be seen as complementary evaluation methods that support one another.

Practical Recommendations for the Topical Treatment of Atopic Dermatitis in South and East Asia

IntroductionThere is some evidence to suggest that the prevalence of atopic dermatitis (AD) in Asia is rising. We have therefore developed an algorithm for the topical treatment of AD throughout South and East Asia for use by primary care physicians, pediatricians and dermatologists.MethodsNine AD experts from South and East Asia and one from Europe developed the algorithm based upon treatment guidelines, relevant literature and local treatment practices. The algorithm outlines current best practice for the use of emollients, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with the intention of simplifying the treatment regimen of mild-to-moderate AD in South and East Asia.ResultsPatients with AD should bathe and cleanse affected skin to remove crusts and scales daily. Emollients should also be applied daily as a maintenance treatment. When selecting appropriate topical anti-inflammatory treatment for AD flares, several factors should be taken into consideration, including the patient’s age, attitude to treatment options and site of AD lesions. Given the concerns regarding the risk of skin atrophy with use of TCS, a TCI should be used to treat AD lesions in sensitive skin areas: pimecrolimus is recommended for mild-to-moderate AD in these locations, while tacrolimus should be considered for moderate and severe cases. Either pimecrolimus or tacrolimus is recommended for flares in other, non-sensitive body locations. A proactive or intermittent maintenance treatment strategy involving regular emollient use and twice-weekly application of a TCI to previously affected areas is encouraged to reduce the risk of flares.ConclusionsThe algorithm proposed here is intended to simplify the topical treatment of mild-to-moderate AD in daily practice in South and East Asian countries.

Can rotations improve management of herbicide-resistant annual sowthistle (Sonchus oleraceus) and prickly lettuce (Lactuca serriola) in lentil production systems of southern Australia?

AbstractIn southern Australia, annual sowthistle and prickly lettuce have become more prevalent following the adoption of reduced tillage cropping systems. They are especially problematic in lentil and other pulse crops, which are weakly competitive and have few herbicide options available for POST control of broadleaf weeds. This study aimed to evaluate the influence of management in a previous cereal crop on weed densities in a subsequent crop. At two field sites, crop seeding density and POST herbicide treatments (a conventional choice that included metsulfuron-methyl and MCPA; and a proactive choice that included bromoxynil, picolinafen, and MCPA) were applied to a wheat crop, and weed density was assessed at the beginning of the following season to measure for a legacy effect of the treatments. Study site populations were also screened for herbicide resistance and were found to have high (≥90% survival) ALS inhibitor resistance. Crop competition treatments had no effect on weed populations, and effects of herbicide treatment were significant at only one of the sites. At this site, both herbicide treatments had lower weed densities than the nontreated in the first year, but the legacy effect was only significant for annual sowthistle density in the proactive treatment. At both sites, even where weeds were extremely sparse or completely controlled following herbicide treatment in the first year, moderate densities were observed the following year, indicating that colonization from the seedbank or adjacent areas could be contributing to weed numbers. Weed density assessments and accurate knowledge of the herbicide resistance status of target weeds should guide herbicide selection to maximize control.

Using weighted blankets in an inpatient mental health hospital to decrease anxiety

ObjectivePatients who are involuntarily committed to a psychiatric facility often experience anxiety or increased anxiety in response to being placed in the institutional environment. The weighted blanket introduced a proactive treatment option. The purpose of this study was to evaluate patients’ anxiety symptoms before and after weighted blanket, compared to a group that did not use a weighted blanket to control anxiety. MethodsThis study was conducted in an inpatient mental health facility from June 10, 2019, through November 7, 2019, with psychiatric patients who were not actively psychotic. Participants were offered the choice of weighted or unweighted blankets for a 20-minute intervention. The treatment group was comprised of individuals who had opted to use a 14-pound weighted blanket, 20-pound weighted blanket or 5-pound weighted lap pad. Participants in the comparison group were active in a wider range of settings. Before application of the blankets, pulse rate was measured using a pulse oximeter, and anxiety was measured using the Spielberger State-Trait Anxiety Inventory shortened form (STAI: Y-6). Both measures were taken again after the intervention. A two-way mixed analysis of variance (ANOVA) was run to examine the interaction effects between time (pre/post) and group (comparison/weighted blanket). Simple main effects were then further examined for the comparison/weighted blanket groups using a repeated measures ANOVA. Within the weighted blanket group, additional two-way mixed ANOVA was run to determine if gender or blanket weight made a statistically significant difference. ResultsThere was a statistically significant difference (P < 0.05) among those who used weighted blankets (n = 61) and those who did not (n = 61) based on the pre/post data for both the STAI: Y-6 inventory and the patients’ pulse rates. The results of two-way ANOVA indicated a significant interaction effect between intervention time and group (P < 0.001). Repeated measures ANOVA indicated a change between pre/post for the weighted blanket group only, and showed significant reductions in both the STAI: Y-6 (P < 0.001) and pulse rates (P = 0.040). Within the weighted blanket group, additional two-way mixed ANOVA showed that neither gender nor blanket weight had significant difference for either the STAI: Y-6 or the pulse measures. ConclusionThe use of weighted blankets is a safe and potentially effective way to help individuals in a psychiatric facility manage anxiety. This study found a statistically significant drop in anxiety for adults at an inpatient facility, as shown by the STAI: Y-6 scores and drop in pulse rates among patients using weighted blankets. This study suggests a possible alternative to medications, seclusion and physical restraints, which are not patient-centered or trauma-supported.

Paediatric atopic eczema (atopic dermatitis) in South Africa: A practical algorithm for the management of mild-to-moderate disease in daily clinical practice.

BackgroundAtopic eczema (AE) is a chronic, highly pruritic, inflammatory skin condition with increasing prevalence worldwide. Atopic eczema mostly affects children, impairing quality of life with poor disease control leading to progression of other atopic disorders. As most patients in South Africa have no access to specialist healthcare, a practical approach is needed for the management of mild-to-moderate AE in paediatric patients for daily clinical practice.MethodsA panel of experts in AE convened to develop a practical algorithm for the management of AE for children and adolescents in South Africa.ResultsRegular moisturising with an oil-based emollient remains the mainstay of AE treatment. Severe AE flares should be managed with topical corticosteroids (TCSs). For mild-to-moderate AE flares in sensitive skin areas, a topical calcineurin inhibitor (TCI) should be applied twice daily from the first signs of AE until complete resolution. Topical corticosteroids may be used when TCIs are unavailable. In non-sensitive skin areas, TCSs should be used for mild-to-moderate AE, but TCIs twice daily may be considered. Proactive maintenance treatment with low-dose TCI or TCS 2–3 times weekly and the liberal use of emollients is recommended for patients with recurrent flares.ConclusionsThis algorithm aims to simplify treatment of paediatric AE, optimising clinical outcomes and reducing disease burden. This approach excludes treatment of patients with severe AE, who should be referred to specialist care. Emphasis has been given to the importance of general skincare, patient education and the topical anti-inflammatory medications available in South Africa (TCSs and TCIs).

Fabrication of Copper Oxide Modified Graphene Composite Sensor for Simultaneous Detection of Biometabolites from Urine

It is a common knowledge that the concentration of certain biomarkers in the body accounts for the presence of some diseases. For instance, the unusual levels of uric acid in body fluids may be indicative of gout and hyperuricemia. These biomarkers may be present within the body but may not be detected at very low concentrations and on time to enable proactive treatments, and the consequences may be dire. The current research report features a new approach developed towards fabricating a new copper oxide modified graphene composite sensor with unique nanostructures on a pencil electrode for sensing three biometabolites (xanthine, uric acid and urea) in urine at very low limit of detection (LOD). The surface structures of this composite sensor composed of several electroactive sites for adsorption of desired analytes. This sensor was appropriately characterized by means of Raman spectroscopy, scanning electron microscopy, cyclic voltammetry as well as localized and normal electrochemical impedance spectroscopy. This sensor was significantly sensitive towards uric acid ((LOD = 10 ppm) and urea (LOD = 20 ppm) sensing compared to xanthine (LOD = 50 ppm). Optimization of key sensor parameters towards efficient sensing (e.g. CuO content) were also examined. The efficiency of the composite sensor toward sensing these analytes in the presence of potential interference was investigated using real human urine. Biomolecular sensing of disease biomarkers at low LOD is important in the assessment of health conditions and monitoring treatment progress of patients. Our experimental results demonstrate the efficacy of simultaneously sensing multiple analytes in a complex biological sample. Keywords: Biosensing; Simultaneous detection; Biometabolites; Disease biomarker; Limit of detection

An Open-Label Prospective Study to Compare the Efficacy and Safety of Topical Fluticasone Versus Tacrolimus in the Proactive Treatment of Atopic Dermatitis.

Atopic dermatitis (AD), a chronic, recurrent inflammatory skin condition primarily affects children. Topical treatment, systemic treatment, and phototherapy are mainstays of treatment. Topical corticosteroids (TCS) are first-line therapy for AD but are associated with various adverse effects. Topical calcineurin inhibitors (TCI) can be used as an alternative to TCS. The aim of the study is to compare the efficacy of topical preparations of fluticasone and tacrolimus in reducing the severity of disease and, to assess the quality of life (QoL), and to estimate if any association exists between severity of disease and QoL. Thirty-seven children with AD randomly received one of the 2 topical treatments, with daily application for the first 4 weeks in the acute phase and twice weekly for next 4 weeks in the maintenance phase. The severity of disease was assessed using SCORing Atopic Dermatitis (SCORAD), and QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI). At the end of the acute phase, there was a reduction in SCORAD score of 69.29% in the fluticasone group and 64.2% in the tacrolimus group (P < 0.001). In the maintenance phase, the score had risen in the fluticasone group by a mean difference of 0.81, while in the tacrolimus group it decreased by 0.99. Both fluticasone and tacrolimus groups improved in children's QoL (P < 0.001). Positive correlation (r = 0.4668) exists between SCORAD and QoL. The most common adverse skin reaction noted was skin burning with tacrolimus. Fluticasone and tacrolimus are equally efficacious in the treatment of AD and have similar benefits with children's QoL. Tacrolimus is better than fluticasone at reducing the extent of lesions.

20 Years of Follow-up Alloimmunization and Hemolytic Disease in Newborn: Has Anything Changed in the Field Over the Years?

of the study is to research the epidemiological aspects of maternal alloimmunization against erythrocyte antigens of fetuses (AB0, Rhesus, Lewis, Kell, Duffy and others) and to identify the most common types of hemolytic disease of the newborn (HDN) in the West Herzegovina region. The 20-year retrospective epidemiological study includes all pregnant women who had been immunologically tested and newborn treated for HDN. The indirect antiglobulin (IAT) detected antibodies against antigens in 545 (1.8%) pregnant women of the 29 663 who were tested at the Department of Transfusion Medicine. During the 20-year-long study 310 (1.0%) newborn with HDN were treated. Our results indicate that 42% (230/545) of the pregnant women had AB0 immunization. The most common form of HDN is AB0 HDN 64% (199/310), whereas RhD HDN was treated in 19% (59/310) of the newborn infants. ETR was performed on 29 (19%) infants, 21 (72.4%) with AB0 HDN, and 7 (26%) with RhD HDN. This 20-year-long study concludes that, even though there has been significant progress in the prevention of immunization and proactive treatment of HDN, precautionary measures are still required as is the need for gynecologists and obstetricians to be active. The reasons for this are the non-existence of preventive measures for non-RhD immunization, the irregular immunological screening of RhD positive women in pregnancy in the region encompassed by the study in the past few years. The above raises new questions and recommends further research and monitoring of immunization and HDN treatment worldwide.

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Crohn Disease: A Theoretical Construct to Apply Pharmacokinetics and Guidelines to Clinical Practice.

Therapeutic drug monitoring (TDM) is the measurement of drug and antidrug antibody concentrations in individuals to guide treatment decisions. In patients with Crohn disease (CD), TDM, used either reactively or proactively, is emerging as a valuable tool for optimization of tumor necrosis factor (TNF) antagonist therapy. Reactive TDM is carried out in response to treatment failure, whereas proactive TDM involves the periodic monitoring of patients responding to TNF antagonist therapy to allow treatment optimization. In patients with CD, most of the available data for TDM relate to the first-to-market TNF antagonist infliximab and, to a lesser extent, to adalimumab and certolizumab pegol. Several gastroenterology associations, including the American Gastroenterology Association, have endorsed the use of reactive TDM in patients with active CD. However, fewer recommendations currently exist for the use of proactive TDM, although several new prospective randomized controlled trials evaluating proactive TDM strategies have been published. In this review, the current evidence for reactive and proactive TDM is discussed, and a proactive treatment algorithm for certolizumab pegol based on previously published threshold concentrations is proposed.

Trends in Real-World Neovascular AMD Treatment Outcomes in the UK.

PurposeTo report trends in real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) over the last decade.DesignSystematic review.MethodsMedline, PubMed, and Embase databases were searched from 9 April 2010 to 8 April 2020 for publications that met the inclusion criteria: treatment-naïve eyes, UK-only data and ≥1 year of follow-up. ICHOM (International Consortium for Health Outcome Measures) outcomes and study quality were assessed. Visual acuity (VA) trends were assessed in studies with ≥100 eyes at baseline.ResultsTwenty-six studies (n=25,761 eyes) were included, meeting 14–17 out of 20 Institute of Health Economics Quality Appraisal of Case Series checklist domains. Only ranibizumab and aflibercept outcome data were available. The mean injection number in the first year of treatment was 5.9 in publications from 2010 to 2015 and 7.1 from 2015 to 2020. Average baseline VA and mean one-year, two-year and three-year VA gains gradually improved over the last decade. Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor.ConclusionUK real-world outcomes have improved over the last decade with improved service delivery and the adoption of more proactive treatment regimens but are still not always as impressive as registration clinical trial results. Access to longer-acting anti-VEGF therapies would reduce the treatment burden for patients, carers, and the healthcare system, potentially making replication of clinical trial results possible in the NHS.