Cell Count Monitoring Research Articles

A novel determination method of milk somatic cell count based on dielectric relaxation parameters

Rapid and accurate raw milk somatic cell count (SCC) monitoring is vital to identify cow mastitis and dairy quality evaluation. This study aimed to explore the influence mechanism of milk SCC on dielectric spectra and the potential of dielectric relaxation parameter (DRP) to predict milk SCC. The dielectric spectra of 272 raw milk samples with different SCC at 20–4500 MHz were measured, and the effects of milk SCC on the DRPs were analyzed. The models based on full spectra (FS), characteristic variables extraction, and DRPs methods were established to predict milk SCC. The results showed that the Cole-Cole plots exhibited apparent differences between sample groups with different SCC. The DRPs-NNuSVR model had the best prediction performance, with the standard error of prediction of 0.166 log SCC/mL and residual predictive deviation of 2.538, better than the FS and characteristic variables extraction models. This study explores the influence of milk SCC on dielectric relaxation and proposes a novel milk SCC prediction method, which helps in dairy farming and raw milk quality assessment.

Azathioprine‐induced pancytopenia: A case report

AbstractAzathioprine (AZA) is commonly used as immunosuppressive therapy for autoimmune diseases, including systemic lupus erythematosus (SLE). Myelosuppression is a common side effect of AZA. Here we report a case of severe myelosuppression following AZA therapy in a 15‐year‐old girl despite a normal thiopurine methyltransferase (TPMT) level. She had been receiving AZA for SLE and presented with neutropenic fever and pancytopenia. AZA was stopped. After stopping AZA, her blood counts steadily improved. When TPMT genotyping results were normal, AZA was reintroduced. Pancytopenia reappeared after starting AZA, despite normal TPMT genotype. AZA was replaced with mycophenolate mofetil which consequently resulted in improvement of blood counts. It is essential to understand the temporal relationship between AZA use and pancytopenia onset in patients with normal TPMT activity. This case illustrates that regular monitoring of blood cell counts should be routine practice after starting AZA regardless of TPMT activity.

Relaxation of the criteria for entry to the UK Clozapine Central Non-Rechallenge Database: a modelling study

Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. None.

Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis.

BackgroundCerebral sinus venous thrombosis (CSVT) is a rare neurovascular entity, usually associated with acquired or genetic hypercoagulable states. In up to 30% of the cases it remains idiopathic. Bone marrow proliferation disorders that are associated with Janus Kinase 2 V617F mutation (JAK-2) are known causes of the systemic and cerebral thrombosis—at times despite normal blood counts—for which hematologic treatment exists. However, JAK-2 prevalence in the CSVT cases is not clear.MethodsIn this retrospective analysis, data of 236 patients with CSVT admitted to two tertiary centers between 2010 and 2020 were analyzed, with emphasis on laboratory and imaging data and clinical and interventional outcomes.ResultsA total of 236 patients were included in the analysis. The patients' median age was 42 years and the average age was 44 years (±19 years), with 59% female patients. JAK-2 positivity rate was 18% (among 77 patients tested for the mutation). Patients with normal blood counts on presentation comprised 36% of the JAK-2 positive cases. Other hypercoagulability states were also investigated, with the antiphospholipid syndrome (APLA) showing the highest prevalence (11%) followed by other etiologies including oral contraceptive use, Factor V Leiden, prothrombin mutation, and malignancy. Selected JAK-2, APLA, and prothrombin mutation cases showed a more severe clinical course.ConclusionJAK-2 mutation is underdiagnosed and its screening may be warranted in the cases of idiopathic CSVT, even despite normal blood counts, to allow disease-modifying treatment and blood cell count monitoring. JAK-2, APLA, and prothrombin mutation may be associated with a more complicated clinical course.

Mutational spectrum and its prognostic significance in childhood acute lymphoblastic leukemia based on next-generation sequencing technology

目的分析儿童急性淋巴细胞白血病（ALL）的基因突变谱及其预后意义。方法回顾性分析2016年11月至2019年12月福建医科大学附属协和医院采用二代测序技术（NGS）行基因突变检测的141例初治ALL患儿的临床资料，分析基因突变谱及其对ALL患儿预后的影响。结果141例患儿中，83例（58.9％）检出体细胞突变，包括37个Ⅰ类及123个Ⅱ类突变位点。单核苷酸变异（SNV）为最常见的突变类型。KRAS（20/160，12.5％）为最常见的突变基因，其次为NOTCH1（11.9％）及NRAS（10.6％）。RAS通路（KRAS、FLT3、PTPN11）、PAX5及TP53突变仅在B-ALL患儿中检出，而FBXW7、PTEN突变仅在T-ALL患儿中检出；NRAS突变主要在B-ALL中检出，而NOTCH1突变主要在T-ALL中检出。每例T-ALL患儿检出的平均基因突变个数显著高于B-ALL患儿（4.16±1.33对2.04±0.92，P＝0.004）。按照有无遗传变异将患儿分为突变组和无突变组，两组的性别、年龄、初诊白细胞计数、微小残留病监测结果、预计3年无事件生存（EFS）率及总生存（OS）率差异均无统计学意义（P值均>0.05）；但突变组T-ALL以及融合基因阴性患儿的比例显著高于无突变组（P值分别为0.021和<0.001）。进一步亚组分析，在融合基因阴性的患儿中，有Ⅰ类突变的患儿预计3年EFS率显著低于无Ⅰ类突变的患儿（85.5％对100.0％，P＝0.039）；在B-ALL患儿中，伴TP53突变的患儿预计3年EFS率显著低于不伴有TP53突变的患儿（37.5％对91.2％，P<0.001）。结论体细胞突变在儿童ALL中较为常见，与临床表型及预后具有一定的相关性，NGS可作为传统MICM分型检查的重要补充。

Management of an iris stromal cyst by fine needle aspiration with absolute alcohol irrigation and argon laser photocoagulation to induce sclerosis

To describe the management of an iris stromal cyst by fine needle aspiration and irrigation with absolute alcohol to induce cyst sclerosis. We present the case of a 45-year-old patient with no previous history referred for a 3-month history of an iris lesion in his right eye. Examination revealed a 2.1×3mm cyst with transparent walls at the right inferonasal iris root, and a primary acquired iris stromal cyst was diagnosed. Initially, observation was recommended, but at the 2-month follow-up, growth of the lesion was observed, so fine needle aspiration and cryotherapy were performed, with recurrence after 2 months. Subsequently, fine needle aspiration and irrigation with absolute alcohol for 2minutes to induce sclerosis of the cyst was carried out. Two weeks after surgery, argon laser was performed on the iris root and remaining walls of the cyst to induce adherence. After 1 year of the procedure, the patient remains asymptomatic, without associated complications. A depression and hyperpigmentation of the iris in the inferonasal sector persists, without recurrence of internal fluid or increase in cyst volume. Endothelial cell count and intraocular pressure monitoring have remained stable. Iris stromal cyst sclerosis by aspiration and irrigation with absolute alcohol was effective and avoided complications associated with resection of the lesion.

COVID-19 infection causes a reduction in neutrophil counts in patients taking clozapine.

BackgroundMonitoring of white cell counts during clozapine treatment leads to cessation of therapy if levels fall below pre-determined values. Reductions in white cell counts, driven by lower levels of lymphocytes, have been observed with coronavirus disease 2019 (COVID-19). Neutropenia during COVID-19 has not been reported. We present data for 56 patients who were taking clozapine and had COVID-19.MethodsWe included patients who were taking clozapine at the time they tested positive for COVID-19. We compared absolute neutrophil counts, lymphocyte counts and white cell counts between baseline and the first week of infection, and baseline and the second week of infection.ResultsWe observed reductions in absolute neutrophil counts (p = 0.005), lymphocyte counts (p = 0.003) and white cell counts (p < 0.001) between baseline and the first 7 days of COVID-19. All cell counts had returned to baseline levels by days 8 to 14. Six patients experienced neutropenia (absolute neutrophil counts < 2.0 × 109/L) and of those, 4 underwent mandatory cessation of clozapine. For 3 patients, clozapine treatment had been established for more than 6 months with no previous neutropenia, neutrophil levels returned to baseline within 2 weeks and no further neutropenia was observed on restarting treatment.LimitationsThis was a retrospective chart review; larger cohorts are required. Clozapine plasma levels were largely not measured by clinicians.ConclusionThese data strongly suggest that mild neutropenia in the acute phase of COVID-19 in patients who are well established on clozapine is more likely to be a consequence of the virus than of clozapine treatment.

Pimavanserin Treatment for Parkinson's Disease Psychosis in Clinical Practice.

Background Parkinson's disease psychosis (PDP) is a common, nonmotor symptom of Parkinson's disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations. A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients' changing life circumstances. Conclusions These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP.

Association between quality-of-care indicators for HIV infection and healthcare resource utilization and costs.

Multiple care quality indicators for HIV infection exist but few studies examine their impact on health outcomes. This study assessed which HIV care quality indicators were associated with healthcare resource utilization and costs. Retrospective analysis of Texas Medicaid claims data (01 January 2012 to 31 September 2016). Included patients had at least two HIV-related medical claims during the identification period (01 July 2012 to 31 August 2014) (index = date of first HIV claim), were 18-62 years at index, and were continuously enrolled in the 6-month pre-index and 1-year post-index periods. Dependent variables included emergency department (ED) visits, inpatient hospitalizations, prescription count, and all-cause healthcare costs. Independent variables included CD4 cell count monitoring, syphilis, chlamydia, gonorrhea, hepatitis B, hepatitis C, and tuberculosis screenings, influenza and pneumococcal vaccinations, retention in care, and HAART initiation. Covariates included age, chronic hepatitis C virus infection, AIDS diagnosis, sex, and baseline healthcare cost. The study objective was addressed using generalized linear modeling. CD4 cell count monitoring and HAART initiation were significantly associated with reduced emergency department visits (P < 0.0001 for each). Influenza vaccination was significantly associated with reduced inpatient hospitalization (P < 0.0001). CD4 cell count monitoring (P < 0.0001), TB screening (P = 0.0006), influenza vaccination (P < 0.0001), and HAART initiation (P < 0.0001) were significantly associated with increase prescription claims. CD4 cell count monitoring, TB screening, and HAART initiation (P < 0.0001 for each) were significantly associated with all-cause healthcare costs. HAART may reduce use of emergency care services as early as 1 year following initiation.

1266P - Prognostic significance of tumour tissue NeuGcGM3 ganglioside expression and predictive value of circulating tumour cell count monitoring in patients receiving racotumomab immunotherapy

BackgroundRacotumomab is an anti-idiotype vaccine, a mirror image of N-Glycolylneuraminic acid (NeuGcGM3), which mimics this ganglioside and triggers an immune response in various tumors. In this study we investigated the prognostic significance of tissue NeuGcGM3 expression level and prognostic as well as predictive value of circulating tumor cell count monitoring in patients on Racotumomab treatment. MethodsOut of 48 patients characterized, 40 were non-small cell lung cancer (NSCLC), 12 stage III and 28 stage IV. 19 Adenocarcinoma and 21 Squamous Ca. 2 were small cell lung cancer (SCLC) and 6 with other carcinomas. Male/Female ratio was 3.36(37/11) and median age was 63 (31-84). All patients received Racotumomab as switch maintenance after chemotherapy. 7 PD-L1 (+) Pts also received check point inhibitors on progression. Expression of NeuGcGM3 was detected with 14F7 monoclonal antibody IHC staining and graded as 0,1+,2+ or 3+ according to intensity. Circulating tumor cell (CTC) count was monitored using Cell Sorter throughout the treatment course, before starting Racotumomab and every 3 months or on clinical progression. ResultsNeuGcGM3 IHC were performed 25 out of 48 patients whose paraffin blocks were available. 9 Patients had strong (3+), 12 had (2+) and 4 patients had (1+) NeuGcGM3 staining intensity. There was no statistically significant difference in the mean overall survival of the patients according to IHC staining level (1+) mean OS:55.3 months, (2+) mean OS:40.9 months, and (3+) OS:39.0 months. In 14 Patients, circulating tumor cell count was monitored from the blood and correlated well with clinical outcomes in 11 out of 14 patients (%78.5). Significant reduction of the CTC counts was compatible with clinical response whereas increased CTC counts were early messengers for clinical progression. ConclusionsThis study revealed that any grade of NeuGcGM3 positivity in the tumor tissue is adequate to select a patient for Racotumomab treatment regardless of the IHC intensity. We also concluded that CTC monitoring in patients receiving immunotherapy is a good predictive and prognostic tool. Legal entity responsible for the studyNecdet Uskent. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Integration of Gender-Affirming Primary Care and Peer Navigation With HIV Prevention and Treatment Services to Improve the Health of Transgender Women: Protocol for a Prospective Longitudinal Cohort Study.

BackgroundPublic health strategies are urgently needed to improve HIV disparities among transgender women, including holistic intervention approaches that address those health needs prioritized by the community. Hormone therapy is the primary method by which many transgender women medically achieve gender affirmation. Peer navigation has been shown to be effective to engage and retain underserved populations living with HIV in stable primary medical care.ObjectiveThis study aims to assess the feasibility and acceptability of an integrated innovative HIV service delivery model designed to improve HIV prevention and care by combining gender-affirming primary care and peer navigation with HIV prevention and treatment services.MethodsA 12-month, nonrandomized, single-arm cohort study was implemented in Lima, Peru, among adult individuals, assigned a male sex at birth, who identified themselves as transgender women, regardless of initiation or completion of medical gender affirmation, and who were unaware of their HIV serostatus or were living with HIV but not engaged in HIV treatment. HIV-negative participants received quarterly HIV testing and were offered to initiate pre-exposure prophylaxis. HIV-positive participants were offered to initiate antiretroviral treatment and underwent quarterly plasma HIV-1 RNA and peripheral CD4+ lymphocyte cell count monitoring. All participants received feminizing hormone therapy and adherence counseling and education on their use. Peer health navigation facilitated retention in care by visiting participants at home, work, or socialization venues, or by contacting them by social media and phone.ResultsPatient recruitment started in October 2016 and finished in March 2017. The cohort ended follow-up on March 2018. Data analysis is currently underway.ConclusionsInnovative and culturally sensitive strategies to improve access to HIV prevention and treatment services for transgender women are vital to curb the burden of HIV epidemic for this key population. Findings of this intervention will inform future policies and research, including evaluation of its efficacy in a randomized controlled trial.Trial RegistrationClinicalTrials.gov NCT03757117; https://clinicaltrials.gov/ct2/show/NCT03757117International Registered Report Identifier (IRRID)DERR1-10.2196/14091

The Continuing Value of CD4 Cell Count Monitoring for Differential HIV Care and Surveillance.

The move toward universal provision of antiretroviral therapy and the expansion of HIV viral load monitoring call into question the ongoing value of CD4 cell count testing and monitoring. We highlight the role CD4 monitoring continues to have in guiding clinical decisions and measuring and evaluating the epidemiology of HIV. To end the HIV/AIDS epidemic, we require strategic information, which includes CD4 cell counts, to make informed clinical decisions and effectively monitor key surveillance indicators.

A meta-analysis of controlled studies comparing the association between clozapine and other antipsychotic medications and the development of neutropenia.

In most countries, clozapine can only be prescribed with regular monitoring of white blood cell counts because of concerns that clozapine has a stronger association with neutropenia than other antipsychotics. However, this has not been previously demonstrated conclusively with meta-analysis of controlled studies. The aim of this study was to assess the strength of the association between clozapine and neutropenia when compared to other antipsychotic medications by a meta-analysis of controlled studies. An electronic search of Medline (1948-2018), PsycINFO (1967-2018) and Embase (1947-2018) using search terms (clozapine OR clopine OR clozaril OR zaponex) AND (neutropenia OR agranulocytosis) was undertaken. Random-effects meta-analysis using Mantel-Haenszel risk ratio was used to assess the strength of the effect size. We located 20 studies that reported rates of neutropenia associated with clozapine and other antipsychotic medications. The risk ratio was not significantly increased in clozapine-exposed groups compared to exposure to other antipsychotic medications (Mantel-Haenszel risk ratio = 1.45, 95% confidence interval = [0.87, 2.42]). This also applied to severe neutropenia (absolute neutrophil count < 500 per µL) when compared to other antipsychotics (Mantel-Haenszel risk ratio = 1.65, 95% confidence interval = [0.58, 4.71]). The relative risk of neutropenia associated with clozapine exposure was not significantly associated with any individual antipsychotic medication. Data from controlled trials do not support the belief that clozapine has a stronger association with neutropenia than other antipsychotic medications. This implies that either all antipsychotic drugs should be subjected to haematological monitoring or monitoring isolated to clozapine is not justified.

A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy

BackgroundCD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression.MethodsTime-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the “msm” package in R.ResultsResults from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count.ConclusionFrom this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.

A Novel Device Suitable for Home Monitoring of White Blood Cell and Neutrophil Counts

White blood cell counts (WBC) and absolute neutrophil counts (ANC) are well-established predictors of a patient's risk of fever and infections or febrile neutropenia (FN). Currently, patients at risk of FN due to cancer chemotherapy, idiosyncratic drug-reactions or congenital neutrophil disorders are monitored at hospital or clinic laboratories. For many patients, effective and frequent monitoring is difficult due to the time required and costs of repeated laboratory visits. We herein present the first results for a novel device called Athelas One, a miniature point-of-care hematology analyzer suitable for at home monitoring of WBC and ANC.Methods: Athelas One (A1) is a small cylindrical device with a built-in, single head, light microscope. To determine the WBC and ANC, a small drop of blood (~ 3.5 uL) from a finger stick or an anticoagulated blood sample is drawn by capillary action onto a specially designed microfluidic test strip which creates a stained, precisely dimensioned monolayer of blood cells. The slide is then inserted into the device which scans the test strip and reports the WBC and ANC based on an image analysis process (Computer Vision). We compared results for A1 with a standard laboratory counter [Sysmex XE5000 (SX)].Results: Initially, A1's reproducibility was demonstrated using 43 blood samples with a wide range of known WBCs (i.e., samples with normal counts, leukocytosis, leukopenia, neutropenia, neutrophilia) run on 4 devices using a single lot of test strips. The A1 results were then compared to SX results using the Passing Bablok Regression with Bootstrap method. These results showed strong linearity and comparability between paired anti-coagulated venous blood samples and the blood samples compared to finger prick capillary blood samples collected almost simultaneously. The slope and intercept indicated a linear relationship, with a 95% confidence for interval slope and intercept containing 1 and 0 respectively. (Comparisons: A1 blood to SX blood: WBC, r=0.998, ANC, r=0.989; A1 capillary to SX blood: WBC, r=0.998, ANC, r=0.97). Table 1 and Figure 1 show a summary of the comparisons. In addition to these results, we have tested 18 samples with WBC < 1.0 x 109/L with closely comparable results for A1 and standard hospital counter.Summary: These initial results show that the WBC and ANC can be accurately determined with a finger stick drop of blood and this point-of-care hematology analyzer. Given its small size, ease of use and accuracy, the device is suitable for home monitoring. [Display omitted] DisclosuresDale:Athelas, Inc.: Equity Ownership; Amgen: Consultancy, Research Funding; Sanofi-Aventi: Consultancy, Honoraria; Cellerant: Other: Scientific Advisory Board; Hospira: Consultancy; Prolong: Consultancy; Beheringer-Ingelheim: Consultancy; Coherus: Consultancy. Navarro-De La Vega:Athelas, Inc.: Employment. Parthasarathy:Athelas, Inc.: Employment, Equity Ownership. Bodapati:Athelas, Inc.: Employment, Equity Ownership, Patents & Royalties: patent owned by Athelas on the Athelas One device. Virey:Athelas, Inc.: Employment, Equity Ownership, Patents & Royalties: patent owned by Athelas on the Athelas One device. Moffatt:Athelas, Inc.: Employment, Equity Ownership, Patents & Royalties: patent owned by Athelas on the Athelas One device. Tandon:Athelas, Inc.: Employment, Equity Ownership, Patents & Royalties: patent owned by Athelas on the Athelas One device.

Task-shifting of CD4 T cell count monitoring by the touchscreen-based Muse™ Auto CD4/CD4% single-platform system for CD4 T cell numeration: Implication for decentralization in resource-constrained settings

BackgroundThe accuracy of CD4 T cell monitoring by the recently developed flow cytometry-based CD4 T cell counting Muse™ Auto CD4/CD4% Assay analyzer (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) was evaluated in trained lay providers against laboratory technicians. MethodsAfter 2 days of training on the Muse™ Auto CD4/CD4% analyzer, EDTA-blood samples from 6 HIV-positive and 4 HIV-negative individuals were used for CD4 T cell counting in triplicate in parallel by 12 trained lay providers as compared to 10 lab technicians. ResultsMean number of CD4 T cells in absolute number was 829 ± 380 cells/μl by lay providers and 794 ± 409 cells/μl by technicians (P > 0.05); and in percentage 36.2 ± 14.8%CD4 by lay providers and 36.1 ± 15.0%CD4 by laboratory technician (P > 0.05). The unweighted linear regression and Passing-Bablok regression analyses on CD4 T cell results expressed in absolute count revealed moderate correlation between CD4 T cell counts obtained by lay providers and lab technicians. The mean absolute bias measured by Bland–Altman analysis between CD4 T cell/μl obtained by lay providers and lab technicians was −3.41 cells/μl. Intra-assay coefficient of variance (CV) of Muse™ Auto CD4/CD4% in absolute number was 10.1% by lay providers and 8.5% by lab technicians (P > 0.05), and in percentage 5.5% by lay providers and 4.4% by lab technicians (P > 0.05). The inter-assay CV of Muse™ Auto CD4/CD4% in absolute number was 13.4% by lay providers and 10.3% by lab technicians (P > 0.05), and in percentage 7.8% by lay providers and 6.9% by lab technicians (P > 0.05). ConclusionsThe study demonstrates the feasibility of CD4 T cell counting using the alternative flow cytometer Muse™ Auto CD4/CD4% analyzer by trained lay providers and therefore the practical possibility of decentralization CD4 T cell counting to health community centers.

Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center.

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening adverse drug reaction that occurs in patients during the treatment of Graves' disease. We aimed to comprehensively examine data for patients with this rare complication and to improve the clinical safety of ATDs. We retrospectively reviewed the medical records of 64 hospitalized patients diagnosed with ATD-induced agranulocytosis between 2000 and 2015. Agranulocytosis occurred in 52 (81.3%) patients within the first 3months after initiation of ATD therapy. Fever (84.4%) and sore throat (82.8%) were the most common symptoms. Although they experienced symptoms, 30 (46.9%) patients did not seek treatment immediately and delayed their diagnosis of agranulocytosis. The minimum granulocyte count was lower in the patients diagnosed after the appearance of symptoms than in those diagnosed before the appearance of symptoms (0.01 × 109/L (0 × 109/L - 0.06 × 109/L) versus 0.26 × 109/L (0.05 × 109/L - 0.40 × 109/L), P < 0.001). The interval days from the appearance of symptoms to the diagnosis of agranulocytosis were negatively correlated with the minimum granulocyte count (r = -0.348, P = 0.005). In addition, a lower minimum granulocyte count was associated with a longer recovery time (β = -11.899, 95% CI -15.304 to -8.496). Our findings have demonstrated that delayed diagnosis of ATD-induced agranulocytosis is common in our population. Delayed diagnosis is associated with severe agranulocytosis and may prolong the recovery time from agranulocytosis. Monitoring of the white blood cell and granulocyte counts may be an effective way to establish an early diagnosis and prevent progression to severe agranulocytosis.

Is it still worthwhile to perform quarterly cd4+ t lymphocyte cell counts on hiv-1 infected stable patients?

BackgroundIn the last 20 years routine T CD4+ lymphocyte (CD4+) cell count has proved to be a key factor to determine the stage of HIV infection and start or discontinue of prophylaxis for opportunistic infections. However, several studies recently showed that in stable patients on cART a quarterly CD4+ cell count monitoring results in limited (or null) clinical relevance. The research is intended to investigate whether performing quarterly CD4+ cell counts in stable HIV-1 patients is still recommendable and to provide a forecast of the cost saving that could be achieved by reducing CD4+ monitoring in such a category of patients.MethodsThe study is based on data referring to all HIV-infected patients > 18 years of age being treated at two large infectious diseases units located in the metropolitan area of Genoa, Italy. The probability of CD4+ cell counts dropping below a threshold value set at 350 cells/mm3 is assessed using confidence intervals and Kaplan-Meier survival estimates, whereas multivariate Cox analysis and logistic regression are implemented in order to identify factors associated with CD4+ cell count falls below 350 cells/mm3.ResultsStatistical analysis reveals that among stable patients the probability of maintaining CD4+ >350 cell/mm3 is more than 98%. Econometric models indicate that HCV co-infection and HIV-RNA values >50 copies/mL in previous examinations are associated with CD4+ falls below 350 cells/mm3. Moreover, results suggest that the cost saving that could be obtained by reducing CD4+ examinations ranges from 33 to 67%.ConclusionsEmpirical findings shows that patients defined as stable at enrollment are highly unlikely to experience a CD4+ value <350 cell/mm3 in the space/arc of a year. The research supports a recommendation for annual CD4+ monitoring in stable HIV-1 patients.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Standardized laboratory monitoring with use of isotretinoin in acne

Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care. We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne. We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined. Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3days for hypertriglyceridemia, 61.9days for alanine transaminitis, and 50.1days for hypercholesterolemia. This was a single-center experience examining variable isotretinoin laboratory monitoring practices. In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended.