Reducing time to differentiated service delivery for newly-diagnosed people living with HIV in Kigali, Rwanda: a pilot, unblinded, randomized controlled trial.

BACKGROUND: Differentiated service delivery (DSD) programs for people living with HIV (PWH) limit eligibility to patients established on antiretroviral therapy (ART), yet uncertainty exists regarding the duration on ART necessary for newly-diagnosed PWH to be considered established. We aimed to determine the feasibility, acceptability, and preliminary impact of entry into DSD at six months after ART initiation for newly-diagnosed PWH. METHODS: We conducted a pilot randomized controlled trial in three health facilities in Rwanda. Participants were randomized to: (1) entry into DSD at six months after ART initiation after one suppressed viral load (DSD-1VL); (2) entry into DSD at six months after ART initiation after two consecutive suppressed viral loads (DSD-2VL); (3) treatment as usual (TAU). We examined feasibility by examining the proportion of participants assigned to intervention arms who entered DSD, assessed acceptability through patient surveys and by examining instances when clinical staff overrode the study assignment, and evaluated preliminary effectiveness by comparing study arms with respect to 12-month viral suppression. RESULTS: Among 90 participants, 31 were randomized to DSD-1VL, 31 to DSD-2VL, and 28 to TAU. Among 62 participants randomized to DSD-1VL or DSD-2VL, 37 (60%) entered DSD at 6 months while 21 (34%) did not enter DSD because they were not virally suppressed. Patient-level acceptability was high for both clinical (mean score: 3.8 out of 5) and non-clinical (mean score: 4.1) elements of care and did not differ significantly across study arms. Viral suppression at 12 months was 81%, 81% and 68% in DSD-1VL, DSD-2VL, and TAU, respectively (p = 0.41). CONCLUSIONS: The majority of participants randomized to intervention arms entered DSD and had similar rates of viral suppression compared to TAU. Results suggest that early DSD at six months after ART initiation is feasible for newly-diagnosed PWH, and support current WHO guidelines on DSD. TRIAL REGISTRATION: Clinicaltrials.gov NCT04567693; first registered on September 28, 2020.

Retention of discharge instructions using an interdisciplinary model for at-risk children with cancer: A quality improvement initiative.

PURPOSE: We sought to improve caregiver retention of critical initial hospital discharge instructions using a multidisciplinary, team-based intervention for newly diagnosed pediatric cancer patients at high risk for unfavorable outcomes. MATERIALS AND METHODS: A multidisciplinary team of pediatric residents, nurses, social workers, pharmacists and hematology/oncology faculty implemented practices to optimize teaching of key discharge material as part of four Plan-Do-Study-Act intervention cycles. An 11-question survey distributed at the first post-discharge clinic visit assessed the efficacy of the intervention, as defined by caregiver retention of critical home instructions. RESULTS: Thirty-nine caregivers of pediatric cancer patients in an urban academic tertiary-care children's hospital took part in this project. Overall retention of key discharge information was greater in the post-intervention cohort compared to the baseline cohort (median total scores: 89 and 63, respectively; p = .001). Improvements in the proportions of correct responses post-intervention were also observed across all subject matters: from 0.57 to 0.88 for fever guidelines (p = .059), from 0.71 to 0.78 for signs of sepsis (p = .65), from 0.57 to 1.00 for accurate choice of on-call number (p = .004), and from 0.71 to 0.94 for antiemetic management (p = .14). CONCLUSION: Initiation of our comprehensive cancer-specific program to improve caregiver retention of discharge instructions at the first post-hospitalization clinic visit has been successful and sustainable. This project demonstrated that a multi-disciplinary collaborative team effort increases caregiver retention of critical health information, and this has potential to lead to improved outcomes for patients.

Up all night? Sleep disruption in parents of young children newly diagnosed with type 1 diabetes.

BACKGROUND: Despite the known challenges of parental adjustment to new-onset type 1 diabetes (T1D) in young children, little is known about parental sleep soon after diagnosis. METHODS: Parents (n = 157) of young children (4.5 ± 1.6 years) with new-onset T1D (29 ± 15 days) self-reported their sleep (Pittsburgh Sleep Quality Index, PSQI) at the baseline of a behavioral randomized control trial. We examined sleep patterns and relations with continuous glucose monitor (CGM) use. RESULTS: Over two-thirds (68.8%) reported poor sleep quality (PSQI > 5, M = 8.3 ± 4.1). The mean reported sleep duration was 5.9 ± 1.4 h/night. PSQI scores did not significantly differ by CGM use. CONCLUSIONS: Sleep disruption is a pervasive self-reported problem among parents of young children emerging early after the T1D diagnosis. Healthcare providers should discuss parental sleep as part of diabetes care soon after diagnosis. Further interventions targeting parental sleep may be of benefit.

Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry.

AIM: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. METHODS: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (~10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, or χ2-tests were used to calculate differences between groups. RESULTS: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. CONCLUSIONS: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.

Assessment of infection in newly diagnosed multiple myeloma patients: risk factors and main characteristics.

BACKGROUND: Infection is a leading cause of morbidity and death in patients with multiple myeloma (MM). The increased susceptibility to infection is complicated and multifactorial. However, no studies have explored the spectrum and risk factors of infections in newly diagnosed MM patients at the first admission. This cross-sectional study aimed to provide ideas for the assessment, prevention and treatment of infection in newly diagnosed MM patients when admitted for the first time. METHODS: Retrospectively, the data from electronic medical records for 161 patients newly diagnosed with MM from May 2013 to December 2018 were analysed. All the information was collected at the time of admission, and the patients had received no antineoplastic therapy previously. Independent risk factors of infection in multiple myeloma were determined by univariate and multivariate analysis. RESULTS: Newly diagnosed patients with MM were highly susceptible to viruses (43.9%), especially Epstein-Barr virus (EBV) (24.4%) and hepatitis B virus (HBV) (17.1%). Advanced stage (ISS stage III, P = 0.040), more severe anaemia (Hb < 90 g/L, P = 0.044) and elevated CRP (> 10 mg/L, P = 0.006) were independent risk factors for infection. Moreover, infections represented a major survival threat to patients with newly diagnosed MM (P = 0.033), and the existence of risk factors for infection was significantly correlated with poor prognosis (P = 0.011), especially ISS stage III (P = 0.008) and lower haemoglobin level (P = 0.039). CONCLUSIONS: Newly diagnosed MM patients are highly susceptible to viruses. Advanced ISS stage, more severe anaemia and the elevation of CRP are independent risk factors of infection, which also have a strong impact on prognosis. Our results suggest that viral infection should be taken into account if antibacterial drugs are not effective, and the prevention of infection and improvement of prognosis should be paid more attention in newly diagnosed patents with advanced stage and more severe anaemia.

MicroRNAs expression profiles as biomarkers and therapeutic tools in Turkish patients with chronic myeloid leukemia.

AIM: In 95 % of Chronic myeloid leukemia (CML) patients, chromosomal translocation resulting in the formation of the Philadelphia (Ph) chromosome (t:9;22) is observed, which in turn leads to the formation of the BCR-ABL fusion gene. MicroRNAs (miRNAs) are a group of small and non-coding RNAs modulating gene expression via binding to the target mRNAs. We aimed to characterize the expression profiles of various miRNAs in different stages of Ph(+) CML patients. METHODS: This case-controlled study was conducted in 75 CML patients and 25 healthy controls. The subjects were categorized into 4 groups; newly diagnosed patients, treatment-response patients, treatment-failure patients, and healthy controls. Expressions of miRNAs was analyzed by RT-PCR. RESULTS: miR-150 expression was downregulated in the treatment failure patients compared to the control group (p = 0.003212) while miRNA 148b expression up-regulated in the treatment failure patients than the control group (p = 0.038016). miR-10a expression was up-regulated in newly diagnosed and treatment response patients compared to control group (p = 0.003934, p = 0.000292, respectively). It was found that miR-10a expression increased 11.17- fold in newly diagnosed patients and 9.82-fold in treatment response patients than in the control group. CONCLUSION: Our data suggest that expression profiles of miR-10a, miR-150, and miRNA 148b were correlated as biomarker and therapeutic tool in Turkish patients with CML (Tab. 2, Fig. 1, Ref. 30).

Minimal residual disease by flow cytometry and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction in patients with myeloma receiving lenalidomide maintenance: A pooled analysis.

BACKGROUND: Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM); however, the impact of maintenance therapy on MRD levels remains unclear. Among patients with newly diagnosed MM (NDMM) who received lenalidomide maintenance until they developed disease progression, the role of MRD status as a predictor of progression-free survival (PFS) was evaluated by multiparameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) analysis. METHODS: Seventy-three patients with NDMM enrolled in the RV-MM-EMN-441 (clinical trials.gov identifier, NCT01091831) and RV-MM-COOP-0556 (clinicaltrials.gov identifier, NCT01208766; European Myeloma Network EMN02/HO95 MM Trial) phase 3 trials who achieved at least a very good partial response after intensification/consolidation were included. The median patient age was 57 years (interquartile range, 53-61 years), and all patients received lenalidomide maintenance until they developed progression. MRD was evaluated on bone marrow after intensification/consolidation, after 6 courses of maintenance, and every 6 months thereafter until clinical relapse using both ASO-RQ-PCR (sensitivity, 10-5 ) and MFC (sensitivity, from 10-4 to 10-5 ). RESULTS: After intensification/consolidation, 33 of 72 patients (46%) achieved a molecular complete response (m-CR), and 44 of 70 (63%) achieved a flow complete response (flow-CR). Almost 27% of patients who were MRD-positive after consolidation became MRD-negative during maintenance. After a median follow-up of 38 months, PFS was prolonged in patients who achieved negative MRD status during maintenance according to results from both ASO-RQ-PCR analysis (hazard ratio, 0.29; 95% confidence interval, 0.14-0.62; P = .0013) and MFC (hazard ratio, 0.19; 95% confidence interval, 0.09-0.41; P < .001). The impact of negative MRD status on PFS was similar in all subgroups (ASCT and no-ASCT; International Staging System stages I, II, and III; high-risk and standard-risk cytogenetics), and the two techniques were highly correlated. CONCLUSIONS: MRD status is a stronger predictor of PFS than standard risk factors, and lenalidomide maintenance further increases the rate of negative MRD results.

Behavioral problems of preschool children with new-onset epilepsy and one-year follow-up - A prospective study.

OBJECTIVES: Childhood emotional/behavioral problems in children with epilepsy have been reported to be higher compared with those with typical development or with other nonneurologic health conditions. Increasing interest towards understanding these behavioral comorbidities is reflected in literature. However, longitudinal investigations regarding the course of behavioral problems in children with newly diagnosed epilepsy and normal development are rare, and majority of them involve school-aged children. We aimed to study the behavioral comorbidities of preschool children with newly diagnosed epilepsy and to explore the changes of behavioral problems after one year from the diagnosis in comparison with the healthy group and subsequently, to elucidate the potential developmental, neurologic, and social risk factors associated with these difficulties. METHODS: Participants were 83 patients, aged between 18 and 59 months, 43 of them were children with new-onset epilepsy, and 40 of them were healthy children as the comparison group. The Child Behavior Check List-1 1/2-5 (CBCL) was used to evaluate emotional/behavioral problems of the children. Maternal anxiety was analyzed by The State-Trait Anxiety Inventory (STAI). The general development of children was evaluated by the Denver-II-Developmental Screening Test (D-II-DST). Sociodemographic characteristics were also collected for all participants. Each evaluation was repeated after one year from the diagnosis. RESULTS: Internalizing, externalizing, and total problem scores were higher in children with epilepsy than the control group at baseline, and despite some reduction in several scales, the differences continued across groups after one year. The analysis for the course revealed that behavior problem scores reduced in children with new-onset epilepsy over a year, but it did not change in healthy children. Among the possible factors related to behavior problem scores, in correlation analysis, the duration of screen viewing, socioeconomic status, and maternal education were associated with behavior problem scores. There was no significant association between epilepsy-related variables and the behavior problem scores and the course. Among all possible risk factors in the regression analyses, maternal trait anxiety level was found to be significantly related to the total problems, internalizing, and externalizing scores in the group with epilepsy. CONCLUSION: Behavioral comorbidities of epilepsy are present very early and can be seen at the time of the diagnosis, however, they do not worsen over time in preschool children. Maternal anxiety should be considered as a risk factor for behavioral problems in preschool children with epilepsy. Assisting children and parents and ensuring necessary guidance and support should be a crucial part of epilepsy treatment initiated as soon as the time of diagnosis.

Experiences of College Students Who Are Newly Diagnosed With Type 1 Diabetes Mellitus.

PURPOSE: To gain insight and understanding of emerging adult experiences after a diagnosed with type 1 diabetes mellitus (T1DM) and prior to or during college life experiences. DESIGN AND METHODS: A qualitative research design using a focus group was conducted with 12 college students recently diagnosed with T1DM during emerging adulthood. The focus group took place during a College Diabetes Network retreat. Using Braun and Clarke's six phase process, two researchers independently conducted a thematic analysis from the transcribed, verbatim audiotaped narratives. RESULTS: The 12 participants attended colleges in 11 different states. The mean age was 21 years (SD = 6.3) and the majority were female (n = 7). Qualitative analysis revealed four themes: 1) diabetes affects all aspects of life and complicates college living; 2) college environment affects diabetes management; 3) diabetes diagnosis facilitates growth and maturity; and 4) strategies used for diabetes management in college. CONCLUSION: T1DM is complex to manage in the college environment. However, these emerging adults newly diagnosed with T1DM highlight strategies for diabetes management while in college and the pivotal role of pediatric providers play in the successful management of T1DM. PRACTICE IMPLICATIONS: Diabetes education for emerging adults in college requires an adaptive focus that supports the developmental needs of this population. Nurses should focus on teaching healthy, modifiable behaviors of sleep, physical activity, and nutrition to improve glycemic control as well as adapting to the college life choices.

Epidemiological, clinical, virological features of hepatitis B newly diagnosed in 2011 in Marseille University hospitals, southeastern France.

Hepatitis B virus (HBV) infection is a public health problem. In France, 0.68% of adults are chronically infected. We aimed to describe the epidemiological, virological and clinical characteristics of HBV infections newly diagnosed in 2011 in University hospitals of Marseille, the second largest French city. HBV serology was performed for 18,130 sera from 15,744 patients. A total of 167 patients were newly-diagnosed with HBV based upon the detection of hepatitis B surface antigen and anti-hepatitis B core antibodies. Clinico-epidemiological features were analyzed for 78 patients. Patients included a majority of men (59%), women being significantly younger with a mean age of 36 ± 17 versus 43.5 ± 16.2 years (P = 0.009). Country of birth was available for 52 patients and 35% of them originated from sub-Saharan Africa. Levels of the liver biological parameters were significantly lower in women compared to men, in whom mean alanine aminotransferase and gammaglutamyl transferase levels were 24 ± 39 versus 37 ± 36 IU/l (P = 0.0001) and 20 ± 20 versus 51 ± 53 IU/l (P = 0.0001), respectively. Co-infections with hepatitis C and human immunodeficiency viruses were found in 5% and 6% of the patients, respectively. HBV DNA was detectable in 90% of the HBeAg-negative patients. In addition, there was a positive correlation between the HBsAg titer and the HBV DNA level (P = 0.001). Genotype D was the most common HBV genotype and was found in 53% of the patients tested, followed by genotype E (21%). HBV remains a major concern with a slightly greater number of new diagnoses than in 2004. HBV genetic diversity was substantial in the present cohort.

Nondisclosure of HIV status in a clinical trial setting: antiretroviral drug screening can help distinguish between newly diagnosed and previously diagnosed HIV infection.

In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)-infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly diagnosed and previously diagnosed HIV infection.

Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity.

DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Newly diagnosed type 2 diabetes - does New Zealand General Practice adequately prepare patients to self-manage their Condition?

BACKGROUND: Type 2 diabetes mellitus (T2D) is predominantly managed in primary care, and patients need to be provided with appropriate knowledge and education to understand how to best self-manage their condition. For optimal T2D self-management, primary care teams should share this information from the time of diagnosis. Little is currently known about how and when these resources are being provided to patients with T2D in New Zealand. METHODS: An online survey was carried out between Oct 2022 and Feb 2023. Patients diagnosed with T2D after Jan 2020 were invited to participate, with recruitment occurring via primary care and social media. Questions included information about demographics, diagnosis, provision of education resources and/or referral services as well as about current diabetes management. All responses were analysed with chi square tests. Free-text comments were summarised only. RESULTS: A total of 203 participants from across New Zealand completed the survey, but 18 were excluded due to being diagnosed more than 3 years ago, or self-reporting with type 1 diabetes rather than T2D. Nearly three quarters (70.7%) of participants reported that they were given appropriate resources to understand and manage their T2D, though half of these would have like more information. Overall, family and friends, self-led research and healthcare-provided education were equally useful, though this differed by ethnic groups. Similarly, approx. 70% of patients thought that medications had been well explained. Free text comments suggested a need for more targeted information around food choice and insulin use as well as a need for empathy and appropriate language from healthcare providers. CONCLUSIONS: Primary care appears to be providing most newly diagnosed patients with appropriate resources to understand and manage their T2D, but there is room for improvement with up to a third of participants not understanding how to manage foods, medication and lifestyle choices to optimise health outcomes. Further work is required to address this gap and should include the use of culturally-appropriate materials to meet the multi-ethnic population needs.

A Structured Discharge Education Intervention for Parents of Newly Diagnosed Pediatric Oncology Patients.

Background: Parents of children newly diagnosed with cancer require specialized knowledge and skills in order to safely care for their children at home. The Children's Oncology Group (COG) developed expert consensus recommendations to guide new diagnosis education; however, these recommendations have not been empirically tested. Methods: We used a sequential two-cohort study design to test a nurse-led Structured Discharge Teaching Intervention (SDTI) that operationalizes the COG expert recommendations in the setting of a tertiary children's hospital. Outcomes included parent Readiness for Hospital Discharge Scale (RHDS); Quality of Discharge Teaching Scale (QDTS); Post-Discharge Coping Difficulty (PDCD); Nurse Satisfaction; and post-discharge unplanned healthcare utilization. Results: The process for discharge education changed significantly before and after implementation of the SDTI, with significantly fewer instances of one-day discharge teaching, and higher involvement of staff nurses in teaching. Overall, parental RHDS, QDTS, and PDCD scores were similar in the unintervened and intervened cohorts. Almost 60% of patients had unplanned healthcare encounters during the first 30 days following their initial hospital discharge. Overall nurse satisfaction with the quality and process of discharge education significantly increased post-intervention. Discussion: Although the structure for and process of delivering discharge education changed significantly with implementation of the SDTI, parent RHDS and QDTS scores remained uniformly high and PDCD scores and non-preventable unplanned healthcare utilization remained similar, while nurse satisfaction with the quality and process of discharge education significantly improved, suggesting that further testing of the SDTI across diverse pediatric oncology settings is warranted.

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients.

The aim of this study is to analyze the efficacy and safety of sequential therapy with bortezomib-based triplet regimens without lenalidomide (PXD, including VTD, PAD, and VCD) followed by continuous lenalidomide and dexamethasone (Rd) or bortezomib and dexamethasone (Vd) treatment. The main objective is to evaluate the advantages of PXD followed by Rd compared to the combinations of bortezomib-lenalidomide-dexamethasone (VRd) in newly diagnosed multiple myeloma (NDMM). Fifty-eight nontransplant NDMM patients who were admitted to our department from 2017 to 2019 were included in this study. Bortezomib-based triplet regimens were initially selected and followed by Rd or Vd as continuous treatment once the patients achieved partial remission (PR) or better response. The efficacy and safety of the patients were observed. The Rd continuous treatment cohort was compared with historical data from the EVOLUTION trial on continuous VRd treatment. In our cohort, the overall survival rate was 100%, and progression-free survival (PFS) was 38.5% after a median of 19 (4-36) cycles of Rd continuous therapy was applied. During the follow-up period, the best outcome assessments achieved were 53.8% complete response (CR) and 84.6% excellent partial response (VGPR). A total of 23.1% had grade 3-4 or higher drug-related adverse reactions, mainly hematological toxicity, and no patients died of adverse reactions. Compared with the Vd group, the Rd group had a better PFS and VGPR rate (2-year PFS: 92.3% vs. 56.3%, P = 0.002; 3-year PFS: 69.2% vs. 8.0%, P < 0.001; VGPR: 84.6% vs. 69.2%, P = 0.02). No significant differences were found in ORR (100% vs. 92.3%) or CR (53.8% vs. 35.7%, P = 0.082). Compared with the EVOLUTION study, patients in the Rd group had a more advanced disease stage (stage III rate of 40% vs. 19%, P = 0.039) and worse physical status (KPS 50-60 rate of 25.0% vs. 2.0%, P = 0.000). However, a higher proportion of ORR (100% vs. 73.0%, P < 0.001), VGPR or better (75.0% vs. 32.0%, P < 0.001), and PFS at 12 months (90.0% vs. 68%, P = 0.011) were achieved. Sequential administration of bortezomib-based triplet regimens without lenalidomide as an initial therapy followed by Rd as a continuous treatment may not be inferior to VRd for first-line treatment in NDMM patients.

Supporting Parents Throughout the Genetic Testing Process and New Diagnosis.

Receiving a genetic diagnosis can be challenging for parents as they learn to cope and adapt to this news. They often experience a myriad of emotions ranging from shock to relief. Yet overwhelmingly, parents report a negative experience with this process. Factors that improve parental satisfaction include being provided written information, emotional and psychosocial support, and connections with other parents. Genetics care providers are particularly equipped to solicit parental needs and provide support before, during, and after receiving a diagnosis. This review will provide suggestions and recommendations for supporting parents throughout the diagnostic testing experience and receiving a genetic diagnosis.

Basic and clinical study of efficacy and adverse effects of flumatinib in Ph+ ALL.

Objective: To investigate the efficacy and safety of chemotherapy in treating Ph+ ALL based on flumatinib. Methods: The clinical data of 29 patients with Ph+ ALL receiving flumatinib-based chemotherapy in Sichuan Provincial People's Hospital from January 2020 to January 2023 were collected for analysis, with the concentrations of TKI in the peripheral blood, bone marrow, and cerebrospinal fluid of some patients monitored, Cytological experiments on SUP-B15 were conducted in a Ph+ ALL cell line. Results: A total of 29 patients were enrolled, showing the induced CR, 3-month CR, and 6-month CR rates of 96.3%, 87.5%, and 86.7%, respectively after flumatinib-based chemotherapy. The negative conversion ratio of MRD was 82.6%, 91.3%, and 95.6% in 1, 2, and 3 months after treatment, respectively, with 4.3% of patients failing the conversion in 3 months after treatment. The rates of MMR were 73.9%, 87.5%, and 93.3% in 1, 3, and 6 months after treatment, and CMR of 52.2%, 62.5%, and 73.3%, respectively. Among the 29 patients, 11 (37.9%) received transplant and the continuous flumatinib for 1 year after transplantation. The deep remission was maintained in all patients up to the time of follow-up, with the median follow-up of 12 months (1-33 months), progression-free survival (PFS) of 11 months (1-33 months), and median overall survival (OS) of 12 months (1-33 months). The adverse reactions mainly referred to myelosuppression, liver insufficiency and infection that were generally tolerable. In terms of blood concentration, the concentration of flumatinib was ordered as bone marrow > serum > cerebrospinal fluid in Ph+ ALL bone marrow. In contrast, the concentration of dasatinib and imatinib was ordered as serum > bone marrow > cerebrospinal fluid. At the same time, flumatinib has a high probability to cross the blood-brain barrier, while the concentration of cerebrospinal fluid in the patients using Dasatinib was lower compared to the lower limit of detection in this study. Compared with Imatinib and Dasatinib, flumatinib exerted the most potent inhibitory effect on Ph+ ALL cell lines according to pharmacodynamic analysis of SUP-B15 cells. Conclusion: Flumatinib combined with chemotherapy could achieve good efficacy and safety in treating Ph+ ALL, with flumatinib in a high probability of crossing the blood-brain barrier. Flumatinib could be a superior choice to Dasatinib and Imatinib in cell experiments.

Epidemiological and Clinical Profile of Newly Diagnosed HIV/AIDS Patients: A Retrospective Analysis of Changing Trends Over 16 Years.

OBJECTIVE: To evaluate the epidemiological profile and clinical findings of newly diagnosed HIV-infected patients in terms of changing trends over 16 years. METHODS: A total of 748 patients (mean ± SD age: 34 ± 11.6 years, 88.9% were males) newly diagnosed with HIV/AIDS at a tertiary care hospital located in Istanbul province between 2002 and 2017 were included in this retrospective study. Data on sociodemographic characteristics, potential routes of transmission, the reason for HIV testing, time from diagnosis to treatment onset, and the HIV RNA values and CD4+ T cell count (at diagnosis and treatment onset) were recorded in each patient and compared between the diagnoses made within the 2002-2009 (n = 141) vs. 2010-2017 (n = 607) periods. RESULTS: When compared to HIV diagnoses within the 2002-2009 period, the diagnoses made within the 2010-2017 period were associated with a significantly higher percentage of males (78.7 vs. 91.3%, p < 0.001), 18-29 years age group (23.6% vs. 35.5%, p = 0.029), singles (34.0 vs. 49.6%, p = 0.004), university graduates (9.9 vs. 23.4%, p < 0.001) and students (0.7 vs. 8.2%, p < 0.001) along with an increased likelihood of voluntary testing (6.4 vs. 15.2%, p = 0.048) and a lower percentage of heterosexual individuals (63.8 vs. 47.0%, p < 0.001). Sexual contact (88.0%) was the leading transmission route, and the presence of complaints (44.3%) was the leading reason for HIV testing. Overall, the time from diagnosis to treatment onset was a median 1 month (range, 1 to 97 months), and the median HIV RNA level at the time of diagnosis was 208065 copies/mL with no significant difference between study periods. The diagnoses within the 2010-2017 vs. 2002-2009 period were associated with significantly higher median (min-max) CD4+ T cell counts (378(0-2522) vs. 319(4-1270) cells/mm3, p < 0.001) and a lower percentage of patients with CD4+ T cell count < 200 cells/mm3 (22.1 vs. 39.0%, p = 0.002) at the time of diagnosis. CONCLUSION: In conclusion, our findings on the epidemiological profile and clinical characteristics of newly diagnosed HIV patients over 16 years (2002-2017) in a tertiary care center in Turkey revealed a considerable increase in the number of new diagnoses, an improved earlier diagnosis and a change in epidemiologic profile over the years with increased likelihood of disease to be more commonly diagnosed among males, 18-29 years age group and MSM.

'You don't want to be seen as a burden' experiences of working with early inflammatory arthritis: a qualitative study.

PURPOSE: To describe the impact of early inflammatory arthritis on work participation. MATERIALS AND METHODS: Thirty individuals (24 women) of working age (age 18-69 years) with inflammatory arthritis (<2 years duration) who were in paid employment or fulltime education were interviewed using qualitative description methodology. Data was analysed using thematic analysis. RESULTS: Half of participants (n = 15) reported work disability within the first two-years of diagnosis. Five descriptive themes were identified that explained the early impact of IA on participation in paid employment. These themes were: (i) altered capacity for work; (ii) work comes first; (iii) the invisible burden; (iv) the disclosure effect; and (v) a reconstructed work future. CONCLUSION: The scale of early work disability appears to be higher than previously understood. Although early medical intervention has improved disease management, significant work-based restrictions requiring intervention remain. Internalised and invisible work-related anxieties present early in the disease and need to be acknowledged and addressed by healthcare providers.IMPLICATIONS FOR REHABILITATIONEarly inflammatory arthritis causes significant challenges in work ability, and early work-based participation restrictions are present despite early use of drug therapy.Assessment of the client's subjective experience, including understanding the invisible burden, is an important aspect in determining the types of work interventions required.Disclosure of diagnosis in the work environment is associated with anxiety and fear, however, disclosure is influential in supporting capacity to retain work participation and should be included in work interventions.Routine healthcare should include early interventions to address work-based restrictions and supporting work retention to avoid work disability.