Newly-diagnosed Individuals Research Articles

Dynamics of clustering rates in the rhode Island HIV-1 epidemic.

: Characterizing HIV clustering rates and their trends over time can improve understanding a local epidemic and enhance its control. Leveraging an academic-public health partnership in Rhode-Island, we explored longitudinal dynamics of statewide clustering rates among key populations from 1991 to 2023. Partial HIV-1 pol sequences were grouped by year of HIV-1 diagnosis. Molecular clusters were identified in cumulative annual phylogenies. Overall clustering rates, and clustering rates of newly-diagnosed and prevalent infections, and of specific socio-demographic characteristics of key populations over time were determined. Mann-Kendall statistics were used to estimate clustering rate trends and relationships among groups. By the end of 2023, 2,630 individuals with sequences represented the statewide epidemic in Rhode Island. Overall clustering rates increased from 7% in 1991 to 46% in 2023, correlating with cumulative sequence increase. Clustering rates of newly-diagnosed and prevalent infections significantly increased over time, higher in newly-diagnosed individuals since the early 2000 s. Increases were also observed among groups defined by gender, age, transmission risks, race, mental illness, HIV-1 subtypes, and country of birth, with some crossovers and divergence patterns over time. Exploring dynamics of HIV clustering rates over three decades in a statewide HIV-1 epidemic expanded its characterization and provided insight into its evolving changes. These dynamics may indicate a gradual shift towards a more concentrated and localized HIV-1 epidemic, highlighting important opportunities for targeted interventions to effectively prevent new HIV transmissions.

DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes

AimsDespite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newly-diagnosed individuals with type 2 diabetes. Methods and ResultsWe found that metformin therapy is associated with altered methylation of 26 sites in blood from Scandinavian discovery and replication cohorts (FDR < 0.05), using MethylationEPIC arrays. The majority (88%) of these 26 sites were hypermethylated in patients taking metformin for ∼ 3 months compared to controls, who had diabetes but had not taken any diabetes medication. Two of these blood-based methylation markers mirrored the epigenetic pattern in muscle and adipose tissue (FDR < 0.05). Four type 2 diabetes-associated SNPs were annotated to genes with differential methylation between metformin cases and controls, e.g., GRB10, RPTOR, SLC22A18AS and TH2LCRR. Methylation correlated with expression in human islets for two of these genes. Three metformin-associated methylation sites (PKNOX2, WDTC1 and MICB) partially mediate effects of metformin on follow-up HbA1c levels. When combining methylation of these three sites into a score, which was used in a causal mediation analysis, methylation was suggested to mediate up to 32% of metformin’s effects on HbA1c. ConclusionMetformin-associated alterations in DNA methylation partially mediates metformin’s antidiabetic effects on HbA1c in newly-diagnosed individuals with type 2 diabetes.

Characterization of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China

BackgroundSichuan province is one of the highest AIDS epidemic provinces in China, with a large number of floating population. The annual number of cases of HIV/AIDS reported in Sichuan has been the highest province in China for several successive years. There is a lack of widespread and representative data on the distribution of HIV genotypes in Sichuan. We aim to investigate the characteristics of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China.MethodArchived plasma samples (n = 1524) from HIV-1 newly-diagnosed individuals in April 2019 were selected by cross-sectional investigation from all 21 cities in Sichuan province. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 polymerase (pol) gene sequences. We also analysed the association of demographic and virological factors with transmitted drug-resistance (TDR) and transmission clusters.ResultsPartial pol gene sequences were obtained from 1297 cases. HIV-1 epidemic strains in Sichuan province: the majority of genotypes were circulating recombinant form (CRF) 07_BC (675, 52.04%), CRF01_AE (343, 26.45%), CRF08_BC (115, 8.87%), CRF85_BC (67, 5.17%), subtype B (33, 2.54%), the other genotypes only accounted for 4.93%, and unique recombinant forms (URFs) (23, 1.77%) were observed in the study, and the difference of age, ethnicity, education, occupation, region and transmission pathway of different genotypes were statistically significant. According to WHO HIVDR surveillance threshold, the level of TDR has reached a medium level, with 72 of 1297 (5.55%) cases carrying drug-resistance mutation sites, TDR mutation frequency to nonnucleoside reverse transcriptase inhibitors (NNRTIs, 3.85%) was much higher than nucleoside reverse transcriptase inhibitors (NRTIs, 0.31%) and protease inhibitors (PIs, 1.70%), and CRF08_BC was a risk factor for TDR (odds ratio, 8.32; 95% CI 4.38–15.80 for CRF07_BC, P < 0.05). The most common drug resistance HIV-1 mutation pattern for NNRTI was V106 (1.31%, 17/1297) and E138 (1.16%, 15/1297), and for PI was M46 (0.69%, 9/1297). A total of 205 (15.8%) pol sequences were involved in the genetic transmission network clusters, CRF01_AE (odds ratio, 2.369; 95% CI 1.659–3.382; P < 0.05), subtype B (odds ratio, 13.723; 95% CI 6.338–29.71; P < 0.05), drug resistance (odds ratio, 0.306; 95% CI 0.106–0.881; P < 0.05) and different levels of education (P < 0.05) were significantly associated to be in clusters.ConclusionThe distribution of HIV-1 genotypes in Sichuan is more diverse and complex, and the Men who have sex with men (MSM) is underrated, arguing for behavior scaling up intervention in this specific population besides the elderly people with heterosexual transmission risk groups. The risk of TDR mutation frequency increased in newly diagnosed patients highlights the significance of genotypic drug resistance monitoring and molecular surveillance of pretreatment HIV-1 drug resistance. The regimen composed of TDF, 3TC and EFV was still currently the preferred solution used free first-line therapy.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF.Serum levels of collagen synthesis neoepitopes, PRO-C3 and PRO-C6 (collagen type 3 and 6), were elevated in IPF compared with controls at baseline, and progressive disease versus stable disease during follow up, (PRO-C3 p < 0.001; PRO-C6 p = 0.029). Assessment of rate of change in neoepitope levels from baseline to 3 months (defined as ‘slope to month 3’: HIGH slope, slope > 0 vs. LOW slope, slope < =0) demonstrated no relationship with mortality for these markers (PRO-C3 (HR 1.62, p = 0.080); PINP (HR 0.76, p = 0.309); PRO-C6 (HR 1.14, p = 0.628)). As previously reported, rising concentrations of collagen degradation markers C1M, C3M, C6M and CRPM were associated with an increased risk of overall mortality (HR = 1.84, CI 1.03–3.27, p = 0.038, HR = 2.44, CI 1.39–4.31, p = 0.002; HR = 2.19, CI 1.25–3.82, p = 0.006; HR = 2.13 CI 1.21–3.75, p = 0.009 respectively).Elevated levels of PRO-C3 and PRO-C6 associate with IPF disease progression. Collagen synthesis and degradation biomarkers have the potential to enhance clinical trials in IPF and may inform prognostic assessment and therapeutic decision making in the clinic.

1274-P: Impact of Type 1 Known Diabetes (T1D) Risk on Health-Care Utilization at Diagnosis

Despite increasing incidence of T1D worldwide, most newly-diagnosed individuals have no family history. Many experience delay in diagnosis, resulting in &amp;gt;30% of children with new-onset T1D presenting in diabetic ketoacidosis (DKA). Screening for T1D is currently restricted to the research setting. We sought to describe differences in health care utilization at T1D diagnosis in known at-risk patients identified through research studies compared to matched controls. Cases (n=39) were known islet autoantibody positive children (0-19 y) diagnosed with T1D between 2010-2017 at the Barbara Davis Center. Controls were matched 3:1 by dates of birth and diagnosis from community-diagnosed patients (n=117). The Colorado All Payer’s Claims Database was used to count diagnoses, procedures, and healthcare claims in the year before and following diagnosis. Continuous variables were compared using t-test or Wilcoxon rank sum test, categorical by chi-square. There was no difference between cases and controls for age of onset (9.6 +/- 3.6 vs. 9.6 +/- 3.5 y p=1.0) or gender (54 vs. 46% male, p=1.0); however, cases had higher rate of private insurance (72 vs. 49%, p=.01) and higher percentage of non-Hispanic whites (87 vs. 65%, p=.008). At diagnosis with T1D, cases had lower HbA1c (6.7 [6.1, 8.1]% vs. 12.1 [10.5, 14.1]%, p&amp;lt;.0001) and rate of DKA (5 vs. 57%, p&amp;lt;.0001). In the year prior to diagnosis, there were no differences in the number of claims, procedures, diagnoses, or medications. In contrast, in the year of diagnosis, cases had fewer emergency room claims (0 [0, 2] vs. 2 [0, 4], p&amp;lt;.0001), total claims (20 [9, 30] vs. 33 [19, 48], p&amp;lt;.0001), procedures (31 [16, 43] vs. 52 [28, 77] p&amp;lt;.0001) and unique diagnoses (7 [4, 10] vs. 12 [7, 19] p=.0003), while there was no difference in number of medications (8 [4, 10] vs10 [7, 13] p=.07). In conclusion, antibody-screened patients had lower healthcare utilization in year of diagnosis. Further study, including cost estimation, may lend insight into benefits of T1D screening programs. Disclosure B.I. Frohnert: None. K. Manseau: None. G.T. Alonso: None. Funding JDRF (5-ECR-2017-388-A-N)

Somatic variants in epigenetic modifiers can predict failure of response to imatinib but not to second-generation tyrosine kinase inhibitors.

There are no validated molecular biomarkers to identify newly-diagnosed individuals with chronic-phase chronic myeloid leukemia likely to respond poorly to imatinib and who might benefit from first-line treatment with a more potent second-generation tyrosine kinase inhibitor. Our inability to predict these ‘high-risk’ individuals reflects the poorly understood heterogeneity of the disease. To investigate the potential of genetic variants in epigenetic modifiers as biomarkers at diagnosis, we used Ion Torrent next-generation sequencing of 71 candidate genes for predicting response to tyrosine kinase inhibitors and probability of disease progression. A total of 124 subjects with newly-diagnosed chronic-phase chronic myeloid leukemia began with imatinib (n=62) or second-generation tyrosine kinase inhibitors (n=62) and were classified as responders or non-responders based on the BCRABL1 transcript levels within the first year and the European LeukemiaNet criteria for failure. Somatic variants affecting 21 genes (e.g. ASXL1, IKZF1, DNMT3A, CREBBP) were detected in 30% of subjects, most of whom were non-responders (41% non-responders, 18% responders to imatinib, 38% non-responders, 25% responders to second-generation tyrosine kinase inhibitors). The presence of variants predicted the rate of achieving a major molecular response, event-free survival, progression-free survival and chronic myeloid leukemia-related survival in the imatinib but not the second-generation tyrosine kinase inhibitors cohort. Rare germline variants had no prognostic significance irrespective of treatment while some pre-leukemia variants suggest a multi-step development of chronic myeloid leukemia. Our data suggest that identification of somatic variants at diagnosis facilitates stratification into imatinib responders/non-responders, thereby allowing earlier use of second-generation tyrosine kinase inhibitors, which, in turn, may overcome the negative impact of such variants on disease progression.

Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel.

Contemporary antiretroviral therapies (ART) and management strategies have diminished both human immunodeficiency virus (HIV) treatment failure and the acquired resistance to drugs in resource-rich regions, but transmission of drug-resistant viruses has not similarly decreased. In low- and middle-income regions, ART roll-out has improved outcomes, but has resulted in increasing acquired and transmitted resistances. Our objective was to review resistance to ART drugs and methods to detect it, and to provide updated recommendations for testing and monitoring for drug resistance in HIV-infected individuals. A volunteer panel of experts appointed by the International Antiviral (formerly AIDS) Society-USA reviewed relevant peer-reviewed data that were published or presented at scientific conferences. Recommendations were rated according to the strength of the recommendation and quality of the evidence, and reached by full panel consensus. Resistance testing remains a cornerstone of ART. It is recommended in newly-diagnosed individuals and in patients in whom ART has failed. Testing for transmitted integrase strand-transfer inhibitor resistance is currently not recommended, but this may change as more resistance emerges with widespread use. Sanger-based and next-generation sequencing approaches are each suited for genotypic testing. Testing for minority variants harboring drug resistance may only be considered if treatments depend on a first-generation nonnucleoside analogue reverse transcriptase inhibitor. Different HIV-1 subtypes do not need special considerations regarding resistance testing. Testing for HIV drug resistance in drug-naive individuals and in patients in whom antiretroviral drugs are failing, and the appreciation of the role of testing, are crucial to the prevention and management of failure of ART.

Immediate Blood Draw for CD4+ Cell Count Is Associated with Linkage to Care in Durban, South Africa: Findings from Pathways to Engagement in HIV Care.

BackgroundTimely linkage to care by newly-diagnosed HIV+ individuals remains a significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health Organization (WHO) guidelines recommend initiating anti-retroviral treatment (ART) regardless of CD4+ count, with priority given to those with CD4+ <350 cells/μl. We evaluated the impact of not having a day-of-diagnosis CD4+ count blood draw, as recommended by South African guidelines, on time to linkage, using data from a prospective cohort study.MethodsIndividuals (N = 2773) were interviewed prior to HIV counseling and testing at three public sector primary care clinics in the greater Durban area; 785 were newly-diagnosed and eligible for the cohort study; 459 (58.5%) joined and were followed for eight months with three structured assessments. Linkage to care, defined as returning to clinic for CD4+ count results, and day-of-diagnosis blood draw were self-reported.ResultsOverall, 72.5% did not have a day-of-diagnosis CD4+ count blood draw, and 19.2% of these never returned. Compared with a day-of-diagnosis blood draw, the adjusted hazard ratio of linkage (AHRlinkage) associated with not having day-of-diagnosis blood draw was 0.66 (95%CI: 0.51, 0.85). By 4 months, 54.8% of those without day-of-diagnosis blood draw vs. 75.2% with one were linked to care (chi-squared p = 0.004). Of those who deferred blood draw, 48.3% cited clinic-related and 51.7% cited personal reasons. AHRlinkage was 0.60 (95%CI: 0.44, 0.82) for clinic-related and 0.53 (95%CI: 0.38, 0.75) for personal reasons relative to having day-of-diagnosis blood draw.ConclusionsNewly-diagnosed HIV+ individuals who did not undergo CD4+ count blood draw on the day they were diagnosed—regardless of the reason for deferring—had delayed linkage to care relative to those with same-day blood draw. To enhance prompt linkage to care even when test and treat protocols are implemented, all diagnostic testing required before ART initiation should be performed on the same day as HIV testing/diagnosis. This may require modifying clinic procedures to enable overnight blood storage if same-day draws cannot be performed, and providing additional counseling to encourage newly-diagnosed individuals to complete day-of-diagnosis testing. Tracking HIV+ individuals via clinic registries should commence immediately from diagnosis to reduce these early losses to care.

High Percentage of Recent HIV Infection Leading to Onward Transmission in Odessa, Ukraine Associated with Young Adults

The proportion of new HIV diagnoses between May and December 2009 across Odessa recently-infected was estimated using the BED-CEIA assay. Logistic regression models were used to explore factors associated with testing as recent. Of 1,313 newly-diagnosed individuals, 321 (24%) were classified as recent. Recent infection was less likely among older adults [odds ratio (OR)=0.70 per 10-year increase, 95% CI 0.60-0.82]. Compared to men residing in Odessa city, women in rural Odessa and non-resident men were more likely to be recently-infected (OR 1.85, 1.26-2.71 and 2.83, 1.15-6.97, respectively). Reason for test was not associated with recent infection. In sensitivity analysis, after excluding individuals tested due to clinical indications, the proportion recently-infected and the association with age remained virtually unchanged. Our findings suggest a high risk of onward transmission, particularly in younger age groups. These findings highlight the need for tailored prevention strategies and ongoing RITA testing to monitor and evaluate effectiveness of prevention programmes.

Mechanisms underpinning effective peer support: a qualitative analysis of interactions between expert peers and patients newly-diagnosed with bipolar disorder

BackgroundThe increasing burden on mental health services has led to the growing use of peer support in psychological interventions. Four theoretical mechanisms have been proposed to underpin effective peer support: advice grounded in experiential knowledge, social support, social comparison and the helper therapy principle. However, there has been a lack of studies examining whether these mechanisms are also evident in clinical populations in which interpersonal dysfunction is common, such as bipolar disorder.MethodThis qualitative study, conducted alongside a randomized controlled trial, examined whether the four mechanisms proposed to underpin effective peer support were expressed in the email exchange between 44 individuals newly-diagnosed with bipolar disorder and their Informed Supporters (n = 4), over the course of a supported online psychoeducation program for bipolar disorder. A total of 104 text segments were extracted and coded. The data were complemented by face-to-face interviews with three of the four Informed Supporters who participated in the study.ResultsQualitative analyses of the email interchange and interview transcripts revealed rich examples of all four mechanisms. The data illustrated how the involvement of Informed Supporters resulted in numerous benefits for the newly-diagnosed individuals, including the provision of practical strategies for illness management as well as emotional support throughout the intervention. The Informed Supporters encouraged the development of positive relationships with mental health services, and acted as role models for treatment adherence. The Informed Supporters themselves reported gaining a number of benefits from helping, including a greater sense of connectedness with the mental health system, as well as a broader knowledge of illness management strategies.ConclusionsExamples of the mechanisms underpinning effective peer support were found in the sample of emails from individuals with newly-diagnosed bipolar disorder and their Informed Supporters. Experiential knowledge, social support, social comparison and helper therapy were apparent, even within a clinical population for whom relationship difficulties are common. Trial registration number ACTRN12608000411347.

Resources, Roadblocks and Turning Points: A Qualitative Study of American Indian/ Alaska Native Adults with Type 2 Diabetes

Type 2 diabetes is a worldwide health problem that has reached epidemic proportions in some communities. Alaska Native and American Indian (AN/AI) people are disproportionately diagnosed with type 2 diabetes and incidence is increasing in many Alaska communities. Developing effective interventions requires understanding the social and psychological factors that impact effective management of diabetes, yet little is known about these factors in AN/AI communities. The objective of this study was to explore perceived psychosocial needs and barriers to management of diabetes among AN/AI adults with type 2 diabetes receiving care at the Alaska Native Primary Care Center (ANPCC) to inform programmatic efforts and potential future research. We conducted three focus groups and five interviews with 13 AN/AI adults with type 2 diabetes. Interview and focus group questions elicited perceived factors that affect management of diabetes, with a focus on the psychological, social and spiritual impacts of diabetes. Data were transcribed, coded and analyzed using thematic analysis. Key themes that emerged from these data included resources and roadblocks, as well as turning points in the trajectory of diabetes. Resources are factors with a perceived positive impact on management of diabetes, including: (1) knowledge and education about diabetes, (2) social support from other people with diabetes, (3) spirituality, and (4) self-efficacy. Roadblocks are factors with a perceived negative impact on management of diabetes and include: (1) self-reported lack of knowledge about nutrition and diet, (2) social difficulties caused by dietary restrictions, and (3) co-morbid medical conditions. Finally, turning points are experiences described by participants as having transformed roadblocks in resources and thus facilitating improvement in the management of diabetes. Future programmatic interventions to improve management of diabetes with this population should focus on improving dietary education and social support opportunities for newly-diagnosed individuals. Also, educational and support opportunities for family members and friends of individuals with diabetes should also be offered to facilitate understanding and support of their loved ones' management of diabetes, especially with regard to dietary restrictions in social settings. Efforts should also focus on strengthening newly-diagnosed individuals' self-efficacy and providing ongoing support as individuals progressively adjust to the illness over time and make behavioral changes. Future research with this population should explore the effects of family support groups and the possibility of Web-based or other alternative interventions for improving psychosocial health and management of diabetes efforts.