Disclosure of New Type 2 Diabetes Diagnoses to Younger Adults: a Qualitative Study.

BACKGROUND: Adults diagnosed with type 2 diabetes at a younger age are at increased risk for poor outcomes. Yet, little is known about the early experiences of these individuals, starting with communication of the diagnosis. Addressing this knowledge gap is important as this initial interaction may shape subsequent disease-related perceptions and self-management. OBJECTIVE: We examined diagnosis disclosure experiences and initial reactions among younger adults with newly diagnosed type 2 diabetes. PARTICIPANTS: Purposive sample of adult members of Kaiser Permanente Northern California, an integrated healthcare delivery system, diagnosed with type 2 diabetes before age 45 years. APPROACH: We conducted six focus groups between November 2017 and May 2018. Transcribed audio recordings were coded by two coders using thematic analysis. KEY RESULTS: Participants (n = 41) were 38.4 (± 5.8) years of age; 10 self-identified as Latinx, 12 as Black, 12 as White, and 7 as multiple or other races. We identified variation in diagnosis disclosure experiences, centered on four key domains: (1) participants' sense of preparedness for diagnosis (ranging from expectant to surprised); (2) disclosure setting (including in-person, via phone, via secure message, or via review of results online); (3) perceived provider tone (from nonchalant, to overly fear-centered, to supportive); and (4) participants' emotional reactions to receiving the diagnosis (including acceptance, denial, guilt, and/or fear, rooted in personal and family experience). CONCLUSIONS: For younger adults, the experience of receiving a diabetes diagnosis varies greatly. Given the long-term consequences of inadequately managed diabetes and the need for early disease control, effective initial disclosure represents an opportunity to optimize initial care. Our results suggest several opportunities to improve the type 2 diabetes disclosure experience: (1) providing pre-test counseling, (2) identifying patient-preferred settings for receiving the news, and (3) developing initial care strategies that acknowledge and address the emotional distress triggered by this life-altering, chronic disease diagnosis.

Effectiveness of a Patient Education Class to Enhance Knowledge about Lung Cancer Screening: a Quality Improvement Evaluation.

Best practices to facilitate high-quality shared decision-making for lung cancer screening (LCS) are not well established. In our LCS program, patients are first referred to attend a free group education class on LCS, taught by designated clinician specialists, before a personal shared decision-making visit is scheduled. We conducted an evaluation on  the effectiveness of this class to enhance patient knowledge and shared decision-making about LCS. For quality improvement purposes, participants were asked to complete one-page surveys immediately before and after class to assess knowledge and decision-making capacity regarding LCS. To evaluate knowledge gained, we tabulated the distributions of correct, incorrect, unsure, and missing responses to eight true-false statements included on both pre- and post-class surveys and assessed pre-post differences in the number of correct responses. To evaluate decision-making capacity, we tabulated the distributions of post-class responses to items on decision uncertainty. From June 2017 to August 2018, 680 participants completed both pre- and post-class surveys. Participants had generally poor baseline knowledge about LCS. The proportion who responded correctly to each knowledge-related statement increased pre- to post-class, with a mean difference of 0.9 (paired t test, p < 0.0001) in the total number of correct responses between surveys. About 70% reported having all the information needed to make a screening decision. Our results suggest that a well-designed group education class is an effective system-level approach for initially educating and equipping patients with appropriate knowledge to make informed decisions about LCS.

Mode-selective optical packet switching in mode-division multiplexing networks.

A novel mode-selective optical packet switching, based on mode-multiplexers/demultiplexers and multi-port optical micro-electro-mechanical systems (MEMS) switches, has been proposed and experimentally demonstrated. The experimental demonstration was performed using the LP(01), LP(11a) and LP(11b) modes of a 30-km long mode-division multiplexed few-mode fiber link, utilizing 40 Gb/s, 16-QAM signals.

Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation.

Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non-thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell transplantation.

Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study.

OBJECTIVE: To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference. METHODS: A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality. RESULTS: Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (P = .07) and disease-specific survival was 84.9% and 87.5% (P = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease. DISCUSSION: A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors. IMPLICATIONS FOR PRACTICE: All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.

Ultra-broad band, low power, highly efficient coherent wavelength conversion in quantum dot SOA.

We report broadband, all-optical wavelength conversion over 100 nm span, in full S- and C-band, with positive conversion efficiency with low optical input power exploiting dual pump Four-Wave-Mixing in a Quantum Dot Semiconductor Optical Amplifier (QD-SOA). We also demonstrate by Error Vector Magnitude analysis the full transparency of the conversion scheme for coherent modulation formats (QPSK, 8-PSK, 16-QAM, OFDM-16QAM) in the whole C-band.

All in the Family: A Qualitative Study of the Early Experiences of Adults with Younger Onset Type 2 Diabetes.

OBJECTIVE: Adults with type 2 diabetes diagnosed at a younger age are at increased risk for poor outcomes. We examined life stage-related facilitators and barriers to early self-management among younger adults with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted 6 focus groups that each met twice between November 2017 and May 2018. Participants (n = 41) were aged 21 to 44 years and diagnosed with type 2 diabetes during the prior 2 years. Transcripts were coded using thematic analysis and themes were mapped to the Capability-Opportunity-Motivation-Behavior framework. RESULTS: Participants were 38.4 (±5.8) years old; 10 self-identified as Latinx, 12 as Black, 12 as White, and 7 as multiple or other races. We identified 9 themes that fell into 2 categories: (1) the impact of having an adult family member with diabetes, and (2) the role of nonadult children. Family members with diabetes served as both positive and negative role models, and, for some, personal familiarity with the disease made adjusting to the diagnosis easier. Children facilitated their parents' self-management by supporting self-management activities and motivating their parents to remain healthy. However, the stress and time demands resulting from parental responsibilities and the tendency to prioritize children's needs were perceived as barriers to self-management. CONCLUSIONS: Our results highlight how the life position of younger-onset individuals with type 2 diabetes influences their early experiences. Proactively addressing perceived barriers to and facilitators of self-management in the context of family history and parenthood may aid in efforts to support these high-risk, younger patients.

Visit Content Analysis: Doctor-Patient Communication in Patients with Type 2 Diabetes.

INTRODUCTION: The primary care visit is an important opportunity to discuss and modify diabetes management. OBJECTIVE: To gain insight into doctor-patient communication during primary care visits among English and Spanish speaking patients with type 2 diabetes and suboptimal glycemic control (HbA1c > 7%). METHODS: We conducted a quantitative content analysis of audiotaped primary care visits in 2 patient cohorts. In Study 1 (31 English-speaking patients), we examined factors associated with management changes, and in Study 2 (20 Spanish-speaking patients and their Spanish-speaking providers), we examined the association of question asking with HbA1c control. This study was conducted between November 2017 and January 2020 across 8 primary care practices within Kaiser Permanente Northern California. RESULTS: In Study 1, the only factor significantly associated with a diabetes management change was patient identification of diabetes as a priority prior to the visit (91.7% had a management change vs 52.6% of patients who did not identify diabetes as a priority; p = 0.02). In Study 2, patients with poorer glycemic control (HbA1c ≥ 10.0) asked significantly fewer questions (3.4 ± 1.8 vs 10.7 ± 6.9 questions per 15 minutes; p = 0.004). Overall, despite receiving primary care from language-concordant providers, Spanish-speaking Study 2 patients asked fewer questions than English-speaking Study 1 patients (4.5 ± 2.9 vs 7.5 ± 3.7 questions per 15 minutes, respectively; p = 0.004). CONCLUSION: Our results highlight 2 potential strategies (preparing patients for their visits through identifying priorities and learning how to ask more questions during visits) for improving diabetes primary care.

Initial Glycemic Control and Care Among Younger Adults Diagnosed With Type 2 Diabetes.

OBJECTIVE: The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual's risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21-44 years) and mid-age onset (45-64 years) of type 2 diabetes. RESEARCH DESIGN AND METHODS: Using data from a large, integrated health care system, we identified 32,137 adults (aged 21-64 years) with incident diabetes (first HbA1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year. RESULTS: Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age-onset type 2 diabetes. Adults with younger onset had higher initial mean HbA1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P < 0.0001) and lower odds of achieving an HbA1c <7% (<53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66-0.74]), even after accounting for HbA1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76-0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99-1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12-1.29]) but lower odds of adhering to that medication (0.74 [0.69-0.80]). CONCLUSIONS: Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease.

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.

Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia.

Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRLIMDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQOl), glutathione S-tranferase (GST)-MI and -TI, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novo acute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQOl at codon 187, causing loss of function, was more frequent in the patients with TRLIMDS (14 of 58, 24.1%; OR = 2.62) than in those with de novo AML (64 of 411, 15.6%), and control (16 of 150, 10.6%; P = 0.002). Allelic frequencies of NQOJ were different between TRL/ MDS and de novo AML (P = 0.01). In GST-MJ and -Ti, the incidence of homologous deletion was similar among the three groups. The polymorphism of the 5' promoter region of CYP3A4 was not found in persons of Japanese ethnicity. These results suggest that the NQOJ polymorphism is significantly associated with the genetic risk of TRLIMDS.

Effect of sublethal total body irradiation on acute graft-versus-host disease and graft-versus-leukemia effect in SCID mice.

SCID mice were transplanted with H-2-incompatible C3H/He splenocytes with or without previous TBI with 2Gy to evaluate the influence of sublethal TBI on GVHD and on the graft-versus-leukemia (GVL) effect. Transplantation immediately after TBI induced lethal GVHD, but delayed donor leukocyte infusion (DLI) 5 days after TBI reduced the severity of the GVHD. SCID mice inoculated with L1210 cells after TBI received a DLI 5 days after TBI to induce the GVL effect. Survival of these mice was longer than that of control nonirradiated mice. Serum levels of tumor necrosis factor-alpha, IL-1alpha, IL-6, IL-2 and IFN-gamma were significantly elevated, and they reached maximum levels at 5 days post-transplantation. Except for IFN-gamma, all cytokine levels were higher in irradiated mice than those in nonconditioned mice. Cytotoxicity against L1210 cells mediated by splenocytes from irradiated recipients was greater than that mediated by effector cells from nonirradiated mice. All the irradiated mice survived more than 120 days after L1210 rechallenge, while all nonirradiated mice died of leukemia within 5 weeks. In conclusion, compared with control mice infused with donor splenocytes without previous TBI, SCID mice which received sublethal TBI and DLI showed superior cytotoxicity against L1210 cells and survived longer without severe GVHD.

Immune reconstitution assessed during five years after allogeneic bone marrow transplantation.

Immune reconstitution is an important component of successful allogeneic bone marrow transplantation. Immune reconstitution was evaluated for 5 years after transplantation. While the number of CD8+ T cells and CD56+ cells recovered early post transplantation, a low number of CD4+ and CD4+ CD45RA+ T cells and reversal of the CD4/CD8 ratio continued up to 5 years. Although early recovery of IgG and IgM was seen at day 100 post transplantation, serum concentration of IgA was below the normal range at 6 months and increased gradually up to 5 years. Development of acute GVHD did not affect the numbers of CD4+, CD8+, CD4+ CD45RA+ and CD4+ CD29+ T cells, but the number of CD56+ cells in patients who developed grades II-IV acute GVHD was low. The number of CD4+ CD29+ T cells had a tendency to be higher in the patients with extensive chronic GVHD than in those without chronic GVHD 2 years after transplantation whereas the number of CD4+ CD45RA+ T cells was low in spite of the absence of chronic GVHD. Serum concentration of IgA was lower in patients with extensive chronic GVHD than in those without chronic GVHD at 180 days. The number of CD4+ CD45RA+ cells in 10-19-year-old patients was higher than that in 40-49-year-old patients. Response to the Con A and PHA in 10-19-year-old patients was higher than that in older patients at 1 and 2 years. There was no significant difference in the ability of immune reconstitution between related transplant recipients and unrelated transplant recipients. These results suggest that chronic GVHD and age of patients affected immune reconstitution post transplant.

Successful pregnancy after allogeneic bone marrow transplantation following conditioning with total body irradiation.

A 23-year-old woman had a normal full-term delivery 78 months after BMT for ALL. Conditioning therapy was Ara C 1.4 g/m2 x 4, CY 60 mg/kg x 2 and TBI 2.5 Gy x 5 at a dose rate of 3.5 cGy/min. Despite GVHD prophylaxis with short-term MTX and CsA, she developed grade I acute GVHD, but showed no evidence of chronic GVHD. Following amenorrhea for 4 years, menstruation recommenced spontaneously. She had a normal pregnancy 6 years after BMT resulting in a healthy infant with simple hypospadias. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 10 Gy.

Evaluation of chimerism after bone marrow transplantation with single locus minisatellite DNA probes.

The origin of cells in almost all allogeneic donor-recipient pairs can be determined through the use of highly polymorphic minisatellite DNA probes. Single-locus probes were cloned from hypervariable fragments in a human DNA fingerprint detected with a multi-locus probe. While each probe is highly polymorphic and locus specific, they all contain repetitive sequences. The properties of single-locus probes have improved the sensitivity of detecting mixed chimerism in comparison with multi-locus probes. The use of single-locus probes permitted detection of mixed chimerism (MC) at levels as low as 0.625%, approaching that obtained by PCR methods. In the present study, five patients who received allogeneic BMT for hematologic malignancies were analyzed. Two patients exhibited MC after BMT. One developed acute GVHD and chronic GVHD and remained in CR while the second patient who had no signs of GVHD suffered a relapse.

Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.

Donor-HLA-incompatible marrow transplantation with an anti-donor cytotoxic antibody in the serum of the patient.

A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.