Increased Risk of Skeletal Toxicity and Infection in Children 10 Years or Older Treated for Acute Lymphoblastic Leukemia (ALL) with Dexamethasone: Results from the DFCI ALL Consortium.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 849-849 ◽  
Author(s):  
Lynda M. Vrooman ◽  
Donna Neuberg ◽  
Jane O’Brien ◽  
Stephen E. Sallan ◽  
Lewis B. Silverman
Keyword(s):  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Invasive Fungal Disease ◽  
P Value ◽  
Older Children ◽  
Childhood All ◽  
Treatment Groups ◽  
Increased Risk ◽  
Significant Difference

Abstract BACKGROUND: Dexamethasone (dex) may be more efficacious but also more toxic than prednisone (pred) in the treatment of childhood ALL. In order to compare the relative toxicities of these 2 steroids, patients (pts) on DFCI ALL Consortium Protocol 00–01 were randomized to receive dex or pred during post-induction therapy. METHODS: Pts received 5-day steroid pulses every 3 weeks for 2 years (yrs) (pred 40mg/m2/day or dex 6 mg/m2/day) beginning at week 7 of therapy. High Risk (HR) pts received 3 times these doses during the Intensification Phase (approximately 6 months). RESULTS: Between 2000–2004, 425 pts (ages 1–18 yrs) were randomized; 423 had evaluable skeletal toxicity data, including 241 Standard Risk (SR) and 182 HR pts. 211 received dex and 212 received pred. Within 26 months of enrollment, 55 pts (13%) experienced at least 1 bony event: 45 pts (11%) with fracture and 17 (4%) with osteonecrosis (ON). Bony events were more common in children ≥10 yrs of age (11% of those <10 yrs vs. 18.5% ≥10 yrs, p=0.007). There was no overall difference in frequency of pts with skeletal toxicity based on steroid type (see table, p=0.89), including no difference in fractures (11% dex vs. 10% pred, p=0.88) or ON (5% dex vs. 3% pred, p=0.23). However, skeletal toxicity was more common in dex-treated older children (≥10 yrs) compared with pred-treated older children (25% vs. 11%, p=0.07) and compared with younger (< 10 yrs) dex-treated pts (25% vs. 9%, p=0.004). There was no difference in frequency of skeletal toxicity by age in pred-treated pts (p=0.31). There was no difference in frequency of skeletal toxicity by steroid type in SR pts (8% dex vs. 14% pred, p=0.22) or in younger HR pts (12% dex vs. 11% pred, p=1.0). In multivariable analysis, children ≥10 yrs treated with dex had 2.7 times the risk of developing skeletal toxicity compared with all other pts (p=0.006). Of 404 pts with evaluable infection data, 37/200 (18.5%) dex-treated pts developed at least 1 infection (bacteremia and/or invasive fungal disease) during intensification or continuation compared to 24/204 (11.8%) pred-treated pts (p=0.07). There was no difference in infection rate by steroid type for those <10 yrs of age (p=0.53). However, for those ≥10 yrs, there were more infections in dex-treated than in pred-treated pts (24% vs. 5%, p=0.01). At 2.8 yrs median follow-up, there was no statistically significant difference in event-free survival (EFS) comparing dex- vs. pred-treated pts (90% vs. 88%, p=0.31), although there was a suggestion of inferior EFS in HR pts randomized to pred. Skeletal Toxicity and Infection: Dexamethasone vs. Prednisone* Dexamethasone Prednisone P value *Depicted are the numbers of pts with at least 1 toxicity event of all pts within particular subgroups. Skeletal Toxicity All 28/211 (13.3%) 27/212 (12.7%) 0.89 Age < 10 yrs 14/160 (9%) 22/166 (13%) 0.21 Age ≥ 10 yrs 13/51 (25%) 5/46 (11%) 0.07 Infection All 37/200 (18.5%) 24/204 (11.8%) 0.07 Age < 10 yrs 26/154 (17%) 22/160 (14%) 0.53 Age ≥ 10 yrs 11/46 (24%) 2/44 (5%) 0.01 CONCLUSION: Dexamethasone was associated with increased risk of skeletal toxicity and infection in pts ≥10 yrs of age. Longer follow-up is needed to fully assess EFS differences between the randomized treatment groups.

Perforin Polymorphism A91V and Susceptibility to Childhood Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1453-1453
Author(s):  
Parinda A. Mehta ◽  
Stella M. Davies ◽  
Ashish Kumar ◽  
Meenakshi Devidas ◽  
Susan Lee ◽  
...  
Keyword(s):  
Nk Cells ◽  
Blood Donors ◽  
Lymphoblastic Leukemia ◽  
Active Form ◽  
Low Frequency ◽  
Variant Allele ◽  
P Value ◽  
Childhood All ◽  
Genotype Frequencies ◽  
Increased Risk

Abstract Perforin plays a key role in the cytotoxicity of NK cells and cytotoxic T lymphocytes. Genetic mutations in perforin gene (PRF1) give rise to 30–40% of cases of familial hemophagocytic lymphohistiocytosis. We recently studied two boys who had been treated for PreB ALL and subsequently developed HLH. Both showed decreased perforin expression in NK cells and were found to be heterozygous for PRF1 A91V. The functional consequences of the PRF1 A91V (resulting from C272T transition) are controversial; between 3 and 17% of apparently normal people are heterozygous for this polymorphism depending on the population studied. Recent data suggest that A91V results in conformational change that may impair processing of perforin protein to the active form, and that the polymorphism may increase susceptibility to ALL in children (Trambas et al, Blood2005; 106:932; Santoro et al, Haematologica2005;90:697). We have genotyped 655 normal blood donors and 2,272 children with ALL treated on Pediatric Oncology Group 9900 clinical trials. Genotyping was performed using a specific PCR assay (Taqman). Genotypes in the normal US blood donors showed significant variation in allele frequency by race, with a very low frequency of the variant allele in black controls (0.7% compared with 4% in white controls). Allele frequencies did not vary by gender and genotype frequencies were in Hardy Weinberg equilibrium (whites C/C 92%; C/T 8%; T/T 0.2%). In light of the low frequency of the variant allele in blacks, analysis of leukemia cases was restricted to a comparison of white cases and white controls. Analyses were performed for all B-lineage ALL cases combined, and were also further stratified for known genetic subtypes of ALL. Perforin genotype CC Perforin genotype CT or TT p-value (cases versus controls Controls (n=507) 464 (91.5%) 43 (8.5%) - Cases (all; n= 1321) 1198 (90.7%) 123 (9.3%) 0.58 BCR-ABL 22 (76%) 7 (24%) 0.0048 Trisomy 4,10 238 (93.7%) 16 (6.3%) 0.29 TEL-AML1 250 (90.6%) 26 (9.4%) 0.66 E2A-PBX 24 (92.3%) 2 (7.7%) 0.89 MLL abn. 40 (87%) 6 (13%) 0.29 Hyperdiploid 244 (92.4%) 20 (7.6%) 0.66 Hypodiploid 8 (100%) 0 (0%) 0.40 Taken together, these data indicate that the A91V polymorphism is not associated with an overall increased risk of childhood ALL, in contrast to the previous report. PRF1 A91V was identified with significantly increased frequency in children with BCR-ABL positive ALL. However, this observation includes a relatively small number of cases and the potential association should be explored further, perhaps in adult ALL series in which the frequency of BCR-ABL positivity is likely to be high.

Analysis of BCL11A gene Variants in Hematological Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2956-2956
Author(s):  
Maria Monne ◽  
Giovanna Piras ◽  
Antonella Uras ◽  
Marco Murineddu ◽  
Angelo D. Palmas ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Myeloproliferative Disorders ◽  
P Value ◽  
T Cell Lymphomas ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 2956 Poster Board II-932 Background. The B-cell leukemia 11A gene (BCL11A/Evi9/CTIP1) is essential for normal lymphoid development and genetic association studies have shown its potential regulator effect in blood related phenotypes. BCL11A encodes a Krüppel-like zinc-finger protein and functions as a transcriptional repressor through its interaction with several proteins including BCL6. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia oncogene. It is down-regulated during hematopoietic cell differentiation and abnormalities involving this gene have been detected in a variety of B-cell malignancies in humans. We genotyped SNP rs11886868 in the BCL11A gene, which has been previously associated with HbF production, in patients with hematological malignancies from Sardinia to investigate a possible contribution of this gene in determining genetic susceptibility to onco-hematological diseases. Patients and Methods. We screened a total of 325 patients with hematological malignancies for rs11886868 SNP at the BCL11A locus using the TaqMan allelic discrimination assay: 51 B-cell Non Hodgkin's lymphoma (NHL), 27 Hodgkin's disease (HD), 42 Chronic Lymphocytic Leukemia (CLL), 52 Multiple Myeloma, 35 Cutaneous T-cell Lymphomas (CTCL), 11 Acute Lymphoblastic Leukemia (ALL), 19 Myelodysplastic Syndromes (MDS), 31 Acute Non Lymphoblastic Leukemia (ANLL), 36 Philadelphia negative Myeloproliferative Disorders (MPD), 21 Chronic Myelogenous Leukemia. Fifty–four DNAs from healthy individuals were used as population controls. Both patients and controls originated from central Sardinia. The frequencies comparisons between controls and cases were performed using chi-square test and Odds Ratio (OR) analysis with Cornfield 95% confidence intervals (CI). Results. Allele frequencies for BCL11A rs11886868 were 22% for the “C” allele and 78% for the “T” allele. No statistically significant difference was observed between cases and controls. All genotypes were in Hardy-Weinberg equilibrium for both patients and controls groups. The genotype frequencies were 65% (T/T), 26% (C/T) and 9% (C/C) in controls and 53% (T/T), 40.5% (C/T), and 6.5% (C/C) in hematological malignancies. When compared with the genotype frequencies reported for Caucasian and healthy controls from Sardinia no statistically significant difference was observed (p=0.4). However, the C/T genotype was more frequent in cases than controls (41% vs 26%) conferring an increased risk for hematological malignancies with an estimated OR=1,9 (95%CI 1.08-3.6; p=0.03). In detail, statistically significant differences in genotype distribution were observed in CTCL (p< 0.0001), MPD (p=0.0006), NHL (p=0.008), HD (p=0.002) and ALL patients (p=0.02). The C/C genotype was not observed in CTCL and HD patients, while heterozygousity conferred an increased risk of 4.2 (2.3-7.7; p value <0.0001) and 2.6 (1.6-4.7; p value <0.002), respectively. The C/T genotype was also overrepresented in MPD with an estimated OR of 3.2 (1.7-5.8; p value= 0.0001) and NHL with OR of 2.7 (1.5-4.9; p value <0.001). Stratification for clinical and biological parameters showed that among CLLs, the C/C genotype was present in 4/27 (15%) of the CD38-negative patients and in none of the CD38-positive subgroup. By contrast, the homozygousity for the ancestral “T” allele was not observed in Mantle Cell and Marginal Zone Lymphomas. Conclusions. We found genetic association of BCL11A gene in several blood disorders with the strongest association for Cutaneous T-cell Lymphomas and Myeloproliferative disorders suggesting a possible role of BCL11A in both lymphoid and myeloid lineages. Specific BCL11A genotypes have been associated with different BCL11A expression levels that influence HbF production. We speculate that BCL11A sequence variants may influence expression of different isoforms that may have effect on cell pathways involved in oncogenetic events as well as in globin gene regulation. This work was supported by Associazione Italiana contro le Leucemie e Linfomi (AIL) Disclosures: No relevant conflicts of interest to declare.

Randomized Comparison of IV PEG and IM E. Coli Asparaginase in Children and Adolescents with Acute Lymphoblastic Leukemia: Results of the DFCI ALL Consortium Protocol 05-01

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 874-874 ◽  
Author(s):  
Lewis B. Silverman ◽  
Kristen Stevenson ◽  
Lynda M Vrooman ◽  
Jeffrey G Supko ◽  
Barbara Asselin ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Serum Samples ◽  
Childhood All ◽  
E Coli ◽  
Significant Difference ◽  
Consolidation Phase

Abstract Abstract 874 E. coli L-asparaginase (E. coli ASP) is an important component of treatment for childhood ALL, but is associated with multiple toxicities, including allergy, pancreatitis, and thrombosis. It is typically given intramuscularly (IM). Because most pediatric ALL patients have indwelling venous catheters, intravenous (IV) administration of asparaginase would be a more convenient and less painful option than IM injection. PEG-asparaginase (PEG), the polyethylene glycol conjugate of E. coli ASP, has a longer circulating half-life and so may be given less frequently. We have previously demonstrated that a single dose of PEG 2500 IU/m2 given IV is tolerable in children with ALL, with potentially therapeutic serum enzyme activity (≥ 0.1 IU/mL) maintained for at least 18 days in most patients.[Blood 2010;115:1351-3] On DFCI ALL Consortium Protocol 05-01, all patients (pts) with newly diagnosed ALL aged 1–18 years (yrs) who achieved complete remission were eligible to participate in a randomized comparison of IM E. coli ASP and IV PEG during the 30-week (wk) multi-agent post-induction Consolidation phase. Beginning at week 7 of therapy, pts received either IM E. Coli ASP 25000 IU/m2 weekly × 30 wks or IV PEG 2500 IU/m2 every 2 wks × 30 wks. Serum samples were obtained every 6 wks just prior to an ASP dose and were assayed for ASP enzyme activity by a validated biochemical assay. Between 2005–2010, 463 pts were enrolled in the randomized comparison. Median age was 5 yrs (range 1.2–17.9 yrs). There was no significant difference in presenting characteristics between the two arms, except that more pts on the E. coli ASP arm presented with a mediastinal mass (9% vs 3%, p=0.04). Median follow-up was 2.8 years. Median nadir serum ASP activity (NSAA) at each assayed timepoint during the Consolidation phase was significantly higher with IV PEG than with IM E. coli ASP (Table 1). An NSAA of ≥ 0.1 IU/mL was achieved in ≥ 95% of IV PEG pts compared with < 50% of IM E. coli ASP pts (p<0.01 at each timepoint). There was no significant difference in ASP-related toxicities (allergy, pancreatitis, thrombosis) between the two types of ASP (Table 2). Older pts (≥ 10 yrs old) had a significantly higher overall rate (p<0.01) of pancreatitis (18% vs 7%) and thrombosis (18% vs 4%), but not of allergy (p=0.49) or infection (p=0.21), compared to younger pts. There was no significant difference in the rates of ASP-related toxicities when comparing IM E. coli ASP vs IV PEG separately within the two age groups (≥10 yrs and < 10 yrs). We conclude that every 2-week IV PEG is no more toxic than weekly IM E. coli ASP in children and adolescents with ALL, and is associated with higher serum ASP activity. Longer follow-up is necessary to determine whether there is any difference in event-free survival between the two treatment arms.Table 1:Nadir Serum ASP activity (NSAA) during 30-week Consolidation phaseIV PEGIM ECOLISample Time (wks)*NMedian IU/mL% pts with NSAA ≧ 0.10 IU/mLNMedian IU/mL% pts with NSAA ≧ 0.10 IU/mL5840.6795%920.09448%11700.7197%740.09447%17730.7697%860.09247%23600.70100%760.09446%29680.70100%630.09544%*Number of weeks after start of Consolidation phaseTable 2:Toxicities by ASP type during 30-week Consolidation phaseToxicityIV PEG # of pts (%)IM E. COLI # of pts (%)p-valueNumber of Patients232231Asparaginase Toxicity59 (25)58 (25)>0.99    Allergy26 (11)20 (9)0.44    Pancreatitis25 (11)21 (9)0.64        Mild/Moderate13 (6)13 (6)        Severe12 (5)8 (3)    Thrombosis14 (6)21 (9)0.22Infection (bacteremia, invasive fungal disease)35 (15)46 (20)0.18 Disclosures: Silverman: Enzon Pharmaceuticals: Honoraria. Supko:Enzon Pharmaceuticals: Research Funding. Sallan:Enzon Pharmaceuticals: Honoraria.

Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4257-4264 ◽  
Author(s):  
Smita Bhatia ◽  
Harland N. Sather ◽  
Olga B. Pabustan ◽  
Michael E. Trigg ◽  
Paul S. Gaynon ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Brain Tumors ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Childhood All ◽  
Second Neoplasms ◽  
Increased Risk ◽  
The Impact

Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). With improvement in survival, it is important to assess the impact of contemporary risk-based therapies on second neoplasms in ALL survivors. A cohort of 8831 children diagnosed with ALL and enrolled on Children's Cancer Group therapeutic protocols between 1983 and 1995 were observed to determine the incidence of second neoplasms and associated risk factors. The median age at diagnosis of ALL was 4.7 years. The cohort had accrued 54 883 person-years of follow-up. Sixty-three patients developed second neoplasms, including solid, nonhematopoietic tumors (n = 39: brain tumors n = 19, other solid tumors n = 20), myeloid leukemia or myelodysplasia (n = 16), and lymphoma (n = 8). The cumulative incidence of any second neoplasm was 1.18% at 10 years (95% confidence interval, 0.8%-1.5%), representing a 7.2-fold increased risk compared with the general population. The risk was increased significantly for acute myeloid leukemia (standardized incidence ratio [SIR] 52.3), non-Hodgkin lymphoma (SIR 8.3), parotid gland tumors (SIR 33.4), thyroid cancer (SIR 13.3), brain tumors (SIR 10.1), and soft tissue sarcoma (SIR 9.1). Multivariate analysis revealed female sex (relative risk [RR] 1.8), radiation to the craniospinal axis (RR 1.6), and relapse of primary disease (RR 3.5) to be independently associated with increased risk of all second neoplasms. Risk of second neoplasms increased with radiation dose (1800 cGy RR 1.5; 2400 cGy RR 3.9). Actuarial survival at 10 years from diagnosis of second neoplasms was 39%. Follow-up of this large cohort that was treated with contemporary risk-based therapy showed that the incidence of second neoplasms remains low after diagnosis of childhood ALL.

Outcome of adolescents with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols, 1991–2000

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9023-9023
Author(s):  
E. Barry ◽  
D. E. Levy ◽  
M. A. Goldwasser ◽  
M. L. Loh ◽  
D. J. Deangelo ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Newly Diagnosed ◽  
Thromboembolic Complications ◽  
Childhood All ◽  
Dana Farber Cancer Institute ◽  
Increased Risk ◽  
Older Adolescents

9023 Background: Historically, adolescents with ALL have had inferior outcomes compared with younger pediatric patients (pts). Recent studies suggest that older adolescents treated on pediatric protocols have better outcomes than similarly aged pts treated on adult protocols. We report the outcome of adolescents enrolled on two consecutive DFCI ALL Consortium protocols conducted between 1991–2000. Methods: Pts aged 1–18 years (yrs) with newly diagnosed ALL were enrolled on two consecutive protocols, 91–01 (1991–1995) and 95–01(1995–2000). All adolescent pts received 20–30 weeks asparaginase (post-remission consolidation), 18 Gy cranial radiation and doxorubicin (cumulative dose 300 mg/m2). Results: 847 pts were enrolled. Median follow-up was 6.5 yrs. Presenting characteristics and outcome of pts according to age are displayed in the table below. Older pts (age ≥ 10 yrs) were more likely to experience pancreatitis (p=0.007) and thromboembolic complications (p<0.001) from asparaginase, but had similar rates of asparaginase-related allergic events (p=0.21) compared to younger pts. Conclusions: Older adolescents (aged 15–18 yrs) with ALL are more likely to present with T-cell phenotype and TEL/AML1-negative disease than younger children. Despite these biologic differences, older adolescents (aged 15–18 yrs) fared relatively well on DFCI ALL Consortium protocols, with a 5-year EFS of 75 ± 6%. This EFS rate compares favorably to published outcomes for older adolescents treated on other childhood ALL protocols. Although adolescents had an increased risk of asparaginase-related toxicity, this therapy was well-tolerated overall. Based on this experience, we are currently piloting our treatment regimen in adults aged 18–50 yrs. [Table: see text] No significant financial relationships to disclose.

Bony Morbidity in Children Treated for Acute Lymphoblastic Leukemia

2001 ◽  
Vol 19 (12) ◽  
pp. 3066-3072 ◽  
Author(s):  
Adam J. Strauss ◽  
Joyce T. Su ◽  
Virginia M. Kimball Dalton ◽  
Richard D. Gelber ◽  
Stephen E. Sallan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Older Children ◽  
Event Free Survival ◽  
Free Survival ◽  
Increased Risk ◽  
High Incidence ◽  
Pediatric All ◽  
Male Sex

PURPOSE: Corticosteroids are widely used in the treatment of acute lymphoblastic leukemia (ALL). To determine the frequency of corticosteroid-associated bony morbidity in children with ALL, we retrospectively evaluated the incidence of fractures and osteonecrosis (ON) on two consecutive pediatric ALL protocols. PATIENTS AND METHODS: One hundred seventy-six consecutive children were treated for ALL between 1987 and 1995 at the Dana-Farber Cancer Institute and Children’s Hospital. Prednisone was used as the corticosteroid during postremission therapy from 1987 to 1991, and dexamethasone was used from 1991 to 1995. Medical records for all patients were reviewed to assess the occurrence of fractures and ON. RESULTS: With a median follow-up of 7.6 years, the 5-year cumulative incidence (CI) ± SE of any bony morbidity for the 176 patients was 30% ± 4%, with a 5-year CI of fractures of 28% ± 3% and of ON of 7% ± 2%. With multivariate analysis, independent predictors of bony morbidity included age 9 to 18 years at diagnosis (P < .01), male sex (P < .01), and treatment with dexamethasone (P = .01). Dexamethasone was associated with a higher risk of fractures (5-year CI, 36% ± 5% v 20% ± 4% with prednisone; P = .04), but not ON (P = .40). The 5-year event-free survival for the 176 patients was 79% ± 3%. CONCLUSION: Children treated for ALL had a high incidence of fractures and ON. Older children, boys, and patients receiving dexamethasone were at increased risk for the development of bony morbidity. Future studies should attempt to minimize corticosteroid-associated bony morbidity without compromising clinical efficacy.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in hospitalized patients at a tertiary referral center in North India (Preprint)

2020 ◽  
Author(s):  
Dr. Animesh Ray ◽  
Dr. Komal Singh ◽  
Souvick Chattopadhyay ◽  
Farha Mehdi ◽  
Dr. Gaurav Batra ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Age Groups ◽  
Hospitalized Patients ◽  
North India ◽  
P Value ◽  
Care Hospital ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Increased Risk ◽  
Significant Difference

BACKGROUND Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India OBJECTIVE The primary objective of this study is to estimate the seroprevalence of SARS-CoV-2 antibody among patients admitted to the Medicine ward and ICU METHODS This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method RESULTS A total of 212 hospitalized patients were recruited in the study with mean age (±SD) of 41.2 (±15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8%patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p-value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity CONCLUSIONS Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)

scholarly journals Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e042246
Author(s):  
Sanjoy K Paul ◽  
Olga Montvida ◽  
Jennie H Best ◽  
Sara Gale ◽  
Attila Pethö-Schramm ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
T Cell ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Therapy ◽  
Treatment Groups ◽  
Significant Difference ◽  
Necrosis Factor

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).Study design, setting and participantsFive treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.ResultsIn the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.ConclusionsTreatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

scholarly journals Acute Dental Periapical Abscess and New-Onset Atrial Fibrillation: A Nationwide, Population-Based Cohort Study

2021 ◽  
Vol 10 (13) ◽  
pp. 2927
Author(s):  
Amaar Obaid Hassan ◽  
Gregory Y. H. Lip ◽  
Arnaud Bisson ◽  
Julien Herbert ◽  
Alexandre Bodin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Multivariable Analysis ◽  
National Database ◽  
Increased Risk ◽  
Periapical Abscess ◽  
The Relationship ◽  
Onset Atrial Fibrillation ◽  
New Onset

There are limited data on the relationship of acute dental infections with hospitalisation and new-onset atrial fibrillation (AF). This study aimed to assess the relationship between acute periapical abscess and incident AF. This was a retrospective cohort study from a French national database of patients hospitalized in 2013 (3.4 million patients) with at least five years of follow up. In total, 3,056,291 adults (55.1% female) required hospital admission in French hospitals in 2013 while not having a history of AF. Of 4693 patients classified as having dental periapical abscess, 435 (9.27%) developed AF, compared to 326,241 (10.69%) without dental periapical abscess that developed AF over a mean follow-up of 4.8 ± 1.7 years. Multivariable analysis indicated that dental periapical abscess acted as an independent predictor for new onset AF (p < 0.01). The CHA2DS2VASc score in patients with acute dental periapical abscess had moderate predictive value for development of AF, with Area Under the Curve (AUC) 0.73 (95% CI, 0.71–0.76). An increased risk of new onset AF was identified for individuals hospitalized with dental periapical abscess. Careful follow up of patients with severe, acute dental periapical infections is needed for incident AF, as well as investigations of possible mechanisms linking these conditions.

scholarly journals An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events

2021 ◽  
Vol 11 (3) ◽  
pp. 178
Author(s):  
Noah R. Delapaz ◽  
William K. Hor ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
Feiran Liang ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Previous History ◽  
Current Treatment ◽  
Careful Consideration ◽  
P Value ◽  
Post Traumatic Stress ◽  
Increased Risk ◽  
History Of ◽  
Almost All

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

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