A Comparison of Dissection-method and Diathermy Tonsillectomies

Objective: To compare the dissection and diathermy methds of tonsillectomy and evaluate their advantages and disadvantages during surgery and convalescence.Methods and Setting: Patients who had tonsillectomy at Aga Khan University Hospital, between January 1994-December 1997.Results: Four year retrospective analysis was done of 200 patients who underwent tonsillectomy by either electrocautery or dissection method. One hundred and eleven underwent tonsillectomy by electrocautery and the other 79 had their tonsils removed by dissection-method and 2 had a combination of both. The average intra­operative blood loss was 10 ml with cautery and 65 ml with dissection method. The average operative time was 15.7 minutes with cautery and 26.9 minutes for dissection. We found higher amounts of blood loss and intra­operative time with dissection method than electrocautery. In comparing diathermy dissection method tonsillectomies, there was marked difference between two, in pen-operative blood loss and operative time.Conclusion: Although post-operative bleeding, pain and infection are complications of both techniques and in our study their incidence in similar in both, but intra-operative blood loss and time are two important factors,technique is a more effective technique in our set up based on which we can conclude that electrocauter

Smokeless tobacco initiation, use and cessation in South Asia : a qualitative assessment

INTRODUCTION: Smokeless tobacco (ST) is a significant South Asian public health problem. This paper reports a qualitative study of a sample of South Asian ST users. METHODS: Interviews, using a piloted topic guide, with 33 consenting, urban dwelling adult ST users explored their ST initiation, continued use, and cessation attempts. Framework data analysis was used to analyze country specific data before a thematic cross-country synthesis was completed. RESULTS: Participants reported long-term ST use and high dependency. All reported strong cessation motivation and multiple failed attempts because of ease of purchasing ST, tobacco dependency, and lack of institutional support. CONCLUSIONS: Interventions to support cessation attempts among consumers of South Asian ST products should address the multiple challenges of developing an integrated ST policy, including cessation services. IMPLICATIONS: This study provides detailed understanding of the barriers and drivers to ST initiation, use, and cessation for users in Bangladesh, India, and Pakistan. It is the first study to directly compare these three countries. The insight was then used to adapt an existing behavioral support intervention for ST cessation for testing in these countries

A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study

Se trata de la publicación del estudio de fase 3 ASPEN que comparó en pacientes con macro-globulinemia de Waldenström (WM) la eficacia y la seguridad de ibrutinib, un inhibidor de la tirosi-na quinasa Bruton (BTK) de primera generación, familia que ha demostrado ser un tratamiento eficaz en estos pacientes, frente a zanubrutinib, un nuevo inhibidor de BTK de 2ª generación, altamente selectivo. Los pacientes con enfermedad MYD88L265P se asignaron al azar 1:1 al tratamiento con ibrutinib o zanubrutinib. El criterio principal de valoración fue la proporción de pa-cientes que lograron una respuesta completa (RC) o una respuesta parcial muy buena (RPMB) mediante una revisión independiente. Los criterios secundarios clave de valoración incluyeron la tasa de respuesta mayor (RM), la supervivencia libre de progresión (SLP), la duración de la res-puesta (DR), la carga de la enfermedad y la seguridad. Se randomizaron 201 pacientes y 199 recibieron al menos 1 dosis del tratamiento del estudio. Veintinueve (28%) pacientes tratados con zanubrutinib y 19 (19%) pacientes tratados con ibrutinib lograron una RPMB, diferencia que no alcanzó la significación estadística (P = 0,09). Las RM fueron del 77% y del 78%, respectivamen-te. No se alcanzó la mediana de DR y SLP, ya que el 84% y el 85% de los pacientes tratados con ibrutinib y zanubrutinib estaban libres de progresión a los 18 meses. La fibrilación auricular, hema-tomas, diarrea, edema periférico, hemorragia, espasmos musculares y neumonía, así como los eventos adversos que condujeron a interrumpir el tratamiento, fueron menos frecuentes entre los receptores de zanubrutinib. La incidencia de neutropenia fue mayor con zanubrutinib, aunque las tasas de infección de grado ≥3 fueron similares en ambos grupos (1,2 y 1,1 eventos por 100 me-ses-persona). Estos resultados demuestran que zanubrutinib e ibrutinib son altamente efectivos en el tratamiento de la WM, pero zanubrutinib se asoció con menor toxicidad y una tendencia hacia una mejor calidad de respuesta y menos toxicidad, particularmente toxicidad cardiovascular.[EN]Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.BeiGene CoBeiGene C

Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer

Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones. When aberrantly expressed in B cells, ZAP70 competes with SYK at the BCR signalosome and redirects SYK from negative selection to tonic PI3K signaling, thereby promoting B cell survival. In genetic mouse models for B-ALL and B-CLL, conditional expression of Zap70 accelerated disease onset, while genetic deletion impaired malignant transformation. Inducible activation of Zap70 during B cell development compromised negative selection of autoreactive B cells, resulting in pervasive autoantibody production. Strict segregation of the two kinases is critical for normal B cell selection and represents a central safeguard against the development of autoimmune disease and B cell malignancies.acceptedVersionPeer reviewe

Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study

The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM). Here, we report long-term follow-up outcomes from ASPEN. The primary end point was the sum of very good partial response (VGPR) + complete response (CR) rates; secondary and exploratory end points were also reported. Cohort 1 comprised 201 patients (myeloid differentiation primary response 88-mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib); cohort 2 comprised 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). At 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) of diarrhea (34.7% v 22.8%), muscle spasms (28.6% v 11.9%), hypertension (25.5% v 14.9%), atrial fibrillation/flutter (23.5% v 7.9%), and pneumonia (18.4% v 5.0%) were more common with ibrutinib versus zanubrutinib; neutropenia (20.4% v 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with lower risk of AE-related treatment discontinuation. Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib

Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia

The phase 3 ASPEN trial (NCT03053440) compared Bruton tyrosine kinase inhibitors (BTKis), zanubrutinib and ibrutinib, in patients with Waldenström macroglobulinemia (WM). Post-hoc biomarker analysis was performed using next-generation sequencing on pretreatment bone marrow samples from 98 patients treated with zanubrutinib and 92 patients treated with ibrutinib with mutated (MUT) MYD88 and 20 patients with wild-type (WT) MYD88 treated with zanubrutinib. Of 329 mutations in 52 genes, mutations in CXCR4 (25.7%), TP53 (24.8%), ARID1A (15.7%), and TERT (9.0%) were most common. TP53MUT, ARID1AMUT, and TERTMUTwere associated with higher rates of CXCR4MUT(P < .05). Patients with CXCR4MUT(frameshift or nonsense [NS] mutations) had lower very good partial response (VGPR) and complete response rates (CR; 17.0% vs 37.2%, P = .020) and longer time to response (11.1 vs 8.4 months) than patients with CXCR4WTtreated with BTKis. CXCR4NSwas associated with inferior progression-free survival (PFS; hazard ratio [HR], 3.39; P = .017) in patients treated with ibrutinib but not in those treated with zanubrutinib (HR, 0.67; P = .598), but VGPR + CR rates were similar between treatment groups (14.3% vs 15.4%). Compared with ibrutinib, patients with CXCR4NStreated with zanubrutinib had a favorable major response rate (MRR; 85.7% vs 53.8%; P = .09) and PFS (HR, 0.30; P = .093). In patients with TP53MUT, significantly lower MRRs were observed for patients treated with ibrutinib (63.6% vs 85.7%; P = .04) but not for those treated with zanubrutinib (80.8% vs 81.9%; P = .978). In TP53MUT, compared with ibrutinib, patients treated with zanubrutinib had higher VGPR and CR (34.6% vs 13.6%; P < .05), numerically improved MRR (80.8% vs 63.6%; P = .11), and longer PFS (not reached vs 44.2 months; HR, 0.66; P = .37). Collectively, patients with WM with CXCR4MUTor TP53MUThad worse prognosis compared with patients with WT alleles, and zanubrutinib led to better clinical outcomes

Assessment of the uptake of neonatal and young infant referrals by community health workers to public health facilities in an urban informal settlement, KwaZulu-Natal, South Africa.

BACKGROUND: Globally, 40% of the 7.6 million deaths of children under five every year occur in the neonatal period (first 28 days after birth). Increased and earlier recognition of illness facilitated by community health workers (CHWs), coupled with effective referral systems can result in better child health outcomes. This model has not been tested in a peri-urban poor setting in Africa, or in a high HIV context. METHODS: The Good Start Saving Newborn Lives (SNL) study (ISRCTN41046462) conducted in Umlazi, KwaZulu-Natal, was a community randomized trial to assess the effect of an integrated home visit package delivered to mothers by CHWs during pregnancy and post-delivery on uptake of PMTCT interventions and appropriate newborn care practices. CHWs were trained to refer babies with illnesses or identified danger signs. The aim of this sub-study was to assess the effectiveness of this referral system by describing CHW referral completion rates as well as mothers' health-care seeking practices. Interviews were conducted using a structured questionnaire with all mothers whose babies had been referred by a CHW since the start of the SNL trial. Descriptive analysis was conducted to describe referral completion and health seeking behaviour of mothers. RESULTS: Of the 2423 women enrolled in the SNL study, 148 sick infants were referred between June 2008 and June 2010. 62% of referrals occurred during the first 4 weeks of life and 22% between birth and 2 weeks of age. Almost all mothers (95%) completed the referral as advised by CHWs. Difficulty breathing, rash and redness/discharge around the cord accounted for the highest number of referrals (26%, 19% and 17% respectively). Only16% of health workers gave written feedback on the outcome of the referral to the referring CHW. CONCLUSIONS: We found high compliance with CHW referral of sick babies in an urban South African township. This suggests that CHWs can play a significant role, within community outreach teams, to improve newborn health and reduce child mortality. This supports the current primary health care re-engineering process being undertaken by the South African National Department of Health which involves the establishment of family health worker teams including CHWs. TRIAL REGISTRATION NUMBER: ISRCTN41046462

The Association Between Inflammatory Bowel Disease and Exposure to Tobacco Smoking: A Case-Control Study in Qatar

Objective: This research investigated the association between childhood and adulthood tobacco smoking exposure with ulcerative colitis (UC) and Crohn’s disease (CD) in Qatar. Study Design and Setting: In this case-control study, CD and UC cases were matched to controls of the same age and sex. The associations between UC and CD and childhood passive smoking and adulthood active smoking were assessed using conditional multivariable logistic regression. Results: A total of 89 CD cases, median age of 37 years (IQR 29–47), and 362 UC cases, median age of 35 years (IQR 28–44), and equal numbers of controls were included. After multivariable logistic regression, CD was associated with higher odds of being a current smoker (OR 2.51, 95% CI 0.85–7.37, p=0.095), with weak evidence against the null hypothesis. This association was more pronounced in women, where CD was associated with both adulthood current smoking (OR 42.71, 95% CI, 1.17–1559.57, p=0.041), and childhood smoking exposure (OR 8.23, 95% CI, 1.36–49.66, p=0.021). In males, no associations were observed between CD and the smoking exposures. No associations were observed between UC and both smoking variables. Conclusion: In Qatar, adulthood tobacco smoking appears to increase the odds of CD. Further, our findings suggest that both childhood and adulthood cigarette smoke exposure may possibly have a detrimental effect on the odds of CD in females but not in males, although further research is needed

A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors

Purpose Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate used in the treatment of several types of lymphomas. Expression of the target antigen has also been reported on a variety of malignant tumors of nonlymphoid origin. This phase 2, open-label study evaluated the safety and antitumor activity of BV in patients with CD30-expressing nonlymphomatous malignancies. Methods Patients were dosed with 1.8 or 2.4 mg/kg BV once every three weeks. Antitumor activity was assessed at Cycles 2, 4, and every 4 cycles thereafter. Patients with stable disease or better were eligible to continue treatment until disease progression, unacceptable toxicity, or study closure. Results Of the 2693 patients screened, 3.8% had solid tumors with CD30 expression and 63 eligible patients with solid tumors enrolled in this study. The most common CD30 positive solid tumors were testicular cancer and mesothelioma. Both subtypes had more than one patient with an objective response. The median duration of BV exposure was 6.1 weeks. The disease control rate, defined as achieving stable disease or better at any point during the study, was 55%. The objective response rate was 11%, with a median duration of response of 2.92 months. The most common adverse events reported were fatigue (57%), nausea (33%), and decreased appetite (32%). Conclusion The safety profile of BV in patients with solid tumors was similar to the known safety profile of BV. In solid tumors, BV had modest activity as a single agent, which was similar to other second-line treatments already available to patients