Tag: nevin manimala

BMJ Open. 2021 Oct 13;11(10):e047979. doi: 10.1136/bmjopen-2020-047979.

ABSTRACT

INTRODUCTION: HIV programmes in sub-Saharan Africa are well funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Healthcare provision is organised from stand-alone clinics. In this cluster randomised trial, we are evaluating a concept of integrated care for people with HIV infection, diabetes or hypertension from a single point of care.

METHODS AND ANALYSIS: 32 primary care health facilities in Dar es Salaam and Kampala regions were randomised to either integrated or standard vertical care. In the integrated care arm, services are organised from a single clinic where patients with either HIV infection, diabetes or hypertension are managed by the same clinical and counselling teams. They use the same pharmacy and laboratory and have the same style of patient records. Standard care involves separate pathways, that is, separate clinics, waiting and counselling areas, a separate pharmacy and separate medical records. The trial has two primary endpoints: retention in care of people with hypertension or diabetes and plasma viral load suppression. Recruitment is expected to take 6 months and follow-up is for 12 months. With 100 participants enrolled in each facility with diabetes or hypertension, the trial will provide 90% power to detect an absolute difference in retention of 15% between the study arms (at the 5% two-sided significance level). If 100 participants with HIV infection are also enrolled in each facility, we will have 90% power to show non-inferiority in virological suppression to a delta=10% margin (ie, that the upper limit of the one-sided 95% CI of the difference between the two arms will not exceed 10%). To allow for lost to follow-up, the trial will enrol over 220 persons per facility. This is the only trial of its kind evaluating the concept of a single integrated clinic for chronic conditions in Africa.

ETHICS AND DISSEMINATION: The protocol has been approved by ethics committee of The AIDS Support Organisation, National Institute of Medical Research and the Liverpool School of Tropical Medicine. Dissemination of findings will be done through journal publications and meetings involving study participants, healthcare providers and other stakeholders.

TRIAL REGISTRATION NUMBER: ISRCTN43896688.

PMID:34645657 | DOI:10.1136/bmjopen-2020-047979

J Immunother Cancer. 2021 Oct;9(10):e002947. doi: 10.1136/jitc-2021-002947.

ABSTRACT

BACKGROUND: Gastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL.

METHODS: A retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed.

RESULTS: The median follow-up of the 252 patients was 66.6 months (range 0.7-119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H. pylori-positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p<0.001) and OS (89.2% vs 76.6%, p<0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival.

CONCLUSION: H. pylori-evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.

PMID:34645670 | DOI:10.1136/jitc-2021-002947

BJGP Open. 2021 Oct 13:BJGPO.2021.0080. doi: 10.3399/BJGPO.2021.0080. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing in high-income countries. HPV-associated OPC generally presents as an invasive disease, often with lymph node involvement, in relatively young patients with minimal or no history of smoking and alcohol consumption. Knowledge on HPV-associated OPC among primary care professionals is essential for disease recognition and early start of treatment.

AIM: To examine the knowledge on HPV-associated OPC among general practitioners (GPs) in The Netherlands.

DESIGN AND SETTING: Cross-sectional postal survey among GPs in The Netherlands.

METHOD: twelve-item questionnaire was sent to 900 randomly selected general practices. Outcome measures included awareness of the link between HPV and OPC, epidemiological trends and patient characteristics. Data were statistically analyzed for gender, years after graduation, and self-rated knowledge of OPC.

RESULTS: 207 GPs participated in this study. 72% recognised HPV as a risk factor for OPC and 76.3% was aware of the increasing incidence rate of HPV-associated OPC. In contrast, 35.3% of participants knew that HPV-associated OPC patients are more often male, and just over half (53.6%) of the participants were aware of the younger age of these patients.

CONCLUSION: More than a quarter of GPs in The Netherlands is unaware of HPV as a causative factor for OPC. Furthermore, there is a gap in knowledge on HPV-associated OPC patient characteristics. Further training on these topics could improve disease recognition and ultimately patient survival.

PMID:34645653 | DOI:10.3399/BJGPO.2021.0080

J Neurosci. 2021 Oct 12:JN-RM-0367-21. doi: 10.1523/JNEUROSCI.0367-21.2021. Online ahead of print.

ABSTRACT

Detection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography was conducted in three male monkeys, who passively listened to the auditory roving oddball stimuli. Local field potentials (LFPs) recorded over the auditory cortex underwent spectral principal component analysis, which decoupled broadband and rhythmic components of the LFP signal. We found that the broadband component captured the prediction error response, whereas none of the rhythmic components were associated with statistical irregularities of sounds. The broadband component displayed more stochastic, asymmetrical multifractal properties than the rhythmic components, which revealed more self-similar dynamics. We thus conclude that the prediction error response is captured by neuronal populations generating asynchronous broadband activity, defined by irregular dynamic states, which, unlike oscillatory rhythms, appear to enable the neural representation of auditory prediction error response.SIGNIFICANCE STATEMENTThis study aimed to examine the contribution of oscillatory and asynchronous components of auditory local field potentials in the generation of prediction error responses to sensory irregularities, as this has not been directly addressed in the previous studies. Here, we show that mismatch negativity-an auditory prediction error response-is driven by the asynchronous broadband component of potentials recorded in the auditory cortex. This finding highlights the importance of nonoscillatory neural processes in the predictive monitoring of the environment. At a more general level, the study demonstrates that stochastic neural processes, which are often disregarded as neural noise, do have a functional role in the processing of sensory information.

PMID:34645605 | DOI:10.1523/JNEUROSCI.0367-21.2021

Clin Cancer Res. 2021 Oct 13:clincanres.1628.2021. doi: 10.1158/1078-0432.CCR-21-1628. Online ahead of print.

ABSTRACT

Purpose: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER+/HER2- breast cancer; (ii) the pharmacodynamic effect of the agents on the biomarkers. Experimental design: 307 postmenopausal women with ER+/HER2- primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1 and CCND1. Results: Higher baseline ER and PgR were significantly associated with a greater chance of Complete Cell Cycle Arrest (CCCA: Ki67 <2.7%) at 14 weeks and higher baseline Ki67, c-PARP and CCNE1 with a lower chance. The interaction with treatment was significant only for c-PARP. CCND1 levels were decreased c.20% by letrozole at 2 and 14 weeks but showed a tendency to increase with palbociclib. CCNE1 levels fell 82% (median) in tumours showing CCCA but were unchanged in those with no CCCA. Only 2/9 tumours showed CCCA 3-9 days after stopping palbociclib. ESR1 mutations were found in 2/4 tumours for which surgery took place {greater than or equal to}6 months after starting treatment. Conclusion: High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3-9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the “off” week of its schedule.

PMID:34645649 | DOI:10.1158/1078-0432.CCR-21-1628

Aerosp Med Hum Perform. 2021 Sep 1;92(9):698-701. doi: 10.3357/AMHP.5882.2021.

ABSTRACT

INTRODUCTION: On December 2020 the U.S. Food and Drug Administration (FDA) authorized the emergency use of Pfizer-BioNTech COVID-19 vaccine. This new vaccine has several side effects that can potentially impair function, which warrants special attention regarding aircrews fitness to fly following vaccination.METHODS: A survey was conducted in the Israeli Air Force (IAF) Aeromedical Center in order to characterize the side effects and their duration following Pfizer-BioNTech COVID-19 vaccine administration to aviators.RESULTS: The most common side effect was injection site pain. Headache, chills, myalgia, fatigue, and weakness were more common following the second dose administration. The difference is statistically significant. Following the second vaccine, duration of side effects was longer compared to the first vaccine (P-value 0.002).CONCLUSION: The IAF Aeromedical center policy for Pfizer-BioNTech COVID-19 vaccine recipients among aircrew members, based on side effects duration and severity, is to temporarily ground from flight duties for 24 and 48 h following the first and the second dose, respectively.Gabbai D, Ekshtein A, Tehori O, Ben-Ari O, Shapira S. COVID-19 vaccine and fitness to fly. Aerosp Med Hum Perform. 2021; 92(9):698701.

PMID:34645549 | DOI:10.3357/AMHP.5882.2021

Aust J Prim Health. 2021 Oct 14. doi: 10.1071/PY21026. Online ahead of print.

ABSTRACT

Optimal parental preconception health improves the likelihood of a successful pregnancy and a healthy child. Although primary healthcare professionals believe that it is within their role to promote preconception health to people of reproductive age, few do this routinely, in part because they lack knowledge on the topic and confidence to discuss it with their patients. The aim of this study was to evaluate the efficacy and acceptability of a free online learning module to assist nurses and midwives in primary health care to promote preconception health in their practice. A repeat online survey was administered before and after completion of the online learning module. The survey included questions gauging knowledge about and attitudes towards promoting preconception health. In all, 121 nurses/midwives completed the two surveys and the learning module. There were statistically significant improvements in the knowledge scores (from 6.42 to 8.31; P < 0.001) and in the proportion of participants who reported feeling confident in their knowledge about preconception health (from 15% to 53%). Almost all (95%) were satisfied with the duration and content of the learning module. The findings of this study suggest that the learning module is acceptable and improves nurses’ and midwives’ capacity to promote preconception health in their practice.

PMID:34645562 | DOI:10.1071/PY21026

Int J Retina Vitreous. 2021 Oct 13;7(1):60. doi: 10.1186/s40942-021-00334-4.

ABSTRACT

BACKGROUND: To evaluate the outcome of intravitreal bevacizumab (IVB) and aflibercept (IVA) injection for patients with retinopathy of prematurity (ROP).

METHODS: In this single-center retrospective cohort, the recorded medical data of the infants who had been undergone intravitreal injection with either bevacizumab or aflibercept for type 1 ROP were reviewed. The infants were allocated into two groups. IVB group included patients who were treated with bevacizumab as initial treatment and the IVA group included patients who were treated with aflibercept as initial treatment. The rate and time of complete regression, as well as the recurrence rates, were compared between the groups.

RESULTS: A total of 889 eyes of 453 infants were enrolled in the study. There were 865 eyes of 441 infants in the IVB group and 24 eyes of 12 infants in the IVA group. Follow-up time was 289 ± 257 days in the IVB group and 143 ± 25 days in the IVA group (p < 0.001). The difference in the ROP zone was not statistically significant between the 2 treatment groups (p = 0.328). All eyes in the IVA group showed initial regression of ROP after the intravitreal injections. These regressions were achieved in 830 (96.0%) eyes that were injected with IVB (p = 0.023). The median observed regression time was 10 days and 16 days in eyes treated with bevacizumab and aflibercept respectively. Recurrence was noted in 3.9% of eyes (34/865) in the IVB group and 58.3% of eyes (14/24) in the IVA group (p < 0.001).

CONCLUSION: While the regression rate in the IVA group was significantly higher than in the IVB group, the recurrence rate was significantly more in the IVA group, which may be attributed to differences in the pharmacokinetics of these drugs in the vitreous body.

PMID:34645516 | DOI:10.1186/s40942-021-00334-4

Prehosp Disaster Med. 2021 Oct 14:1-6. doi: 10.1017/S1049023X21001084. Online ahead of print.

ABSTRACT

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a life-threatening condition with an overall survival rate that generally does not exceed 10%. Several factors play essential roles in increasing survival among patients experiencing cardiac arrest outside the hospital. Previous studies have reported that implementing a dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) program increases bystander CPR, quality of chest compressions, and patient survival. This study aimed to assess the effectiveness of a DA-CPR program developed by the Thailand National Institute for Emergency Medicine (NIEMS).

METHODS: This was an experimental study using a manikin model. The participants comprised both health care providers and non-health care providers aged 18 to 60 years. They were randomly assigned to either the DA-CPR group or the uninstructed CPR (U-CPR) group and performed chest compressions on a manikin model for two minutes. The sequentially numbered, opaque, sealed envelope method was used for randomization in blocks of four with a ratio of 1:1.

RESULTS: There were 100 participants in this study (49 in the DA-CPR group and 51 in the U-CPR group). Time to initiate chest compressions was statistically significantly longer in the DA-CPR group than in the U-CPR group (85.82 [SD = 32.54] seconds versus 23.94 [SD = 16.70] seconds; P <.001). However, the CPR instruction did not translate into better performance or quality of chest compressions for the overall sample or for health care or non-health care providers.

CONCLUSION: Those in the CPR-trained group applied chest compressions (initiated CPR) more quickly than those who initiated CPR based upon dispatch-based CPR instructions.

PMID:34645532 | DOI:10.1017/S1049023X21001084

World J Emerg Surg. 2021 Oct 13;16(1):52. doi: 10.1186/s13017-021-00398-5.

ABSTRACT

BACKGROUND: Recent studies have reported promising outcomes of non-operative treatment for uncomplicated appendicitis; however, the preoperative prediction of complicated appendicitis is challenging. We developed models by incorporating fat stranding (FS), which is commonly observed in perforated appendicitis.

MATERIAL AND METHODS: We reviewed the data of 402 consecutive patients with confirmed acute appendicitis from our prospective registry. Multivariate logistic regression was performed to select clinical and radiographic factors predicting complicated acute appendicitis in our model 1 (involving backward elimination) and model 2 (involving stepwise selection). We compared c statistics among scoring systems developed by Bröker et al. (in J Surg Res 176(1):79-83. https://doi.org/10.1016/j.jss.2011.09.049 , 2012), Imaoka et al. (in World J Emerg Surg 11(1):1-5, 2016), Khan et al. (in Cureus. https://doi.org/1010.7759/cureus.4765 , 2019), Kim et al. (in Ann Coloproctol 31(5):192, 2015), Kang et al. (in Medicine 98(23): e15768, 2019), Atema et al. (in Br J Surg 102(8):979-990. https://doi.org/10.1002/bjs.9835 , 2015), Avanesov et al. (in Eur Radiol 28(9):3601-3610, 2018), and Kim et al. (in Abdom Radiol 46:1-12, 2020). Finally, we examined our models by performing the integrated discrimination improvement (IDI) test.

RESULTS: Among enrolled patients, 64 (15.9%) had complicated acute appendicitis. We developed new 10-point scoring models by including the following variables: C-reactive protein, neutrophil to lymphocyte ratio, and computed tomography features of FS, ascites, and appendicolith. A cutoff score of ≥ 6 exhibited a high sensitivity of 82.8% and a specificity of 82.8% for model 1 and 81.3% and 82.3% for model 2, respectively, with c statistics of 0.878 (model 1) and 0.879 (model 2). Compared with the model developed by Bröker et al. which included C-reactive protein and the abdominal pain duration (c statistic: 0.778), the models developed by Atema et al. (c statistic: 0.826, IDI: 5.92%, P = 0.0248), H.Y Kim et al. (c statistics: 0.838, IDI: 13.82%, P = 0.0248), and our two models (IDI: 18.29%, P < 0.0001) demonstrated a significantly higher diagnostic accuracy.

CONCLUSION: Our models and the scoring systems developed by Atema et al. and Kim et al. were validated to have a high diagnostic accuracy; moreover, our models included the lowest number of variables.

PMID:34645500 | DOI:10.1186/s13017-021-00398-5