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Background: Use of fine-needle aspiration biopsy (FNAB) specimens on Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA), a CE-marked in-vitro diagnostic medical device, could potentially increase access to breast cancer biomarker testing in resource-constrained settings. We aimed to assess the performance of a research use-only version of STRAT4 using FNAB specimens in Tanzania., Methods: In this prospective diagnostic accuracy study, patients aged 18 years or older with palpable breast masses presenting to the FNAB Clinic at Muhimbili National Hospital (Dar es Salaam, Tanzania) were recruited consecutively. Patients who were pregnant, lactating, or had a previous diagnosis of breast cancer were excluded. STRAT4 testing was performed on off-label FNAB samples using four protocols: the 1 × protocol (using the standard lysate method) on FNAB smears (1 × FNAB), quick lysis and Maui protocols (both on FNAB smears), and the 1 × protocol on formalin-fixed paraffin-embedded (FFPE) cell block material (1 × cell block). For 1 × FNAB and 1 × cell block, tissue was processed using FFPE lysis reagent, incubated at 80°C with proteinase K, and followed by addition of 95% or higher ethanol. Quick lysis was processed using FFPE lysis reagent and 95% or higher ethanol, whereas Maui was processed using a proprietary research-use only lysis reagent. The primary outcomes were overall concordance, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of STRAT4 as compared with immunohistochemistry or immunohistochemistry plus fluorescence in-situ hybridisation performed on cell blocks using clinically validated protocols in a Clinical Laboratory Improvement Amendments-accredited laboratory at the University of California, San Francisco (San Francisco, CA, USA)., Findings: Between Nov 29, 2017, and Dec 17, 2020, 208 patients were enrolled. Of 208 cases, 51 (25%) were excluded from analysis because of insufficient tissue in the cell block or absent cell blocks, leaving 157 participants (all female) for analysis. For oestrogen receptor, 1 × FNAB had the best performance, with an overall concordance of 95% (95% CI 90-100), sensitivity of 94% (85-100), specificity of 97% (90-100), and AUC of 0·96 (0·81-1·00). For progesterone receptor, 1 × cell block had the best overall performance (overall concordance 89% [95% CI 84-95], sensitivity 91% [82-99], and specificity 89% [81-97], with an AUC of 0·93 [0·89-0·99]) and 1 × FNAB performed the best among the smear protocols, with a concordance of 84% (95% CI 74-93), sensitivity of 63% (43-82), specificity of 97% (92-100), and AUC of 0·91 (0·72-0·97). For HER2, Maui had the highest agreement, with an overall concordance of 93% (95% CI 89-98), sensitivity of 96% (88-100), specificity of 92% (87-98), and AUC of 0·95 (0·98-1·00). For Ki67, Maui had the best performance of smear protocols, with a concordance of 73% (95% CI 64-82), sensitivity of 70% (58-81), specificity of 81% (66-96), and AUC of 0·80 (0·54-0·82)., Interpretation: Processing FNAB samples with STRAT4 is feasible in Tanzania, and performance for the oestrogen receptor is robust. Further optimisation of STRAT4 for FNAB has the potential to improve timely access to breast cancer diagnostics in resource-constrained settings., Funding: US National Institutes of Health; UCSF Global Cancer Program, Helen Diller Family Comprehensive Cancer Center; UCSF Department of Pathology; and Cepheid., Competing Interests: Declaration of interests KEH, JW, and MB are employees of Cepheid and own stock shares in Cepheid's parent company, Danaher. DLN and EV received funding, equipment, and study materials for the project from Cepheid. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Understanding the prevalence of abnormal lung function and its associated factors among patients recovering from COVID-19 is crucial for enhancing post-COVID care strategies. This study primarily aimed to determine the prevalence and types of spirometry abnormalities among post-COVID-19 patients in Malaysia, with a secondary objective of identifying its associated factors. Conducted at the COVID-19 Research Clinic, Faculty of Medicine, University Technology MARA, from March 2021 to December 2022, this study included patients at least three months post-discharge from hospitals following moderate-to-critical COVID-19. Of 408 patients studied, abnormal spirometry was found in 46.8%, with 28.4% exhibiting a restrictive pattern, 17.4% showing preserved ratio impaired spirometry (PRISm), and 1.0% displaying an obstructive pattern. Factors independently associated with abnormal spirometry included consolidation on chest X-ray (OR 8.1, 95% CI 1.75-37.42, p = 0.008), underlying cardiovascular disease (OR 3.5, 95% CI 1.19-10.47, p = 0.023), ground-glass opacity on chest X-ray (OR 2.6, 95% CI 1.52-4.30, p < 0.001), and oxygen desaturation during the 6-min walk test (OR 1.9, 95% CI 1.20-3.06, p = 0.007). This study highlights that patients recovering from moderate-to-critical COVID-19 often exhibit abnormal spirometry, notably a restrictive pattern and PRISm. Routine spirometry screening for high-risk patients is recommended., (© 2024. The Author(s).)

Context.—: Breast pathology reports include many important details to guide clinical management. Reports with missing critical data elements are commonly seen in non-subspecialized pathology practices. The use of synoptic templates has been shown to improve pathology reports. Although synoptic templates are readily available by professional societies, many are not tailored to low-resource settings., Objective.—: To perform an assessment of current breast pathology reporting at 3 referral hospitals in sub-Saharan Africa and design a locally adapted breast cancer synoptic template., Design.—: We conducted semi-structured interviews with key stakeholders involved in breast cancer care including pathologists, radiologists, oncologists, and surgeons from Nigeria, Tanzania, and Mozambique. Moreover, each stakeholder reviewed a preliminary synoptic template that was compiled by using templates from the College of American Pathologists, Royal College of Pathologists, and International Collaboration on Cancer Reporting, and was asked to score each data element as essential, optional, or exclude. A locally adapted synoptic template was then designed from the needs assessment. Using the adapted templates, a retrospective review of breast cancer pathology reports from 2020 to 2022 was conducted to determine the completeness of reports at the 3 institutions., Results.—: A total of 17 physicians were interviewed. Review of pathology reports revealed that none of the reports across all 3 sites contained all data elements considered essential by local physicians., Conclusions.—: There is an urgent need to improve breast pathology reporting in sub-Saharan Africa. Development and implementation of synoptic templates in collaboration with key stakeholders has the potential to improve pathology reporting practices in low-resource settings., (© 2024 College of American Pathologists.)

Context.—: Rapid onsite evaluation (ROSE) is critical in determining sample adequacy and triaging cytology samples. Although fine-needle aspiration biopsy (FNAB) is the primary method of initial tissue sampling in Tanzania, ROSE is not practiced., Objective.—: To investigate the performance of ROSE in determining cellular adequacy and providing preliminary diagnoses in breast FNAB in a low-resource setting., Design.—: Patients with breast masses were recruited prospectively from the FNAB clinic at Muhimbili National Hospital. Each FNAB was evaluated by ROSE for overall specimen adequacy, cellularity, and preliminary diagnosis. The preliminary interpretation was compared to the final cytologic diagnosis and histologic diagnosis, when available., Results.—: Fifty FNAB cases were evaluated, and all were adequate for diagnosis on ROSE and final interpretation. Overall percentage of agreement (OPA) between preliminary and final cytologic diagnosis was 84%, positive percentage of agreement (PPA) was 33%, and negative percentage of agreement (NPA) was 100% (κ = 0.4, P < .001). Twenty-one cases had correlating surgical resections. OPA between preliminary cytologic and histologic diagnoses was 67%, PPA was 22%, and NPA was 100% (κ = 0.2, P = .09). OPA between final cytologic and histologic diagnoses was 95%, PPA was 89%, and NPA was 100% (κ = 0.9, P = <.001)., Conclusions.—: False-positive rates of ROSE diagnoses for breast FNAB are low. While preliminary cytologic diagnoses had a high false-negative rate, final cytologic diagnoses had overall high concordance with histologic diagnoses. Therefore, the role of ROSE for preliminary diagnosis should be considered carefully in low-resource settings, and it may need to be paired with additional interventions to improve pathologic diagnosis., (© 2024 College of American Pathologists.)

Introduction: Malaysia entered the transition to the endemic phase of Coronavirus 2019 (COVID-19) on 1st April 2022. This study aims to determine the public's willingness to perform COVID-19 self-testing. Factors that influenced their willingness were also assessed., Methods: A nationwide, cross-sectional, and population-based study was conducted online in Malaysia from 28th April 2023 to 4th June 2023. Individuals aged 18 years and above were enrolled through the snowball sampling method. Data were analyzed by using the Chi-Square test, independent t -test, and binary logistic regression., Results: One thousand four hundred fifty-three responses were included in the analysis. Of these respondents, 89.3% were willing, 4.1% were reluctant, and 6.6% remained hesitant to perform COVID-19 self-testing, The common reasons given by those willing to perform COVID-19 self-testing included being able to self-isolate (99.0%) and seek treatment (96.3%) earlier if tested positive. The common reasons against COVID-19 self-testing included the belief that COVID-19 is equivalent to the common flu (91.7%) and having received the COVID-19 vaccine (78.3%). The isolation policy for COVID-19 was the most significant consideration for those who were still hesitant (85.4%). Women [adjusted odds ratios (OR): 2.1, 95% confidence intervals (95% CI): 1.44-3.00, p < 0.001], individuals with tertiary education (OR: 2.1, 95% CI: 1.32-3.26, p = 0.002), those vaccinated against COVID-19 (OR: 8.1, 95% CI: 2.63-24.82, p < 0.001), and individuals with prior experience of COVID-19 self-testing (OR: 4.2, 95% CI: 2.84-6.12, p < 0.001) showed a significantly higher willingness to engage in COVID-19 self-testing., Conclusion: The public exhibited a high willingness to perform COVID-19 self-testing during the transition to the endemic phase in Malaysia. Future strategies to promote COVID-19 self-testing uptake in Malaysia should focus on vulnerable groups, address the common concerns among those hesitant and reluctant, and highlight the advantages of COVID-19 self-testing., Competing Interests: The authors declare no potential conflicts of interest in respect to the finance, research, authorship, and publication of this article., (© 2023 Ng et al.)

Background: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC., Methods: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA)., Results: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort., Conclusions: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites., Impact: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date., (©2023 American Association for Cancer Research.)

Introduction: Phantoms and simulators are widely accepted methods to gain valuable experience and confidence for inexperienced trainees prior to seeing their patient and for refining their skills. A phantom model that is durable, simple, and inexpensive to produce and use would be ideal to train practitioners in ultrasound-guided fine-needle aspiration biopsy (USFNA) technique., Materials and Methods: In this study, we systematically compared several low-cost phantom models including gelatin, extra firm tofu, canned cooked pork, ballistics gel, and chicken breast for their haptic properties, echogenicity, teaching utility, and overall performance based on a Likert scale (1-5; 5 = best). Nine cytopathologists and cytopathology fellows who perform FNA regularly evaluated these models and completed the survey., Results: The gelatin phantom, with a gelatin to water ratio of 1:8 by weight, was found to be the best for USFNA practice and overall performance, followed by the 1:10 gelatin phantom. Tofu and chicken breast phantoms were also good low-cost alternatives that needed only a few minutes of total preparation time., Conclusions: Low-cost, homemade phantoms can serve as excellent alternatives to commercial phantoms for practicing and teaching USFNA., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Management strategies of chronic obstructive pulmonary disease (COPD) need to be tailored to the forced expiratory volume in one second (FEV 1) , exacerbations, and patient-reported outcomes (PROs) of individual patients. In this study, we analyzed the association and correlation between the FEV 1 , exacerbations, and PROs of patients with stable COPD., Methods: This was a post-hoc analysis of pooled data from two cross-sectional studies that were previously conducted in Malaysia from 2017 to 2019, the results of which had been published separately. The parameters measured included post-bronchodilator FEV 1 (PB-FEV 1 ), exacerbations, and scores of modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). Descriptive, association, and correlation statistics were used., Results: Three hundred seventy-four patients were included in the analysis. The PB-FEV 1 predicted was < 30% in 85 (22.7%), 30-49% in 142 (38.0%), 50-79% in 111 (29.7%), and ≥ 80% in 36 (9.6%) patients. Patients with PB-FEV 1  < 30% predicted had significantly more COPD exacerbations than those with PB-FEV 1 30-49% predicted (p < 0.001), 50-79% predicted (p < 0.001), and ≥ 80% predicted (p = 0.002). The scores of mMRC, CAT, and SGRQ-c were not significantly higher in patients with more severe airflow limitation based on PB-FEV 1 (p = 0.121-0.271). The PB-FEV 1 predicted had significant weak negative correlations with exacerbations (r = - 0.182, p < 0.001), mMRC (r = - 0.121, p = 0.020), and SGRQ-c scores (r = - 0.114, p = 0.028). There was a moderate positive correlation between COPD exacerbations and scores of mMRC, CAT, and SGRQ-c (r = 0.407-0.482, all p < 0.001). There were significant strong positive correlations between mMRC score with CAT (r = 0.727) and SGRQ-c scores (r = 0.847), and CAT score with SGRQ-c score (r = 0.851) (all p < 0.001)., Conclusions: In COPD patients, different severity of airflow limitation was not associated with significant differences in the mMRC, CAT, and SGRQ-c scores. Exacerbations were significantly more frequent in patients with very severe airflow limitation only. The correlation between airflow limitation with exacerbations, mMRC, and SGRQ-c was weak., (© 2023. The Author(s).)

Urinary cytology is indispensable both for the evaluation of gross hematuria and surveillance of patients with urothelial neoplasms. A positive urine cytology usually indicates the presence of urothelial carcinoma somewhere in the urinary tract. However, in women, it may also signal urothelial carcinoma involvement of the lower gynecologic tract or be the presenting sign for a primary cancer of the lower gynecologic tract or rectum. Guidelines for the evaluation of women with a positive cytology and normal urinary tract are lacking. We present a review of the current literature with case scenarios to bring clinicians attention to this diagnostic dilemma., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context.—: The incidence of human epidermal growth factor receptor 2 (HER2) positivity in gastric cancers differs widely across various populations and is unknown in many low-resource settings., Objective.—: To evaluate the rates of HER2 positivity in gastric and gastroesophageal adenocarcinoma at a national referral hospital in East Africa. We also assessed the association between HER2 overexpression and patient clinicopathologic characteristics., Design.—: A retrospective review of cases diagnosed as either gastric or gastroesophageal adenocarcinoma between 2013 and 2017 was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Of 1205 specimens meeting inclusion criteria, stratified random sampling was conducted to select 150 cases for HER2 immunohistochemistry and clinicopathologic analysis., Results.—: The median age of patients was 56.5 years, with 65.3% (98 of 150) of the cohort composed of male patients, and 34.7% (52 of 150) of female patients. HER2 overexpression was identified in 6.0% (9 of 150) of cases. Approximately half of the tumors (51.3%; 77 of 150) were intestinal-type gastric adenocarcinoma, and 36.0% (54 of 150) were moderately differentiated. Intestinal-type (P = .01) and well-differentiated tumors (P = .001) were associated with HER2 overexpression., Conclusions.—: HER2 overexpression was primarily seen in intestinal-type and well-differentiated tumors. Therefore, prioritizing HER2 testing for patients with intestinal-type, well-differentiated, or moderately differentiated gastric and gastroesophageal adenocarcinomas may be appropriate in Tanzania in efforts to allocate testing for patients who are most likely to benefit from trastuzumab therapy., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2022 College of American Pathologists.)

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients., (© 2022 UICC.)

Introduction: Although erectile dysfunction (ED) is one of known long-term complications among male lymphoma survivors, it is not commonly reported, particularly in Southeast Asia. This study aimed to determine the prevalence of ED in lymphoma survivors in Malaysia and its association with anxiety and depression, and effects on quality of life., Methods: This was a cross-sectional study conducted at a tertiary hospital in Malaysia. Patients were all male lymphoma survivors. The self-administered International Index of Erectile Function questionnaire was used to screen for ED. The Hospital Anxiety and Depression Score questionnaire was used to assess for anxiety and depression, and quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire., Results: Overall, 106 patients were recruited. Mean age was 55.7 years, with 61.3% of patients aged above 50 years. Only 67.0% of patients were sexually active and 81.7% of these reported the presence of ED, with only 4.2% having severe ED. Prevalence of ED among younger patients (age ≤50 years old) was 64.5%.The most common reason given by patients who were not sexually active was fatigue. Age was the only factor found to be associated with ED (p <0.005) and severity of ED increased with age. There was no association between ED and psychological stress or quality of life., Conclusion: Prevalence of ED and absence of sexual activity in lymphoma survivors was high. This should serve as a reminder to the treating clinician to offer early treatment and counselling., Competing Interests: None

Background: The initiation of a new drug, for instance, the coronavirus disease 2019 (COVID-19) vaccine in children could be a source of major concern for parents. This study aims to determine the willingness of parents in Malaysia to vaccinate their children younger than 12 years against COVID-19., Methods: An online cross-sectional survey was conducted nationwide in Malaysia from August 29, 2021, to October 17, 2021. Parents with children younger than 12 years were enrolled via the snowball sampling method., Results: The analysis included data from 3,528 parents (79.5%) of the 4,438 survey responses received. Of these parents, 2,598 (73.6%) were willing, 486 (13.8%) were not willing, and 444 (12.6%) were still hesitant to vaccinate their children against COVID-19. Single parents (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.32-3.04; P = 0.001), parents with secondary or lower education (OR, 1.5; 95% CI, 1.21-1.96; P < 0.001), healthcare workers (OR, 1.7; 95% CI, 1.34-2.26; P < 0.001), parents who had significant contact with COVID-19 (OR, 1.3; 95% CI, 1.09-1.63; P = 0.006), and parents who had been vaccinated against COVID-19 (OR, 15.4; 95% CI, 9.76-24.33; P < 0.001) were found more willing to immunize their children. The common reasons for vaccination given by parents who were willing to immunize their children include protection of children (99.4%), protection of other family members (99.3%), and effectiveness (98.2%). The common reasons against vaccination given by parents who were not willing to immunize their children were uncertainty about the new vaccine (96.1%), concerns about vaccine contents (93.2%), limited vaccine information from physicians (82.3%), and the belief of vaccine was unsafe (79.8%)., Conclusions: In this study, nearly three-quarters of parents were willing to vaccinate their children younger than 12 years against COVID-19. The parents' history of COVID-19 vaccination was the strongest independent predictor of their willingness to vaccinate their children. Therefore, future health education for the COVID-19 vaccine should focus on parents who are prone to vaccine refusal or hesitation, address the common reasons for vaccine refusal, and highlight the vaccine's benefits., (© 2022. The Author(s).)

Purpose: A different pattern of mental health issues was reported during the later stage of the COVID-19 pandemic; however, few studies have examined Malaysians' knowledge, attitudes, and practices (KAP) prevalent during this time., Patients and Methods: A nationwide online cross-sectional study was conducted in Malaysia from June 1, 2021 to June 14, 2021, ie, 18-months from the first reported COVID-19 case in the country. Citizens aged 18 years and above were recruited by means of the snowball sampling method. ANOVA, Pearson correlation, and linear regression tests were used., Results: Of the 2168 respondents, most were young adults (62.7%), females (62.4%), tertiary educated individuals (84%), non-health care workers (85.9%), and individuals who knew someone diagnosed with COVID-19 (75.2%). The mean score for knowledge was 10.0 ± 1.52 (maximum score = 12); correct response rate for each question ranged from 54.2% to 99%. The mean score in terms of attitude was 1.3 ± 0.85 (maximum score = 2); 68.7% respondents agreed that control over COVID-19 would finally be achieved; and 62.3% believed that Malaysia could conquer COVID-19. The mean score for practices was 5.1 ± 1.10 (maximum score = 6); 81.5%, 88.1%, and 74.1% respondents avoided crowded places, confined spaces, and conversations in close physical proximity, respectively. Furthermore, 94.2% wore masks when leaving home; 89.0% practiced hand hygiene; and 83.8% adhering to COVID-19 warnings. Small but significant correlations were found between knowledge and attitude ( r = 0.078, p < 0.001) as well as between knowledge and practices ( r = 0.070, p = 0.001)., Conclusion: Malaysians exhibited sound knowledge but negative attitudes and inadequate practices pertaining to COVID-19 during the pandemic's later stage. At this phase, unlike at the early stage, the public's sound knowledge ensured little improvement in their attitudes and practices. Therefore, health education at the later pandemic stage should focus on promoting positive attitudes and developing better practices., Competing Interests: The authors declare no conflicts of interest for this work and no potential conflicts of interest in respect to the research, authorship, and publication of this article., (© 2022 Chai et al.)

Background: Patients with haematological cancer had considerable symptom burden, in which fatigue was the most prevalent. Almost 70% of haematological cancer patients reported fatigue., Methods: We conducted a parallel-group, non-blinded, randomised control trial at the haemato-oncology unit of University Malaya Medical Centre, from 1st October 2019 to 31st May 2020. Patients included were ≥ 18 years, had histopathological diagnosis of haematological cancer, and fatigue score of ≥4 based on the fatigue subscale of Edmonton Symptom Assessment System (ESAS). Patients allocated to the intervention group received standard care plus a guided 30-min mindful breathing session, while those in control group received standard care. The study outcomes include fatigue severity according to the fatigue subscale of ESAS, visual analogue scale of 0 - 10, and Functional Assessment of Chronic Illness Therapy Fatigue Scale Version 4, at minute 0 and minute 30., Results: Of 197 patients screened, 80 were eligible and they were equally randomised into 30-min mindful breathing versus standard care. Lymphoma (58.9%) was the commonest haematological malignancy, followed by multiple myeloma (13.8%), acute leukaemia (11.3%), myeloproliferative neoplasm (6.3%), chronic leukaemia (5.0%) and myelodysplastic syndrome (5.0%). There was no difference in the demographic and clinical characteristics between the 2 groups. At minute 0, both arms of patients had similar ESAS-fatigue score (median, 5) and FACIT-fatigue score (mean ± SD, 24.7 ± 10.6 for intervention group versus 24.7 ± 9.7 for control group). At minute 30, intervention group had lower ESAS-fatigue score (median, 3 versus 5) and FACIT-fatigue score (mean ± SD, 17.1 ± 10.5 versus 24.8 ± 11.3) compared to control group. Both the ESAS-fatigue score reduction (median, - 2 versus 0, p = 0.002) and FACIT-fatigue score reduction (mean ± SD, - 6.7 versus + 0.8; p < 0.001) for the intervention group were statistically significant. The calculated effect size Cohen's d was 1.4 for between-group comparison of differences in total FACIT-fatigue score., Conclusions: Our results provide evidence that a single session of 30-min mindful breathing was effective in reducing fatigue in haematological cancer patients. On top of all the currently available methods, 30-min mindful breathing can prove a valuable addition., Trial Registration: NCT05029024 , date of registration 15th August 2021. (Retrospectively registered)., (© 2021. The Author(s).)

Background: Prior studies evaluating thyroid fine needle aspiration biopsies (FNABs) have limited the calculation of risk of malignancy (ROM) to cytologic specimens with corresponding histologic specimens, and clinical follow-up for those patients who do not undergo immediate surgery has been largely disregarded. Moreover, there is marked variability in how researchers have approached thyroid FNAB statistical analyses. This study addresses the urgent need for information from a large cohort of patients with long-term clinical follow-up to more accurately determine the performance of thyroid FNAB and ROM for each diagnostic category. Methods: A retrospective review of the University of California, San Francisco (UCSF), pathology database for thyroid FNABs from January 1, 1997, to December 31, 2004, was performed. Diagnoses were coded using the 2017 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and patients were matched to both the UCSF cancer registry and California Cancer Registry. Data were analyzed using the Kaplan-Meier method, and stratified by TBSRTC diagnostic category. Kaplan-Meier curves were used to estimate incidence rates of malignancy, stratified by FNAB category. Cox proportional hazards models were used to determine the instantaneous ROM. Results: Initial FNABs from 2207 patients were included. Median follow-up period after the first thyroid FNAB was 13.9 years (range: 10.5-18.4 years). During follow-up, there were 279 confirmed diagnoses of thyroid malignancy. Estimates derived from Kaplan-Meier curves demonstrated that the risk of having a thyroid malignancy was low for nondiagnostic and benign categories, intermediate for atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), AUS/FLUS combined, and follicular neoplasm, and high for suspicious and malignant categories. A total of 52/1575 false-negative cases (3.2%) were identified. Excluding papillary microcarcinomas, the false-negative rate was 1.5% (23/1575). No patients with a false-negative diagnosis died of thyroid cancer during the follow-up period. Conclusions: Asymptomatic patients with low-risk clinical and radiologic features and initially benign or unsatisfactory biopsy are unlikely to develop thyroid malignancy and highly unlikely to die of thyroid cancer. FNAB is highly accurate in detecting malignancy. Additional studies evaluating similar large data sets after the adoption of TBSRTC and the integration of molecular testing are needed.

Context.—: Breast cancer biomarker assessment is critical in determining treatment and prognosis. In Tanzania, immunohistochemistry (IHC) is limited to surgical specimens and core biopsies. However, performing IHC on fine-needle aspiration biopsy cell blocks would offer numerous advantages., Objective.—: To compare the performance between estrogen receptor (ER) IHC performed at Muhimbili National Hospital (MNH) in Tanzania and ER IHC performed at University of California, San Francisco (UCSF), to demonstrate feasibility of performing IHC using cell blocks in Tanzania., Design.—: Patients with breast masses were recruited prospectively from the fine-needle aspiration biopsy clinic at MNH. Estrogen receptor IHC results on cell blocks, performed at both MNH and UCSF, and corresponding tissue blocks, performed at MNH, were compared to determine concordance., Results.—: Eighty-six cell blocks were evaluated by ER IHC at MNH, with 41 of 86 (47.7%) positive and 45 of 86 (52.3%) negative. Among 65 UCSF and MNH cell block pairs, overall ER IHC concordance was 93.8% (61 of 65) and positive concordance was 93.5% (29 of 31) (κ = 0.88, P > .99). Among 43 paired UCSF cell blocks and MNH tissue blocks, overall ER IHC concordance was 88.3% (38 of 43) and positive concordance was 90.5% (19 of 21) (κ = 0.77, P > .99). We compared 62 MNH cell block and tissue block pairs. Overall ER IHC concordance was 90.3% and positive concordance was 87.9% (κ = 0.81, P = .69)., Conclusions.—: Pairwise comparisons between ER IHC at MNH, on cell blocks and tissue blocks, with ER IHC at UCSF on cell blocks showed excellent concordance. We demonstrate that ER IHC on fine-needle aspiration biopsy specimens can be implemented in resource-constrained settings.

Background and Objectives: The treatment paradigm for advanced hypopharyngeal cancer has shifted from surgical approaches to organ preservation. However, recent studies indicated that surgical approaches may be associated with better survival rates. This study aimed to conduct a head-to-head comparison of survival outcomes and complications with surgical versus nonsurgical approaches using a nationwide database., Methods: Using a nationwide data set, we gathered 2196 propensity score-matched patients with stage III/IVa hypopharyngeal cancer. We compared survival rates and complications among patients with surgical and nonsurgical cancer treatment., Results: Patients with stage III and IVa hypopharyngeal cancer who underwent initial surgery had significantly better 5-year overall survival and disease-free survival rates compared to their nonsurgical counterparts. There were no significant differences in long-term complications with regard to swallowing., Conclusions: These results suggest that patients who underwent initial surgery for advanced hypopharyngeal cancers had better survival rates and equivalent long-term function., (© 2021 Wiley Periodicals LLC.)

Background: Coronavirus 2019 disease (COVID-19) is a highly infectious disease prompting extreme containment measures, including lockdown, travel restrictions, social distancing, and stringent personal hygiene. This study investigates the depression level and coping responses toward the lockdown, referred as the movement control order (MCO) during COVID-19 pandemic in Malaysia and its impact on quality of life., Method: This cross-sectional study was conducted from April to May 2020. The outcomes were assessed using the Depression, Anxiety and Stress Scale-21, Coping Orientation to Problems Experienced Inventory, and World Health Organisation Quality of Life-BREF Scale (WHOQOL-BREF) in both English and validated Malay versions., Results: Mild-to-severe depression was found in 28.2% (n = 149) of the 528 respondents. Respondents with mild-to-severe depression were significantly younger (33.09 ± 10.08 versus 36.79 ± 12.47 years), without partner (71.8% versus 45.6%), lived in the red zone (85.9% versus 71.0%), and had lower household income as defined in the category of B40 (51.7% versus 39.3%) compared to those without depression (all p < 0.01). The avoidant coping score was significantly higher (25.43 ± 5.69 versus 20.78 ± 5.65), while the religious coping score was significantly lower (5.10 ± 2.07 versus 5.94 ± 2.11) among those with mild-to-severe depression compared to those without depression (both p < 0.001). Respondents with mild-to-severe depression also had significantly lower mean score in each domain of WHOQOL-BREF compare to those without depression [(physical health, 13.63 ± 2.66 versus 16.20 ± 2.11), (psychological, 12.5 ± 2.79 versus 16.10 ± 2.14), (social relationships, 12.17 ± 3.49 versus 15.28 ± 2.93), environment (14.50 ± 2.39 versus 16.21 ± 2.14), all p < 0.001] after controlling for age, marital status, zone, household income, and coping scores., Conclusion: COVID-19 lockdown had adverse mental health effects. Our study highlighted that approximately one in three individual experienced mild-to-severe depression during the nationwide MCO. The varied impact of the pandemic on mental health could be due to different population characteristics and coping strategies used. Identifying those at higher risk to develop depression during MCO for COVID-19 pandemic could help mental healthcare service providers to plan services for those susceptible, thereby mitigating the pandemic's effect on quality of life.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

Heart failure is the leading cause of morbidity and mortality worldwide. Standard treatment for heart failure includes pharmacotherapy and cardiac device implants. However, supportive approaches in managing dyspnea in heart failure are limited. This study aimed to test the efficacy of 20-minute mindful breathing in reducing dyspnea among patients admitted for acute decompensated heart failure. We conducted a parallel-group, non-blinded, randomized controlled trial of a single session of 20-minute mindful breathing plus standard care versus standard care alone among patients admitted for moderate to severe dyspnea due to acute decompensated heart failure, using the dyspnea score based on the Edmonton Symptom Assessment System (ESAS), at the Cardiology Unit of University Malaya Medical Centre in Malaysia. Thirty participants were randomly assigned to a single session of 20-minute mindful breathing plus standard care (n = 15) or standard care alone (n = 15), with no difference in their demographic and clinical characteristics. There was statistically significant reduction in dyspnea in the intervention group compared to the control group at minute 20 (U = 49.5, n 1 = 15, n 2 =15, median reduction in ESAS dyspnea score 1 = 2, median reduction in ESAS dyspnea score 2 = 0, mean rank 1 = 11.30, mean rank 2 = 19.70, z = -2.692, r = 0.4, P = 0.007). Our results provided evidence that a single session of 20-minute mindful breathing was efficacious in reducing dyspnea for patients admitted for acute decompensated heart failure.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: Clinical breast examination (CBE) is one of the most common methods used for early detection of breast cancer in low- and middle-income countries. CBE alone is limited by lack of specificity and may result in unnecessary diagnostic procedures. We evaluated the feasibility of integrating CBE, fine-needle aspiration biopsy (FNAB), and rapid on-site evaluation (ROSE) in triaging palpable breast masses for specialized cancer care., Materials and Methods: An intensive breast cancer screening event was conducted at a national trade fair by a multidisciplinary team of care providers targeting a healthy population in Dar es Salaam, Tanzania. All adults age ≥ 18 years were invited to participate. CBE was performed by oncologists and/or pathologists. FNAB was performed by a pathologist on palpable masses that were then categorized as benign, indeterminate, or suspicious for malignancy or definitively malignant based on ROSE., Results: A total of 208 individuals (207 females, one male; median age, 36 years; range, 18-68 years) were screened. Most (90.8%, 189 of 208) had normal findings, whereas 7.2% (15 of 208), 1% (2 of 208), and 1% (2 of 208) had a palpable mass, breast pain, and nipple discharge, respectively. Two participants had lesions too small for palpation-guided biopsy and clinically consistent with fibroadenomas; the participants were counseled, and observation was recommended. FNAB was performed on 13 breast masses, with 9 of 13 (69%) categorized as benign and 4 of 13 (31%) suspicious for malignancy. Final cytopathologic review of referred patients confirmed one case to be breast adenocarcinoma, one was suggestive of fibroadenoma, and two showed inflammations., Conclusion: Integration of CBE with ROSE and FNAB was feasible in a breast cancer screening program in Tanzania. In settings with constrained resources for cancer care, this may be an effective method for triaging patients with breast masses.

Background: The use of warfarin in patients with non-valvular atrial fibrillation (NVAF) can be challenging. In this study, we evaluate the time in therapeutic range (TTR), health-related quality of life (HRQoL) and treatment satisfaction of patients on long-term warfarin for NVAF. The HRQoL and treatment satisfaction were compared based on the TTR., Methods: A cross-sectional study was conducted among patients on warfarin for NVAF who attended the anticoagulant clinic of a tertiary cardiology referral center in Sarawak from 1st June 2018 to 31st May 2019. Patients' TTR was calculated by using Rosendaal technique, while their HRQoL and treatment satisfaction were assessed by using Short Form 12 Health Survey version 2 (SF12v2) and Duke Anticoagulant Satisfaction Scale (DASS), respectively., Results: A total of 300 patients were included, with mean TTR score of 47.0 ± 17.3%. The physical component summary (PCS) and mental component summary (MCS) score of SF-12v2 were 47.0 ± 9.0 and 53.5 ± 9.6, respectively. The total score for DASS was 55.2 ± 21.3, while the score for limitations (L), hassles and burdens (H&B) and positive psychological impacts (PPI) were 18.0 ± 10.0, 15.6 ± 9.1 and 21.6 ± 5.9, respectively. Seventy-three (24.3%) patients had good TTR (≥ 60%), with mean of 70.2 ± 8.7%; while 227 (75.5%) patients with poor TTR had significantly lower mean of 39.5 ± 11.9% (p = 0.006). There was no significant difference in the score of PCS (p = 0.150), MCS (p = 0.919) and each domain of SF-12v2 (p = 0.184-0.684) between good and poor TTR, except for social functioning (p = 0.019). The total DASS score was also not significantly different between group (p = 0.779). Similar non-significant difference was also reported in all the DASS sub dimensions (p = 0.502-0.699)., Conclusions: Majority of the patients on long-term warfarin for NVAF in the current study have poor TTR. Their HRQoL and treatment satisfaction are independent of their TTR. Achieving a good TTR do not compromise the HRQoL and treatment satisfaction. Therefore, appropriate measures should be taken to optimise INR control, failing which direct oral anticoagulant therapy should be considered.

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.

Background: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes., Methods: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c)., Results: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p <  0.001). There were significantly more patients with mMRC 2-4 among AE (68.6%) (p <  0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p <  0.001) and SGRQ-c (both p <  0.001) scores than those with ACO and NON-AE. Patients with ACO had significantly higher total CAT and SGRQ-c (both p <  0.001) scores than those with NON-AE. AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p <  0.001), and ACO [(p = 0.003-0.016; p = < 0.001-0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001-0.040; p <  0.001) except CAT 2 and activity components of SGRQ-c., Conclusions: The HRQoL of COPD patients was significantly different across different COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3-11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.

Introduction: Fine needle aspiration biopsies (FNABs) have become increasingly important in the assessment of infectious diseases. We assess the ability of cytopathology to predict the presence of a pathogen and review how often neoplasia occurs concurrently with infection., Materials and Methods: A 3-year retrospective review of FNABs with concurrent culture results was performed at the Zuckerberg San Francisco General Hospital and Trauma Center. Rapid onsite evaluation was performed for all cases by a pathologist. The results of the special and immunohistochemical stains and polymerase chain reaction testing were correlated, when available., Results: A total of 231 samples from 11 different tissue sites were submitted for microbial culture, of which 49 (21%) were positive for pathogenic organisms. Only 2 false-negative cases by cytology were found in immunosuppressed patients. A total of 38 patients had a diagnosis of neoplasia, with 2 (5%) having concurrent infection. Overall, the sensitivity and specificity of cytology in predicting the presence of infection was 96% (95% confidence interval, 86%-100%) and 42% (95% confidence interval, 34%-50%), respectively. Molecular testing was performed in 11 cases, 2 of which were positive for Mycobacterium tuberculosis complex and had cytologic findings of necrosis. Polymerase chain reaction and other ancillary tests were unable to further characterize 2 cases with acid-fast bacilli., Conclusions: Our study has shown that FNABs have high sensitivity in detecting infection and that negative cytology findings will correlate with a negative infectious workup. Although infection in the setting of neoplasia is uncommon, it should be considered if clinical data are available to suggest infection., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Fine-needle aspiration biopsy (FNAB) is a minimally invasive biopsy technique and an important tool for diagnosing infectious diseases. Rapid onsite evaluation allows for triage for ancillary testing, including microbiologic cultures. We aimed to determine the etiology of granulomatous inflammation diagnosed by FNAB by correlating with culture results and clinical history., Materials and Methods: A 16-year retrospective review of cases diagnosed as "granulomatous inflammation" or "granuloma" was performed at the Departments of Pathology at the Zuckerberg San Francisco General Hospital and Trauma Center and University of California, San Francisco., Results: A total of 339 FNABs diagnosed as granulomatous inflammation were identified. Necrotizing granulomatous inflammation was present in 117 of 339 cases (34.5%) and non-necrotizing granulomatous inflammation was present in 222 of 339 cases (65.5%). A pathogen was detected in 100 of 339 (29.5%) FNABs by either cytomorphology, special stains, or culture, or a combination of more than one test. Of the 100 pathogen-positive cases, necrotizing granulomatous inflammation was seen in 50 of 100 (50%) and non-necrotizing granulomatous inflammation was identified in 50 of 100 (50%) cases. Culture results were available in 239 cases and positive in 70 (29%). Positive culture results included 40 of 239 (17%) cases with Mycobacterium tuberculosis complex, 15 of 239 (6.3%) with atypical mycobacterial species, 6 of 239 (3%) with Coccidioides immitis, 2 of 239 (<1%) with Histoplasma capsulatum, and 2 of 239 with Talaromyces marneffei (<1%)., Conclusions: Granulomatous inflammation is a nonspecific finding and suggests a broad range of disease processes, ranging from infection to malignancy. FNAB is an excellent minimally invasive technique that allows for ancillary testing critical for definitive diagnosis., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction and Aim: Patient quality of life (QOL) while on long-term oral anticoagulant therapy has been receiving greater attention in recent years due to the increase in life expectancy brought about by advances in medical care. This study aimed to compare the QOL, treatment satisfaction, hospitalization and bleeding rate in patients on long-term warfarin versus direct oral anticoagulants (DOAC)., Methods: This was a cross-sectional study of patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) on long-term anticoagulant therapy attending the cardiology clinic and anticoagulation clinic of the University Malaya Medical Centre from July 1, 2016, to June 30, 2018. Patient QOL was assessed by using the Short Form 12 Health Survey (SF12), while treatment satisfaction was assessed by using the Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2)., Results: A total of 208 patients were recruited; 52.4% received warfarin and 47.6% received DOAC. There was no significant difference in QOL between warfarin and DOAC based on SF12 (physical QOL, P =0.083; mental QOL, P =0.665). Nevertheless, patients in the DOAC group were significantly more satisfied with their treatment compared to the warfarin group based on PACT-Q2 ( P =0.004). The hospitalisation rate was significantly higher in the warfarin group than the DOAC group (15.6% versus 3.0%, P =0.002). Clinically relevant minor bleeds and severe bleeding events were non-significantly higher in the warfarin group than the DOAC group (66.7% versus 40.0%, P =0.069)., Conclusion: Compared to warfarin, treatment of NVAF and VTE with DOAC showed comparable QOL, higher treatment satisfaction, lesser hospitalization, and a non-significant trend toward fewer bleeding episodes., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Ng et al.)

Introduction: The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations. In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes., Methods: This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018. Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD (SGRQ-c)., Results: Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS). The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes ( P <0.001). Patients who were AE CB had significantly higher total CAT score than those with ACOS ( P =0.033), AE NON-CB ( P =0.001), and NON-AE ( P <0.001). Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB ( P =0.001) and NON-AE ( P <0.001). However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS ( P =0.187). There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them., Conclusion: Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components. Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques., Methods: A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants., Results: Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears., Conclusion: An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

Purpose: The survival for patients with lymphoma has improved over the past decades with the introduction of novel agents. Quality of life of these survivors is now being studied with focus on minimising the late effects of chemotherapy and improving psychosocial support. This study aims to determine the prevalence of anxiety and depression of lymphoma survivors and to investigate the possible association between these disorders and quality of life., Methods: Patients with previous diagnosis of lymphoma who remained in remission were recruited from a major hospital in Malaysia. Quality of life of these patients was measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30). Anxiety and depression symptoms were assessed using Hospital Anxiety and Depression scale (HADS)., Results: A total of 156 patients participated in this study. Eighteen percent (18 %) of patients had symptoms of anxiety, and 10 % had symptoms of depression. Patients who had higher depression scores were older, of lower education level and had more than one comorbidity illness. Patients with anxiety were associated with lower overall quality of life (QOL) score, lower emotional and cognitive functioning and complained more of fatigue and insomnia (p < 0.05). Patients who had depression were associated with lower physical functioning and complained more of insomnia (p < 0.05)., Conclusion: It is important for the treating physicians to ensure follow-up of lymphoma survivors for any psychological disorders in order early counseling and support can be provided. This may improve patients' quality of life.

Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues., (Published by Elsevier Inc.)

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Peroxisome proliferator activated receptor-alpha (PPARα) plays a major role in the regulation of lipid and glucose homeostasis, and inflammatory responses. The objectives of the study were to systematically investigate the effects of TNF-α and its regulatory pathway on PPARα expression in HepG2 cells using Real-Time RT-PCR and western blot analysis. Here, TNF-α suppressed PPARα mRNA expression in a dose- and time-dependent manner at the level of gene transcription. Pre-treatment of cells with 10μM of Wedelolactone for 2h was sufficient to restore PPARα expression to basal levels and also affected the expression of PPARα-regulated genes. This study also demonstrated that TNF-α represses PPARα expression by augmenting the activity of canonical NF-κB signalling pathway. This was shown by the abrogation of TNF-α-mediated PPARα down-regulation, after both p65 and p50 were knocked down via siRNA. The IKK contributes to IκBα degradation and mediates inducible phosphorylation of p105 at Ser933. Surprisingly, phosphorylation of p65 at Ser468 and Ser536 were severely abrogated with Wedelolactone inhibition, suggesting that Ser468 and Ser536, but not Ser276, may mediate the TNF-α inhibitory action on PPARα gene expression. These results suggest that TNF-α might, at least in part, suppress PPARα expression through activation of IKK/p50/p105/p65 pathway. Furthermore, phosphorylation of p65 at Ser468 and Ser536 may play a crucial role in the mechanism that limits PPARα production in the human HepG2 cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The only treatment for coeliac disease is lifelong adherence to a rigorous gluten-free diet. The present study aimed to evaluate the influence of coeliac disease on the social aspects of daily life of individuals in the U.S.A., Methods: The present study used a self-administered survey including the standard Quality of Life questionnaire (12-item short-form) with validated disease-specific questions. sas statistical software 2010 (SAS Institute, Cary, NC, U.S.A.) was used to calculate the mean (SD)., Results: Individuals with coeliac disease overall had a low positive health perception. Validated diet and disease-specific questions revealed a significant negative impact on quality of life in social settings. Specifically, the areas of travel, dining out and family life are most affected. The negative impact of diet significantly decreased over time, although it did not resolve for the domains of dining out of the home and travel. Those diagnosed in childhood and maintained on the diet had less of an impact on the quality of life as an adult., Conclusions: Individuals with coeliac disease in the U.S.A. have a diminished quality of life, especially in the social aspects of life., (© 2012 The Authors. Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.)

Background: The only treatment for coeliac disease is lifelong adherence to a gluten-free diet. Several studies have reported nutritional deficiencies in individuals on a gluten-free diet. The present study aimed to determine whether the nutritional profile of gluten-free diet could be improved through the use of alternative grains., Methods: A retrospective review of diet history records by a celiac specialist dietitian were used to establish a 'standard' gluten-free dietary pattern. An 'alternative' gluten-free dietary pattern was developed that substituted naturally gluten-free grains or gluten-free products made from 'alternative' flours (oats, high fibre gluten-free bread and quinoa) in the standard pattern. A paired t-test was performed to identify statistical significance between the 'alternative' and standard gluten-free dietary pattern., Results: Analysis of standard pattern indicated that 38% of meals and snacks contained no grain or starch choice. Of those meals that contained a grain or starch component, rice was the grain chosen 44% of the time. The inclusion of alternative grains or grain products provided a higher nutrient profile compared to the standard gluten-free dietary pattern (P = 0.002). Several nutrients; protein (20.6 g versus 11 g), iron (18.4 mg versus 1.4 mg), calcium (182 mg versus 0 mg) and fibre (12.7 g versus 5 g) were significantly increased by changing the grain or starch component in the dietary pattern. The B vitamin content (riboflavin, niacin and folate) was improved, although this was not statistically significant (P = 0.125)., Discussion: The inclusion of alternative grain-based products increased the nutrient profile of the gluten-free dietary pattern significantly.

Background: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet., Methods: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed., Results: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P

Legionellosis is endemic in Singapore, with sporadic cases reported throughout the year. The absence of outbreak could be due to the low prevalence of the highly pathogenic Pontiac subtype of Legionella pneumophila in the urban environment. Mandatory maintenance of cooling towers and water fountains has been put in place, and the effectiveness of legislation in minimizing the occurrence and risk of outbreak of legionellosis is being evaluated.

During the period 1986 to 1996, a total of 258 sporadic cases of community-acquired legionellosis was reported, giving a mean annual morbidity rate of 0.9 per 100,000 population. Majority of the cases (91.5%) was serologically diagnosed by the indirect fluorescent antibody (IFA) test against Legionella pneumophila based on single sera with a titre of > or = 1:1024. The others were confirmed by a four-fold increase in IFA titre to a minimum of 1:128 (7.4%) and by culture (1.1%). Cases were reported predominantly among males, ethnic Indians, the elderly and those with concurrent medical conditions. The overall case-fatality rate was 14.7%, with the rate significantly higher among those aged > or = 45 years (21%), smokers (20.4%) and those with concurrent medical conditions (22.5%). Seroepidemiological studies among the healthy population based on an IFA titre of > or = 1:32 showed a prevalence of between 10.3% and 21.9%. Of the various occupational groups investigated, high seroprevalence rates were found in foreign construction workers (52.6%) and occupants of a building investigated for an unusual building-related illness (76.1%). Environmental surveillance of Legionella bacteria showed that 36% of cooling towers, 15% to 19% of decorative fountains and waterfalls and 2% of spa pools were positive. The majority (85%) of environmental isolates was identified as Legionella pneumophila: 54.8% of serogroup 1 and 5% of Pontiac subtype.

A total of 80 cooling tower water samples were investigated for legionellae using both cultural and polymerase chain reaction (PCR) methods. PCR was performed with the Perkin Elmer EnviroAmp Legionella kit. Forty-seven samples (58.8%) were found positive by both methods; 29 samples (36.3%) were positive by PCR only, while four samples (5%) showed PCR inhibition despite the adoption of the more stringent sample preparation protocol especially designed to eliminate inhibitors.

The urinary codeine-to-morphine ratios in fifteen volunteers administered codeine tablets at intervals were studied by gas chromatography (GC) and compared with one month's GC results for enzyme multiplied immunoassay technique (EMIT)-screened urine specimens in a mass-screening programme for abuse of opiate drugs, particularly heroin. It appears that when M less than 2 and C/M greater than 0 or when M greater than 2 and C/M greater than 0.5, where C and M are codeine and morphine concentrations in micrograms per 10 ml of urine, codeine consumption has to be presumed.