Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial.

Background: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. Methods: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381). Findings: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms. Interpretation: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients. Funding: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.

Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

OBJECTIVE: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. METHODS: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. RESULTS: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. CONCLUSIONS: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Real world evaluation of kidney failure risk equations in predicting progression from chronic kidney disease to kidney failure in an Australian cohort.

BACKGROUND: Chronic kidney disease progression to kidney failure is diverse, and progression may be different according to genetic aspects and settings of care. We aimed to describe kidney failure risk equation prognostic accuracy in an Australian population. METHODS: A retrospective cohort study was undertaken in a public hospital community-based chronic kidney disease service in Brisbane, Australia, which included a cohort of 406 adult patients with chronic kidney disease Stages 3-4 followed up over 5 years (1/1/13-1/1/18). Risk of progression to kidney failure at baseline using Kidney Failure Risk Equation models with three (eGFR/age/sex), four (add urinary-ACR) and eight variables (add serum-albumin/phosphate/bicarbonate/calcium) at 5 and 2 years were compared to actual patient outcomes. RESULTS: Of 406 patients followed up over 5 years, 71 (17.5%) developed kidney failure, while 112 died before reaching kidney failure. The overall mean difference between observed and predicted risk was 0.51% (p = 0.659), 0.93% (p = 0.602), and - 0.03% (p = 0.967) for the three-, four- and eight-variable models, respectively. There was small improvement in the receiver operating characteristic-area under the curve from three-variable to four-variable models: 0.888 (95%CI = 0.819-0.957) versus 0.916 (95%CI = 0.847-0.985). The eight-variable model showed marginal receiver operating characteristic-area under the curve improvement: 0.916 (95%CI = 0.847-0.985) versus 0.922 (95%CI = 0.853-0.991). The results were similar in predicting 2 year risk of kidney failure. CONCLUSIONS: The kidney failure risk equation accurately predicted progression to kidney failure in an Australian chronic kidney disease population. Younger age, male sex, lower estimated glomerular filtration rate, higher albuminuria, diabetes mellitus, tobacco smoking and non-Caucasian ethnicity were associated with increased risk of kidney failure. Cause-specific cumulative incidence function for progression to kidney failure or death, stratified by chronic kidney disease stage, demonstrated differences within different chronic kidney disease stages, highlighting the interaction between comorbidity and outcome.

Results from a type two hybrid-effectiveness study to implement a preoperative anemia and iron deficiency screening, evaluation, and management pathway.

BACKGROUND: Implementation of pathways to screen surgical patients for preoperative anemia and iron deficiency remains limited. This study sought to measure the impact of a theoretically informed, bespoke change package on improving the uptake of a Preoperative Anemia and Iron Deficiency Screening, Evaluation, and Management Pathway. STUDY DESIGN AND METHODS: Pre-post interventional study using a type two hybrid-effectiveness design evaluated implementation. Four hundred (400) patient medical record reviews provided the dataset (200 pre- and 200-post implementation). The primary outcome measure was compliance with the pathway. Secondary outcome measures (clinical outcomes) were anemia on day of surgery, exposure to a red blood cell (RBC) transfusion, and hospital length of stay. Validated surveys facilitated data collection of implementation measures. Propensity score-adjusted analyses determined the effect of the intervention on clinical outcomes, and a cost analysis determined the economic impact. RESULTS: For the primary outcome, compliance improved significantly post-implementation (Odds Ratio 10.6 [95% CI 4.4-25.5] p < .000). In secondary outcomes, adjusted analyses point estimates showed clinical outcomes were slightly improved for anemia on day of surgery (Odds Ratio 0.792 [95% CI 0.5-1.3] p = .32), RBC transfusion (Odds Ratio 0.86 [95% CI 0.41-1.78] p = .69) and hospital length of stay (Hazard Ratio 0.96 [95% CI 0.77-1.18] p = .67), although these were not statistically significant. Cost savings of $13,340 per patient were realized. Implementation outcomes were favorable for acceptability, appropriateness, and feasibility. CONCLUSION: The change package significantly improved compliance. The absence of a statistically significant change in clinical outcomes may be because the study was powered to detect an improvement in compliance only. Further prospective studies with larger samples are needed. Cost savings of $13,340 per patient were achieved and the change package was viewed favorably.

Pediatric Prediction Model for Low Immunoglobulin G Level Based on Serum Globulin and Illness Status.

Hypogammaglobulinemia is a condition that requires prompt diagnosis and treatment. Unfortunately, serum immunoglobulin (Ig) measurements are not widely accessible in numerous developing countries. Serum globulin is potentially the best candidate for screening of low IgG level (IgGLo) due to its high availability, low cost, and rapid turnover time. However, multiple factors may influence the probability of prediction. Our study aimed to establish a simple prediction model using serum globulin to predict the likelihood of IgGLo in children. For retrospective data of patients who were suspected of having IgGLo, both serum IgG and globulin were simultaneously collected and measured. Potential factors interfering with serum globulin and IgG levels were investigated for their impact using bivariate binary logistic regression. A multivariate binary logistic regression was used to generate a formula and score to predict IgGLo. We obtained 953 samples from 143 pediatric patients. A strong positive correlation between serum globulin and IgG levels was observed (r=0.83, p < 0.001). A screening test model using serum globulin and illness status was constructed to predict IgGLo. The formula for predicting IgGLo was generated as follows; Predicted score = (2 x globulin (g/dl)) - illness condition score (well=0, sick=1). When the score was <4, the patient has the probability of having IgGLo with a sensitivity of 0.78 (0.71, 0.84), a specificity of 0.71 (0.68, 0.74), PPV of 0.34 (0.29, 0.40) and NPV of 0.94 (0.92, 0.96). This formula will be useful as rapid and inexpensive screening tool for early IgGLo detection, particularly in countries/locations where serum IgG measurement is inaccessible.

Factors associated with successful extubation following the first course of systemic dexamethasone in ventilator-dependent preterm infants with or at risk of developing bronchopulmonary dysplasia.

OBJECTIVES: We aimed to identify factors present at the start of an initial course of systemic dexamethasone that would be associated with successful extubation in mechanically ventilated neonates <30 weeks gestational age (GA) with or at risk of developing bronchopulmonary dysplasia (BPD). METHODS: We studied a retrospective cohort of neonates (23+0 -29+6 weeks GA), with or at risk of developing BPD, prescribed their first course of systemic dexamethasone to aid in extubation from mechanical ventilation. The data collected only pertained to the first course of dexamethasone. Neonates given dexamethasone for airway edema were not included. The primary outcome of interest was successful extubation (i.e., extubated within 14 days of starting dexamethasone and remaining extubated for at least 7 days). Binary logistic regression was employed. RESULTS: A total of 287 neonates were included. Each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation (95% CI: 1.122-2.096, p < 0.01). Higher average fraction of inspired oxygen (FiO2 ) requirements in the preceding 24 h resulted in a 0.94 decrease in the odds of successful extubation (p < 0.05) and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation (p < 0.01). CONCLUSIONS: Mechanically ventilated neonates with or at risk of developing BPD, born at <30 week GA and initiated on dexamethasone to facilitate extubation, had a lower likelihood of successful extubation by Day 14 if they had younger GA at birth, and at the time of commencing steroids had higher MAPs and had higher oxygen requirements.

A Theoretically Informed Approach to Support the Implementation of Pre-Operative Anemia and Iron Deficiency Screening, Evaluation, and Management Pathways: Protocol for a Type Two Hybrid-Effectiveness Study.

INTRODUCTION: Blood transfusions are a risk factor for increased morbidity, mortality, and length of hospital stay. Patient blood management guidelines provide guidance to reduce risk and improve patient outcomes. They outline steps to help prevent transfusions and considerations for when deciding to transfuse. One recommendation to prevent unnecessary transfusion is to optimize patients using Pre-operative Anemia and Iron Deficiency Screening, Evaluation and Management Pathways (PAIDSEM-P). The uptake of these recommendations is highly variable, and an effective approach to implementing them in a tailored and context-specific manner remains elusive. METHOD AND DESIGN: A mixed-methods, interventional study, using a type two-hybrid effectiveness-implementation design, will evaluate the impact of a change package to improve the uptake of PAIDSEM-P. The change package consists of the intervention (PAIDSEM-P) supported by theoretically informed implementation strategies. Pre- and post-implementation, retrospective health record reviews will determine the effect of the change package on provider outcomes, including compliance with guideline recommendations as measured by the proportion of patients who have the appropriate tests performed, and, if required, appropriate treatment and/or referrals. Patient outcomes will be measured by checking for any difference in the proportion of patients with anemia on the day of surgery and the proportion of patients who receive a blood transfusion during the peri-operative period. An economic evaluation will be conducted to compare health outcomes and costs. The feasibility, acceptability and appropriateness of the PAIDSEM-P will be assessed using a quantitative, validated survey to measure implementation outcomes. DISCUSSION: Testing of implementation theory is required to advance understanding of what works, in what context, and the impact on implementation success. This study aims to evaluate the impact of a theoretically informed change package on improving the uptake of PAIDSEM-P. If successful, it will also provide a framework for health care facilities to follow when addressing other evidence-practice gaps.

Preoperative Anemia Screening and Treatment Practices in Patients Having Total Joint Replacement Surgery: A Retrospective, Observational Audit.

BACKGROUND: Surgical patients with preoperative anemia are more likely to experience adverse outcomes. Patient blood management (PBM) guidelines recommend screening and treating patients for anemia preoperatively to enable optimisation before surgery. This study investigates compliance with PBM guidelines and reports the association between length of stay and transfusion risk in patients with preoperative anemia. STUDY DESIGN AND METHODS: A retrospective, observational, chart audit that included all patients having primary, total hip and knee replacement surgery between July-December 2018 at a tertiary, metropolitan healthcare facility. RESULTS: Six hundred and seven patients patients were included, 96% (n = 583) patients had blood tests available (full blood count), and 8.1% (n = 49) had iron studies. Most patients 53% (n = 324) were screened between 2 and 6 days before surgery; 14.6% (n = 85) were anaemic preoperatively and only 5.9% (n = 5) of anaemic patients received treatment. Patients who had anemia preoperatively were more likely to receive a blood transfusion (odds ratio 8.65 [95% CI 3.98-18.76]) and stayed longer in hospital (median difference = 1, χ2 LR = 17.2, df=1, p<0.007). CONCLUSION: Tests ordered for patients having major surgery should include iron studies, renal function, CRP and full blood count to enable detection and classification of preoperative anemia. Timing of screening relative to surgery needs to be sufficient to allow patient optimisation to occur. Appropriate treatment should be provided to anaemic patients to prevent unnecessary blood transfusions and reduce the length of stay. A standardised preoperative anemia pathway may assist in improving practice.

The impact of maternal asthma during pregnancy on offspring retinal microvascular structure and its relationship to placental growth factor production in utero.

Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms are unknown. This study explored whether maternal asthma in pregnancy is associated with the development of offspring microvascular structure and whether it was related to biomarkers of angiogenesis in utero. Children aged 4 to 6 years, born to either asthmatic mothers (n = 38) or healthy controls (n = 25), had their retinal microvascular structure examined. Maternal plasma PlGF concentrations at 18 and 36 weeks' gestation were measured. There was a significant global difference in all retinal microvascular measures between children of asthmatic mothers relative to controls and increased retinal venular tortuosity in children born to asthmatic mothers (7.1 (95% CI 0.7-13.5); P = .031). A rise in plasma PlGF from 18 to 36 weeks' gestation was observed in the control population which was significantly lower in the asthma group by 190.9 pg/mL. PlGF concentrations were correlated with microvascular structure including arteriolar branching and venular tortuosity. These exploratory findings indicate that exposure to maternal asthma during pregnancy is associated with persistent changes in microvascular structure in childhood that may be driven by alterations to angiogenic mechanisms in utero.

Diabetes care: addressing psychosocial well-being in young adults with a newly developed assessment tool.

BACKGROUND: Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM). AIMS: To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes. METHODS: Over a 12-month period, young adults (18-25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID-20) questionnaire, the Patient Health Questionnaire-4 (PHQ-4) and the World Health Organization Well-Being Index-5 (WHO-5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included. RESULTS: Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes-related distress (PAID-20 ≥ 40) was found in 19.4%. Low WHO-5 scores (28-50 points) were seen in 14.8%. PHQ-4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%. CONCLUSION: DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team.

Factors Associated with Breast Cancer Awareness in Thai Women.

Background: Breast cancer is the most common cancer in women worldwide. In south-east Asia, both the incidence and mortality rates of breast cancer are on the rise, and the latter is likely due to the limited access to large-scale community screening program in these resource-limited countries. Breast cancer awareness is an important tool which may, through increasing breast self-examination and the seeking of clinical examination, reduce breast cancer mortality. Investigating factors associated with breast cancer awareness of women is likely to help identify those at risk, and provide insights into developing effective health promotion interventions. Objective: To investigate factors associated with breast cancer awareness in Thai women. Methods: A cross-sectional sample of Thai women aged 20-64 years was collected during August to October, 2015 from two provinces of southern Thailand (Surat Thani and Songkla). A questionnaire including the Breast Cancer Awareness Scale along with demographic characteristics was administered and Proportional Odds Logistic regression was then used to investigate factors associated with breast cancer awareness. Results: In total, 660 Thai women participated in this study. Factors most often associated with the various breast cancer awareness domains were age and rurality. While rural women had poorer knowledge of breast cancer signs and symptoms, they also had lower levels of perceived barriers and considerably better breast cancer awareness behaviors. Conclusion: Despite lower knowledge of breast cancer risk factors and no evidence of better knowledge of signs and symptoms, we found rural Thai women had considerably better breast cancer awareness behavior. This may be due to these women's lower levels of perceived barriers to breast cancer screening services. Indeed this suggests, at least in Thai women, that interventions aimed at lowering perceived barriers rather than enhancing disease knowledge may be more successful in engaging women with breast cancer screening services and increasing breast self-examination.

Awareness Level about Breast Cancer Risk Factors, Barriers, Attitude and Breast Cancer Screening among Indonesian Women

Background: Globally, breast cancer is the second most common cancer in women and is a leading cause of mortality in Indonesia. Raising awareness of breast cancer is particularly important to help at risk women seek medical treatment for this disease. This study aimed to comprehensively investigate the Indonesian women's level of knowledge about breast cancer risk factors, barriers, attitude and breast cancer screening. Methods: This population-based cross-sectional study administered the breast cancer awareness Indonesian scale (BCAS-I) to 856 Indonesian women. Samples were selected in rural and urban combinations from three provinces by stratified random sampling. The ordinal logistic model was used to investigate the clustering effect of the participant's characteristics in this study. Results: Of the women, 62% lived in rural areas and 38% lived in urban areas. Living in an urban area was significantly associated with a lower knowledge of the risk factors. However, living in an urban area was significantly associated with better attitudes and healthier behaviours related to breast cancer awareness. Women with higher education levels had 70% worse attitudes toward breast cancer awareness. Women living South of Sumatera, women living in Yogyakarta, and unmarried women were 5.03, 3.84, and 1.56 times as likely to have higher perceived barriers, respectively. Conclusion: Urban women had a poorer level of knowledge of breast cancer risk factors compared to women living in more rural areas. The result of this study may reflect inadequate breast cancer awareness campaigns or a lack of breast cancer awareness campaigns. These findings suggest that additional education programs aiming to increase awareness and educate the public are needed.

Uncomplicated common bile duct stone removal guided by cholangioscopy versus conventional endoscopic retrograde cholangiopancreatography.

BACKGROUND: Although previous studies have reported the possibility of therapeutic ERCP without fluoroscopy, more robust documentation of fluoroscopy-free common bile duct stone (CBDS) clearance is needed. Technically, "digital cholangioscopy" (DCS) may be used to confirm CBDS clearance. We aimed to compare the feasibility, safety, and radiation exposure between patients with CBDS undergoing stone removal by DCS and conventional ERCP (cERCP). METHODS: Fifty (50) consecutive patients with a CBDS size < 15 mm underwent DCS (SpyGlass DS Direct Visualization System, Boston Scientific, Marlboro, MA, USA) between December 2015 and October 2016. Of 202 consecutive patients undergoing cERCP during the same time frame, 50 matched pairs were created using propensity score matching analysis. In the DCS group, patients underwent biliary cannulation and CBDS removal without fluoroscopy followed by DCS to confirm complete CBDS clearance. A final occlusion cholangiogram was performed as the current standard of care to confirm CBDS clearance. RESULTS: Cannulation success rates were similar between the DCS and cERCP groups (98 vs. 98%). By intention-to-treat analysis, CBDS clearance in the DCS and cERCP groups was not different (90 vs. 98%; p = 0.20, respectively). DCS had successful CBDS removal in 45 cases, whereas 5 (10%) failed for clearance by DCS due to technical limitations. Adverse events were not different between both groups. CONCLUSIONS: In the management of uncomplicated CBDS, our data confirmed the feasibility of DCS for CBDS clearance as it showed efficacy and safety comparable to those of cERCP. Although certain conditions may limit its effectiveness, DCS offers the ability to perform CBDS clearance without the need for fluoroscopy unit and can avoid radiation exposure while ERCP under fluoroscopy remains the current standard of care in patients with CBDS.

The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a hospital-based matched case-control study.

BACKGROUND: Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population. METHODS: Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression. RESULTS: The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30-10.72) compared with Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer was modified by both a high intake of vegetable oils and salt (p = 0.036 and p = 0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no additive effects on the risk of stomach cancer between variants of the XRCC1gene and smoking,alcohol or pork oil consumption. CONCLUSIONS: The effect of the XRCC1 gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was elevated by a high intake of vegetable oils and salt.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

OBJECTIVES: Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. DESIGN: A randomized, double-blind, double dummy, placebo-controlled clinical trial. SETTING: Ubon Ratchathani Cancer Hospital, Thailand. PARTICIPANTS: Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). METHODS: Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). RESULTS: Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. CONCLUSION: Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Assessing Breast Cancer Awareness in Thai Women: Validation of the Breast Cancer Awareness Scale (B-CAS)

Background: Raising breast cancer awareness is a well-established first line strategy to reduce breast cancer mortality. A properly validated instrument is needed to gain a better understanding of breast cancer awareness. Objective: The objective of this study was to develop and validate an instrument to assess breast cancer awareness in Thai women. Methods: In this study, we develop and evaluate the validity of the Breast Cancer Awareness Scale (B-CAS). Construct validity was evaluated by using exploratory factor analysis and confirmatory factor analysis, and criterion validity was investigated using ROC curves to examine the associations between B-CAS subscales and breast self-examination. Internal consistency and test-retest reliability were also investigated. This validation process employed two independent samples of Thai women aged 20-64 years collected from communities in southern Thailand. Results: In total, 660 Thai women (mean age 41 years) participated in this study. Confirmatory factor analysis demonstrated the construct validity of B-CAS (CFI =0.91; NNFI=0.90; GFI=0.95; AGFI= 0.95; RMSEA=0.044, 95%CI 0.041 to 0.047; P< 0.05). Several of the B-CAS subscales demonstrated strong utility in discriminating between women who do and do not regularly conduct breast self-examination. B-CAS also demonstrated strong internal consistency (Cronbach's α=0.86) and test-retest reliability. The final version of B-CAS contains 35 items across five domains: knowledge of risk factors, knowledge of signs and symptoms, attitude to breast cancer prevention, barriers of breast screening, and health behaviour related to breast cancer awareness. Conclusion: The breast cancer awareness scale (B-CAS) was shown to have good psychometric properties in Thai women, and is likely to prove useful in studying the epidemiology of breast cancer awareness in Thai women, and evaluating breast cancer prevention programs for raising awareness.

Fish sharing as a risk factor for Opisthorchis viverrini infection: evidence from two villages in north-eastern Thailand.

BACKGROUND: Foodborne trematodiasis (FBT) is a significant global health problem, with the liver flukes Opisthorchis viverrini, O. felineus, and Clonorchis sinensis contributing to half of the global burden of FBT. North-eastern Thailand where O. viverrini is endemic and un-cooked fish dishes remain an integral part of the food culture has the highest reported incidence of opisthorchiasis, including associated cholangiocarcinoma. Both food sharing and eating practices are potentially important factors in FTB, suggesting an important role for the social ecology of disease transmission in these rural communities. METHODS: Two rural Thai-Lao villages that were part of a 12-village project in Northeastern Thailand were selected for detailed investigation of O. viverrini infection risk associated with sharing of raw fish dishes among households. The project included screening individuals for infection and cholangiocarcinoma, a household questionnaire, and offering treatment options for positive individuals. Social network mapping was used to construct raw fish dish-sharing networks and create a proxy variable capturing variability in the degree of food sharing (DFS), measured as the number of different households with which each household shared fish dishes. Measures of associations between DFS, O. viverrini infection, the frequency of raw fish consumption, and the number of raw fish dishes consumed were generated using binary logistic regression, proportional odds ordinal logistic regression, and Poisson regression. RESULTS: The results showed that the probability that a household has members infected with O. viverrini increased by ~7% (P < 0.01) for each additional household included in its network. Moreover, the frequency and number of types of raw fish dishes consumed increased significantly as the DFS increased. Of the two villages, that with the highest infection prevalence (48% versus 34.6%) had significantly higher social connectivity overall (P < 0.001). CONCLUSIONS: Our findings suggest that the social ecology of human settlements may be key to understanding the transmission dynamics of some FBT. In the case of O. viverrini in Thai-Lao communities, for which food sharing is a traditional practice supporting social cohesion, food sharing network mapping should be incorporated into community-based interventions. These should encourage fish dish preparation methods that minimize infection risk by targeting households with high DFS values.

Validation of an Indonesian Version of the Breast Cancer Awareness Scale (BCAS-I)

Background: Raising breast cancer awareness is a key strategy to reduce associated mortality. While a paucity of adequately validated instruments for breast cancer awareness is applicable across cultures, even outside the health care setting such instruments have been developed. Objective: This study investigated the validity and psychometric properties of a breast cancer awareness scale in Indonesia (BCAS-I). Methods: This cross-sectional study was carried out among Indonesian women conveniently selected within three provinces (Yogyakarta, South of Sumatera and East Nusa Tenggara) located in rural-urban areas using stratified random sampling. First, we translated all questionnaires from English to the local language and then back-translated. The third step was to perform psychometric testing of the adapted instrument by establishing internal consistency (Cronbach's alpha score 0.79) and construct validity by confirmatory factor analysis (CFA). Results: In the 856 participants who responded (responded rate = 98.28%), the age ranged from 18 to 80 years old (mean = 30, SD = 11). The BCAS-I was shown to have good internal consistency, and CFA demonstrated the model fit data adequately (χ2 = 922.267, df = 515, p <0.001, comparative fit index = 0.965, Tucker-Lewis Index = 0.96, goodness-of-fit index = 0.97, adjusted goodness-of-fit index = 0.97, root-mean-square error of approximation = 0.03 95% confidence interval: 0.027, 0.034). The final version of BCAS-I consists of 33 items across 5 domains that cover most key aspects of breast cancer awareness for this population. Conclusion: The BCAS-I demonstrated good psychometric properties and was found to be valid to provide a measurement of breast cancer awareness in Asian women in general and Indonesian women in particular.

Anterior Tragal Crease Is Associated With Atherosclerosis: A Study Evaluating Carotid Artery Intima-Media Thickness.

The utility of the ear crease sign, anterior tragal crease (ATC), as a marker of atherosclerosis is yet to be established. The intima-media thickness of the common carotid artery (IMT-CCA) has been used as a noninvasive surrogate marker for atherosclerosis. History of traditional risk factors for atherosclerosis was obtained from 147 volunteers; ear examination was also performed and venous blood was drawn for laboratory analysis. The volunteers then underwent an ultrasonography measurement of the IMT-CCA. In univariate analysis, presence of ATC, age, underlying hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular disease, cigarette smoking, low-density lipoprotein, and high-sensitivity C-reactive protein were significantly associated with the IMT-CCA. Further multivariate analysis confirmed a significant association between the presence of ATC and IMT-CCA, when adjusted for other factors (adjusted ßATC = .010, 95% confidence interval: 0.0021-0.019). Anterior tragal crease is a potential clinical sign that can predict atherosclerosis. The sign is easily recognizable and may help health-care professionals to identify those at risk of atherosclerosis, especially in people with no clinical signs of the disease.

Development of a Breast Cancer Awareness Scale for Thai Women: Moving towards a Validated Measure.

BACKGROUND: Breast cancer is a major health problem among women around the world. Recent developments in screening and treatment have greatly improved the prognosis of patients with breast cancer in developed countries. However, in developing countries breast cancer mortality remains high.Breast cancer awareness is a first and important step in reducing breast cancer mortality. The development of a validated instrument to measure breast cancer awareness is crucial for the understanding and implementation of suitable health education programs to facilitate early deletion and minimize mortality. OBJECTIVE: The objective of this study was to develop an instrument for the assessment of breast cancer awareness in Thai women. MATERIALS AND METHODS: This methodological study was conducted in two stages: (1) literature searches and semi-structured interviews were conducted to generate items of the breast cancer awareness scale (B-CAS) which were subsequently examined for content and face validity, and (2) an exploration of the factor structure of the resulting instrument and an examination of its reliability. Data were collected using a self-administered questionnaire in Thai women aged 20-64 in August, 2015. RESULTS: A total of 219 women (response rate 97.4 %) participated in this validation study. The B-CAS contains five domains with 53 items on breast cancer awareness: 1) knowledge of risk factors, 2) knowledge of signs and symptoms, 3) attitude to breast cancer prevention, 4) barriers of breast screening, and 5) health behavior related to breast cancer awareness. Items with a content validity index <0.80 were excluded, and factor structure for the remaining items reflected the hypothesized five factor model. The scales based on all retained items was shown to have strongly internal consistency reliability (Cronbach's α=0.86). CONCLUSIONS: The B-CAS provides good psychometric properties to assess breast cancer awareness in women. It can be used to examine breast cancer awareness in Thai women and it could lead to the development and evaluation of suitable educational interventions for raising breast cancer awareness. Future research should focus on further validating the B-CAS including an assessment of construct and criterion-based validity.