Clinical outcomes of ovarian stimulation with follitropin delta in a mixed regimen with HP-hMG: a real-world retrospective analysise.

INTRODUCTION: Optimising controlled ovarian stimulation (COS) procedures for in vitro fertilisation (IVF) requires an assessment of the patients' medical history, ovarian reserve, prognostic factors and resources to personalise the treatment plan. Treatment personalisation in IVF is increasingly recognised as being vital in providing a balance of efficacy and safety for patients undergoing the COS procedure. In this study, we aimed to assess the efficacy of an ovarian stimulation protocol employing a personalised dosing algorithm for a novel recombinant FSH (rFSH) derived from a human cell-line - follitropin delta, in a mixed gonadotrophin regimen with human menotrophin (HP-HMG). The main outcome of interest in this study is clinical pregnancy rate (CPR) per embryo transfer cycle. MATERIALS AND METHODS: In this single-centre, retrospective, non-interventional study of 20 infertility patients, each individual was provided with a personalised COS regimen based on her ovarian reserve biomarker-serum anti- Mullerian hormone (AMH) and body weight, in a gonadotrophin-receptor hormone (GnRH) antagonist protocol. Personalised dosing of follitropin delta was coadministered with 75 IU of HP-hMG during the COS duration until the final oocyte maturation trigger injection. Ovarian response, pregnancy and safety outcomes resulting from this procedure were assessed and reported here. RESULTS: Following a mean COS duration of 11 days and 50% of patients who underwent frozen embryo transfers, the CPR per started cycle was 70%. The observed CPR from this study was higher than that reported in the follitropin delta Phase 3 studies using rFSH monotherapy stimulation, and additionally showed no incidents of cycle cancellations and no iatrogenic safety risks such as ovarian hyperstimulation syndrome. CONCLUSION: The present study provides a first glimpse into the favourable benefit: risk profile of a mixed protocol regimen using follitropin delta combined with HP-hMG in a cohort of Asian patients in Malaysia.

The associations among executive planning, self-determination, and quality of life in adolescents with intellectual disability.

BACKGROUND: Skills such as planning and problem solving that are required in self-determination can be cognitively demanding. It has not yet been examined whether executive functions and intelligence are associated with levels of self-determination in individuals with intellectual disability (ID), and how that is related to quality of life (QoL). This study examined the associations among executive functions, intelligence, self-determination, and QoL in adolescents with ID. METHODS: Seventy-nine adolescents aged between 17 and 20 years with mild ID participated in the study. Executive functions were assessed by experimental tasks. Non-verbal IQ and survey data regarding QoL and self-determination capacity were collected from the participants. RESULTS: In a regression model with QoL as the dependent variable, only executive planning and self-determination capacity (but not working memory, inhibition and IQ) were significant predictors of QoL. Two mediation models were tested based on the hypotheses, literature and current findings. Model 1 revealed that executive planning had a negative direct effect on QoL when the mediator, self-determination capacity, was held constant. Model 2 indicated that the significant association between self-determination and QoL was not mediated by executive planning. CONCLUSIONS: The findings highlighted the crucial significance of self-determination, in comparison with executive functions and intelligence, for improving the QoL in adolescents with ID. Importantly, higher executive planning skill was even associated with lower QoL if self-determination was not concurrently strengthened. These findings carry implications for the design of education and intervention programmes aimed at improving QoL of adolescents with ID.

Significant Psychosocial Influence in Frail People Living with HIV Independent of Frailty Instrument Used.

BACKGROUND: Antiretroviral therapy (ART) usage among people living with HIV (PLWH) has led to significant mortality declines and increasing lifespan. However, high incidence and early onset of aging-related conditions such as frailty, pose as a new threat to this population. OBJECTIVES: We aimed to characterize frailty by comparing health domains consisting of psychosocial, functional and physical deficits between frail PLWH and matched uninfected controls; identify associated risk factors and the impact on negative health outcomes including mortality risk score, quality of life, healthcare utilization, functional disability and history of falls among virally suppressed PLWH. DESIGN: Cross-sectional study. SETTING: Infectious disease clinic in a tertiary institution. PARTICIPANTS: Individuals aged >25 years, on ART >12 months, not pregnant and without acute illness; multi-ethnic, Asian. MEASUREMENTS: Frailty instruments included Frailty phenotype (FP), FRAIL scale (FS) and Frailty index (FI). FI health deficits were categorized into health domains (psychosocial, functional and physical) and used as standard comparator to characterize frailty. Health domains of frail PLWH were compared with frail matched, uninfected controls. Regression analyses were applied to explore associated risk factors and health-related frailty outcomes. RESULTS: We recruited 336 PLWH. Majority were male (83%), Chinese (71%) with CD4+ count 561 (397-738) cells/µl. Frailty prevalence among PLWH were 7% (FP); 16% (FS) and 22% (FI). Proportions of psychosocial, functional, and physical domains were similarly distributed among frail PLWH measured by different frailty instruments. When compared with matched controls, psychosocial dominance was significant among the PLWH, but not in functional and physical domains. Identified frailty risk factors included poor nutritional status, higher CD4+ count nadir, depression, metabolic syndrome, higher highly sensitive C-reactive protein (hsCRP) and history of AIDS-defining illness (ADI). Frailty influenced the risk for negative health outcomes including increased mortality risk scores, poor quality of life (QOL), frequent healthcare utilization and increased functional disability (p<0.05). CONCLUSIONS: This study highlighted the importance of psychosocial influence in the development of frailty among treated PLWH in a multi-ethnic, Asian setting.

Adult-onset nasopharyngeal diphtheria: an uncommon but rapidly progressive and potentially fatal infection.

Nasopharyngeal diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheriae. We report a case of a young adult who presented to us with a short history of fever, sore throat, hoarseness of voice and neck swelling. He claimed to have received all his childhood vaccinations and had no known medical illnesses. During laryngoscopy, a white slough (or membrane) was seen at the base of his tongue. The epiglottis was also bulky and the arytenoids were swollen bilaterally. The membrane was sent to the microbiology laboratory for culture. A diagnosis of nasopharyngeal diphtheria was made clinically and the patient was treated with an antitoxin together with erythromycin, while awaiting the culture result. Nevertheless, the patient's condition deteriorated swiftly and although the laboratory eventually confirmed an infection by toxin-producing C. diphtheriae, the patient had already succumbed to the infection.

N95 respirator decontamination: a study in reusability.

The coronavirus disease 2019 (COVID-19) pandemic had caused a severe depletion of the worldwide supply of N95 respirators. The development of methods to effectively decontaminate N95 respirators while maintaining their integrity is crucial for respirator regeneration and reuse. In this study, we systematically evaluated five respirator decontamination methods using vaporized hydrogen peroxide (VHP) or ultraviolet (254 nm wavelength, UVC) radiation. Through testing the bioburden, filtration, fluid resistance, and fit (shape) of the decontaminated respirators, we found that the decontamination methods using BioQuell VHP, custom VHP container, Steris VHP, and Sterrad VHP effectively inactivated Cardiovirus (3-log10 reduction) and bacteria (6-log10 reduction) without compromising the respirator integrity after 2-15 cycles. Hope UVC system was capable of inactivating Cardiovirus (3-log10 reduction) but exhibited relatively poorer bactericidal activity. These methods are capable of decontaminating 10-1000 respirators per batch with varied decontamination times (10-200 min). Our findings show that N95 respirators treated by the previously mentioned decontamination methods are safe and effective for reuse by industry, laboratories, and hospitals.

Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy.

OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Prevalence of hypoxia and correlation with glycolytic metabolism and angiogenic biomarkers in metastatic colorectal carcinoma.

PURPOSE: Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metastatic colorectal cancer with [18F]Fluoromisonidazole ([18F]FMISO PET) and correlate these findings with glycolytic metabolism ([18F]FDG PET) and angiogenic blood biomarkers and patient outcomes. METHODS: Patients with metastatic colorectal cancer received routine staging investigations and both [18F] FMISO PET and [18F] FDG PET scans. Correlative blood specimens were also obtained at the time of the [18F] FMISO PET scan. Patient follow-up was performed to establish progression-free survival. RESULTS: A total of 40 patients were recruited into the trial. [18F]FMISO and [18F]FDG PET scans showed a significant correlation of SUVmax (p = 0.003). A significant correlation of progression-free survival and [18F] FMISO TNR (p = 0.02) and overall survival with [18F]FMISO TNR (p = 0.003) and [18F]FDG TGV (p = 0.02) was observed. Serum levels of osteopontin, but not VEGF, correlated with [18F] FMISO and [18F]FDG PET scan parameters. CONCLUSION: [18F]FMISO PET uptake in metastatic colorectal cancer significantly correlates with glycolytic metabolism and is predictive of progression-free and overall survival. These findings have implications for the assessment and treatment of metastatic colorectal cancer patients with novel therapies which affect tumour angiogenesis and hypoxia.

Adult-onset nasopharyngeal diphtheria: an uncommon but rapidly progressive and potentially fatal infection

@#Nasopharyngeal diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheriae. We report a case of a young adult who presented to us with a short history of fever, sore throat, hoarseness of voice and neck swelling. He claimed to have received all his childhood vaccinations and had no known medical illnesses. During laryngoscopy, a white slough (or membrane) was seen at the base of his tongue. The epiglottis was also bulky and the arytenoids were swollen bilaterally. The membrane was sent to the microbiology laboratory for culture. A diagnosis of nasopharyngeal diphtheria was made clinically and the patient was treated with an antitoxin together with erythromycin, while awaiting the culture result. Nevertheless, the patient’s condition deteriorated swiftly and although the laboratory eventually confirmed an infection by toxin-producing C. diphtheriae, the patient had already succumbed to the infection.

Optimal Scree-CNN for Detecting NS1 Molecular Fingerprint from Salivary SERS Spectra.

Dengue fever (DF) is a viral infection with possible fatal consequence. NS1 is a recent antigen based biomarker for dengue fever (DF), as an alternative to current serum and antibody based biomarkers. Convolutional Neural Network (CNN) has demonstrated impressive performance in machine learning problems. Our previous research has captured NS1 molecular fingerprint in saliva using Surface Enhanced Raman Spectroscopy (SERS) with great potential as an early, noninvasive detection method. SERS is an enhanced variant of Raman spectroscopy, with extremely high amplification that enables spectra of low concentration matter, such as NS1 in saliva, readable. The spectrum contains 1801 features per sample, at a total of 284 samples. Principal Component Analysis (PCA) transforms high dimensional correlated signal to a lower dimension uncorrelated principal components (PCs), at no sacrifice of the original signal content. This paper aims to unravel an optimal Scree-CNN model for classification of salivary NS1 SERS spectra. Performances of a total of 490 classifier models were examined and compared in terms of performance indicators [accuracy, sensitivity, specificity, precision, kappa] against a WHO recommended clinical standard test for DF, enzyme-linked immunosorbent assay (ELISA). Effects of CNN parameters on performances of the classifier models were also observed. Results showed that Scree-CNN classifier model with learning rate of 0.01, mini-batch size of 64 and validation frequency of 50, reported an across-the-board 100% for all performance indicators.

Human Immunodeficiency Virus-infected men who have sex with men with syphilis: A 5-year multicentre study in Malaysia.

OBJECTIVES: High rates of syphilis have been reported worldwide among men who have sex with men (MSM). This study aims to describe the clinical pattern and treatment response of syphilis among human immunodeficiency virus (HIV)-infected MSM in Malaysia. METHODS: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh. RESULTS: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/µl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582). CONCLUSION: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.

Barriers to implementing a national health screening program for men in Malaysia: An online survey of healthcare providers.

INTRODUCTION: This study aimed to determine the views and practices of healthcare providers and barriers they encountered when implementing the national health screening program for men in a public primary care setting in Malaysia. METHODS: An online survey was conducted among healthcare providers across public health clinics in Malaysia. All family medicine specialists, medical officers, nurses and assistant medical officers involved in the screening program for adult men were invited to answer a 51-item questionnaire via email or WhatsApp. The questionnaire comprised five sections: participants' socio-demographic information, current screening practices, barriers and facilitators to using the screening tool, and views on the content and format of the screening tool. RESULTS: A total of 231 healthcare providers from 129 health clinics participated in this survey. Among them, 37.44% perceived the implementation of the screening program as a "top-down decision." Although 37.44% found the screening tool for adult men "useful," some felt that it was "time consuming" to fill out (38.2%) and "lengthy" (28.3%). In addition, 'adult men refuse to answer' (24.1%) was cited as the most common patient-related barrier. CONCLUSIONS: This study provided useful insights into the challenges encountered by the public healthcare providers when implementing a national screening program for men. The screening tool for adult men should be revised to make it more user-friendly. Further studies should explore the reasons why men were reluctant to participate in health screenings, thus enhancing the implementation of screening programs in primary care.