Policy and programmatic directions for the Lesotho tuberculosis programme: Findings of the national tuberculosis prevalence survey, 2019.

INTRODUCTION: The Kingdom of Lesotho has one of the highest burdens of tuberculosis (TB) in the world. A national TB prevalence survey was conducted to estimate the prevalence of bacteriologically confirmed pulmonary TB disease among those ≥15 years of age in 2019. METHOD: A multistage cluster-based cross-sectional survey where residents ≥15 years in 54 clusters sampled from across the country were eligible to participate. Survey participants were screened using a symptom screen questionnaire and digital chest X-ray (CXR). Respondents who acknowledged cough of any duration, fever, weight loss, night sweats and/or had any CXR abnormality in the lungs were asked to provide two spot sputum specimens. All sputum testing was conducted at the National TB Reference Laboratory (NTRL), where samples underwent Xpert MTB/RIF Ultra (1st sample) and MGIT culture (2nd sample). HIV counselling and testing was offered to all survey participants. TB cases were those with Mycobacterium tuberculosis complex-positive samples with culture; and where culture was not positive, Xpert MTB/RIF Ultra (Xpert Ultra) was positive with a CXR suggestive of active TB and no current or prior history of TB. RESULT: A total of 39,902 individuals were enumerated, and of these, 26,857 (67.3%) were eligible to participate; 21,719 (80.9%) participated in the survey of which 8,599 (40%) were males and 13,120 (60%) were females. All 21,719 (100%) survey participants underwent symptom screening and a total of 21,344 participants (98.3%) had a CXR. Of the 7,584 (34.9%) participants who were eligible for sputum examination, 4,190 (55.2%) were eligible by CXR only, 1,455 (19.2%) by symptom screening, 1,630 by both, and 309 by CXR exemption. A total of 6,780 (89.4%) submitted two sputum specimens, and 311 (4.1%) submitted one sample only. From the 21,719 survey participants, HIV counseling and testing was offered to 17,048, and 3,915 (23.0%) were documented as HIV-positive. The survey identified 132 participants with bacteriologically confirmed pulmonary TB thus providing an estimated prevalence of 581 per 100,000 population (95% CI 466-696) for those ≥15 years in 2019. Using the survey results, TB incidence was re-estimated to be 654 per 100,000 (95% CI 406-959), which was comparable to the 2018 TB incidence rate of 611 per 100,000 (95% CI 395-872) reported by the World Health Organization (WHO). The highest TB burden was found in those ≥55 years and among men. The ratio of prevalence to case notification was estimated at 1.22. TB/HIV coinfection was identified in 39 (29.6%) participants. Out of the 1,825 participants who reported a cough, 50% of these participants, mostly men, did not seek care. Those who sought care predominantly went to the public health facilities. CONCLUSION: The TB prevalence survey results confirmed that burden of TB and TB/HIV coinfection remains very high in Lesotho. Given that TB prevalence remains high, and there is a significant proportion of participants with confirmed TB that did not report TB suggestive symptoms. The National TB Programme will need to update its TB screening and treatment algorithms to achieve the End TB targets. A major focus will need to be placed on finding the "missing cases" i.e., undiagnosed or under-reported TB cases, or ensuring that not only TB symptomatic but also those who do not present with typical TB symptoms are promptly identified to reduce further onward transmission.

National population-based tuberculosis prevalence survey in Ghana, 2013.

BACKGROUND: The prevalence of tuberculosis (TB) disease is one of the three main indicators used to assess the epidemiological burden of TB and the impact change of TB control; the other two are incidence and mortality.OBJECTIVE: To estimate the prevalence of TB disease among adults in Ghana.METHODS: A nationally representative cross-sectional survey was conducted. Participants were screened for TB using interview and chest X-ray (CXR). For those participants with cough ≥2 weeks and/or abnormal CXR, spot and morning sputum specimens were collected and examined by smear microscopy and culture.RESULTS: The study revealed that the prevalence of smear-positive TB among adults (age ≥15 years) was 111 (95%CI 76-145) and that of bacteriologically confirmed TB was 356 (95%CI 288-425) per 100 000 population. Males and older people had a higher prevalence than their counterparts. The majority of TB cases were smear-negative and had an abnormal CXR without reported chronic cough.CONCLUSION: The survey revealed much higher TB disease burden than previously estimated. This implies that the programme needs more effort and resources to find undiagnosed and unreported cases. The higher proportion of smear-negative and asymptomatic TB cases suggests the need to revise the existing screening and diagnostic algorithms.

Influence of volumetric modulated arc therapy and FET-PET scanning on treatment outcomes for glioblastoma patients.

BACKGROUND: We sought to assess the influence of the clinical introduction of new radiotherapy technologies on glioblastoma patients' outcomes. METHODS: Newly diagnosed glioblastoma patients treated with 60 Gy and temozolomide (2005-2014) were analyzed. The patients' GTV and CTV were defined based on MR (n = 521) or FET-PET/MR (n = 190), and were treated using conformal radiotherapy (CRT, n = 159) or image-guided volumetric modulated arc therapy with hippocampal sparing (IG-VMAT, n = 362). Progression-free survival (PFS) was assessed using the McDonald criteria. Associations between clinical data, dosimetry data, treatment technology, for PFS and overall survival (OS) were explored. RESULTS: The PFS (7 months) and OS (15 months) were unaffected by CRT, IG-VMAT and FET-PET technology. Mean brain dose was correlated with tumor volume, and was lower for IG-VMAT vs. CRT (p < 0.001). Larger mean brain dose was associated with inferior PFS (univariate/multivariate Cox models, p < 0.001) and OS (univariate, p < 0.001). Multivariate Cox models revealed association of larger mean brainstem dose (p < 0.001), BTV (p = 0.045), steroid use at baseline (p = 0.003), age (p = 0.019) and MGMT status (p = 0.022) with lower OS. CONCLUSIONS: Introduction of hippocampal-sparing IG-VMAT technology appeared to be safe, and may have reduced toxicity and cognitive impairment. Larger mean brain dose was strongly associated with inferior PFS and OS.

Transvenous Versus Epicardial Pacing in Fontan Patients.

Up to 10% of Fontan patients require pacemakers; an epicardial approach has historically been used. A transvenous approach can be used but carries risk of Fontan obstruction, thromboembolism, and can be technically challenging. The safety and efficacy of these approaches is not well described. The aim of this study was to compare epicardial and transvenous pacemaker outcomes in Fontan patients, specifically, device performance and adverse event rate. A retrospective review was performed on Fontan pacemaker patients followed at a single institution. Thirty-one Fontan pacemaker patients were identified between 1985 and 2017. Twenty-six had an epicardial system, five transvenous, and three converted from epicardial to transvenous. Average atrial lead sensing at placement was 3.23 versus 2.35 mV (p = 0.52) for epicardial and transvenous leads, respectively. Median atrial and ventricular lead longevity was 86.4 versus 98.8 months (p = 0.56) and 73.2 versus 140 months (p = 0.3) with generator longevity of 65.5 versus 73.9 (p = 0.16) months for epicardial versus transvenous systems, respectively. One major complication occurred in a transvenous patient, and two minor complications occurred in epicardial patients. All transvenous patients received warfarin except one, who converted to dabigatran. Epicardial patients received aspirin (n = 20), warfarin (n = 3) or a warfarin/aspirin combination (n = 3). No thromboembolic events occurred. System revision was required in 13 epicardial and 5 transvenous patients. There were two deaths, none related to the pacemaker system. Transvenous pacemakers can be utilized with equal efficacy compared to epicardial pacemakers with trends toward longer lead longevity in transvenous pacemaker systems.

Automated real-time detection of drug-resistant Mycobacterium tuberculosis on a lab-on-a-disc by Recombinase Polymerase Amplification.

With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR. In our platform, real-time RPA (RT-RPA) was integrated on a lab-on-a-disc (LOAD) with on-board power to maintain temperature for DNA amplification. Sputa collected from healthy volunteers were spiked with respective target M. tb samples for testing. A limit of detection of 102 colony-forming unit per millilitre in 15 min was achieved, making early detection and differentiation of M. tb strains highly feasible in extreme POC settings. Our RT-RPA LOAD platform has also been successfully applied in the differentiation of MDR-TB from H37Ra, an attenuated TB strain. In summary, a quantitative RT-RPA on LOAD assay with a high level of sensitivity was developed as a foundation for further developments in medical bedside and POC diagnostics.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

Sample-to-answer on molecular diagnosis of bacterial infection using integrated lab--on--a--disc.

Sepsis by bacterial infection causes high mortality in patients in intensive care unit (ICU). Rapid identification of bacterial infection is essential to ensure early appropriate administration of antibiotics to save lives of patients, yet the present benchtop molecular diagnosis is time-consuming and labor-intensive, which limits the treatment efficiency especially when the number of samples to be tested is extensive. Therefore, we hereby report a microfluidic platform lab-on-a-disc (LOAD) to provide a sample-to-answer solution. Our LOAD customized design of microfluidic channels allows automation to mimic sequential analytical steps in benchtop environment. It relies on a simple but controllable centrifugation force for the actuation of samples and reagents. Our LOAD system performs three major functions, namely DNA extraction, isothermal DNA amplification and real-time signal detection, in a predefined sequence. The disc is self-contained for conducting sample heating with chemical lysis buffer and silica microbeads are employed for DNA extraction from clinical specimens. Molecular diagnosis of specific target bacteria DNA sequences is then performed using a real-time loop-mediated isothermal amplification (RT-LAMP) with SYTO-9 as the signal reporter. Our LOAD system capable of bacterial identification of Mycobacterium tuberculosis (TB) and Acinetobacter baumanii (Ab) with the detection limits 103cfu/mL TB in sputum and 102cfu/mL Ab in blood within 2h after sample loading. The reported LOAD based on an integrated approach should address the growing needs for rapid point-of-care medical diagnosis in ICU.

The effect of household poverty on tuberculosis.

pSETTING: Households in Malawi, Mongolia, Myanmar, the Philippines, Rwanda, Tanzania, Viet Nam and Zambia.OBJECTIVE To assess the relationship between household socio-economic level, both relative and absolute, and individual tuberculosis (TB) disease. DESIGN: We analysed national TB prevalence surveys from eight countries individually and in pooled multicountry models. Socio-economic level (SEL) was measured in terms of both relative household position and absolute wealth. The outcome of interest was whether or not an individual had TB disease. Logistic regression models were used to control for putative risk factors for TB disease such as age, sex and previous treatment history. RESULTS: Overall, a strong and consistent association between household SEL and individual TB disease was not found. Significant results were found in four individual country models, with the lowest socio-economic quintile being associated with higher TB risk in Mongolia, Myanmar, Tanzania and Viet Nam. CONCLUSIONS: TB prevalence surveys are designed to assess prevalence of disease and, due to the small numbers of cases usually detected, may not be the most efficient means of investigating TB risk factors. Different designs are needed, including measuring the SEL of individuals in nested case-control studies within TB prevalence surveys or among TB patients seeking treatment in health care facilities.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Early postoperative outcome of bipolar transurethral enucleation and resection of the prostate.

OBJECTIVES: To report the early postoperative outcome of bipolar transurethral enucleation and resection of the prostate. Our results were compared with those published from various centres. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 28 consecutive patients who had undergone bipolar transurethral enucleation and resection of the prostate by a single surgeon between January and June 2014. All patients were evaluated preoperatively by physical examination, digital rectal examination, transrectal ultrasonography, and laboratory studies, including measurement of haemoglobin, sodium, and prostate-specific antigen levels. Patients were assessed perioperatively and at 4 weeks and 3 months postoperatively. RESULTS: The mean resected specimen weight of prostatic adenoma in 28 patients was 48.2 g with a mean enucleation and resection time of 13.6 and 47.7 minutes, respectively. There was a mean decrease in serum prostate-specific antigen by 85.9% (from 6.4 ng/mL to 0.9 ng/mL) postoperatively. Prostate volume was decreased by 68.2% (from 71.9 cm(3) to 22.9 cm(3)) at 4 weeks postoperatively. The mean postoperative haemoglobin drop was 11.5 g/L. The rate of transient urinary incontinence at 3 months was 3.6%. Patients who underwent bipolar transurethral enucleation and resection of the prostate had a short catheterisation time and hospital stay, which is comparable to conventional transurethral resection of the prostate. CONCLUSIONS: Bipolar transurethral enucleation and resection of the prostate should become the endourological equivalent to open adenomectomy with fewer complications and short convalescence. The technique of bipolar transurethral enucleation and resection of the prostate can be acquired safely with a relatively short learning curve.

Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.

Giant urethral diverticulum calculus presenting as scrotal abscess.

We report herein a patient with a urethral calculus associated with urethral diverticulum. A 39-year-old man presented with scrotal swelling and acute retention of urine. Computed tomography of the pelvis and cystoscopy demonstrated a giant calculus in the proximal penile urethra. Emergency in-situ lithotripsy was performed. Complete stone clearance was achieved and a large urethral diverticulum was encountered. The rare occurrence of urethral diverticulum and associated stone disease were discussed.

Added Diagnostic Value of (11)C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis.

INTRODUCTION: The added diagnostic value of (11)C-PiB-PET for the assessment of the accumulation of cortical beta-amyloid in memory clinic patients with uncertain diagnosis remains undetermined. METHODS: All patients who underwent PiB-PET at the Copenhagen Memory Clinic between March 2008 and November 2011 were included in this uncontrolled, retrospective study. The standard diagnostic evaluation program included physical and neurological examination, cognitive and functional assessment, a cranial CT or MRI, functional imaging and cerebrospinal fluid sampling. Based on anonymized case reports, three experienced clinicians reached a consensus diagnosis and rated their confidence in the diagnosis before and after disclosure of PiB-PET ratings. PiB-PET scans were rated as either positive or negative. RESULTS: A total of 57 patients (17 females, 30 males; age 65.7 years, range 44.2-82.6) were included in the study. Twenty-seven had a positive PiB-PET scan. At the first diagnostic evaluation, 16 patients were given a clinical Alheimer's disease diagnosis (14 PiB positive). Of the 57 patients, 13 (23%) were diagnostically reclassified after PiB-PET ratings were disclosed. The clinicians' overall confidence in their diagnosis increased in 28 (49%) patients. CONCLUSION: PiB-PET adds to the specialist clinical evaluation and other supplemental diagnostic investigations in the diagnostic classification of patients with uncertain diagnosis in a specialized memory clinic.

Hypoxia-inducible factors--regulation, role and comparative aspects in tumourigenesis.

Hypoxia-inducible factors (HIFs) play a key role in the cellular response experienced in hypoxic tumours, mediating adaptive responses that allow hypoxic cells to survive in the hostile environment. Identification and understanding of tumour hypoxia and the influence on cellular processes carries important prognostic information and may help identify potential hypoxia circumventing and targeting strategies. This review summarizes current knowledge on HIF regulation and function in tumour cells and discusses the aspects of using companion animals as comparative spontaneous cancer models. Spontaneous tumours in companion animals hold a great research potential for the evaluation and understanding of tumour hypoxia and in the development of hypoxia-targeting therapeutics.