An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag.

The diagnosis of tuberculosis (TB) in HIV-infected patients is challenging. Both a urinary lipoarabinomannan (LAM) test (Alere TB LAM) and GeneXpert-MTB/RIF (Xpert) are useful for the diagnosis of TB. However, how to optimally integrate Xpert and LAM tests into clinical practice algorithms remain unclear. We performed a post hoc analysis of 561 HIV-infected sputum-expectorating patients (median CD4 count of 130 cells/ml) from a previously published randomized controlled trial evaluating the LAM test in hospitalized HIV-infected patients with suspected TB. We evaluated 5 different diagnostic strategies using sputum culture as a reference standard (Xpert alone, LAM alone, sequential Xpert followed by LAM and vice versa [LAM in Xpert-negative patients and Xpert in LAM-negative patients], and both tests concurrently [LAM + Xpert]). A cost-consequence analysis was performed. Strategy-specific sensitivity and specificity, using culture as a reference, were similar with the Xpert-only and sequential and concurrent strategies. However, when any positive TB-specific test was used as a reference, the incremental yield of LAM over Xpert was 29.6% (45/152) and that of Xpert over LAM was 75% (84/11). The incremental yield of LAM increased with decreasing CD4 count. The costs per TB case diagnosed were similar for the sequential and concurrent strategies ($1,617 to $1,626). In sputum-expectorating hospitalized patients with advanced HIV and access to both tests, concurrent testing with Xpert and LAM may be the best strategy for diagnosing TB. These data inform clinical practice in settings where TB and HIV are endemic.

Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa.

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL-1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Effect of Sex on Neutrophil to Lymphocyte Ratio and Coronary Flow in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Female patients show poorer outcomes after coronary interventions compared to males. This study aims to investigate the role of enhanced inflammatory response in female ST-elevation myocardial infarction (STEMI) patients in poor outcomes post primary percutaneous coronary intervention (PPCI). METHODS: This study included 120 STEMI patients who went to PPCI in two tertiary cardiac centers over 6 months. All STEMI patients who are eligible for PPCI are included. We excluded those who had previous coronary artery bypass grafting (CABG) with venous grafts, previous PCI with in-stent restenosis (ISR), and those who had signs of infection on admission. These are then divided into two groups according to sex (males and females). Impaired coronary flow (also known as no-reflow) is defined as a coronary TIMI (thrombolysis in myocardial infarction) flow less than 3 after PCI in the absence of mechanical coronary occlusion. RESULTS: The studied groups included 88 males and 32 females. The median age in females was higher than males (62 vs. 57.5 years respectively, P = 0.005). The prevalence of hypertension (34 vs. 21 patients, P = 0.01), non-insulin-dependent diabetes mellitus (NIDDM) (22 vs. 16 patients, P = 0.01) and smoking (61 vs. 0 patients, P < 0.001) was higher in male patients. The incidence of impaired coronary flow did not differ significantly between the two groups (10 males and six females, P = 0.363). The median neutrophil to lymphocyte (N/L) ratio showed to be non-significantly higher in females (5 in males vs. 6 in females, P = 0.342). However, the mean N/L ratio was significantly higher in female patients with impaired coronary flow compared to males (9.35 vs. 5.79, P = 0.003). CONCLUSIONS: The enhanced inflammatory response in female STEMI patients may be responsible for poorer outcomes after PPCI. Larger-scale studies are required to define immune mechanisms as a potential target to improve outcomes in STEMI patients.

A Life-Threatening Presentation of Primary Small Cell Colorectal Non-Hodgkin Lymphoma as Cardiac Tamponade and Its Challenging Management.

Colorectal non-Hodgkin lymphoma (NHL) is quite aggressive and rare, only constituting less than 1% of all cases of colorectal cancer. The pericardium is an extremely rare first site of metastasis. Cardiac tamponade can be a life-threatening initial presentation. We report a 55-year-old female who presented with severe shortness of breath, intermittent abdominal pain and altered bowel habits. She had low blood pressure with congested neck veins. Her echocardiogram showed pericardial and cardiac infiltration with tumour mass; a large pericardial effusion with signs of cardiac tamponade. There was no safe window for percutaneous drainage, and the patient was not physically fit for surgical drainage. A multidisciplinary approach was used to diagnose and manage the case involving a cardiologist, gastroenterologist, pathologist, radiologist and oncologist. CT scans of the whole body showed a large rectosigmoid mass infiltrating the uterus and adnexa. Flexible sigmoidoscopy showed a large bleeding mass at the rectosigmoid junction. The biopsy confirmed small cell NHL. Three cycles of chemotherapy were urgently commenced over a period of 5 weeks (1 cycle of CVP; 2 cycles of CHOP). The patient showed significant symptomatic improvement. A 5-week follow-up echocardiogram showed significant shrinkage of the pericardial tumour and only a small rim of pericardial effusion. The effusion did not recollect in her follow-up echocardiograms. A year later, she was referred to the palliative care team due to the further spreading of her lymphoma. In conclusion, colorectal small cell NHL may initially present as cardiac tamponade. Urgent initiation of chemotherapy can be a treatment option whenever a drainage procedure is unsafe. LEARNING POINTS: Colorectal small cell NHL is a quite rare malignancy that may present initially with pericardial metastasis.Cardiac tamponade secondary to colorectal NHL is a life-threatening presentation. It can be managed by timely chemotherapy alone whenever the usual drainage procedures are not safe.A multidisciplinary approach is a cornerstone in the management of unstable lymphoma patients. It helps the rapid diagnosis and initiation of appropriate chemotherapy.

Impact of a personalised, digital, HIV self-testing app-based program on linkages and new infections in the township populations of South Africa.

INTRODUCTION: Implementation data for digital unsupervised HIV self-testing (HIVST) are sparse. We evaluated the impact of an app-based, personalised, oral HIVST program offered by healthcare workers in Western Cape, South Africa. METHODS: In a quasirandomised study (n=3095), we recruited consenting adults with undiagnosed HIV infection from township clinics. To the HIVST arm participants (n=1535), we offered a choice of an offsite (home, office or kiosk based), unsupervised digital HIVST program (n=962), or an onsite, clinic-based, supervised digital HIVST program (n=573) with 24/7 linkages services.With propensity score analyses, we compared outcomes (ie, linkages, new HIV infections and test referrals) with conventional HIV testing (ConvHT) arm participants (n=1560), recruited randomly from geographically separated clinics. RESULTS: In both arms, participants were young (HIVST vs ConvHT) (mean age: 28.2 years vs 29.2 years), female (65.0% vs 76.0%) and had monthly income <3000 rand (80.8% vs 75%).Participants chose unsupervised HIVST (62.7%) versus supervised HIVST and reported multiple sex partners (10.88% vs 8.7%), exposure to sex workers (1.4% vs 0.2%) and fewer comorbidities (0.9% vs 1.9%). Almost all HIVST participants were linked (unsupervised HIVST (99.7%), supervised HIVST (99.8%) vs ConvHT (98.5%)) (adj RR 1.012; 95% CI 1.005 to 1.018) with new HIV infections: overall HIVST (9%); supervised HIVST (10.9%) and unsupervised HIVST (7.6%) versus ConvHT (6.79%) (adj RR 1.305; 95% CI 1.023 to 1.665); test referrals: 16.7% HIVST versus 3.1% ConvHT (adj RR 5.435; 95% CI 4.024 to 7.340). CONCLUSIONS: Our flexible, personalised, app-based HIVST program, offered by healthcare workers, successfully linked almost all HIV self-testers, detected new infections and increased referrals to self-test. Data are relevant for digital HIVST initiatives worldwide.

Does the use of adjunct urine lipopolysaccharide lipoarabinomannan in HIV-infected hospitalized patients reduce the utilization of healthcare resources? A post hoc analysis of the LAM multi-country randomized controlled trial.

BACKGROUND: The World Health Organization (WHO) recommends the use of adjunctive urine lipopolysaccharide lipoarabinomannan (LAM) testing in hospitalized HIV-infected persons with suspected tuberculosis (TB) and a CD4 count <100cells/ml. However, the recommendation is conditional, and uptake by individual treatment programmes depends on perceived additional benefit. The aim of this study was to determine whether adjunctive LAM testing has additional clinical benefits including a reduction in healthcare-related use of resources. METHODS: A post hoc analysis was performed of a published multicentre, multi-country, randomized controlled trial that showed an approximate 20% mortality benefit in HIV-infected hospitalized patients who underwent adjunctive LAM testing as part of their diagnostic workup. In that parent study, adult HIV-infected hospitalized patients with suspected TB (n=2528) were randomly allocated to either routine diagnostics (smear microscopy, Xpert MTB/RIF, and culture; n=1271), or routine diagnostics plus adjunctive urine LAM testing (n=1257). Data were further analyzed to determine whether there were other potential benefits of LAM usage based on CD4 count and illness severity. Aspects evaluated included: (1) the reduction in number of diagnostic sputum samples tested, (2) the utilization of additional imaging, (3) disease resolution based on follow-up signs and symptoms of illness severity, and (4) the reduction in hospital readmission. RESULTS: Adjuvant LAM did not reduce the number of diagnostic sputum samples requested, the need for additional imaging, or the hospital readmission rate. However, adjunctive LAM was associated with a more rapid rate of disease resolution (dyspnoea) in the severely ill subgroup. Higher LAM grade (grades 4 and 5), compared to lower grade positivity (≤3), was associated with lower use of ultrasound, lower Karnofsky performance score, lower CD4 cell count, and shorter time to culture positivity. CONCLUSIONS: Although, adjunct LAM was associated with a mortality benefit in the parent study, no benefit could be demonstrated in the secondary analysis with respect to the number of diagnostic sputum samples requested, the use of additional imaging, or hospital readmission rates. However, given the limitations of the present study, further appropriately designed studies are required to determine the effect of adjunct urine LAM on the utilization of healthcare resources.