Is there a role for glycosuria testing in sub-Saharan Africa?

BACKGROUND: With increasing urbanization and westernization, rates of diabetes in sub-Saharan Africa (sSA) are likely to rise. Early detection and intervention plays an important role in delaying development of complications. In sSA in particular there is need for an affordable, reliable, safe, feasible test to avert human suffering and exhausting already stressed health facilities. METHODS: Data from two large community-based studies were used to assess the value of glycosuria testing in the detection of diabetes in adults in a sub-Saharan country. A first study (A) tested participants for glycosuria by dipstick; if positive, fasting capillary glucose was measured. A later study (B) measured glucose concentration in venous blood 2 h after a 75-g glucose load; if glycaemia was > or = 10 mmol/l, urine was tested for glycosuria. RESULTS: The positive predictive value of glycosuria for a diagnosis of diabetes (fasting glucose > or = 6.7 mmol/l) was 48%. Sensitivity was 64% (57% if a 2-h-value > or = 10 mmol/l was used as gold standard). Sensitivity was higher among overweight and/or hypertensive subjects, among elderly people in the urban area, and among subjects with higher blood glucose levels. Extrapolated specificity was 99.7%, and the likelihood ratio 190. CONCLUSIONS: Glycosuria testing can identify a considerable number of undiagnosed diabetic patients when specially targeted at high-risk groups (obese, hypertensive, or elderly people). Dipstick glycosuria testing is an appropriate, safe, feasible test for sSA, where the prevalence of diabetes is expected to increase considerably in the near future.     

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study

BackgroundCombining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation.MethodsIn this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery.ResultsOf 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy.ConclusionSignificant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.     

Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.     

Cognitive complaints after mild traumatic brain injury: things are not always what they seem

OBJECTIVE: To compare nonreferred, emergency department (ED)-admitted mild traumatic brain injury (MTBI) patients with and without self-reported cognitive complaints on (1) demographic variables and injury characteristics; (2) neuropsychological test performance; (3) 12-day self-monitoring of perceived cognitive problems; and (4) emotional distress, physical functioning, and personality. METHODS: (Neuro)psychological assessment was carried out 6 months post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged 18-60, who attended the ED of our level I trauma centre. Cognitive complaints were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ). In addition, patients monitored concentration problems and forgetfulness during 12 consecutive days. RESULTS: Self-reported cognitive complaints were reported by 39% of the patients. These complaints were strongly related to lower educational levels, emotional distress, personality, and poorer physical functioning (especially fatigue) but not to injury characteristics. Severity of self-reported cognitive complaints was neither associated with the patients' daily observations of cognitive problems nor with outcome on a range of neuropsychological tests. CONCLUSION: Self-reported cognitive complaints were more strongly related to premorbid traits and physical and emotional state factors than to actual cognitive impairments. In line with previous work, this suggests that treatment of emotional distress and fatigue may also reduce cognitive complaints. Cognitive outcome assessment of symptomatic MTBI patients should not be restricted to checklist ratings only, but also include a (neuro)psychological screening. In addition, daily monitoring of complaints is a useful method to gather information about the frequency and pattern of cognitive problems in daily life.     

Rapid time-stamped analysis of filament motility

The in vitro motility assay is a valuable tool to understand motor protein mechanics, but existing algorithms are not optimized for accurate time resolution. We propose an algorithm that combines trace detection with a time-stamped analysis. By tracking filament ends, we minimize data loss from overlapping and crossing filaments. A movement trace formed by each filament end is created by time-stamping when the filament either first (filament tip) or last (filament tail) occupies a pixel. A frame number vs. distance curve is generated from this trace, which is segmented into regions by slope to detect stop-and-go movement. We show, using generated mock motility videos, accurate detection of velocity and motile fraction changes for velocities?<?0.05 pixels per frame, without manual trace dropping and regardless of filament crossings. Compared with established algorithms we show greatly improved accuracy in velocity and motile fraction estimation, with greatly reduced user effort. We tested two actual motility experiments: (1) adenosine triphosphate (ATP) added to skeletal myosin in rigor; (2) myosin light chain phosphatase (MLCP) added to phasic smooth muscle myosin. Our algorithm revealed previously undetectable features: (1) rapid increase in motile fraction paralleled by a slow increase in velocity as ATP concentration increases; (2) simultaneous reductions in velocity and motile fraction as MLCP diffuses into the motility chamber at very low velocities. Our algorithm surpasses existing algorithms in the resolution of time dependent changes in motile fraction and velocity at a wide range of filament lengths and velocities, with minimal user input and CPU time.     

Fatigue after treatment for malignant and benign bone and soft tissue tumors

Fatigue has been mentioned as an important complaint in several groups of disease-free patients after curative treatment for cancer. However, it has never been investigated in a sample of patients who have been treated for a bone or soft tissue tumor in the past. In the current study, these patients participated. Measurement included posted questionnaires at baseline and at follow-up (two years later). Baseline results indicated that fatigue is a severe problem for 28% of the investigated patients. Percentages were equal for patients who were treated for malignant or benign tumors. Fatigue complaints seem to be most severe for patients who finished treatment relatively recently, and for patients who had to undergo more than one operation. In addition, fatigue was associated with several psychological and physical variables. At follow-up, the majority of all patients who were severely fatigued at baseline continued to be severely fatigued. Severe fatigue at follow-up was predicted by oncological complications after initial treatment, less optimism, and more somatization. It can be concluded that fatigue is an important problem for more than a quarter of a sample of patients who have been treated for a malignant or benign bone or soft tissue tumor in the past.     

Point-of-care blood analyzer during the interhospital transport of critically ill children.

OBJECTIVES: To investigate the influence of point-of-care laboratory results (arterial blood gases, ionized calcium, potassium, sodium, glucose, hematocrit and hemoglobin) on therapeutic interventions during interhospital pediatric intensive care transport. DESIGN: Prospective observational study. SETTINGS: Specialist pediatric intensive care retrieval team of a university hospital. PARTICIPANTS: Critically ill pediatric patients who were referred from a community hospital to a pediatric intensive care of a tertiary center. The retrieval team sampled arterial blood during the time of stabilization in the referring hospital and during transport. All results were recorded and for each result the physician of the specialist retrieval team wrote down the influence on the treatment (none, partly, only). The physician specified the kind of intervention. RESULTS: Point-of-care blood analyses influenced the therapeutic management in 76.5% of all blood samples and in 86.2% of the referred patients. Of all interventions, 42.9% were based only on the laboratory results. The majority of interventions were adjustments of the mechanical ventilation. Point-of-care blood analyses reduced the delay in treatment of potentially life-threatening abnormalities of laboratory results (severe hypokalemia and low hematocrit). CONCLUSIONS: During interhospital pediatric intensive care transport, point-of-care blood analyses frequently led to therapeutic interventions. Some abnormal blood results were potentially life threatening and could not have been discovered without point-of-care measurement. We therefore recommend the use of a point-of-care blood analyzer during interhospital intensive care transports, not only for blood gases but also for electrolytes, glucose and hematocrit.