Locked down: Impact of COVID-19 restrictions on trauma presentations to the emergency department.

BACKGROUND: COVID-19 was recognised as a global pandemic on 11 March 2020. In South Africa (SA), a nationwide lockdown was implemented at midnight on 26 March to prepare for the predicted surge and slow the spread of the virus. OBJECTIVES: To compare the volume and type of presentations of trauma secondary to interpersonal violence and road traffic collisions (RTCs) during two 5-month periods, from February to June 2019 and 2020, in the emergency department (ED) of an academic tertiary hospital in Gauteng Province, SA. In 2020, February - June included the lockdown period. METHODS: An observational retrospective audit of the patient register at the Helen Joseph Hospital ED was conducted, comparing the number of trauma presentations secondary to interpersonal violence (assaults with gunshot wounds, general assaults including mob assaults, assaults with stab wounds) and RTC presentations between February and June 2019 and 2020. RESULTS: A total of 4 300 trauma presentations secondary to interpersonal violence and RTCs were noted in the 5-month period February - June 2019, as opposed to 3 239 presentations in February - June 2020 (25% decline). A 40% decline in the number of RTCs, from 1 704 in February - June 2019 to 1 026 in the corresponding period for 2020, was noted and found to be statistically significant (p=0.03). Declines in the volume of trauma cases secondary to interpersonal violence and of overall trauma cases were only directional in favour of 2020, but not statistically significant. CONCLUSIONS: The volume of trauma presentations secondary to interpersonal violence and RTCs in the Helen Joseph Hospital ED decreased during the lockdown period. The decline in the volume of RTCs was statistically significant, but declines in the volume of trauma presentations secondary to interpersonal violence and in the volume of overall trauma presentations were not.

Time to liquid culture positivity can substitute for colony counting on agar plates in early bactericidal activity studies of antituberculosis agents.

The measurement of early bactericidal activity (EBA) is the first step in the clinical investigation of antituberculosis agents. EBA is determined by quantifying the viable sputum mycobacterial load on consecutive days of treatment. To investigate whether time to positivity (TTP) in mycobacterial liquid culture can substitute for colony forming unit (CFU) counting on agar plates we compared the error variation of TTP and CFU in 2115 pooled sputum samples collected overnight from 250 individuals included in five EBA studies. We found that the technical variation between duplicate laboratory measurements and the within-subject or day-to-day variation were similar for TTP (8.5% and 27.4% of total variation, respectively) and CFU (6.7% and 29.3% of total variation). The ability of the measurements to separate the EBA of 22 treatment arms was determined with group rank correlation of means and one-way analysis of variance. Except for the EBA over 0-2 days, individual and group EBAs measured with TTP and CFU were highly correlated. Treatment group means rank correlation coefficients were r=0.472, r=0.910 and r=0.818, respectively, for EBA 0-2 days, EBA 0-7 days and EBA 0-14 days. Analysis of variance significantly favoured TTP over CFU for discrimination between groups with F values of 6.58 and 1.87, 7.77 and 4.58, and 8.71 and 3.56, respectively. We conclude that TTP is an acceptable alternative to CFU counting for the determination of the viable sputum mycobacterial load in EBA studies of up to 14 days duration.

Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients.

BACKGROUND: Delamanid (OPC-67683) is a novel mycolic acid biosynthesis inhibitor active against Mycobacterium tuberculosis at a low minimum inhibitory concentration. METHODS: Forty-eight patients with smear-positive tuberculosis (63% male; 54.7 ± 9.9 kg; 30.7 ± 10.8 years) were randomly assigned to receive delamanid 100, 200, 300 or 400 mg daily for 14 days. Colony forming units (cfu) of M. tuberculosis were counted on agar plates from overnight sputum collections to calculate early bactericidal activity (EBA), defined as fall in log(10) cfu/ml sputum/day. RESULTS: The EBA of delamanid was monophasic and not significantly different between dosages; however, more patients receiving 200 mg (70%) and 300 mg (80%) experienced a response of ≥0.9 log(10) cfu/ml sputum decline over 14 days than those receiving 100 mg (45%) and 400 mg (27%). The average EBA of all dosages combined (0.040 ± 0.056 log(10) cfu/ml sputum/day) was significant from day 2 onward. Delamanid exposure was less than dosage-proportional, reaching a plateau at 300 mg, likely due to dose-limited absorption. Moderate but significant correlation was found between C(max) and EBA, indicating exposure dependence. Delamanid was well tolerated without significant toxicity. CONCLUSIONS: Delamanid at all dosages was safe, well tolerated and demonstrated significant exposure-dependent EBA over 14 days, supporting further investigation of its pharmacokinetics and anti-tuberculosis activity.

Guideline for the management of chronic obstructive pulmonary disease--2011 update.

OBJECTIVE: To revise the South African Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD) based on emerging research that has informed updated recommendations. KEY POINTS: (1) Smoking is the major cause of COPD, but exposure to biomass fuels and tuberculosis are important additional factors. (2) Spirometry is essential for the diagnosis and staging of COPD. (3) COPD is either undiagnosed or diagnosed too late, so limiting the benefit of therapeutic interventions; performing spirometry in at-risk individuals will help to establish an early diagnosis. (4) Oral corticosteroids are no longer recommended for maintenance treatment of COPD. (5) A therapeutic trial of oral corticosteroids to distinguish corticosteroid responders from non-responders is no longer recommended. (6) Primary and secondary prevention are the most cost-effective strategies in COPD. Smoking cessation as well as avoidance of other forms of pollution can prevent disease in susceptible individuals and ameliorate progression. Bronchodilators are the mainstay of pharmacotherapy, relieving dyspnoea and improving quality of life. (7) Inhaled corticosteroids are recommended in patients with frequent exacerbations and have a synergistic effect with bronchodilators in improving lung function, quality of life and exacerbation frequency. (8) Acute exacerbations of COPD significantly affect morbidity, health care units and mortality. (9) Antibiotics are only indicated for purulent exacerbations of chronic bronchitis. (10) COPD patients should be encouraged to engage in an active lifestyle and participate in rehabilitation programmes. OPTIONS: Treatment recommendations are based on the following: annual updates of the Global Obstructive Lung Disease (GOLD), initiative, that provide an evidence-based comprehensive review of management; independent evaluation of the level of evidence in support of some of the new treatment trends; and consideration of factors that influence COPD management in South Africa, including lung co-morbidity and drug availability and cost. OUTCOME: Holistic management utilising pharmacological and nonpharmacological options are put in perspective. EVIDENCE: Working groups of clinicians and clinical researchers following detailed literature review, particularly of studies performed in South Africa, and the GOLD guidelines. BENEFITS, HARMS AND COSTS. The guideline pays particular attention to cost-effectiveness in South Africa, and promotes the initial use of less costly options. It promotes smoking cessation and selection of treatment based on objective evidence of benefit. It also rejects a nihilistic or punitive approach, even in those who are unable to break the smoking addiction. RECOMMENDATIONS: These include primary and secondary prevention; early diagnosis, staging of severity, use of bronchodilators and other forms of treatment, rehabilitation, and treatment of complications. Advice is provided on the management of acute exacerbations and the approach to air travel, prescribing long-term oxygen and lung surgery including lung volume reduction surgery. VALIDATION: The COPD Working Group comprised experienced pulmonologists representing all university departments in South Africa and some from private practice, and general practitioners. Most contributed to the development of the previous version of the South African guideline. GUIDELINE SPONSOR: The meeting of the Working Group of the South African Thoracic Society was sponsored by an unrestricted educational grant from Boehringer Ingelheim and Glaxo-Smith-Kline.

Spray desorption collection of free fatty acids onto a solid phase microextraction fiber for trap grease analysis in biofuel production.

Spray desorption collection (SDC) is a sample collection and preparation method that allows for the collection of soluble chemical compounds directly from solid surfaces. Here the analysis of trap grease, a potential biofuel feedstock, is demonstrated by combining SDC with solid phase micro-extraction (SPME) collection followed by direct GC-MS analysis. The SPME fiber collects droplets of solvent, which has picked up analytes from the solid sample surface. It is found that the SDC-SPME combination is a simple and convenient method to collect sample components from surfaces when they are less volatile than heptanoic acid, while the collection efficiency of highly volatile compounds is increasingly reduced due to the purging effect of the nebulising gas. In a real trap grease analysis the SDC-SPME method was able to analyze both the longer chain fatty acids in the sample, important for energy production evaluation of the sample, as well as volatile sample components down to pentanoic acid, which may add to off-odours produced during biofuel use.

Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents.

Evaluation of early bactericidal activity (EBA) by the determination of a fall in viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum is a first step in the clinical study of new antituberculosis agents. The time to detection (TTD) of growth in liquid media is more sensitive and could substitute for CFU counting on solid media. Overnight sputum samples collected during the evaluation of the novel agent TMC207 in comparison to isoniazid and rifampicin were studied. For the determination of CFU, we incubated 10-fold dilutions of homogenized sputum on selective 7H10 agar. The TTD was measured by incubating decontaminated sputum in the BACTEC MGIT 960 system. The fall in bacillary load over 7 days determined by CFU counting closely matched the prolongation of the TTD in the BACTEC MGIT 960 system. The CFU counts correlated significantly with the TTD. While the ranking of agents and different dosages of TMC207 was similar, the highest dose of TMC207 showed markedly better activity when measured by the TTD than CFU counting when compared to the activity of isoniazid. Automated TTD could augment, or, in future, replace, CFU counting to determine sputum bacillary load in EBA clinical trials pending a more formal evaluation of the correlation of the measurements.

Ethionamide cross- and co-resistance in children with isoniazid-resistant tuberculosis.

BACKGROUND: Ethionamide (ETH) is a structural analogue of isoniazid (INH). Both are pro-drugs requiring activation by separate and common enzyme pathways, which could lead to co- and/or cross-resistance. OBJECTIVE: To characterise paediatric INH-resistant mycobacterial isolates to investigate the presence of ETH resistance and mutations in the katG gene and the inhA promoter region. METHODS: Forty-five INH-resistant and 19 INH-susceptible Mycobacterium tuberculosis control isolates from children from the Western Cape Province, South Africa, were analysed to quantify INH minimal inhibitory concentration, test for ETH resistance and investigate mutations in the katG gene and/or inhA promoter region. RESULTS: Among 45 INH-resistant children, ETH resistance was present in 19 of 39 (49%). An inhA promoter mutation was identified in 15 (33.3%); 12/14 (86%) of these isolates were also ETH-resistant. Of the 21 isolates with a katG mutation, six (29%) were ETH-resistant. No isolate had both katG and inhA promoter mutations. Nine (20%) isolates had neither inhA promoter nor katG mutations. Of 15 isolates with inhA promoter mutation, 14 (93%) displayed low- or intermediate-level INH resistance. Among the 19 INH-susceptible isolates, ETH resistance was present in 1/18 (6%) and none showed inhA or katG gene mutations. CONCLUSION: We found a high level of cross- and co-resistance with ETH among INH-resistant M. tuberculosis isolates from children in this geographic area.

Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment of pulmonary tuberculosis.

Tibotec Medicinal Compound 207 (TMC207) is a novel diarylquinoline with a unique mode of action that targets mycobacterial ATP synthase. TMC207 exhibits high in vitro activity against mycobacterial strains either susceptible or resistant to all first-line and many second-line drugs, including fluoroquinolones, and has shown exceptional in vivo activity against several mycobacterial species in different animal models. In this early bactericidal activity study, 75 treatment-naïve patients with smear-positive pulmonary tuberculosis were randomized to once-daily oral TMC207 (25 mg, 100 mg, or 400 mg), 600 mg rifampin (RIF), or 300 mg isoniazid (INH) for 7 days. Sixteen-hour overnight sputum collected at baseline and on each treatment day was plated in serial dilutions on selective agar plates. The bactericidal activity was expressed as the log(10) decrease in CFU/ml sputum/day. Pharmacokinetic sampling was performed on day 7 of TMC207 administration up to 24 h postdose. The decreases in log(10) CFU counts (+/- standard deviation) from baseline to day 7 were 0.04 +/- 0.46 for 25 mg TMC207 (n = 14), 0.26 +/- 0.64 for 100 mg TMC207 (n = 14), 0.77 +/- 0.58 for 400 mg TMC207 (n = 14), 1.88 +/- 0.74 for INH (n = 11), and 1.70 +/- 0.71 for RIF (n = 14). Significant bactericidal activity of 400 mg TMC207 was observed from day 4 onward and was similar in magnitude to those of INH and RIF over the same period. The pharmacokinetics of TMC207 were linear across the dose range. In summary, TMC207 demonstrated bactericidal activity with a delayed onset and was well tolerated, and no study drug-related serious adverse events occurred.

Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears.

We studied the early bactericidal activity of twice the standard dose of rifampin in subjects with pulmonary tuberculosis evidenced by positive smears. The observed mean 2-day activity was almost double that reported at the standard dose. Further studies are warranted to establish whether higher rifampin doses might assist in shortening tuberculosis treatment.

The influence of dose and N-acetyltransferase-2 (NAT2) genotype and phenotype on the pharmacokinetics and pharmacodynamics of isoniazid.

OBJECTIVE: This study evaluated the pharmacokinetics of isoniazid (INH) associated with optimal early bactericidal activity (EBA), defined as 90% of the maximum EBA (EBA(90)) and the influence of N-acetyltransferase-2 (NAT2) subtype on the ability of pulmonary tuberculosis (PTB) patients to reach the identified pharmacokinetic values after INH doses ranging from 0.2 to 10-12 mg/kg body weight. METHODS: INH serum concentrations and NAT2 subtype were determined during four studies of PTB patients in three of whom the EBA of INH was determined. The relationship of EBA to area under the curve (AUC) (AUC(0-infinity)) and 2-h serum concentrations was examined by exponential regression and fitted curves estimated the AUC(0-infinity) and 2-h serum concentrations at which EBA(90) was reached. RESULTS: EBA(90) was reached at an AUC(0-infinity) of 10.52 microg/ml per hour and 2-h serum concentrations of 2.19 microg/ml. An AUC(0-infinity) of 10.52 microg/ml per hour was reached by all 66 patients receiving a 10-12 mg/kg INH dose and all 21 receiving 6 mg/kg, except 1 of 10 (10%) homozygous fast (FF) acetylators; however, at 5 mg/kg, 4 of 12 (33%) FF and 26 of 27 (96%) heterozygous fast (FS), but all 21 homozygous slow (SS) acetylators did so; and 1 of 3 (33%) FF, 2 of 6 (33%) FS, but all 4 SS acetylators at dose 3 mg/kg. An INH 2-h serum concentration of 2.19 microg/ml was reached by all 66 patients receiving 10-12 mg/kg and all 21 receiving 6 mg/kg, except for 2 (20%) FF acetylators at a dose of 5 mg/kg; however, only 3 (25%) of 12 FF acetylators, but 26 (96%) of 27 FS acetylators, and all 21 SS acetylators reached this concentration; and at a dose of 3 mg/kg, 1 (33%) of 3 FF acetylators, 2 (33%) of 6 FF, but all 4 SS acetylators. CONCLUSIONS: At a 6 mg/kg dose, all except a minority of FF NAT2 acetylators, achieve an INH AUC(0-infinity) and 2-h INH serum concentrations associated with EBA(90), as did all 4 SS acetylators receiving 3 mg/kg. Any dose reduction below 6 mg/kg body weight will tend to disadvantage a significant proportion of faster acetylators, but, conversely, SS acetylators require only a 3 mg/kg dose to achieve a satisfactory exposure to INH.

Radionuclides in fruit systems: model prediction-experimental data intercomparison study.

This paper presents results from an international exercise undertaken to test model predictions against an independent data set for the transfer of radioactivity to fruit. Six models with various structures and complexity participated in this exercise. Predictions from these models were compared against independent experimental measurements on the transfer of 134Cs and 85Sr via leaf-to-fruit and soil-to-fruit in strawberry plants after an acute release. Foliar contamination was carried out through wet deposition on the plant at two different growing stages, anthesis and ripening, while soil contamination was effected at anthesis only. In the case of foliar contamination, predicted values are within the same order of magnitude as the measured values for both radionuclides, while in the case of soil contamination models tend to under-predict by up to three orders of magnitude for 134Cs, while differences for 85Sr are lower. Performance of models against experimental data is discussed together with the lessons learned from this exercise.

Radionuclides in fruit systems: model-model intercomparison study.

Modeling is widely used to predict radionuclide distribution following accidental radionuclide releases. Modeling is crucial in emergency response planning and risk communication, and understanding model uncertainty is important not only in conducting analysis consistent with current regulatory guidance, but also in gaining stakeholder and decision-maker trust in the process and confidence in the results. However, while methods for dealing with parameter uncertainty are fairly well developed, an adequate representation of uncertainties associated with models remains rare. This paper addresses uncertainty about a model's structure (i.e., the relevance of simplifying assumptions and mathematical equations) that is seldom addressed in practical applications of environmental modeling. The use of several alternative models to derive a range of model outputs or risks is probably the only available technique to assess consistency in model prediction. Since each independent model requires significant resources for development and calibration, multiple models are not generally applied to the same problem. This study uses results from one such model intercomparison conducted by the Fruits Working Group, which was created under the International Atomic Energy Agency (IAEA) BIOMASS (BIOsphere Modelling and ASSessment) Program. Model-model intercomparisons presented in this study were conducted by the working group for two different scenarios (acute or continuous deposition), one radionuclide ((137)Cs), and three fruit-bearing crops (strawberries, apples, and blackcurrants). The differences between models were as great as five orders of magnitude for short-term predictions following acute radionuclide deposition. For long-term predictions and for the continuous deposition scenario, the differences between models were about two orders of magnitude. The difference between strawberry, apple, and blackcurrant contamination predicted by one model is far less than the difference in prediction of contamination for a single plant species given by different models. This study illustrates the importance of problem formulation and implementation of an analytic-deliberative process in risk characterization.

Monitoring the ingestion of anti-tuberculosis drugs by simple non-invasive methods.

This investigation retrospectively assessed inexpensive non-invasive qualitative methods to monitor the ingestion of anti-tuberculosis drugs isoniazid, rifampicin and rifapentine. Results showed that commercial test strips detected the isoniazid metabolites isonicotinic acid and isonicotinylglycine as efficiently as the isonicotinic acid method in 150 urine samples. The presence of rifamycins in urine samples (n=1085) was detected by microbiological assay techniques and the sensitivity compared to the n-butanol extraction colour test in 91 of these specimens. The proportions detected by the two methods were significantly different and the sensitivity of the n-butanol procedure was only 63.8% (95% CL 51.2-76.4%) as compared to that of the superior microbiological method. Final validation (n=691) showed that qualitative assays measure isoniazid and rifamycin ingestion with an efficiency similar to high-performance liquid chromatography. The qualitative procedures may therefore be valuable in clinical trials and in tuberculosis clinics to confirm drug ingestion.

Scientific Letter : Profile of Children Diagnosed with Cerebral Palsy at Universitas Hospital; Bloemfontein; 1991-2001

Cerebral palsy is a term used for a group of non-progressive but often changing motor deficits; which are a result of a lesion of the brain occurring at an early developmental stage

The effect of confidence and method of questioning on eyewitness testimony.

Very often eyewitnesses are perceived as being accurate due to the confidence in the accuracy of their own testimony. The confidence displayed by an eyewitness may possibly be increased by the method of questioning used by legal professionals and police. The present study examines the confidence-accuracy relationship and the effect the method of questioning (open-ended versus closed-ended questions) may have on the confidence of eyewitnesses. The sample of 412 respondents consisted of scholars (11 to 14-year-olds), university students, the public and Police College students. A significant relationship between memory accuracy and confidence was found for more than 70% of the questions. Closed-ended questions provided a significantly higher rate of accuracy than open-ended questions. A significantly larger proportion of respondents to the closed-ended questions were more confident about their answers than those who responded to the open-ended questions.

Radionuclide migration in forest ecosystems--results of a model validation study.

The primary objective of the IAEA's BIOMASS Forest Working Group (FWG) was to bring together experimental radioecologists and modellers to facilitate the exchange of information which could be used to improve our ability to understand and forecast radionuclide transfers within forests. This paper describes a blind model validation exercise which was conducted by the FWG to test nine models which members of the group had developed in response to the need to predict the fate of radiocaesium in forests in Europe after the Chernobyl accident. The outcomes and conclusions of this exercise are summarised. It was concluded that, as a group, the models are capable of providing an envelope of predictions which can be expected to enclose experimental data for radiocaesium contamination in forests over the time scale tested. However, the models are subject to varying degrees of conceptual uncertainty which gives rise to a very high degree of divergence between individual model predictions, particularly when forecasting edible mushroom contamination. Furthermore, the forecasting capability of the models over future decades currently remains untested.

Modelling and experimental studies on the transfer of radionuclides to fruit.

Although fruit is an important component of the diet, the extent to which it contributes to radiological exposure remains unclear, partially as a consequence of uncertainties in models and data used to assess transfer of radionuclides in the food chain. A Fruits Working Group operated as part of the IAEA BIOMASS (BIOsphere Modelling and ASSessment) programme from 1997 to 2000, with the aim of improving the robustness of the models that are used for radiological assessment. The Group completed a number of modelling and experimental activities including: (i) a review of experimental, field and modelling information on the transfer of radionuclides to fruit; (ii) discussion of recently completed or ongoing experimental studies; (iii) development of a database on the transfer of radionuclides to fruit; (iv) development of a conceptual model for fruit and (v) two model intercomparison studies and a model validation study. The Group achieved significant advances in understanding the processes involved in transfer of radionuclides to fruit. The work demonstrated that further experimental and modelling studies are required to ensure that the current generation of models can be applied to a wide range of scenarios.

Method of questioning and the accuracy of eyewitness testimony.

System variables are integrally part of factors that can be controlled by the legal system to enhance the accuracy of testimony by eyewitnesses. Apart from examining the relationship between questioning as system variable and the accuracy of testimony, the present study furthermore explores the relationship between type of questioning and certain biographical variables (occupation, age, gender and race). To achieve the aim of the study, 412 respondents consisting of 11 to 14-year-olds, university students, the public and Police College students participated and were exposed to open-ended or closed-ended questions. It was found that the participants who responded to the closed-ended questions were significantly more accurate than those who answered the open-ended questions. All the biographical groups, except the public, were more accurate in responding to the closed-ended questions. The scholars obtained the lowest scores (although not always significant) for both the open-ended and closed-ended questions. With respect to age the 18 to 25-year-olds obtained significantly higher scores than the other groups for the closed-ended questions. Whites performed significantly better than blacks in response to the open-ended and closed-ended questions.