Medical Device Regulation in Australia: Safe and Effective?

Objective: To describe the frequency, characteristics and outcomes of reports of possible harms related to medical devices submitted to the Australian Therapeutic Goods Administration (TGA) using data made publicly available on the TGA website. Design and setting: A retrospective analysis, conducted in January 2012, of data made publicly available on the TGA website from January 2000 to December 2011. Main outcome measures: The number and nature of reports of medical device incidents, recalls and alerts. Results: Up to December 2011, 6812 incidents involving medical devices were reported to the TGA, although there were several periods where data were unavailable. Incidents were reported more frequently in later years, most often by device sponsors, and were often attributed to mechanical problems. 295 deaths and 2357 serious injuries have been related to incidents, with serious injury (597) highest in 2009. Most incidents involving medical devices were not investigated (47.5%), or, after investigation, no further action was taken (25.0%). During the same time period, there were 35 medical device recalls and 34 medical device alerts issued by the TGA, with no consistent increase over time. Conclusions: Despite TGA reform proposals, greater transparency is still needed. Issues that have not been addressed include patchy and conflicting data in the public domain and lack of explanations for the large proportion of uninvestigated reports. To maintain public confidence in the national regulatory system these problems need to be resolved

Systematic reviews of surgical procedures in children: Quantity, coverage and quality

Aim Systematic reviews have the potential to map those areas where children are under‐represented in surgical research. We aimed to describe and evaluate the quantity, coverage and the quality of conduct and reporting of systematic reviews of surgical procedures in children. Methods We searched four biomedical databases, a systematic review register, reference lists and conducted hand searching to identify relevant reviews. Two reviewers worked independently to critically appraise included studies and abstract data. We assessed reporting quality using the preferred reporting items for systematic reviews and meta‐analysis statement and methodological quality using the Assessment of Multiple SysTemAtic Reviews tool. Results Fifteen systematic reviews were identified, representing 0.01% of all paediatric surgical citations in MEDLINE and E mbase. Thirteen of the reviews were C ochrane reviews, and most reviews (12/15) addressed subspecialty interests such as otorhinolaryngology. The median number of included trials per systematic review was four (interquartile range 1 to 9.5), the median number of primary outcomes was 5.5 (interquartile range 3.5 to 7.5). In general, reporting and methodological quality was good although there were several omissions, particularly around completeness of reporting of statistical methods used, and utilisation of quality assessments in analyses. Outcomes were often not clearly defined and descriptions of procedures lacked sufficient detail to determine the similarities and differences among surgical procedures within the contributing trials. Conclusion Systematic reviews of surgical procedures in children are rarely published. To improve the evidence base and guide research agendas, more systematic reviews should be conducted, using standard guidelines for conduct and reporting

Tests for latent tuberculosis in people with end stage kidney disease: a systematic review

BACKGROUND: The relative diagnostic accuracy of interferon γ release assays (IGRAs; based on ELISA [enzyme-linked immunosorbent assay] or ELISPOT [enzyme-linked immunosorbent spot], ie, the QuantiFERON and T-SPOT.TB tests, respectively) and the tuberculin skin test (TST) for latent tuberculosis (TB) infection in people with end-stage kidney disease is uncertain and national guidelines for their use are inconsistent. STUDY DESIGN: Systematic review. SELECTION CRITERIA FOR STUDIES: Evaluated performance of tests for latent TB with clinical risk-factor assessment. SETTING & POPULATION: People with end-stage kidney disease (chronic kidney disease stage 5 [eGFR <15] or kidney transplant recipients). No limits on setting. INDEX TESTS: ELISA- or ELISPOT-based IGRAs, TST, assays to detect antimycobacterial antibodies, and flow cytometry-based tests. OUTCOMES: Odds of test positivity with clinical risk factor for latent TB, expressed as ORs and relative ORs (RORs). RESULTS: 47 studies (6,828 participants) were included, but only 30 studies (4,546 participants) contained sufficient data to contribute to meta-analysis. Studies were predominately in the dialysis population (23/30; 3,700 participants) in countries with low to moderate TB prevalence (0.0-50.0 cases/10(5) persons). BCG vaccination rate was variable (2.7%-100.0%). 9 studies compared IGRAs with the TST directly, 17 studies evaluated the TST only, and the other 4 studies evaluated other tests. Compared to a positive TST result, a positive ELISA-based IGRA result was associated more strongly with radiologic evidence of past TB (ROR, 4.29; 95% CI, 1.83-10.3; P = 0.001) and contact with active TB (ROR, 3.36; 95% CI, 1.61-7.01; P = 0.001). Compared to a negative TST result, a negative ELISA-based IGRA result was associated more strongly with BCG vaccination (ROR, 0.30; 95% CI, 0.14-0.63; P = 0.002). There were insufficient data to compare performance of the ELISPOT-based IGRA with the TST or ELISA-based IGRA. LIMITATIONS: 17 of 47 included studies (36.2%) did not contain sufficient data to contribute to meta-analysis. CONCLUSIONS: Compared to the TST, the ELISA-based IGRA was associated more strongly with risk factors for latent TB in end-stage kidney disease

“You know that's a rip-off”: policies and practices surrounding micro-enterprises and poverty alleviation in South African township tourism

Supporting the development of small tourism businesses has been seen by policy-makers as a valuable means of alleviating poverty in South African townships. This perspective has been endorsed by several ‘responsible’ tourism businesses and academics. Following a review of the literature, this paper reports the findings of an empirical study that examined the practices of micro-business owners and the factors that shape their behaviour in two South African townships. In spite of significant visitor numbers, it finds that their narrow social networks and the imbalances of power between them and intermediaries such as travel agencies and tour operators prevent them from developing their businesses and sharing in the material gains that become available because of tourism. This analysis has important implications for local policy-makers and those advocating responsible tourism. For the former, it suggests a cessation of current initiatives in favour of greater regulation and alternative forms of investment. For the latter, it implies the need to reassess the utility of advocating responsible tourism to consumers in a context where they do not understand the dynamics which fashion what is on offer or the full implications of their choices

Cognitive and physical fatigue—the experience and consequences of ‘brain fog’ after spontaneous coronary artery dissection: a qualitative study

AIMS: Brain fog and fatigue are common issues after acute coronary syndrome. However, little is known about the nature and impact of these experiences in spontaneous coronary artery dissection (SCAD) survivors. The aims of this study were to understand the experiences of brain fog and the coping strategies used after SCAD.METHODS AND RESULTS: Participants were recruited from the Victor Chang Cardiac Research Institute Genetics Study database and were considered eligible if their event occurred within 12-months. Seven semi-structured online focus groups were conducted between December to January 2021-2022, with this study reporting findings related to brain fog and fatigue. Interviews were transcribed and thematically analysed using an iterative approach. Participants (N=30) were a mean age of 52.2 ((9.5) and mostly female (n=27, 90%). The overarching theme of brain fog after SCAD included four main themes: how brain fog is experienced, perceived causes, impacts, and how people cope. Experiences included memory lapses, difficulty concentrating and impaired judgement, and perceived causes included medication, fatigue and tiredness, and menopause and hormonal changes. Impacts of brain fog included rumination, changes in self-perception, disruption to hobbies/pastimes, and limitations at work. Coping mechanisms included setting reminders and expectations, being one's own advocate, lifestyle and self-determined medication adjustments, and support from peers.CONCLUSION: Brain fog is experienced by SCAD survivors and the impacts are varied and numerous, including capacity to work. SCAD survivors reported difficulty understanding causes and found their own path to coping. Recommendations for clinicians are provided.</p

Effect of spironolactone and potassium canrenoate on cytosolic and nuclear androgen and estrogen receptors of rat liver

Spironolactone and potassium canrenoate are diuretics that are used widely for management of cirrhotic ascites. The administration of spironolactone frequently leads to feminization, which has been noted less frequently with the use of potassium canrenoate, a salt of the active metabolite of spironolactone. The use of these two drugs has been associated with decreases in serum testosterone levels and spironolactone with a reduction in androgen receptor (AR) activity. This decrease in AR has been cited as the cause of the antiandrogen effect of these drugs. We therefore assessed the effect of both drugs on levels of androgen and estrogen receptors (ER) in the liver, a tissue that is responsive to sex steroids. Three groups of male rats (n = 12 rats each) were studied. Group 1 (control) received vehicle only; group 2 received spironolactone (5 mg/day); group 3 received potassium canrenoate (5 mg/day). After 21 days of treatment, the animals of all groups were killed and liver tissue was assayed for nuclear and cytosolic AR and ER, and for male specific estrogen binder (MEB), an androgen-responsive protein. Both drugs drastically decreased the nuclear AR content, as compared with the control group, but only spironolactone decreased cytosolic AR. When the total hepatic content of AR is considered, a highly significant decrease is observed only in rats treated with spironolactone. This reduction in hepatic AR content suggested loss of androgen responsiveness of liver. We confirmed this by assessing levels of MEB, and found that livers from group 2 animals had no detectable MEB activity, whereas livers from both group 1 and 3 had normal MEB activity. No changes were observed in nuclear ER and cytosolic ER of group 3 as compared with group 1. Nuclear estrogen receptor decreased and cytosolic ER increased in group 2, but with no change in total ER content. These results indicate that (a) only spironolactone appears to act as an antiandrogen in liver, resulting in a decrease in both AR and male specific estrogen binder content, and (b) neither drug results in elevated hepatic ER content, although spironolactone-treated animals show an altered subcellular localization. © 1987

Circulating Soluble Endoglin Levels in Pregnant Women in Cameroon and Malawi—Associations with Placental Malaria and Fetal Growth Restriction

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM

Hopes and Fears: Community cohesion and the ‘White working class’ in one of the ‘failed spaces’ of multiculturalism

Since 2001, community cohesion has been an English policy concern, with accompanying media discourse portraying a supposed failure by Muslims to integrate. Latterly, academia has foregrounded White majority attitudes towards ethnic diversity, particularly those of the ‘White working class’. Whilst questioning this categorisation, we present data on attitudes towards diversity from low income, mainly White areas within Dewsbury, West Yorkshire, a town portrayed in media discourse as one of the ‘failed spaces’ of multiculturalism. Drawing on mixed methods research, we present and discuss data that provide a complex message, seemingly confirming pessimistic analyses around ethnic diversity and predominantly White neighbourhoods but also highlighting an appetite within the same communities for greater and more productive inter-ethnic contact. Furthermore, anxieties about diversity and integration have largely failed to coalesce into broad support for organised anti-minority politics manifest in groups such as the English Defence League

Community-based benchmarking improves spike rate inference from two-photon calcium imaging data

In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience

Is small beautiful? Understanding the contribution of small businesses in township tourism to economic development

The increased importance attached by policy-makers to the anticipated developmental effects of tourism in developing countries has been insufficiently examined by academic researchers, particularly in the context of the contribution of small firms in urban areas. This deficiency is addressed by providing a review of existing research followed by an analysis of interviews with 90 tourism business located within and outside the townships of Langa and Imizamo Yethu, Cape Town, South Africa. The findings reveal tensions between the different actors involved in township tourism. While the involvement of small, locally owned, businesses is beneficial, it is limited by conflicts of interest, lack of trust, limited social networks and little attachment to the township locality. The discussion highlights the complexity of tourism's role in economic development, which has significant implications for local policy-makers