Conservative versus interventional treatment for spontaneous pneumothorax

BACKGROUND: Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS: In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks. RESULTS: A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservative-management group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, -4.1 percentage points; 95% confidence interval [CI], -8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of -9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of -11.0 percentage points (95% CI, -18.4 to -3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. CONCLUSIONS: Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events. (Funded by the Emergency Medicine Foundation and others; PSP Australian New Zealand Clinical Trials Registry number, ACTRN12611000184976.)

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

The Fruits of Weeds: Taking Justice at the Commemoration of the Twentieth Anniversary of Operasi Lalang in Malaysia

On 27 October 2007, five Malaysian civil society organizations collaborated to commemorate the 20th anniversary of Operasi Lalang. This police operation was sanctioned by the government in 1987 and saw 107 Malaysians, mainly opposition party members and activists, detained without trial for as long as two years. Operasi Lalang is regarded by many critics of the Malaysian government as the most egregious deployment of the repressive Internal Security Act, under which these detentions were made. This article examines the social and political impacts of the Internal Security Act and Operasi Lalang before describing the commemoration which was styled as a court hearing with the Internal Security Act as the accused. Evident at the commemoration was a comprehensive loss of faith in the infrastructures of the state that are supposed to carry out justice and protect the citizenry from abuses of power. Thus the commemoration-cum-trial declared guilt and took justice, rather than seeking it through infrastructures of the Malaysian state

Barisan Nasional - Political Dominance and the General Elections of 2004 in Malaysia

This paper examines how the Barisan Nasional (National Front, BN) coalition has held power in Malaysia since that country’s independence in 1957. The first of two perspectives taken in this examination looks at the practical impediments to opposition party participation during general elections. This is refracted through the prism of the campaign during the 2004 general elections of a Parti KeADILan Rakyat candidate. The second perspective looks at the broader cultural environment in which elections occur in Malaysia. In particular, the BN plays upon popular fears of a recurrence of ethnic violence that occurred in 1969 when opposition parties polled strongly to portray itself as the keeper of the country’s peace. The examination of both practical mechanisms and the cultural environment allow a more complete understanding of how the BN maintains its political dominance in Malaysia.Die Partei Barisan Nasional (BN) ist die bestimmende Kraft im politischen Prozess Malaysias seit 1957. Die vorliegende Analyse stellt sich in diesem Zusammenhang die Frage, wie diese Dominanz zu erklären ist. Es wird argumentiert, dass sowohl wahlkampftechnische als auch kulturelle Faktoren die schwachen Chancen der Oppositionsparteien und die Stärke der BN erklären können. Nur durch die analytische Integration beider Variablengruppen können Phänomene wie das schlechte Abschneiden des Kandidaten der Oppositionspartei KeADILan Rakyat sowie die erfolgreiche Kampagne der BN im Jahre 1969, bei der die Angst vor ethnischen Unruhen geschürt wurde, im Hinblick auf die Dominanz der Regierungspartei erklärt werden

Islamization and activism in malaysia

Islamization and activism in Malaysia examines aspects of the increasing political and social profile of islam in Malaysia and describes how different kinds of activists in Malaysia have sought to protect fundamental liberties and to improve the State of democracy in Malaysia. In particular, focus is paid to activists who engage with the lectroral process, the law and the public sphere, and in particular, to movements that cut across or combine these realisms of action

Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells

Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequence normal tissue DNAs from 10 individuals with MAP. Somatic base substitution mutation rates in intestinal epithelial cells were elevated 2 to 4-fold in all individuals, except for one showing a 31-fold increase, and were also increased in other tissues. The increased mutation burdens were of multiple mutational signatures characterised by C > A changes. Different mutation rates and signatures between individuals are likely due to different MUTYH mutations or additional inherited mutations in other BER pathway genes. The elevated base substitution rate in normal cells likely accounts for the predisposition to neoplasia in MAP. Despite ubiquitously elevated mutation rates, individuals with MAP do not display overt evidence of premature ageing. Thus, accumulation of somatic mutations may not be sufficient to cause the global organismal functional decline of ageing