A tutorial on sensitivity analyses in clinical trials : the what, why, when and how

Background: Sensitivity analyses play a crucial role in assessing the robustness of the findings or conclusions based on primary analyses of data in clinical trials. They are a critical way to assess the impact, effect or influence of key assumptions or variations - such as different methods of analysis, definitions of outcomes, protocol deviations, missing data, and outliers - on the overall conclusions of a study. The current paper is the second in a series of tutorial-type manuscripts intended to discuss and clarify aspects related to key methodological issues in the design and analysis of clinical trials. Discussion. In this paper we will provide a detailed exploration of the key aspects of sensitivity analyses including: 1) what sensitivity analyses are, why they are needed, and how often they are used in practice; 2) the different types of sensitivity analyses that one can do, with examples from the literature; 3) some frequently asked questions about sensitivity analyses; and 4) some suggestions on how to report the results of sensitivity analyses in clinical trials. Summary. When reporting on a clinical trial, we recommend including planned or posthoc sensitivity analyses, the corresponding rationale and results along with the discussion of the consequences of these analyses on the overall findings of the study

Fil-lejl li kiber miegħi

Ġabra ta’ poeżiji u proża li tinkludi: Flus lura ta’ Charles Clews – Afrika ta’ Oliver Friggieri – 5 ta’ Ottubru 1798: Ir-rewwixta taż-Żabbarin kontra l-Franċiżi ta’ Achille Mizzi – Durham ta’ Joe Friggieri – Tifkiriet: Għand Majsi l-parrukkier ta’ Maurice Mifsud Bonnici – Jacqueline ta’ Carmel Azzopardi – Is-Sibt 29 ta’ Marzu 1986 ta’ Alfred Massa – Lill-għasfur ta’ Nikol Vella Apap – Nixtieq nibki ta’ John Caruana – Imbierka s-sapjenza ta’ Charles Clews – Par għajnejn fid-dlam ta’ Val. V. Barbara – Iż-żmien u l-bniedem ta’ Paul J. Debono – Dixx ta’ l-istejnles stil ta’ Paul P. Borg – Nota bene ta’ Sergio Grech – Ħitan ta’ Alfred Degabriele – Data base ta’ Philip Sciberras – Freddie Mercury – Ġieħ ta’ Charles Briffa – Ħolma ta’ Joe Bugeja – L-imsiebaħ firxu d-dwal ta’ Emanuel F. Attard – Żamma ta’ Manwel Cassar – Awtur tal-baħar ta’ Charles Bezzina – Nixxiegħa tal-kuxjent minn Triq Ħas-Sajjied Birkirkara ta’ Tarcisio Zarb – Ċfuf u żigarelli ta’ Ġorġ Borg – Taħt is-saffi tqal ta’ Ġorġ Borg – Fil-lejl li kiber miegħi ta’ Ġorġ Borg.peer-reviewe

Agriculture adaptation in climate change : adaptation report

There is the need for a legal instrument that would first and foremost establish the executive powers of a new entity with overarching responsibilities and powers over all the authorities that have sectoral responsibilities for climate change. Such a legal instrument should also identify these sectoral authorities and their responsibilities, preferably within an Annex which could be amended and adjusted in a flexible manner. This instrument should be managed by a new unit on climate change within MRA and it should ensure integration without causing fragmentation between the sectors. At the same time, retaining the sectoral input would ensure that there is no duplication of roles, that the institutions are specialised within their own field and that the overarching institution does not becomes a bottle neck. In other words, different competent authorities responsible for the different sectoral policies and obligations should remain, but these must be answerable to an institution that has executive powers to ensure compliance and to coordinate long and short term planning with respect to climate change targets and impacts. By way of recommendation therefore, a legal instrument of this sort should seek to intervene as little as possible in the daily running of the sectoral policies and only apply its powers in situations of emergency when non compliance by the different sectors stalls the fulfilment of Malta’s obligations. Its main role should be to ensure implementation of a National Strategy on Mitigation and Adaptation. This legal instrument would not duplicate the role of public institutions that are already regulators for various sectors on climate change. It would however empower the new entity to take enforcement measures against the said institutions if they fail to do so. It would also ensure the implementation and enforcement of existing legislation that regulates the various sectors in order to rationalize their sustainable use and provide for conservation measures. This would benefit both the implementation of mitigation and adaptation measures. An entity entrusted with the overall responsibility for climate change law and policy must be legally empowered to ensure the implementation of national adaptation programmes. It must also coordinate the various sectors to carry out the necessary research to adopt and implement mitigation and adaptation measures. It must necessarily be supported by a parallel capacity building process in the various entities that run the day-to- day implementation functions. On an administrative level, without necessarily being included in a legal instrument, memoranda of understanding and stakeholder dialogue are indispensable tools to ensure cooperation. This will facilitate reaching mitigation and adaptation targets within the stipulated time frames. The mainstreaming of climate change impacts in national policies ensures the adoption of mitigation and adaptation measures and guarantees synergy and linkages amongst various public plans and programmes. Response to climate change should take place at a strategic level to assess beforehand the socio-economic impacts of any mitigation and adaptation measures adopted as a consequence prior to mainstreaming into national policy making. The existing Regulations on the Strategic Environment Assessment already include climate change impacts as one of the issues that needs to be taken into consideration in an SEA. Furthermore, for all those situations where an SEA is not required, Maltese authorities should promote pro-active adaptation measures such as, for example, in development planning, rather than take reactive adaptation measures. The new climate change legal instrument must ensure effective monitoring and stakeholder engagement, particularly the involvement of NGOS and Local Councils which increases public awareness on climate change issues. The new law should also take into consideration national security issues relating to climate change when formulating mitigation and adaptation strategies. The new law should also target the development of a research programme for climate change, including access to funding programmes. It is vital that Investment in research and development in all sectors should not remain on a voluntary basis. It will provide local industry with the necessary technology and it will generate specialised local expertise in a rapidly growing sector that is assuming a tremendous economic potential. Procrastination is detrimental on two main fronts. First because Malta will miss out in securing a place in this niche-market and second because we will keep relying upon foreign technology and expertise. Since Malta can rely on and pool from the scientific and technical advice of the European Environmental agency, it is best to concentrate on investing in scientific and technical research that addresses the local scenario. This should be earmarked as a priority for EU funded projects and care should be taken not to duplicate research conducted by EU agencies to which Malta has access, but rather to build upon it and apply it at the local level. It is also essential to include as a legal obligation the publication to civil society of information acquired as a result of research conducted at the EU level or carried out locally. It must be ensured that all sectors surmount the constraints due to the lack of a sound knowledge base on local ecosystem dynamics. Filling such a gap would serve to build local scientific evidence that would identify to what extent marine, terrestrial and aquatic flora and fauna groups are vulnerable to the impacts of climate change. Emphasis should be placed on minor and already vulnerable groups. All sectors should be legally bound to maintain a Geographic Information System to integrate data related to climate change, and any other data required apart from spatial information. Adopting and implementing the recommendations suggested by the National Sustainable Development Strategy for Malta would greatly enhance the implementation of adaptation measures relating to climate change, both on a cross-sectoral and sectoral level. At present it is envisaged that the government is currently preparing a new Bill on sustainable development, in the meantime the applicable provisions of the EPA by virtue of which the sustainable development strategy was published should continue to apply. Malta should also endeavour to promote more regional cooperation in the Mediterranean under the Barcelona Convention framework and Euro Med, to identify the adaptation needs of the Mediterranean littoral to the impacts of climate change. Authorities should initiate immediately, even at the regional Mediterranean level, studies to assess vulnerability due to climate change, how new opportunities may be tapped, how to meet with the negative consequences of climate change in the sector, how to ensure that local operators adapt to the shift in tourism trends as a result of climate change. There is the need of systematic and sustained awareness building programmes to educate all. This will intensify awareness and promote a change in behavioural patterns to improve adaptation to climate change. Increasing awareness of climate change impacts within the government, industry, and community sectors will support cultural change transitions that are required for the adoption of more climate change friendly technologies, designs, and operations by public and private operators. The new climate change law should also obligate the various sectors to formulate contingency plans. This serves to: address the negative impacts envisaged as a result of climate change particularly upon vulnerable groups. assess socio-economic implications, with increased insurance covers for risks resulting from the likely impacts of climate change. identify financial guarantees and incentives amongst the various stakeholders in all sectors.peer-reviewe

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients