What's the evidence that NICE guidance has been implemented? Results from a national evaluation using time series analysis, audit of patients' notes, and interviews

OBJECTIVES: To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence (NICE). DESIGN: Interrupted time series analysis, review of case notes, survey, and interviews. SETTING: Acute and primary care trusts in England and Wales. PARTICIPANTS: All primary care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17 mental health trusts, and 21 primary care trusts; and senior clinicians and managers from five acute trusts. MAIN OUTCOME MEASURES: Rates of prescribing and use of procedures and medical devices relative to evidence based guidance. RESULTS: 6308 usable patient audit forms were returned. Implementation of NICE guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P <0.002) and orlistat for obesity (P <0.001) significantly increased in line with guidance. Prescribing of drugs for Alzheimer’s disease and prophylactic extraction of wisdom teeth showed trends consistent with, but not obviously a consequence of, the guidance. Prescribing practice often did not accord with the details of the guidance. No change was apparent in the use of hearing aids, hip prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair, and laparoscopic colorectal cancer surgery after NICE guidance had been issued. CONCLUSIONS: Implementation of NICE guidance has been variable. Guidance seems more likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated. Guidance needs to be clear and reflect the clinical context

The magmatic and eruptive evolution of the 1883 caldera-forming eruption of Krakatau: Integrating field- to crystal-scale observations

Explosive, caldera-forming eruptions are exceptional and hazardous volcanic phenomena. The 1883 eruption of Krakatau is the largest such event for which there are detailed contemporary written accounts, allowing information on the eruptive progression to be integrated with the stratigraphy and geochemistry of its products. Freshly exposed sequences of the 1883 eruptive deposits of Krakatau, stripped of vegetation by a tsunami generated by the flank collapse of Anak Krakatau in 2018, shed new light on the eruptive sequence. Matrix glass from the base of the stratigraphy is chemically distinct and more evolved than the overlying sequence indicating the presence of a shallow, silicic, melt-rich region that was evacuated during the early eruptive activity from May 1883 onwards. Disruption of the shallow, silicic magma may have led to the coalescence and mixing of chemically similar melts representative of a range of magmatic conditions, as evidenced by complex and varied plagioclase phenocryst zoning profiles. This mixing, over a period of two to three months, culminated in the onset of the climactic phase of the eruption on 26th August 1883. Pyroclastic density currents (PDCs) emplaced during this phase of the eruption show a change in transport direction from north east to south west, coinciding with the deposition of a lithic lag breccia unit. This may be attributed to partial collapse of an elevated portion of the island, resulting in the removal of a topographic barrier. Edifice destruction potentially further reduced the overburden on the underlying magmatic system, leading to the most explosive and energetic phase of the eruption in the morning of 27th August 1883. This phase of the eruption culminated in a final period of caldera collapse, which is recorded in the stratigraphy as a second lithic lag breccia. The massive PDC deposits emplaced during this final phase contain glassy blocks up to 8 m in size, observed for the first time in 2019, which are chemically similar to the pyroclastic sequence. These blocks are interpreted as representing stagnant, shallow portions of the magma reservoir disrupted during the final stages of caldera formation. This study provides new evidence for the role that precursory eruptions and amalgamation of shallow crustal magma bodies potentially play in the months leading up to caldera-forming eruptions

Avaliação da embebição e do desenvolvimento inicial das estruturas embrionárias de sementes de milho submetidas a diferentes potenciais hídricos

Substrates with water potentials between O and -12atm, were used to evaluate the behavior of corn seeds during the germination process. Water deficiency treatments were compared with the control (adequate available water) using seeds with and without fungicide treatment. The analysis and the interpretation of the results permitted to conclude that the absorption of water, the emergency and the initial development of the embryonic structures are interdependent and vary with the water deficit. For these cases the reduction of water potential promotes difficulties in the evolution of the processes. The presence of fungicide treatment may not influence quantitatively the processes occurring in the beginning of the germination.Empregando substratos com potenciais hídricos variáveis entre 0 e -12atm, o presente trabalho objetivou avaliar o comportamento das sementes de milho postas a germinar. As situações de deficiência hídrica foram diretamente comparadas à testemunha (plena disponibilidade de água), usando sementes com e sem tratamento fungicida. A análise e a interpretação dos resultados permitiram concluir que a absorção de água, a emergência e o desenvolvimento inicial das estruturas embrionárias são interdependentes e reagem no mesmo sentido ao déficit hídrico; para esses casos, a redução do potencial hídrico promove dificuldades na evolução dos processos. Paralelamente, a presença de tratamento fungicida pode não influenciar, quantitativamente, os fenômenos envolvidos no início da germinação

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Vulcanian explosion cycles: patterns and predictability

Repetitive and violent Vulcanian explosion sequences are common hazards at many volcanoes. Statistical analyses of such sequences form the basis of forecasting models and reveal underlying explosive processes. However, no single statistical model describes interexplosion repose intervals in Vulcanian systems. Soufrière Hills, Montserrat, is best described by a log-logistic model, while Sakurajima, Japan, shows a transition from a log-logistic to a Weibull model as activity intensifies. Anak Krakatau, Indonesia, displays two failure modes on different time scales, both described by Weibull distributions. At the Kameni Islands, Santorini, Greece, model-fitting parameters vary between eruption cycles. Rates of magma rise and pressurization may be the most important controls in determining the statistical distribution of repose intervals in Vulcanian systems