Research on Environmental Regulation and Green Total Factor Productivity in Yangtze River Delta: From the Perspective of Financial Development.

This paper employs the global Malmquist Luenberger (GML) index and the System Generalized method of moments (GMM) estimation method to investigate the influence of both environmental regulation and financial development on green total factor productivity in 41 cities of the Yangtze River Delta (YRD) in China from 2003-2019. We select the relevant input-output data to measure the green total factor productivity (GTFP) and its decomposition index including undesirable output. The results show that the GTFP and its decomposition index in the YRD have a slow fluctuating upward trend. The YRD mainly depends on improving the level of technological progress and environmental governance to promote the improvement of regional economic green development level. The empirical research results show that there is an inverted U relationship between environmental regulation and GTFP in the YRD, too strict environmental regulation will inhibit the growth of green total factor productivity. By adding control variables, the inflection point of environmental regulation is 0.5034, which is lower than that without control variables. There is a strong interaction and superposition effect between financial development and environmental regulation, which is closely related to the established financial cooperation mechanism, perfect financial system arrangement and cross-regional financial cooperation platform in the YRD. Government intervention should be reduced, the introduction of foreign capital should be controlled appropriately, foreign capital should be guided to green industries, and the use efficiency of foreign capital should be improved. This paper holds that we should pay attention to the strength of environmental regulation, prevent overcorrection, increase the guidance of credit funds, deepen the reform of the financial system, appropriately intervene in the market by the government, strengthen the guidance of foreign capital, and promote the development and transformation of the green economy in the YRD region with the help of several policies.

Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB-CHMICA. A report from the Identification Of Novel psychoActive substances (IONA) study.

CONTEXT: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects. OBJECTIVE: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA. MATERIALS AND METHODS: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE REPORTS: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine. CONCLUSIONS: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions.

Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

AIMS: To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). METHODS: Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. RESULTS: In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration < 20 mg l(-1) and a normal ALT/AST on initial presentation or when RSPI was first suspected, but both of these values were only available for 79 (40%) cases. CONCLUSIONS: Severe liver damage is reported after RSPI in adults and children, sometimes involving reported doses below current thresholds for intervention. Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases.

Bolus-Infusion Delays of Alteplase during Thrombolysis in Acute Ischaemic Stroke and Functional Outcome at 3 Months.

Background. The efficacy of alteplase in acute ischaemic stroke (AIS) is highly time dependent. Hence, alteplase is administered as soon as possible with a bolus followed by an infusion. Delays between bolus and infusion may occur, but the extent of these delays and the impact on outcome are unclear. Aims. We investigated the extent of bolus-infusion delays and the relationship between delays and stroke outcome. Method. We reviewed medical records of 276 patients who received alteplase for AIS at our centre between April, 2008, and June, 2013. Complete demographic and clinical data including 3-month modified Rankin Score (mRS) from 229 patients were analysed comparing delays of 0-8 and >8 minutes. Results. Overall mean (SD) bolus-infusion delay was 9 (7) minutes. Baseline characteristics were similar apart from more severe strokes in delays >8 minutes. Three-month outcomes were not significantly different although delays >8 minutes had lower functional independence rate (mRS 0-1: 23.1% versus 28.1%; adjusted OR 1.2 (95% CI 0.6 to 2.4, P = 0.68)) and higher mortality rate (18% versus 11%, OR 1.0, 95% CI 0.6 to 1.7, P = 0.95). Conclusions. In this single centre series, bolus-infusion delays of alteplase in AIS were common and no effect of bolus-infusion delays on independence and mortality was found.

Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study.

BACKGROUND: In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators. OBJECTIVE: To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres. METHODS: We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography. RESULTS: Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1-30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively). CONCLUSION: Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

Effects of MHRA drug safety advice on time trends in prescribing volume and indices of clinical toxicity for quinine.

AIMS: To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. METHODS: We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volume for individual Primary Care Trusts in the North East of England from 2007/8 to 2011/12 obtained from the ePACT.net database. We also analysed quinine toxicity enquiries to the National Poisons Information Service (NPIS) via Toxbase(®) and by telephone between 2004/5 and 2011/12. Joinpoint regression and Pearson's correlation tests were used to ascertain changes in trends in prescribing and indices of toxicity and associations between prescribing and indices of toxicity, respectively. RESULTS: Total prescribing continued to increase, but annual growth in quinine prescribing in England declined from 6.0 to -0.6% following the MHRA update [difference -0.04 (95% confidence interval -0.07 to -0.01) quinine prescriptions per 100 patients per quarter, P = 0.0111]. Much larger reductions were observed in Primary Care Trusts that introduced comprehensive prescribing reviews. The previously increasing trend in Toxbase(®) quinine searches was reversed [difference -19.76 (95% confidence interval -39.28 to -9.20) user sessions per quarter, P = 0.0575]. Telephone enquiries to NPIS for quinine have declined, with stabilization of the proportion of moderate to severe cases of quinine poisoning since the update. CONCLUSIONS: The MHRA advice was followed by limited reductions in the growth in quinine prescribing and in indicators of quinine overdose and toxicity. Quinine prescribing, however, remains common, and further efforts are needed to reduce availability and use.

Prevalence, seriousness and effect of previous adverse drug reactions on prescribing during acute medical admission.

BACKGROUND: Adverse drug reactions (ADRs) are associated with significant morbidity, mortality and cost. Knowledge of the prevalence of previous ADRs at admission highlights the potential burden of ADR risks to hospital in-patients. However, the proportion of acute medical admissions with previous ADRs and how this affects inpatient prescribing is uncertain. OBJECTIVES: To determine the prevalence and seriousness of previous ADRs in newly admitted medical patients, and ascertain the effect of previous ADRs on choice of prescribed medications during acute hospitalisation. Also, we compared the seriousness of ADRs as classified by patients and standard definition. SETTING: Acute admissions within the medical directorate of a district general hospital serving a population of about 280,000 people in the north east of England. METHOD: Newly admitted medical patients over a period of 8 weeks were prospectively screened to identify those with a previous history of ADR using patient interviews. Reviews of hospital notes and general practice summaries were undertaken for patients we were unable to interview. A structured form was used to collect relevant data from patients identified to have previous ADRs from the aforementioned sources. MAIN OUTCOME MEASURES: Prevalence and seriousness of previous ADRs, and the proportion of acute medical prescriptions affected by previous ADRs. RESULTS: A total of 509 acute admissions were screened. Of these, 19.8 % had ADRs to previously prescribed medications. Whereas 62.7 % of patients deemed their ADRs to be serious, only 20.9 % of previous ADRs were so by standard definition. 18.8 % of previous ADRs affected choice of prescribed medications during the present admission but this was not influenced by the seriousness of previous ADRs. CONCLUSION: The prevalence of previous ADRs at admission is high and significantly affects choice of drugs used during acute hospitalisation. There are clear inconsistencies between patient perspective and standard definition of the seriousness of ADRs which is likely to be due to patients' heightened subjective perception of harm.

Pharmacokinetics of alteplase in the treatment of ischaemic stroke.

INTRODUCTION: Alteplase is the only approved drug for thrombolysis in acute ischaemic stroke (AIS) after its initial use in acute myocardial infarction (AMI). Its role in functional recovery is time-dependent while its major adverse effect, intracranial haemorrhage, is dose-dependent. These underline the importance of the pharmacokinetics of alteplase to its clinical use. AREAS COVERED: The authors discuss the pharmacology of alteplase with a major focus on its pharmacokinetics based on literature obtained from the OVID electronic database and other institutional resources. EXPERT OPINION: The pharmacokinetic profile of alteplase is almost entirely derived from studies in AMI. Differences in the pathophysiology of AMI and AIS mean it cannot be assumed that the pharmacokinetics of alteplase is similar in these two populations. During AMI, cardiac function and, hence, hepatic perfusion and clearance of alteplase may be impaired. The relatively older population in AIS may have impaired metabolic clearance which may increase plasma concentrations. The concurrent use of medications such as nitrates in the management of elevated blood pressure during AIS thrombolysis is also associated with reduced plasma concentrations of alteplase. Again, differences in clot size and type between AMI and AIS and between subtypes of AIS may influence response to alteplase. There is an inherently higher risk of intracranial haemorrhage in AIS compared to AMI emanating from cerebral infarction and BBB disruption. Accordingly, stroke-specific pharmacokinetics of alteplase and its relationship to efficacy and safety outcomes are required.

Procedures to evaluate the importance of dietary polyamines.

Polyamines not only play vital physiological functions including modulating transcription and translation of genetic material, cell proliferation and growth, ion channel regulation and cell signaling, but have also been cited in the pathogenesis of diseases. Many plant and animal sources used as food contain high amounts of polyamines. Knowledge of the content of polyamines in food as a source of these growth factors is therefore critical. A 2-step perchloric acid precipitation method to obtain acid soluble extracts from food that are subsequently taken through a dansylation process to produce dansyl polyamine derivatives for HPLC measurement is described. Examples are provided to illustrate mathematical correction factors.