Contribution of avoidable mortality to life expectancy inequalities in Wales: a decomposition by age and by cause between 2002 and 2020.

OBJECTIVES: To explore the contribution of avoidable mortality to life expectancy inequalities in Wales during 2002-2020. DESIGN: Observational study. SETTING: Wales, 2002-20, including early data from the COVID-19 pandemic. METHODS: We used routine statistics for 2002-2020 on population and deaths in Wales stratified by age, sex, deprivation quintile and cause of death. We estimated the contribution of avoidable causes of death and specific age-categories using the Arriaga decomposition method to highlight priorities for action. RESULTS: Life expectancy inequalities rose 2002-20 amongst both sexes, driven by serial decreases in life expectancy amongst the most deprived quintiles. The contributions of amenable and preventable mortality to life expectancy inequalities changed relatively little between 2002 and 2020, with larger rises in non-avoidable causes. Key avoidable mortality conditions driving the life expectancy gap in the most recent period of 2018-2020 for females were circulatory disease, cancers, respiratory disease and alcohol- and drug-related deaths, and also injuries for males. CONCLUSIONS: Life expectancy inequalities widened during 2002-20, driven by deteriorating life expectancy in the most deprived quintiles. Sustained investment in prevention post-COVID-19 is needed to address growing health inequity in Wales; there remains a role for the National Health Service in ensuring equitable healthcare access to alongside wider policies that promote equity.

Detecting Drop-offs in Electronic Laboratory Reporting for Communicable Diseases in New York City.

CONTEXT: The Bureau of Communicable Disease at the New York City Department of Health and Mental Hygiene receives an average of more than 1000 reports daily via electronic laboratory reporting. Rapid recognition of any laboratory reporting drop-off of test results for 1 or more diseases is necessary to avoid delays in case investigation and outbreak detection. PROGRAM: We modified our outbreak detection approach using the prospective space-time permutation scan statistic in SaTScan. Instead of searching for spatiotemporal clusters of high case counts, we reconceptualized "space" as "laboratory" and instead searched for clusters of recent low reporting, overall and for each of 52 diseases and 10 hepatitis test types, within individual laboratories. Each analysis controlled for purely temporal trends affecting all laboratories and accounted for multiple testing. IMPLEMENTATION: A SAS program automatically created input files, invoked SaTScan, and further processed SaTScan analysis results and output summaries to a secure folder. Analysts reviewed output weekly and reported concerning drop-offs to coordinators, who liaised with reporting laboratory staff to investigate and resolve issues. EVALUATION: During a 42-week evaluation period, October 2017 to July 2018, we detected 62 unique signals of reporting drop-offs. Of these, 39 (63%) were verified as true drop-offs, including failures to generate or transmit files and programming errors. For example, a hospital laboratory stopped reporting influenza after changing a multiplex panel result from "positive" to "detected." Six drop-offs were detected despite low numbers of expected reports missing (<10 per drop-off). DISCUSSION: Our novel application of SaTScan identified a manageable number of possible electronic laboratory reporting drop-offs for investigation. Ongoing maintenance requirements are minimal but include accounting for laboratory mergers and referrals. Automated analyses facilitated rapid identification and correction of electronic laboratory reporting errors, even with small numbers of expected reports missing, suggesting that our approach might be generalizable to smaller jurisdictions.

Cardiac interventions in Wales: A comparison of benefits between NHS Wales specialties.

OBJECTIVES: The study aimed to assess if specialised healthcare service interventions in Wales benefit the population equitably in work commissioned by the Welsh Health Specialised Services Committee (WHSSC). APPROACH: The study utilised anonymised individual-level, population-scale, routinely collected electronic health record (EHR) data held in the Secure Anonymised Information Linkage (SAIL) Databank to identify patients resident in Wales receiving specialist cardiac interventions. Measurement was undertaken of associated patient outcomes 2-years before and after the intervention (minus a 6-month clearance period on either side) by measuring events in primary care, hospital attendance, outpatient and emergency department. The analysis controlled for comorbidity (Charlson) and deprivation (Welsh Index of Multiple Deprivation), stratified by admission type (elective or emergency) and membership of top 5% post-intervention costs. Costs were estimated by multiplying events by mean person cost estimates. RESULTS: We identified 5,999 percutaneous coronary interventions (PCI) and 1,640 coronary artery bypass graft (CABG) between 2014-06-01 to 2020-02-29. The ratio of emergency to elective interventions was 2.85 for PCI and 1.04 for CABG. In multivariate analysis significant associations were identified for comorbidity (OR = 1.52, CI = (1.01-2.27)), deprivation (OR = 1.34, CI = (1.03-1.76)) and rurality (OR = 0.81, CI = (0.70-0.95)) for PCI interventions, and comorbidity (OR = 1.47, CI = (1.10-1.98)) for CABG. Higher costs post-intervention were associated with increased comorbidity for PCI and CABG in the top 5% cost groups, but for PCI this was not seen outside the top 5%. For PCI, moderate cost increase was associated with increased deprivation, but the picture was more mixed following CABG interventions. For both interventions, lower costs post intervention were seen in rural locations. CONCLUSION: We identified and compared health outcomes for selected specialist cardiac interventions amongst patients resident in Wales, with these methods and analyses, providing a template for comparing other cardiac interventions.

Effect of Policy Change to Require Laboratory Reporting With Pregnancy Indicated for Syphilis and Hepatitis B Virus Infection, New York City, January 2013-June 2018.

OBJECTIVES: We evaluated the impact of a 2014 New York City health code change requiring laboratories to indicate if a patient is pregnant or probably pregnant in the electronic laboratory report (ELR) when reporting syphilis and hepatitis B virus (HBV) cases to the New York City Department of Health and Mental Hygiene (DOHMH). METHODS: We calculated the number of pregnant persons with syphilis or HBV infection reported to DOHMH from January 1, 2013, through June 30, 2018. We compared the proportion in which the first report to DOHMH was an ELR with pregnancy indicated before and after the policy change. We calculated time between first ELR with pregnancy indicated and subsequent reporting by a method other than ELR and the proportion of cases in which ELR with pregnancy indicated was the only report source. RESULTS: A total of 552 new syphilis and 8414 HBV-infected cases were reported to DOHMH. From January 2013-June 2014 (pre-change) to January 2017-June 2018 (post-change), the proportion of cases in which ELR with pregnancy indicated was the first report to DOHMH increased significantly (14.7% [23/156] to 46.2% [80/173] for syphilis; 8.0% [200/2498] to 45.3% [851/1879] for HBV infection [P < .001]). Median time between first ELR with pregnancy indicated and subsequent reporting by a method other than ELR was 9.0 days for syphilis and 51.0 days for HBV infection. ELR with pregnancy indicated was the only report for 43.1% (238/552) of syphilis cases and 23.4% (1452/6200) of HBV cases during the study period. CONCLUSION: Including pregnancy status with ELR can increase the ability of public health departments to conduct timely interventions to prevent mother-to-child transmission.

Gibberellins and flowering of grasses and cereals: prizing open the lid of the "florigen" black box.

Comprehensive studies in grasses show that gibberellins (GAs) play a role as a florigen. For Lolium temulentum, which flowers in response to a single long day (LD), GAs are a transmitted signal, their content increasing in the leaf early in the LD and then, hours later, at the shoot apex. There is a continuous trail of evidence of hormonal action of these GAs for L. temulentum and support for a similar role in the flowering of other LD-responsive temperate grasses and cereals. A characteristic of the initial flowering responses of grasses and cereals is their limited stem elongation. Interestingly, it is GAs with low effectiveness for stem elongation, GA5 and GA6, that reach the shoot apex and, structurally, are probably not degraded by 2-oxidase enzymes. By contrast, GA1 and GA4 cause stem elongation, may be inactive for floral evocation, and do not reach the vegetative shoot apex apparently because of susceptibility to degradation. However, GA4 can be florally active if protected against 2-oxidases either structurally or by using a 2-oxidase inhibitor. Later in inflorescence development, GA1 and GA4 can be detected at the shoot apex and are florally active if applied. The 2-oxidase restricting accessibility to the apex has probably declined at this time so there is a second florigenic, LD-regulated GA action. A growing body of molecular evidence supporting these actions of GA may provide a future basis for manipulating flowering of grasses and cereals.

Diagnostic aids: the Surgical Sieve revisited.

BACKGROUND: Diagnostic errors are well documented in the literature and emphasise the need to teach diagnostic skills at an early stage in medical school to create effective and safe clinicians. Hence, there may be a place for diagnostic aids (such as the Surgical Sieve) that provide a framework for generating ideas about diagnoses. With repeated use of the Surgical Sieve in teaching sessions with students, and prompted by the traditional handheld wheels used in antenatal clinics, we developed the Compass Medicine, a handheld diagnostic wheel comprising three concentric discs attached at the centre. We report a preliminary study comparing the Surgical Sieve and the Compass Medicine in generating differential diagnoses. METHODS: A total of 48 third-year medical students from Cardiff University participated in a study aimed at measuring the efficacy of diagnostic aids (Surgical Sieve and Compass Medicine) in generating diagnoses. We quantified the effect each aid had on the number of diagnoses generated, and compared the size of the effect between the two diagnostic aids. There may be a place for diagnostic aids that provide a framework for generating ideas about diagnoses RESULTS: The study suggests that both diagnostic aids prompted users to generate a greater number of diagnoses, but there was no significant difference in the size of effect between the two diagnostic aids. DISCUSSION: We hope that our study with diagnostic aids will encourage the use of robust tools to teach medical students an easily visualised framework for diagnostic thinking.

Steroids, drugs and stuttering priapism; the rock-and-roll lifestyle of a 24-year-old man.

The authors present a case of a 24-year-old, poorly controlled insulin-dependent type 1 diabetic Caucasian man who presented to the emergency department, with a painful erection of 36 h duration that had failed to resolve with conservative management. This was the patient's seventh priapism, with his most recent attendance 1 week previously for which he underwent a distal cavernosal shunt. He admitted to taking several recreational drugs, including marijuana and cocaine, during the preceding few days, in addition to the long-term use of the oral anabolic steroid oxandrolone. He had no family history of sickle cell disease or trait. On examination, a tensely erect penis was noted. A diagnosis of stuttering priapism was made and 750 mL of blood subsequently drained via a distal corporoglandular shunt resulting in successful detumescence.

Impact of service redesign on the socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction: a natural experiment and electronic record-linked cohort study.

AIM: To investigate the impact of service redesign in the provision of revascularisation procedures on the historical socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction (AMI). DESIGN: Natural experiment and retrospective cohort study using linked data sets in the Secure Anonymised Information Linkage databank. NON-RANDOMISED INTERVENTION: An increase in the capacity of revascularisation procedures and service redesign in the provision of revascularisation in late 2011 to early 2012. SETTING: South Wales cardiac network, Census 2011 population 1 359 051 aged 35 years and over. PARTICIPANTS: 9128 participants admitted to an NHS hospital with a first AMI between 1 January 2010 and 30 June 2013, with 6-months follow-up. MAIN OUTCOME MEASURE: Hazard ratios (HRs) for the time to revascularisation for deprivation quintiles, age, gender, comorbidities, rural-urban classification and revascularisation facilities of admitting hospital. RESULTS: In the preintervention period, there was a statistically significant decreased adjusted risk of revascularisation for participants in the most deprived quintile compared to the least deprived quintile (HR 0.80; 95% CI 0.69 to 0.92, p=0.002). In the postintervention period, the increase in revascularisation rates was statistically significant in all quintiles, and there was no longer any statistically significant difference in the adjusted revascularisation risk between the most and the least deprived quintile (HR 1.04; 95% CI 0.89 to 1.20, p<0.649). However, inequity persisted for those aged 75 years and over (HR 0.40; 95% CI 0.35 to 0.46, p<0.001) and women (HR 0.77; 95% CI 0.70 to 0.86, p<0.001). CONCLUSIONS: Socioeconomic inequity of access to revascularisation was no longer apparent following redesign of revascularisation services in the south Wales cardiac network, although inequity persisted for women and those aged 75+ years. Increasing the capacity of revascularisation did not differentially benefit participants from the least deprived areas.

Group 4 metal compounds incorporating the amide ligand, [N(SiMe2{C6H4-2-OMe})2](-).

The anisole-substituted silyl-amide anion, [N(SiMe2{C6H4-2-OMe})2](-) (L), has been used as a pincer-type ligand in coordination chemistry. X-ray diffraction data for the lithium salt shows a trimetallic structure consisting of two equivalents of Li(L) that sequester a molecule of LiCl. The potassium salt K(L) is dimeric in the solid-state with bridging amide ligands. Each structure shows chelation of both O-donor groups to the electropositive metal. In contrast, the titanium compound Ti(L)Cl3 is four-coordinate with a monodentate amide. The zirconium compound Zr(L)2Cl2 is monometallic with a six-coordinate metal and two N,O-bidentate amides.

Synthesis of gibberellin GA6 and its role in flowering of Lolium temulentum.

The induction of flowering by one long day (LD) in the grass Lolium temulentum is most closely mimicked by application of the gibberellins (GAs) GA(5) or GA(6), both of which occur naturally. These gibberellins promote floral development but have little effect on stem elongation. Endogenous GA(5) and GA(6) contents in the shoot apex double on the day after the LD and, for GA(5) (and we presume for GA(6) as well) reach a concentration known to be inductive for the excised shoot apex in vitro. They are, therefore, strong candidates as LD floral stimuli in this grass. The synthesis of GA(6) and an examination of its florigenic properties in L. temulentum are described.

Selective deactivation of gibberellins below the shoot apex is critical to flowering but not to stem elongation of Lolium.

Gibberellins (GAs) cause dramatic increases in plant height and a genetic block in the synthesis of GA(1) explains the dwarfing of Mendel's pea. For flowering, it is GA(5) which is important in the long-day (LD) responsive grass, Lolium. As we show here, GA(1) and GA(4) are restricted in their effectiveness for flowering because they are deactivated by C-2 hydroxylation below the shoot apex. In contrast, GA(5) is effective because of its structural protection at C-2. Excised vegetative shoot tips rapidly degrade [14C]GA(1), [14C]GA(4), and [14C]GA(20) (>80% in 6 h), but not [14C]GA(5). Coincidentally, genes encoding two 2beta-oxidases and a putative 16-17-epoxidase were most expressed just below the shoot apex (<3 mm). Further down the immature stem (>4 mm), expression of these GA deactivation genes is reduced, so allowing GA(1) and GA(4) to promote sub-apical stem elongation. Subsequently, GA degradation declines in florally induced shoot tips and these GAs can become active for floral development. Structural changes which stabilize GA(4) confirm the link between florigenicity and restricted GA 2beta-hydroxylation (e.g. 2alpha-hydroxylation and C-2 di-methylation). Additionally, a 2-oxidase inhibitor (Trinexapac Ethyl) enhanced the activity of applied GA(4), as did limiting C-16,17 epoxidation in 16,17-dihydro GAs or after C-13 hydroxylation. Overall, deactivation of GA(1) and GA(4) just below the shoot apex effectively restricts their florigenicity in Lolium and, conversely, with GA(5), C-2 and C-13 protection against deactivation allows its high florigenicity. Speculatively, such differences in GA access to the shoot apex of grasses may be important for separating floral induction from inflorescence emergence and thus could influence their survival under conditions of herbivore predation.

Deactivation pathways of ethylene polymerization catalysts derived from titanium and zirconium 1,3-bis(furyl)-1,1,3,3-tetramethyldisilazide complexes.

The stoichiometric reaction between the previously described lithium amide salts, LiN(SiMe2R)2 [Li{i}, R = furyl, Li{ii}, R = 2-methylfuryl] and titanium(iv)chloride at low temperature afforded the mono-amide compounds Ti{i}Cl3 (1a) and Ti{ii}Cl3 (1b). The analogous zirconium derivatives Zr{i}Cl3 (3a) and Zr{ii}Cl3 (3b) were accessed via the reaction of excess trimethylsilylchloride with the mixed tetra-amide species, Zr{i}(NMe2)3 (2a) and Zr{ii}(NMe2)3 (2b). The bis-amide complexes Ti{ii}2Cl2 (4b), Zr{i}2Cl2 (5a) and Zr{ii}2Cl2 (5b) were synthesized in a straightforward salt metathesis reaction employing two equivalents of Li{i} or Li{ii} with the metal salts, MCl4(THF)2. The reactivity of the halide compounds 1 and 3-5 with a variety of alkylating agents was studied, with ligand transfer from the transition-element to the main group metal-alkyl reagent being the predominant reaction pathway. The reaction of 4b with MeLi was, however, partially successful affording the titanium(III) complex, Ti{ii}2X (X = Cl/Me, 6b'); this compound was subsequently made as the pure chloride from the reaction of two equivalents of Li{iii} with TiCl3(THF)3. The targeted dialkyl species, Ti{ii}Me2 (7b), was successfully isolated from the reaction between the dichloride 4b and dimethylmagnesium. The molecular structures of 1a, 1b, [3a]2 [3b]2, 4b, 5b and 6b have been solved using single-crystal X-ray diffraction techniques, indicating varying nuclearity of the complexes and hapticities for the amide ligands in the solid-state. The catalytic activity of selected complexes in the polymerization of ethylene is reported.

Regulation of flowering in the long-day grass Lolium temulentum by gibberellins and the FLOWERING LOCUS T gene.

Seasonal control of flowering often involves leaf sensing of daylength coupled to time measurement and generation and transport of florigenic signals to the shoot apex. We show that transmitted signals in the grass Lolium temulentum may include gibberellins (GAs) and the FLOWERING LOCUS T (FT) gene. Within 2 h of starting a florally inductive long day (LD), expression of a 20-oxidase GA biosynthetic gene increases in the leaf; its product, GA(20), then increases 5.7-fold versus short day; its substrate, GA(19), decreases equivalently; and a bioactive product, GA(5), increases 4-fold. A link between flowering, LD, GAs, and GA biosynthesis is shown in three ways: (1) applied GA(19) became florigenic on exposure to LD; (2) expression of LtGA20ox1, an important GA biosynthetic gene, increased in a florally effective LD involving incandescent lamps, but not with noninductive fluorescent lamps; and (3) paclobutrazol, an inhibitor of an early step of GA biosynthesis, blocked flowering, but only if applied before the LD. Expression studies of a 2-oxidase catabolic gene showed no changes favoring a GA increase. Thus, the early LD increase in leaf GA(5) biosynthesis, coupled with subsequent doubling in GA(5) content at the shoot apex, provides a substantial trail of evidence for GA(5) as a LD florigen. LD signaling may also involve transport of FT mRNA or protein because expression of LtFT and LtCONSTANS increased rapidly, substantially (>80-fold for FT), and independently of GA. However, because a LD from fluorescent lamps induced LtFT expression but not flowering, the nature of the light response of FT requires clarification.

Effects of 17-alkyl-16,17-dihydrogibberellin A(5) derivatives on growth and flowering in Lolium temulentum.

Several gibberellins in which the 16-methyl group of the 16-epimers of dihydro-GA(5) had been replaced by ethyl, n-propyl and n-butyl were prepared and tested at doses of 1, 5 or 25&mgr;g per plant for their effects on stem growth and flowering of the grass Lolium temulentum. The ethyl and n-propyl derivatives were most inhibitory of elongation, the exo-isomers being more active than the endo-forms. While both isomers of dihydro-GA(5) promoted flowering, among the 17-alkyl analogues, only the exo-ethyl derivative showed significant activity.