Developing a timeline for evaluating public health nutrition policy interventions: what are the outcomes and when should we expect to see them?

Objective: To develop a timeline for evaluating public health nutrition policy interventions. Design: Concept mapping, a stakeholder-driven approach for developing an evaluation framework to estimate the ‘time to impact’ for policy interventions. The Schools (Health Promotion and Nutrition) (Scotland) Act 2007 was used as the model to develop the evaluation timeline as it had typical characteristics of government policy. Concept mapping requires stakeholders to generate a list of the potential outcomes, sort and rate the outcomes. Multidimensional scaling and hierarchical cluster data analysis were used to develop an anticipated timeline to impact for the policy. Setting: United Kingdom. Subjects: One hundred and eleven stakeholders representing nutrition, public health, medicine, education and catering in a range of sectors: research, policy, local government, National Health Service and schools. Results: Eighty-five possible outcomes were identified and grouped into thirteen clusters describing higher-level themes (e.g. long-term health, food literacy, economics, behaviour, diet, education). Negative and unintended consequences were anticipated relatively soon after implementation of the policy, whereas positive outcomes (e.g. dietary changes, health benefits) were thought likely to take longer to emerge. Stakeholders responsible for implementing the legislation anticipated that it would take longer to observe changes than those from policy or research. Conclusions: Developing an anticipated timeline provides a realistic framework upon which to base an outcome evaluation for policy interventions and identifies positive and negative outcomes as well as considering possible unintended consequences. It offers benefit to both policy makers and researchers in mapping the progress expected towards long-term health goals and outcomes

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Do Home Invasion Serial Killers Warrant a Distinct Classification from Other Serial Killer Location Types? A Retrospective Comparative Examination

This dissertation seeks to address the research gap in serial homicide regarding home invasion serial killers (HISKs) and add to existing policy by providing insight and approaches to assist in serial murder investigations of such killers. Data for the study was obtained from the 2019 Radford University/Florida Gulf Coast University Serial Killer Database (RU/FGCU SKD) and additional public information searches. A retrospective comparative design and proportionate stratified random sampling of 326 serial killers from the RU/FGCU SKD (2019) were used to examine the differences and classifications of HISKs and non-home invasion serial killers (non-HISKs) in three investigations: (1) common characteristics; (2) geospatial patterns; and (3) criminal precipitators. The study contributes to knowledge in three key ways. First, Study One revealed that HISKs warrant a distinct classification from non-HISKs regarding their modus operandi and crime scene actions (stalked attacks and single location crime scenes). These findings lend further evidence to support Routine Activity and Rational Choice perspectives regarding the offense patterns of residential sex offenders. Such findings can also aid law enforcement in serial murder investigations by providing sets of characteristics for both groups that could lead to swifter apprehensions, prevent future murders in a series, and assist in cold cases. Second, this dissertation raises public awareness of the problem of HISKs. Home invasion serial homicide is one of the most prevalent forms of serial murder, indicating that an individual’s home does not unequivocally safeguard residents from serial killers. Public awareness of HISKs, and situational crime prevention measures can result in policy-relevant implications, leading to reactive and proactive strategies to reduce or prevent home invasion serial homicide. Finally, this study addresses the research gap and advances our understanding of HISKs in the three analytical dimensions investigated in this dissertation. The findings also serve as a comparative baseline relevant to environmental criminology and developmental/life-course perspectives. Future research is recommended to bridge the gap in serial homicide literature concerning HISKs to provide a more comprehensive understanding and preventative approaches to deter such serial killers in the future

How much damage do serial homicide offenders wrought while the innocent rot in prison? A tabulation of preventable deaths as outcomes of sentinel events

The criminal justice system has allowed serial homicide offenders (SHOs) to commit additional homicides by failing to identify them after their initial homicide. Recidivism has been possible in instances where the SHO benefited from the wrongful incarceration of an innocent person for one of their homicides. Data from the National Registry of Exonerations was utilized to tabulate the full extent of these sentinel events, defined as the number of deaths that could have been prevented. Additional research was conducted to identify where victims fell in the offender’s killing sequence. This ancillary data revealed the number of victims whose deaths could have been prevented had the offender been apprehended earlier in their series of homicides. Sixty-two SHOs were responsible for 249 deaths, 114 of which were committed after an innocent person was incarcerated for the SHO’s initial homicide. To prevent further loss of life, law enforcement must: act upon accurate information; lower the SHO evidentiary threshold; prevent personal bias from influencing investigative steps; obtain training in the behavior of SHOs; admit mistakes; and re-examine convictions if wrongdoing is suspected