Implications for health system reform, workforce recovery and rebuilding in the context of the Great Recession and COVID-19: a case study of workforce trends in Ireland 2008-2021.

BACKGROUND: Workforce is a fundamental health systems building block, with unprecedented measures taken to meet extra demand and facilitate surge capacity during the COVID-19 pandemic, following a prolonged period of austerity. This case study examines trends in Ireland's publicly funded health service workforce, from the global financial crisis, through the Recovery period and into the COVID-19 pandemic, to understand resource allocation across community and acute settings. Specifically, this paper aims to uncover whether skill-mix and staff capacity are aligned with policy intent and the broader reform agenda to achieve universal access to integrated healthcare, in part, by shifting free care into primary and community settings. METHODS: Secondary analysis of anonymised aggregated national human resources data was conducted over a period of almost 14 years, from December 31st 2008 to August 31st 2021. Comparative analysis was conducted, by professional cadre, across three keys periods: 'Recession period' December 31st 2008-December 31st 2014; 'Recovery period' December 31st 2014-December 31st 2019; and the 'COVID-19 period' December 31st 2019-August 31st 2021. RESULTS: During the Recession period there was an overall decrease of 8.1% (n = 9333) between December 31st 2008 and December 31st 2014, while the Recovery period saw the overall staff levels rebound and increase by 15.2% (n = 16,789) between December 31st 2014 and December 31st 2019. These figures continued to grow, at an accelerated rate during the most recent COVID-19 period, increasing by a further 8.9% (n = 10,716) in under 2 years. However, a notable shift occurred in 2013, when the number of staff in acute services surpassed those employed in community services (n = 50,038 and 49,857, respectively). This gap accelerated during the Recovery and COVID-19 phase. By August 2021, there were 13,645 more whole-time equivalents in acute settings compared to community, a complete reverse of the 2008 situation. This was consistent across all cadres. Workforce absence trends indicate short-term spikes resulting from shocks while COVID-19 redeployment disproportionately impacted negatively on primary care and community services. CONCLUSIONS: This paper clearly demonstrates the prioritisation of staff recruitment within acute services-increasing needed capacity, without the same commitment to support government policy to shift care into primary and community settings. Concerted action including the permanent redistribution of personnel is required to ensure progressive and sustainable responses are learned from recent shocks.

Trends in, and predictors of, swallowing and social eating outcomes in head and neck cancer survivors: A longitudinal analysis of head and neck 5000.

OBJECTIVE: To investigate the recovery trajectory and predictors of outcome for swallowing difficulties following head and neck cancer treatment in a large prospective cohort. MATERIALS AND METHODS: Data from 5404 participants of the Head and Neck 5000 study were collected from 2011 to 2014. Patient-reported swallowing was measured using the EORTC HN35, recorded at baseline (pre-treatment) and 4 and 12 months post-baseline. Mixed-effects linear multivariable regression was used to investigate time trends, compare cancer sites, and identify associations between clinical, socio-demographic and lifestyle variables. RESULTS: 2458 participants with non-recurrent oral (29%) oropharyngeal (46%) and laryngeal (25%) cancer were included in the analysis. There was a clinically significant deterioration in scores between baseline and four months for swallowing (11.7 points; 95% CI 10.7-12.8) and trouble with social eating (17.9 points; 95% CI 16.7-19.2), but minimal difference between baseline and 12 months. Predictors of better swallowing and social eating were participants with larynx cancer, early-stage disease, treatment type, age, gender, co-morbidity, socio-economic status, smoking behaviour and cohabitation. CONCLUSION: Swallowing problems persist up to a year after head and neck cancer treatment. These findings identify disease and demographic characteristics for particularly vulnerable groups, supporting the need for holistic interventions to help improve swallowing outcomes. People diagnosed with head and neck cancer at risk of severe eating and drinking problems following treatment can be identified earlier in the pathway, receive more accurate information about early and late post-treatment side-effects, which can inform shared decision-making discussions.

Effectiveness and cost-effectiveness of out-of-hours palliative care: a systematic review.

Background: Out-of-hours palliative care is a priority for patients, caregivers and policymakers. Approximately three quarters of the week occurs outside of typical working hours, and the need for support in care of serious and terminal illness during these times is commonplace. Evidence on relevant interventions is unclear. Aim: To review systematically the evidence on the effect of out-of-hours specialist or generalist palliative care for adults on patient and caregiver outcomes, and costs and cost-effectiveness. Methods: A systematic review of peer-reviewed and grey literature was conducted. We searched Embase, MEDLINE [Ovid], Cochrane Library, CINAHL, Allied and Complementary Medicine [Ovid], PsycINFO, Web of Science, Scopus, EconLit (Ovid), and grey literature published between 1 January 2000 and 12 th November 2019. Studies that comparatively evaluated the effect of out-of-hours specialist or generalist palliative care for adults on patient and caregiver outcomes, and on costs and cost-effectiveness were eligible, irrespective of design. Only English-language studies were eligible. Two reviewers independently examined the returned studies at each stage (title and abstract review, full-text review, and quality assessment). Results: We identified one eligible peer-reviewed study, judged as insufficient quality. Other sources returned no eligible material. The systematic review therefore included no studies. Conclusions: The importance of integrated, 24-hour care for people in line with a palliative care approach is not reflected in the literature, which lacks evidence on the effects of interventions provided outside typical working hours. Registration: PROSPERO CRD42018111041.

Sláintecare - A ten-year plan to achieve universal healthcare in Ireland.

In May 2017, an Irish cross-party parliamentary committee published the 'Houses of the Oireachtas Committee on the Future of Healthcare "Sláintecare" report'. The report, known as 'Sláintecare', is unique and historic as it is the first time there has been a cross-party political consensus on major health reform in Ireland. Sláintecare sets out a high level policy roadmap to deliver whole system reform and universal healthcare, phased over a ten year period and costed. Sláintecare details reform proposals which, if delivered, will establish; a universal, single-tier health service where patients are treated solely on the basis of health need; the reorientation of the health system 'towards integrated primary and community care, consistent with the highest quality of patient safety in as short a time-frame as possible'. Sláintecare has five interrelated components: population health; entitlements and access to healthcare; integrated care; funding; and implementation. In this article, the authors use documents in the public domain (parliamentary reports, public hearings, submissions to the Committee, media coverage, the final report of the Committee, speeches by Committee members) to describe the policy process and the main contents of the proposed Sláintecare reforms. It is too soon tell if the political consensus in the policy formation can hold for its implementation.

Clinical pharmacokinetics of thalidomide

Thalidomide is a racemic glutamic acid derivative approved in the US for erythema nodosum leprosum, a complication of leprosy. In addition, its use in various inflammatory and oncologic conditions in being investigated. Thalidomide interconverts between the (R)- and (S)-enantiomers in plasma, with protein binding of 55% and 65%, respectively. More than 90% of the absorbed drug is excreted in the urine and faeces within 48 hours. Thalidomide is minimally metabolised by the liver, but is spontaneously hydrolysed into numerous renally excreted products. After a single oral dose of thalidomide 200mg (as the US-approved capsule formulation) in healthy volunteers, absorption is slow and extensive, resulting in a peak concentration (Cmax) of 1-2mg/L at 3-4 hours after administration, absorption lag time of 30 minutes, total exposure (AUCoo) of 18mg - h/L, apparent elimination half-life of 6 hours and apparent systemic clearence of 10 L/H. Thalidomide pharmacokinetics are best described by a one-comportment model with first-order absorption and elimination. Because of the low solubility of the drug in the gastrointestinal tract, thalidomide exhibits absorption rate-limited pharmacolinetics (the 'flip-flop' phenomenon), with its elimination rate being faster than in absorption rate. The apparent elimination half-life of 6 hours therefore represents absorption, not elimination. The 'true' apparent volume of distribution was estimated to be 16L by use of the faster elimination-rate half-life. Multiple doses of thalidomide 200 mg/day over 21 days cause no change in the pharmacokinetics, with a steady-state Cmax (Cssmax) of 1.2 mg/L. Simulation of 400 and 800 mg/day also shows no accululation, with Css of 3.5 and 6.0 mg/L, respectively. Multiple-dose studies in cancer patients show pharmacokinetics comparable with those in healthy populations at similar dosages. Thalidomide exhibits a dose-proportional increase in AUC at doses from 50 to 400mg. Because of the low solubility of thalidomide Cmax is less than proportional to dose, and tmax is prolonged with increasing dose. Age, sex and smoking have no effect on the pharmacokinetics of thalidomide, and the effect of food is minimal. Thalidomide does not alter the pharmacokinetics of oral contraceptives, and is also unlikely to interact with warfarin and grapefruit juice. Since thalidomide is mainly hydrolysed and passively excreted, its pharmacokonetics are not expected to change in patients with impaired liver...

A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in beagle dogs.

d-Methylphenidate (d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d,l-methylphenidate (d,l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d,l-MPH for 90 days, followed by a 30-day recovery period. The top d-MPH dose of 10 mg/kg was equimolar to 20 mg/kg d,l-MPH in d-MPH content. The 10-mg/kg d-MPH and d,l-MPH doses were at least 13 times the maximum therapeutic dose giving rise to systemic exposures that were equivalent to or at least 2 times greater than those at the maximum therapeutic doses in children. The 10-mg/kg d-MPH and 20-mg/kg d,l-MPH doses had systemic exposures that were equivalent to or two to five times greater than the maximum therapeutic plasma levels in children respectively. There was no treatment-related mortality in all doses tested. Reversible salivation, hyperactivity, and diarrhea were seen in the high-dose d-MPH and d,l-MPH groups. Significant body weight loss and reduction in food consumption were observed in males for both high-dose groups with weights comparable to control values by the end of the recovery period. There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day.

Investigating mechanisms involved in the self-incompatibility response in Papaver rhoeas.

Sexual reproduction in flowering plants is controlled by recognition mechanisms involving the male gametophyte (the pollen) and the female sporophyte (the pistil). Self-incompatibility (SI) involves the recognition and rejection of self- or incompatible pollen by the pistil. In Papaver rhoeas, SI uses a Ca(2+)-based signalling cascade triggered by the S-protein, which is encoded by the stigmatic component of the S-locus. This results in the rapid inhibition of incompatible pollen tube growth. We have identified several targets of the SI signalling cascade, including protein kinases, the actin cytoskeleton and nuclear DNA. Here, we summarize progress made on currently funded projects in our laboratory investigating some of the components targeted by SI, comprising (i) the characterization of a pollen phosphoprotein (p26) that is rapidly phosphorylated upon an incompatible SI response; (ii) the identification and characterization of a pollen mitogen-activated protein kinase (p56), which exhibits enhanced activation during SI; (iii) characterizing components involved in the reorganization and depolymerization of the actin cytoskeleton during the SI response; and (iv) investigating whether the SI response involves a programmed cell death signalling cascade.

Neurobehavioral effects of racemic threo-methylphenidate and its D and L enantiomers in rats.

D,L-methylphenidate (Ritalin) is used to treat attention deficit hyperactivity disorder (ADHD) in children. The therapeutic effect is predominantly due to the d enantiomer. Dexmethylphenidate (D-MPH; Focalin) was therefore developed for its better therapeutic index. The present study determined and compared the acute behavioral toxicity of D,L-MPH, D-MPH and L-MPH in rats after oral dosing. Comprehensive functional observational battery (FOB) evaluations and rota-rod tests were performed 30, 60 and 120 min after dosing. Ten rats/sex/dose were administered a single dose of vehicle, 2, 20, 100 mg/kg D,L-MPH and 1, 10, 50 mg/kg D-MPH or 1, 100, 500 mg/kg L-MPH. There was no mortality. Certain FOB evaluations were statistically significant from vehicle control at any of the time points with most occurring at 60 and 120 min in the high D,L-MPH dose. These included increases in rearing, difficulty in removal from box, arousal, click, tail-pinch and decreases in hind-limb splay distance, hind-limb grip strength and handling reactivity. Behavioral responses were also present at the mid-dose D,L-MPH and high dose D- and L-MPH. Responses in female were significantly different from males in D,L- and L-MPH groups suggesting a sex difference in sensitivity. In the rota-rod test, mean latency to remain on the rod was significantly less for males compared to control given high dose D-MPH and D,L-MPH. In females, latency times were significantly less for high doses of all three compounds. In summary, fewer significant FOBs were seen with D- and L-MPH compared to equimolar doses of D,L-MPH. L-MPH was the least potent in producing FOBs. These results were supported by rota-rod studies.