The impact of devolution on local health systems: Evidence from Greater Manchester, England.

Devolution and decentralisation policies involving health and other government sectors have been promoted with a view to improve efficiency and equity in local service provision. Evaluations of these reforms have focused on specific health or care measures, but little is known about their full impact on local health systems. We evaluated the impact of devolution in Greater Manchester (England) on multiple outcomes using a whole system approach. We estimated the impact of devolution until February 2020 on 98 measures of health system performance, using the generalised synthetic control method and adjusting for multiple hypothesis testing. We selected measures from existing monitoring frameworks to populate the WHO Health System Performance Assessment framework. The included measures captured information on health system functions, intermediatory objectives, final goals, and social determinants of health. We identified which indicators were targeted in response to devolution from an analysis of 170 health policy intervention documents. Life expectancy (0.233 years, S.E. 0.012) and healthy life expectancy (0.603 years, S.E. 0.391) increased more in GM than in the estimated synthetic control group following devolution. These increases were driven by improvements in public health, primary care, hospital, and adult social care services as well as factors associated with social determinants of health, including a reduction in alcohol-related admissions (-110.1 admission per 100,000, S.E. 9.07). In contrast, the impact on outpatient, mental health, maternity, and dental services was mixed. Devolution was associated with improved population health, driven by improvements in health services and wider social determinants of health. These changes occurred despite limited devolved powers over health service resources suggesting that other mechanisms played an important role, including the allocation of sustainability and transformation funding and the alignment of decision-making across health, social care, and wider public services in the region.

Lactate and hydrogen ions play a predominant role in evoking the exercise pressor reflex during ischaemic contractions but not during freely perfused contractions.

We investigated the role played by lactate and hydrogen in evoking the exercise pressor reflex (EPR) in decerebrated rats whose hindlimb muscles were either freely perfused or ischaemic. Production of lactate and hydrogen by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (pygm). In knockout rats (pygm-/-; n = 13) or wild-type rats (pygm+/+; n = 13), the EPR was evoked by isometrically contracting the triceps surae muscles. Blood pressure, tension, blood flow, renal sympathetic nerve activity and blood lactate concentrations were measured. Intramuscular metabolites and pH changes induced by the contractions were quantified by 31P-magnetic resonance spectroscopy (n = 5). In a subset of pygm-/- rats (n = 5), contractions were evoked with prior infusion of lactate (pH 6.0) in an attempt to restore the effect of lactate and hydrogen ions. Contraction of freely perfused muscles increased blood lactate and decreased muscle pH in pygm+/+ rats only. Despite these differences, the reflex pressor and sympathetic responses to freely perfused contraction did not differ between groups (P = 0.992). During ischaemia, contraction increased muscle lactate and hydrogen ion production in pygm+/+ rats (P < 0.0134), whereas it had no effect in pygm-/- rats (P > 0.783). Likewise, ischaemia exaggerated the reflex pressor, and sympathetic responses to contraction in pygm+/+ but not in pygm-/- rats. This exaggeration was restored when a solution of lactate (pH 6.0) was infused prior to the contraction in pygm-/- rats. We conclude that lactate and hydrogen accumulation in contracting myocytes play a key role in evoking the metabolic component of the EPR during ischaemic but not during freely perfused contractions. KEY POINTS: Conflicting results exist about the role played by lactate and hydrogen ions in evoking the exercise pressor reflex. Using CRISP-Cas9, we rendered the myophosphorylase gene non-functional to block the production of lactate and hydrogen ions. The exercise pressor reflex was evoked in decerebrated rats by statically contracting the triceps surae muscles with or without muscle ischaemia. Static contraction elevated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Despite these differences, the exercise pressor reflex was not different between groups. Acute muscle ischaemia exaggerated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Likewise, acute muscle ischaemia exaggerated the exercise pressor reflex in pygm+/+ but not in pygm-/- rats. We conclude that lactate and hydrogen play a key role in evoking the exercise pressor reflex during ischaemic but not during freely perfused contractions.

Paradoxical potentiation of the exercise pressor reflex by endomorphin 2 in the presence of naloxone.

When contracting muscles are freely perfused, the acid-sensing ion channel 3 (ASIC3) on group IV afferents plays a minor role in evoking the exercise pressor reflex. We recently showed in isolated dorsal root ganglion neurons innervating the gastrocnemius muscles that two mu opioid receptor agonists, namely endomorphin 2 and oxycodone, potentiated the sustained inward ASIC3 current evoked by acidic solutions. This in vitro finding prompted us to determine whether endomorphin 2 and oxycodone, when infused into the arterial supply of freely perfused contracting hindlimb muscles, potentiated the exercise pressor reflex. We found that infusion of endomorphin 2 and naloxone in decerebrated rats potentiated the pressor responses to contraction of the triceps surae muscles. The endomorphin 2-induced potentiation of the pressor responses to contraction was prevented by infusion of APETx2, an ASIC3 antagonist. Specifically, the peak pressor response to contraction averaged 19.3 ± 5.6 mmHg for control (n = 10), 27.2 ± 8.1 mmHg after naloxone and endomorphin 2 infusion (n = 10), and 20 ± 8 mmHg after APETx2 and endomorphin 2 infusion (n = 10). Infusion of endomorphin 2 and naloxone did not potentiate the pressor responses to contraction in ASIC3 knockout rats (n = 6). Partly similar findings were observed when oxycodone was substituted for endomorphin 2. Oxycodone infusion significantly increased the exercise pressor reflex over its control level, but subsequent APETx2 infusion failed to restore the increase to its control level (n = 9). The peak pressor response averaged 23.1 ± 8.6 mmHg for control (n = 9), 33.2 ± 11 mmHg after naloxone and oxycodone were infused (n = 9), and 27 ± 8.6 mmHg after APETx2 and oxycodone were infused (n = 9). Our data suggest that after opioid receptor blockade, ASIC3 stimulation by the endogenous mu opioid, endomorphin 2, potentiated the exercise pressor reflex.NEW & NOTEWORTHY This paper provides the first in vivo evidence that endomorphin 2, an endogenous opioid peptide, can paradoxically increase the magnitude of the exercise pressor reflex by an ASIC3-dependent mechanism even when the contracting muscles are freely perfused.

Inhibition and potentiation of the exercise pressor reflex by pharmacological modulation of TRPC6 in male rats.

We determined the role played by the transient receptor potential canonical 6 (TRPC6) channel in evoking the mechanical component of the exercise pressor reflex in male decerebrated Sprague-Dawley rats. TRPC6 channels were identified by quadruple-labelled (DiI, TRPC6, neurofilament-200 and peripherin) immunohistochemistry in dorsal root ganglion (DRG) cells innervating the triceps surae muscles (n = 12). The exercise pressor reflex was evoked by statically contracting the triceps surae muscles before and after injection of the TRPC6 antagonist BI-749327 (n = 11; 12 µg kg-1 ) or SAR7334 (n = 11; 7 µg kg-1 ) or the TRPC6 positive modulator C20 (n = 11; 18 µg kg-1 ). Similar experiments were conducted while the muscles were passively stretched (n = 8-12), a manoeuvre that isolated the mechanical component of the reflex. Blood pressure, tension, renal sympathetic nerve activity (RSNA) and blood flow were recorded. Of the DRG cells innervating the triceps surae muscles, 85% stained positive for the TRPC6 antigen, and 45% of those cells co-expressed neurofilament-200. Both TRPC6 antagonists decreased the reflex pressor responses to static contraction (-32 to -42%; P < 0.05) and to passive stretch (-35 to -52%; P < 0.05), whereas C20 increased these responses (55-65%; P < 0.05). In addition, BI-749327 decreased the peak and integrated RSNA responses to both static contraction (-39 to -43%; P < 0.05) and passive stretch (-56 to -62%; P < 0.05), whereas C20 increased the RSNA to passive stretch only. The onset latency of the decrease or increase in RSNA occurred within 2 s of the onset of the manoeuvres (P < 0.05). Collectively, our results show that TRPC6 plays a key role in evoking the mechanical component of the exercise pressor reflex. KEY POINTS: The exercise pressor reflex plays a key role in the sympathetic and haemodynamic responses to exercise. This reflex is composed of two components, namely the mechanoreflex and the metaboreflex. The receptors responsible for evoking the mechanoreflex are poorly documented. A good candidate for this function is the transient receptor potential canonical 6 (TRPC6) channel, which is activated by mechanical stimuli and expressed in dorsal root ganglia of rats. Using two TRPC6 antagonists and one positive modulator, we investigated the role played by TRPC6 in evoking the mechanoreflex in decerebrated rats. Blocking TRPC6 decreased the renal sympathetic and the pressor responses to both contraction and stretch, the latter being a manoeuvre that isolates the mechanoreflex. In contrast, the positive modulator increased the pressor reflex to contraction and stretch, in addition to the sympathetic response to stretch. Our results provide strong support for a role played by the TRPC6 channel in evoking the mechanoreflex.

Evaluating whole system reforms: A structured approach for selecting multiple outcomes.

Whole-system reforms, including devolution and integration of health and social care services, have the potential to impact multiple dimensions of health system performance. Most evaluations focus on a single or narrow subsets of outcomes amenable to change. This approach may not: (i) capture the overall effect of the reform, (ii) identify the mechanisms through which system-wide changes may have occurred, (iii) prevent post-hoc selection of outcomes based on significant results; and (iv) facilitate comparisons across settings. We propose a structured approach for selecting multiple quantitative outcome measures, which we apply for evaluating health and social care devolution in Greater Manchester, England. The approach consists of five-steps: (i) defining outcome domains based on a framework, in our case the World Health Organisation's Health System Performance Assessment Framework; (ii) reviewing performance metrics from national monitoring frameworks; (iii) excluding similar and condition specific outcomes; (iv) excluding outcomes with insufficient data; and (v) mapping implemented policies to identify a subset of targeted outcomes. We identified 99 outcomes, of which 57 were targeted. The proposed approach is detail and time-intensive, but useful for both researchers and policymakers to promote transparency in evaluations and facilitate the interpretation of findings and cross-settings comparisons.

Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats.

The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1+/+ , TRPV1+/- and TRPV1-/- rats. Carotid arterial injection of capsaicin (0.5 µg), evoked significant pressor responses in TRPV1+/+ and TRPV1+/- rats, but not in TRPV1-/- rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1+/+ and TRPV1+/- rats but not in neurons isolated from TRPV1-/- rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1+/+ , TRPV1+/- and TRPV1-/- rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid-sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1-/- rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply. KEY POINTS: A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise. The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand. The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel. Using genetically engineered rats in which the TRPV1 channel is rendered non-functional, we have shown that it is not needed to evoke the metaboreflex.

Analysing changes to the flow of public funding within local health and care systems: An adaptation of the System of Health Accounts framework to a local health system in England.

Financial flows relating to health care are routinely analysed at national and international level. They have rarely been systematically analysed at local level, despite sub-national variation due to population needs and decisions enacted by local organisations. We illustrate an adaptation of the System of Health Accounts framework to map the flow of public health and care funding within local systems, with an application for Greater Manchester (GM), an area in England which agreed a health and social care devolution deal with the central government in 2016. We analyse how financial flows changed in GM during the four years post-devolution, and whether spending was aligned with local ambitions to move towards prevention of ill-health and integration of health and social care. We find that GM decreased spending on public health by 15%, and increased spending on general practice by 0.1% in real terms. The share of total local expenditure paid to NHS Trusts for general and acute services increased from 70.3% to 71.6%, while that for community services decreased from 11.7% to 10.3%. Results suggest that GM may have experienced challenges in redirecting resources towards their goals. Mapping financial flows at a local level is a useful exercise to examine whether spending is aligned with system goals and highlight areas for further investigation.

The impact of devolution on experienced health and well-being.

Devolution of health systems from national to local levels is a common focus of policymakers across the world. The overarching aim is to improve population health by better meeting the specific needs of local citizens. We examine the case of a coordinated devolution across several public service sectors in Greater Manchester, England, in 2016. We estimate the impact on experienced health and well-being using Short-Form 12 scores from 13,938 adult respondents to the UK Household Longitudinal Survey between 2012 and 2020. We use difference-in-differences and lagged-dependent variable regressions to compare Greater Manchester to the rest of England. We find no statistically significant changes in experienced health and well-being over the four years following the start of devolution. Our findings suggest that devolving population health management alone without budgetary powers and local accountability mechanisms may not be effective in improving experienced health and well-being in the relatively short-term.

Early effects of COVID-19 on maternal and child health service disruption in Mozambique.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Introduction: After the World Health Organization declared COVID-19 a pandemic, more than 184 million cases and 4 million deaths had been recorded worldwide by July 2021. These are likely to be underestimates and do not distinguish between direct and indirect deaths resulting from disruptions in health care services. The purpose of our research was to assess the early impact of COVID-19 in 2020 and early 2021 on maternal and child healthcare service delivery at the district level in Mozambique using routine health information system data, and estimate associated excess maternal and child deaths. Methods: Using data from Mozambique's routine health information system (SISMA, Sistema de Informação em Saúde para Monitoria e Avaliação), we conducted a time-series analysis to assess changes in nine selected indicators representing the continuum of maternal and child health care service provision in 159 districts in Mozambique. The dataset was extracted as counts of services provided from January 2017 to March 2021. Descriptive statistics were used for district comparisons, and district-specific time-series plots were produced. We used absolute differences or ratios for comparisons between observed data and modeled predictions as a measure of the magnitude of loss in service provision. Mortality estimates were performed using the Lives Saved Tool (LiST). Results: All maternal and child health care service indicators that we assessed demonstrated service delivery disruptions (below 10% of the expected counts), with the number of new users of family planing and malaria treatment with Coartem (number of children under five treated) experiencing the largest disruptions. Immediate losses were observed in April 2020 for all indicators, with the exception of treatment of malaria with Coartem. The number of excess deaths estimated in 2020 due to loss of health service delivery were 11,337 (12.8%) children under five, 5,705 (11.3%) neonates, and 387 (7.6%) mothers. Conclusion: Findings from our study support existing research showing the negative impact of COVID-19 on maternal and child health services utilization in sub-Saharan Africa. This study offers subnational and granular estimates of service loss that can be useful for health system recovery planning. To our knowledge, it is the first study on the early impacts of COVID-19 on maternal and child health care service utilization conducted in an African Portuguese-speaking country.

The impact of performance-based financing within local health systems: Evidence from Mozambique.

Most evidence on Performance Based Financing (PBF) in low-income settings has focused on services delivered by providers in targeted health administrations, with limited understanding of how effects on health and care vary within them. We evaluated the population effects of a program implemented in two provinces in Mozambique, focusing on child, maternal and HIV/AIDS care and knowledge. We used a difference-in-difference estimation strategy applied to data on mothers from the Demographic Health Surveys, linked to information on their closest health facility. The impact of PBF was limited. HIV testing during antenatal care increased, particularly for women who were wealthier, more educated, or residing in Gaza Province. Knowledge about transmission of HIV from mother-to-child, and its prevention, increased, particularly for women who were less wealthy, less educated, or residing in Nampula Province. Exploiting the roll-out by facility, we found that the effects were concentrated on less wealthy and less educated women, whose closest facility was in the referral network of a PBF facility. Results suggest that HIV testing and knowledge promotion increased in the whole district, as a strategy to boost referral for highly incentivized HIV services delivered in PBF facilities. However, demand-side constraints may prevent the use of those services.