Key Learnings from the Development and Early Use of Global Guidance on the Integration of COVID-19 Vaccination into Broader Health Systems.

More than 13.5 billion COVID-19 vaccine doses were delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the continued circulation of SARS-CoV2 and the need for periodic boosters being most likely, countries were required to plan for more sustainable approaches to provide COVID-19 vaccinations. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programs and as part of broader health systems was published jointly by the WHO and UNICEF to respond to country needs. This paper summarizes the approach to, and lessons learned during, the development of a global guidance document and describes some examples of its early use in low- and middle-income countries (LMICs). The guidance leveraged existing health system frameworks, proposed four steps for planning and implementing the COVID-19 vaccination integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support countries with the integration of COVID-19 vaccination. The rapid dissemination of the guidance document allowed countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programs (beyond immunization) remain challenges, particularly in LMICs. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders within and beyond immunization towards a common objective is powerful and can allow progress to be made in terms of integrating health services and better preparing for future pandemics.

Estimating the delivery costs of COVID-19 vaccination using the COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool: the Lao People's Democratic Republic experience.

BACKGROUND: The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People's Democratic Republic (Lao PDR). METHODS: From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar. RESULTS: From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79-0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15-34% and 15-24% of the total costs in all scenarios, respectively. 17-26% went to data management, monitoring and evaluation, and oversight, and 13-22% to vaccine delivery. CONCLUSIONS: With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost-benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.

ICP during head movement: significance of the venous system.

BACKGROUND: It is thought that the internal jugular veins (IJV) are the primary route for cranial venous outflow in supine position and the vertebral venous plexus when upright. Previous studies have noted a greater increase in intracranial pressure (ICP) when subjects turn their head in one direction compared to the other, but no clear cause had been investigated. We hypothesised that in the supine position, head turning and consequently obstructing the IJV draining the dominant transverse sinus (TVS) would lead to a greater rise in ICP compared to turning to the non-dominant side. METHODS: A prospective study in a large-volume neurosurgical centre. Patients undergoing continuous ICP monitoring as part of their standard clinical management were recruited. Immediate ICP was measured in different head positions (neutral, rotated to the right and left) when supine, seated, and standing. TVS dominance was established by consultant radiologist report on venous imaging. RESULTS: Twenty patients were included in the study, with a median age of 44 years. Venous system measurements revealed 85% right-sided vs 15% left-sided dominance. Immediate ICP rose more when head turning from neutral to the dominant TVS (21.93mmHg ± 4.39) vs non-dominant side (16.66mmHg ± 2.71) (p= <0.0001). There was no significant relationship in the sitting (6.08mmHg ± 3.86 vs 4.79mmHg ± 3.81, p = 0.13) or standing positions (8.74mmHg ± 4.30 vs 6.76mmHg ± 4.14, p =0.07). CONCLUSION: This study has provided further evidence that the transverse venous sinus to internal jugular system pathway is the likely primary venous drainage when supine; and quantified its effect when head turning on ICP. It may guide patient-specific nursing care and advice.

Consumption and tax gains attributable to Covid-19 vaccinations in 12 EU countries with low vaccination rates.

BACKGROUND: The Covid-19 pandemic is an economic and a health crisis. Households reduced consumption expenditures as large-scale physical distancing measures, lower disposable incomes and fear of infection when engaging in many types of economic activity took hold. This, in turn, reduced domestic tax revenues at a time when governments were facing increased financial pressures to strengthen and sustain welfare states. METHODS: We developed a simulation model, the Covid-19 Taxination Simulator, to estimate potential economic gains and tax revenues attributable to vaccine rollouts. We apply the model to 12 European Union countries which had low vaccination rates at the beginning of 2022. RESULTS: The highest growth in aggregate personal consumption expenditure attributable to Covid-19 vaccines administered as of January 2022 is in Greece (10.8%), Slovenia (8.6%) and Czechia (8.6%), while the lowest is in Bulgaria (2.2%) and Slovakia (2.1%). If countries had vaccinated 85% of their adult population, the largest gains in consumption tax revenues would be expected in Romania (830 million Euros) and Poland (738 million Euros). Consumption tax revenues generated by meeting the 85% of the adult population target would, on their own, be large enough to fully cover the costs of expanding the vaccine rollout itself in Estonia, Latvia, Slovenia, Croatia, Czechia, Hungary and Greece. CONCLUSION: Covid-19 vaccination rollouts not only save lives and relieve pressures on health systems, they also support economic growth and generate additional tax revenues. These revenues can partially offset the costs of vaccines programmes themselves.

Real-world evaluation of Brainomix e-Stroke software.

BACKGROUND AND PURPOSE: Brainomix e-Stroke is an artificial intelligence-based decision support tool that aids the interpretation of CT imaging in the context of acute stroke. While e-Stroke has the potential to improve the speed and accuracy of diagnosis, real-world validation is essential. The aim of this study was to prospectively evaluate the performance of Brainomix e-Stroke in an unselected cohort of patients with suspected acute ischaemic stroke. METHODS: The study cohort included all patients admitted to the University College London Hospital Hyperacute Stroke Unit between October 2021 and April 2022. For e-ASPECTS and e-CTA, the ground truth was determined by a neuroradiologist with access to all clinical and imaging data. For e-CTP, the values of the core infarct and ischaemic penumbra were compared with those derived from syngo.via, an alternate software used at our institution. RESULTS: 1163 studies were performed in 551 patients admitted during the study period. Of these, 1130 (97.2%) were successfully processed by e-Stroke in an average of 4 min. For identifying acute middle cerebral artery territory ischaemia, e-ASPECTS had an accuracy of 77.0% and was more specific (83.5%) than sensitive (58.6%). The accuracy for identifying hyperdense thrombus was lower (69.1%), which was mainly due to many false positives (positive predictive value of 22.9%). Identification of acute haemorrhage was highly accurate (97.8%) with a sensitivity of 100% and a specificity of 97.6%; false positives were typically caused by areas of calcification. The accuracy of e-CTA for large vessel occlusions was 91.5%. The core infarct and ischaemic penumbra volumes provided by e-CTP strongly correlated with those provided by syngo.via (ρ=0.804-0.979). CONCLUSION: Brainomix e-Stroke software provides rapid and reliable analysis of CT imaging in the acute stroke setting although, in line with the manufacturer's guidance, it should be used as an adjunct to expert interpretation rather than a standalone decision-making tool.

Classical infratentorial superficial siderosis of the central nervous system: pathophysiology, clinical features and management.

The term superficial siderosis (SS) is derived from the Greek word 'sideros', meaning iron. It includes two subtypes, distinguished by their anatomical distribution, causes and clinical features: 'classical' infratentorial SS (iSS, which sometimes also affects supratentorial regions) and cortical SS (cSS, which affects only supratentorial regions). This paper considers iSS, a potentially disabling disorder usually associated with very slow persistent or intermittent subarachnoid bleeding from a dural defect, and characterised by progressive hearing and vestibular impairment, ataxia, myelopathy and cognitive dysfunction. The causal dural defect-most often spinal but sometimes in the posterior fossa-typically follows trauma or neurosurgery occurring decades before diagnosis. Increasing recognition of iSS with paramagnetic-sensitive MRI is leading to an unmet clinical need. Given the diagnostic challenges and complex neurological impairments in iSS, we have developed a multidisciplinary approach involving key teams. We discuss pathophysiology, diagnosis and management of iSS, including a proposed clinical care pathway.

Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis.

BACKGROUND AND IMPORTANCE  : Classical infratentorial superficial siderosis (iSS) is characterised by repeated insidious bleeding into the subarachnoid space, leading to haemosiderin deposition within the subpial layers of the brainstem, cerebellum and spinal cord, sometimes with supratentorial involvement. Although nearly always associated with a dural defect (usually from previous trauma or neurosurgery) there is little evidence to support definitive investigation and management strategies. Here, we present a novel investigation strategy to identify a dural defect and subsequent successful surgical repair with biochemical resolution of subarachnoid bleeding. CLINICAL PRESENTATION: A 55-year-old gentleman presented with a 15-year progressive history of sensorineural deafness, followed by a slowly worsening gait ataxia. He had previously sustained cranio-spinal trauma. On examination there were features of myelopathy and ataxia. MRI demonstrated classical iSS, affecting cerebellum and cerebral cortices, with a cervicothoracic epidural CSF collection. Lumbar puncture (LP) revealed elevated ferritin 413 ng/mL and red cell count of 4160. Reverse CT myelography, a novel technique involving contrast injection into the collection, delineated a dural defect at the T9/T10 level that was not present on conventional myelography. Following surgical repair, repeat LP twelve months later demonstrated biochemical improvement (ferritin 18 ng/mL, red cells < 1). There was no further neurological deterioration in symptoms during eighteen months follow-up. CONCLUSION: We show the value of a rational targeted investigation pathway in identifying a surgically reparable dural defect underlying classical iSS. We also provide proof of concept that surgical repair can facilitate biochemical resolution of subarachnoid bleeding and might prevent progression of neurological disability.

How precise is PreSize Neurovascular? Accuracy evaluation of flow diverter deployed-length prediction.

OBJECTIVE: The use of flow-diverting stents has been increasingly important in intracranial aneurysm treatment. However, accurate sizing and landing zone prediction remain challenging. Inaccurate sizing can lead to suboptimal deployment, device waste, and complications. This study presents stent deployment length predictions offered in medical software (PreSize Neurovascular) that provides physicians with real-time planning support, allowing them to preoperatively "test" different devices in the patient's anatomy in a safe virtual environment. This study reports the software evaluation methodology and accuracy results when applied to real-world data from a wide range of cases and sources as a necessary step in demonstrating its reliability, prior to impact assessment in prospective clinical practice. METHODS: Imaging data from 138 consecutive stent cases using the Pipeline embolization device were collected from 5 interventional radiology centers in the United Kingdom and retrospectively analyzed. Prediction accuracy was calculated as the degree of agreement between stent deployed length measured intraoperatively and simulated in the software. RESULTS: The software predicted the deployed stent length with a mean accuracy of 95.61% (95% confidence interval [CI] 94.87%-96.35%), the highest reported accuracy in clinical stent simulations to date. By discounting 4 outlier cases, in which events such as interactions with coils and severe push/pull maneuvers impacted deployed length to an extent the software was not able to simulate or predict, the mean accuracy further increases to 96.13% (95% CI 95.58%-96.69%). A wide discrepancy was observed between labeled and measured deployed stent length, in some cases by more than double, with no demonstrable correlation between device dimensions and deployment elongation. These findings illustrate the complexity of stent behavior and need for simulation-assisted sizing for optimal surgical planning. CONCLUSIONS: The software predicts the deployed stent length with excellent accuracy and could provide physicians with real-time accurate device selection support.

Neuropsychological and neuroimaging characteristics of classical superficial siderosis.

OBJECTIVE: To define the neuropsychological and neuroimaging characteristics of classical infratentorial superficial siderosis (iSS), a rare but disabling disorder defined by hemosiderin deposition affecting the superficial layers of the cerebellum, brainstem and spinal cord, usually associated with a slowly progressive neurological syndrome of deafness, ataxia and myelopathy. METHODS: We present the detailed neuropsychological and neuroimaging findings in 16 patients with iSS (mean age 57 years; 6 female). RESULTS: Cognitive impairment was present in 8/16 (50%) of patients: executive dysfunction was the most prevalent (44%), followed by impairment of visual recognition memory (27%); other cognitive domains were largely spared. Disease symptom duration was significantly correlated with the number of cognitive domains impaired (r = 0.59, p = 0.011). Mood disorders were also common (anxiety 62%, depression 38%, both 69%) but not associated with disease symptom duration. MRI findings revealed siderosis was not only in infratentorial brain regions, but also in characteristic widespread symmetrical supratentorial brain regions, independent of disease duration and degree of cognitive impairment. The presence of small vessel disease markers was very low and did not account for the cognitive impairment observed. CONCLUSION: Neuropsychological disturbances are common in iSS and need to be routinely investigated. The lack of association between the anatomical extent of hemosiderin and cognitive impairment or disease duration suggests that hemosiderin itself is not directly neurotoxic. Additional biomarkers of iSS disease severity and progression are needed for future research and clinical trials.

Economic Contraction from COVID-19 in the Pacific: Implications for Health Financing.

Pacific Island countries (PIC) have emerged as among the most at-risk globally from the collateral economic damage resulting from the COVID-19 pandemic, despite being largely spared its direct health effects so far. Current projections indicate that all PIC will experience an economic contraction in 2020, ranging from -1.0% in Tuvalu to -21.7% in Fiji, worse than most countries globally on average. Given that more than 80% of financing for health in the Pacific comes from domestic and external public sources, the net impact of the economic contraction on resources for health will depend on whether overall public spending can offset the decline in economic activity and how health will be prioritized in government budgets relative to other sectors. Without active reprioritization, most countries could see a slowdown or even decline in per capita levels of public spending for health in the region, risking gains made in advancing universal health coverage in recent years. If health ministries do not act quickly and in consort with other ministries (particularly ministries of finance), including by taking active steps to improve the efficient use of existing resources and other measures to mitigate the economic effects of the crisis on resources for health, it is likely that current economic circumstances will result in unplanned changes. These changes may not deliver the health outcomes that the health ministries would select themselves and may result in a reversal of hard-fought health gains.

Cerebral venous thrombosis: a practical guide.

All neurologists need to be able to recognise and treat cerebral venous thrombosis (CVT). It is difficult to diagnose, partly due to its relative rarity, its multiple and various clinical manifestations (different from 'conventional' stroke, and often mimicking other acute neurological conditions), and because it is often challenging to obtain and interpret optimal and timely brain imaging. Although CVT can result in death or permanent disability, it generally has a favourable prognosis if diagnosed and treated early. Neurologists involved in stroke care therefore also need to be aware of the treatments for CVT (with varying degrees of supporting evidence): the mainstay is prompt anticoagulation but patients who deteriorate despite treatment can be considered for endovascular procedures (endovascular thrombolysis or thrombectomy) or neurosurgery (decompressive craniotomy). This review summarises current knowledge on the risk factors, diagnosis, treatment and prognosis of CVT in adults, and highlights some areas for future research.

Case Report: Auditory Neuropathy and Central Auditory Processing Deficits in a Neuro-Otological Case-Study of Infratentorial Superficial Siderosis.

Hearing and balance impairment are the most frequently reported features of infratentorial (classical) superficial siderosis (iSS). There are few comprehensive descriptions of audiovestibular function in iSS and therefore limited understanding of the affected segment(s) of the audiovestibular pathway. In addition, monitoring disease progression and response to treatment is challenging and currently mainly guided by subjective patient reports and magnetic resonance imaging. To the best of our knowledge, there have been no previous reports assessing central auditory function in iSS. We describe such findings in a patient with iSS in an attempt to precisely localize the site of the audiovestibular dysfunction, determine its severity and functional impact. We confirm the presence of (asymmetrical) auditory neuropathy and identify central auditory processing deficits, suggesting involvement of the central auditory pathway beyond the brainstem. We correlate the audiological and vestibular findings with self-report measures and the siderosis appearances on brain magnetic resonance images.

Health Financing Reforms for Moving towards Universal Health Coverage in the Western Pacific Region.

This article provides an overview of health financing reforms across countries in the Western Pacific Region as progress is made toward universal health coverage (UHC). Moving toward UHC requires a strong health system with sustainable financing, which countries strive to achieve through various approaches appropriate to their country contexts. Great efforts have been made by financing reforms through resource mobilization, risk pooling, resource allocation, and strategic purchasing. Overall governance of health financing systems has improved within the context of service delivery and budget reforms. But there are still challenges and ongoing needs to continue expanding health financing mechanisms equitably and efficiently, improving stewardship and accountability, strengthening the transition to domestic financing, and enabling evidence-informed priority setting and benefits design processes. Asian countries are rapidly developing and moving to more prepaid financing mechanisms with government subsidies to reduce relatively high out-of-pocket expenses, while facing implementation challenges in the governance and expansion of social health insurance. The Pacific island countries, on the other hand, face stagnating economic growth and rely on government financing, with some countries receiving significant external funding, making it important to have strong stewardship and public financing systems in place. The way forward calls for continuing to strengthen the evidence generation and monitoring function to assess country progress, reorienting primary health care as the foundation of the health sector to ensure that continuity of care is affordable and accountable, and leveraging the private sector to contribute to an equitable and efficient health system.

Revolution in acute ischaemic stroke care: a practical guide to mechanical thrombectomy.

Rapid, safe and effective arterial recanalisation to restore blood flow and improve functional outcome remains the primary goal of hyperacute ischaemic stroke management. The benefit of intravenous thrombolysis with recombinant tissue-type plasminogen activator for patients with severe stroke due to large artery occlusion is limited; early recanalisation is generally less than 30% for carotid, proximal middle cerebral artery or basilar artery occlusion. Since November 2014, nine positive randomised controlled trials of mechanical thrombectomy for large vessel occlusion in the anterior circulation have led to a revolution in the care of patients with acute ischaemic stroke. Its efficacy is unmatched by any previous therapy in stroke medicine, with a number needed to treat of less than 3 for improved functional outcome. With effectiveness shown beyond any reasonable doubt, the key challenge now is how to implement accessible, safe and effective mechanical thrombectomy services. This review aims to provide neurologists and other stroke physicians with a summary of the evidence base, a discussion of practical aspects of delivering the treatment and future challenges. We aim to give guidance on some of the areas not clearly described in the clinical trials (based on evidence where available, but if not, on our own experience and practice) and highlight areas of uncertainty requiring further research.

The Cost-Effectiveness of Integrating HIV Counseling and Testing into Primary Health Care in the Ukraine.

We estimate the number of HIV cases diagnosed, costs, and cost per HIV case detected associated with integrating HIV counseling and testing (HCT) into primary health care facilities in Ukraine. The study uses a difference-in-difference design with four districts implementing the intervention compared to 20 districts where HCT were offered only at specialized HIV clinics. There was a 2.01 (95 % CI: 1.12-3.61) times increase in the number of HIV cases detected per capita in intervention districts compared to other districts. The incremental cost of the intervention was $21,017 and the incremental cost per HIV case detected was $369. The average cost per HIV case detected before the intervention was $558. Engaging primary health care facilities to provide HCT is likely desirable from an efficiency point-of-view. However, the affordability of the intervention needs to be assessed because expansion will require additional investment.

Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway.

Central nervous system infratentorial superficial siderosis (iSS) is increasingly detected by blood-sensitive magnetic resonance imaging (MRI) sequences. Despite this, there are no standardized diagnostic criteria, and the clinical-radiological spectrum, causes, and optimum investigation strategy are not established. We reviewed clinical and radiological details of patients with iSS assessed at a specialist neurological center during 2004-2016 using predefined standardized radiological criteria. All imaging findings were rated blinded to clinical details. We identified 65 patients with iSS, whom we classified into 2 groups: type 1 (classical) and type 2 (secondary) iSS. Type 1 (classical) iSS included 48 patients without any potentially causal radiologically confirmed single spontaneous or traumatic intracranial hemorrhage, of whom 39 (83%) had hearing loss, ataxia, or myelopathy; type 2 (secondary) iSS included 17 patients with a potentially causal radiologically confirmed spontaneous or traumatic intracranial hemorrhage, of whom none had hearing loss, ataxia, or myelopathy. Of the patients with type 1 (classical) iSS, 40 (83%) had a potentially causal cranial or spinal dural abnormality, 5 (11%) had an alternative cause, and 3 (6%) had no cause identified. Intra-arterial digital subtraction angiography did not identify any underlying causal lesions for type 1 iSS. Type 1 (classical) iSS, defined using simple radiological criteria, is associated with a characteristic neurological syndrome. Rational investigation, including spinal MRI, nearly always reveals a potential cause, most often a dural abnormality. Catheter angiography appears to be unhelpful, suggesting that classical iSS is not associated with macrovascular arterial pathology. Recognition of type 1 (classical) iSS should allow timely diagnosis and early consideration of treatment. Ann Neurol 2017;81:333-343.

Neuroimaging of Spinal Canal Stenosis.

Spinal stenosis is common and presents in a variety of forms. Symptomatic lumbar stenosis occurs in approximately 10% of the population and cervical stenosis in 9% over age 70. Imaging is central to the management decision process and first-choice MR imaging may be substituted with CT and CT myelography. A review of the literature is presented with particular emphasis on the clinical-radiologic correlation in both neurogenic intermittent claudication and cervical spondylotic myelopathy. Advanced techniques promise improvements, particularly with radicular compressive lesions, but remain underutilized in routine clinical practice.

Cerebral aneurysms and accelerated atherosclerosis in Russell-Silver syndrome: a new subtype? Case report.

The authors describe the case of a 32-year-old woman known to have Russell-Silver syndrome who presented with repeated aneurysmal subarachnoid hemorrhage. Multiple intracranial aneurysms and advanced peripheral vascular disease were demonstrated. The authors postulate a link between these vascular features and the patient's genetic condition.

Essential medicines in Tanzania: does the new delivery system improve supply and accountability?

Objective: Assess whether reform in the Tanzanian medicines delivery system from a central 'push' kit system to a decentralized 'pull' Integrated Logistics System (ILS) has improved medicines accountability. Methods: Rufiji District in Tanzania was used as a case study. Data on medicines ordered and patients seen were compiled from routine information at six public health facilities in 1999 under the kit system and in 2009 under the ILS. Three medicines were included for comparison: an antimalarial, anthelmintic and oral rehydration salts (ORS). Results: The quality of the 2009 data was hampered by incorrect quantification calculations for orders, especially for antimalarials. Between the periods 1999 and 2009, the percent of unaccounted antimalarials fell from 60 to 18%, while the percent of unaccounted anthelmintic medicines went from 82 to 71%. Accounting for ORS, on the other hand, did not improve as the unaccounted amounts increased from 64 to 81% during the same period. Conclusions: The ILS has not adequately addressed accountability concerns seen under the kit system due to a combination of governance and system-design challenges. These quantification weaknesses are likely to have contributed to the frequent periods of antimalarial stock-out experienced in Tanzania since 2009. We propose regular reconciliation between the health information system and the medicines delivery system, thereby improving visibility and guiding interventions to increase the availability of essential medicines.