Informing a cost-effectiveness threshold for Saudi Arabia.

BACKGROUND: Saudi Arabia's Vision 2030 aims to reform health care across the Kingdom, with health technology assessment being adopted as one tool promising to improve the efficiency with which resources are used. An understanding of the opportunity costs of reimbursement decisions is key to fulfilling this promise and can be used to inform a cost-effectiveness threshold. This paper is the first to provide a range of estimates of this using existing evidence extrapolated to the context of Saudi Arabia. METHODS AND MATERIALS: We use four approaches to estimate the marginal cost per unit of health produced by the healthcare system; drawing from existing evidence provided by a cross-country analysis, two alternative estimates from the UK context, and based on extrapolating a UK estimate using evidence on the income elasticity of the value of health. Consequences of estimation error are explored. RESULTS: Based on the four approaches, we find a range of SAR 42,046 per QALY gained (48% of GDP per capita) to SAR 215,120 per QALY gained (246% of GDP per capita). Calculated potential central estimates from the average of estimated health gains based on each source gives a range of SAR 50,000-75,000. The results are in line with estimates from the emerging literature from across the world. CONCLUSION: A cost-effectiveness threshold reflecting health opportunity costs can aid decision-making. Applying a cost-effectiveness threshold based on the range SAR 50,000 to 75,000 per QALY gained would ensure that resource allocation decisions in healthcare can in be informed in a way that accounts for health opportunity costs. LIMITATIONS: A limitation is that it is not based on a within-country study for Saudi Arabia, which represents a promising line of future work.

Healthcare in Saudi Arabia is undergoing wide-ranging reform through Saudi Arabia's Vision 2030. One aim of these reforms is to ensure that money spent on healthcare generates the most improvement in population health possible. To do this requires understanding the trade-offs that exist: funding one pharmaceutical drug means that same money is not available to fund another pharmaceutical drug. This is relevant whether the new drug would be funded from within the existing budget for healthcare or from an expansion of it. If the drugs apply to the same patient population and have the same price, the question is simply, "which one generates more health?" In reality, we need to compare pharmaceutical drugs for different diseases, patient populations, and at a range of potential prices to understand whether the drug in question would generate more health per riyal spent than what is currently funded by the healthcare system. This paper provides the first estimates of the amount of health, measured in terms of quality adjusted life years (QALYs), generated by the Saudi Arabian healthcare system. We find that the healthcare system generates health at a rate of one QALY produced for every 50,000­75,000 riyals spent (58­86% of GDP per capita). Using the range we estimate to inform cost-effectiveness threshold can aid decision-making.

Saudi consensus recommendations on the management of multiple sclerosis: MS management in children and adolescents.

Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.

Saudi consensus recommendations on the management of Neuromyelitis Optica Spectrum Disorders (NMOSD).

This article focuses on the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an autoimmune, demyelinating condition characterized by inflammation of the optic nerve and/or the spinal cord, with symptoms that can range from mild impairment of movement to paralysis. The newly approved diagnostic criteria have improved the accuracy of NMOSD diagnosis. The management of NMOSD is under major revolution due to the many new therapeutic options. The role of the antibodies directed at aquaporin-4 (AQP4) has materialized as a biomarker for NMOSD. Several new treatments that target variable aspects in immunopathology such as IL-6, complement, or depletion of B cells are emerging. The management of AQP4-negative patients remains challenging.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: An international consensus statement.

In this consensus statement, we provide updated recommendations on multiple sclerosis (MS) management during the COVID-19 crisis and the post-pandemic period applicable to neurology services around the world. Statements/recommendations were generated based on available literature and the experience of 13 MS expert panelists using a modified Delphi approach online. The statements/recommendations give advice regarding implementation of telemedicine; use of disease-modifying therapies and management of MS relapses; management of people with MS at highest risk from COVID-19; management of radiological monitoring; use of remote pharmacovigilance; impact on MS research; implications for lowest income settings, and other key issues.

Family Planning for People with Multiple Sclerosis in Saudi Arabia: an Expert Consensus.

More than half of all patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) are women of childbearing age. Raising a family is an important life goal for women in our region of the world. However, fears and misconceptions about the clinical course of relapsing-remitting MS (RRMS) and the effects of disease-modifying drugs (DMDs) on the foetus have led many women to reduce their expectations of raising a family, sometimes even to the point of avoiding pregnancy altogether. The increase in the number of DMDs available to manage RRMS and recent studies on their effects in pregnancy have broadened management options for these women. Interferon beta now has an indication in Europe for use during pregnancy (according to clinical need) and can be used during breastfeeding. Glatiramer acetate is a further possible option for women with lower levels of RRMS disease activity who are, or about to become, pregnant; natalizumab may be used up to 30 weeks in patients with higher levels of disease activity. Where possible, physicians need to support and encourage women to pursue their dream of a fulfilling family life, supported where necessary by active interventions for RRMS that are increasingly evidence based.

Extensive acute axonal damage in pediatric multiple sclerosis lesions.

OBJECTIVE: Axonal damage occurs early in multiple sclerosis (MS) and contributes to the degree of clinical disability. Children with MS more often show disabling and polyfocal neurological symptoms at disease onset than adults with MS. Thus, axonal damage may differ between pediatric and adult MS patients. METHODS: We analyzed axonal pathology in archival brain biopsy and autopsy samples from 19 children with early MS. Lesions were classified according to demyelinating activity and presence of remyelination. Axonal density and extent of acute axonal damage were assessed using Bielschowsky silver impregnation and immunohistochemistry for amyloid precursor protein (APP), respectively. Axonal injury was correlated with the inflammatory infiltrate as well as clinical characteristics. Results were compared with data from adult MS patients. RESULTS: Acute axonal damage was most extensive in early active demyelinating (EA) lesions of pediatric patients and correlated positively with the Expanded Disability Status Scale at attack leading to biopsy/autopsy. Comparison with 12 adult patients showed a 50% increase in the extent of acute axonal damage in EA lesions from children compared to adults, with the highest number of APP-positive spheroids found prior to puberty. The extent of acute axonal damage correlated positively with the number of lesional macrophages. Axonal density was reduced in pediatric lesions irrespective of the demyelinating activity or the presence of remyelination. Axonal reduction was similar between children and adults. INTERPRETATION: Our results provide evidence for more pronounced acute axonal damage in inflammatory demyelinating lesions from children compared to adults.

Evidence of aquaporin involvement in human central pontine myelinolysis.

BACKGROUND: Central pontine myelinolysis (CPM) is a demyelinating disorder of the central basis pontis that is often associated with osmotic stress. The aquaporin water channels (AQPs) have been pathogenically implicated because serum osmolarity changes redistribute water and osmolytes among various central nervous system compartments. RESULTS: We characterized the immunoreactivity of aquaporin-1 and aquaporin-4 (AQP1 and AQP4) and associated neuropathology in microscopic transverse sections from archival autopsied pontine tissue from 6 patients with pathologically confirmed CPM. Loss of both AQP1 and AQP4 was evident within demyelinating lesions in four of the six cases, despite the presence of glial fibrillary acidic protein (GFAP)-positive astrocytes. Lesional astrocytes were small, and exhibited fewer and shorter processes than perilesional astrocytes. In two of the six cases, astrocytes within demyelinating lesions exhibited increased AQP1 and AQP4 immunoreactivities, and gemistocytes and mitotic astrocytes were numerous. Blinded review of medical records revealed that all four cases lacking lesional AQP1 and AQP4 immunoreactivities were male, whereas the two cases with enhanced lesional AQP1 and AQP4 immunoreactivities were female. CONCLUSIONS: This report is the first to establish astrocytic AQP loss in a subset of human CPM cases and suggests AQP1 and AQP4 may be involved in the pathogenesis of CPM. Further studies are required to determine whether the loss of AQP1 and AQP4 is restricted to male CPM patients, or rather may be a feature associated with specific underlying precipitants of CPM that may be more common among men. Non-rodent experimental models are needed to better clarify the complex and dynamic mechanisms involved in the regulation of AQPs in CPM, in order to determine whether it occurs secondary to the destructive disease process, or represents a compensatory mechanism protecting the astrocyte against apoptosis.

Do not treat from CIS onset: evaluate disease course and prognosis first--yes.

As physicians how do we counsel our patients with clinically isolated syndrome (CIS) when they ask, 'what is the benefit of injecting disease-modifying agents (DMAs) over many years? What disability will they prevent in my future?' In this debate, we will provide three core points supporting the concept that a watchful waiting approach (annual neurological evaluation and magnetic resonance imaging of the head (with gadolinium) at least for the first few years after diagnosis) for most patients with CIS represents appropriate medical care.

Acute demyelinating disorders: emergencies and management.

Central nervous system (CNS) inflammatory demyelinating diseases are a group of disorders that include multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica. These conditions may result in emergencies because of severe inflammatory destruction of CNS tissues or complications thereof. Most of these conditions are responsive to appropriate therapy and early diagnosis and treatment leads to better outcomes. We discuss the spectrum of emergencies associated with these disorders, as well as clinical features, investigations, and management.

Inflammatory cortical demyelination in early multiple sclerosis.

BACKGROUND: Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease. METHODS: We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and a topographic association between cortical demyelination and meningeal inflammation. Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years). RESULTS: Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study. CONCLUSIONS: In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.).

Childhood-onset multiple sclerosis with progressive dementia and pathological cortical demyelination.

OBJECTIVE: To describe a case of childhood-onset progressive multiple sclerosis with dementia and evidence of extensive cortical demyelination from brain biopsy specimen. DESIGN: Case report. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENT: A 26-year-old man with a history of behavioral changes starting at the age of 13 years followed by progressive dementia. INTERVENTIONS: Neurological examination, magnetic resonance imaging, cerebrospinal fluid studies, neuropsychological testing, and brain biopsy. RESULTS: Magnetic resonance imaging scans showed numerous T2-weighted hyperintensities throughout the central nervous system not associated with contrast enhancement. Brain biopsy specimens showed cortical and subcortical demyelination. All 3 types of cortical demyelinating lesions were observed: leukocortical, intracortical, and subpial. Lesions were associated with profound microglial activation. The patient continued to progress despite attempts to treat with multiple sclerosis disease-modifying therapies. CONCLUSIONS: Multiple sclerosis should be considered in the diagnosis of progressive dementia in children and young adults. Cortical demyelination may contribute to cognitive decline in patients with dementia due to multiple sclerosis.

Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting.

This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI), which is considered a new modality.