Guillain-Barré syndrome in low-income and middle-income countries: challenges and prospects.

The epidemiology, clinical characteristics, management and outcome of Guillain-Barré syndrome (GBS) differ between low-income and middle-income countries (LMIC) and high-income countries (HIC). At present, limited data are available on GBS in LMIC and the true incidence of GBS in many LMIC remains unknown. Increased understanding of GBS in LMIC is needed because poor hygiene and high exposure to infections render populations in LMIC vulnerable to GBS outbreaks. Furthermore, insufficient diagnostic and health-care facilities in LMIC contribute to delayed diagnosis in patients with severe presentations of GBS. In addition, the lack of national clinical guidelines and absence of affordable, effective treatments contribute to worse outcomes and higher mortality in LMIC than HIC. Systematic population-based surveillance studies, cohort and case-control studies are required to understand the incidence and risk factors for GBS. Novel, targeted and cost-effective treatment strategies need to be developed in the context of health system challenges in LMIC. To ensure integrative rehabilitation services in LMIC, existing prognostic models must be validated, and responsive outcome measures that are cross-culturally applicable must be developed. Therefore, fundamental and applied research to improve the clinical management of GBS in LMIC should become a critical focus of future research programmes.

Guillain-Barré syndrome associated with Zika virus infection in Brazil: a cost-of-illness study.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious, acute paralytic neuropathy of autoimmune aetiology, usually associated with a previous infection. The current study aims to estimate the costs of GBS associated with Zika virus (ZIKV) infection in Brazil. METHODS: A cost-of-illness study was conducted from the perspective of the Brazilian public health system (Sistema Único de Saúde [SUS]) and Brazilian society for the year 2016. Direct and indirect costs were estimated by a mixed macrocosting and microcosting approach. RESULTS: The total cost of ZIKV-associated GBS in Brazil was US$11 997 225.85, consisting of the costs of symptomatic ZIKV infection before onset of GBS (direct costs US$2011.51, indirect costs US$19 780.53) and the costs that followed development of GBS (direct costs US$4 722 980.89, indirect costs US$7 252 452.92). The cost of treatment with human immunoglobulin (US$3 263 210.50) and the cost of productivity losses associated with potential years of working life lost due to early mortality (US$4 398 551.72) were particularly noteworthy. CONCLUSIONS: These findings suggest that ZIKV-associated GBS is costly to Brazil, especially due to productivity losses and hospitalization. This highlights the importance of investing in the prevention of ZIKV infection and in the care of patients with GBS.

Cost-minimization analysis in the Indian subcontinent for treating Guillain Barre Syndrome patients with therapeutic plasma exchange as compared to intravenous immunoglobulin.

BACKGROUND: Therapeutic Plasma Exchange (TPE) and Intravenous Immunoglobulin both are first-line treatments for Guillain Barre Syndrome; however, there is a significant difference in cost. We undertook this study to assess the cost minimization for treating Guillain Barre Syndrome patients. METHODS: A prospective randomized controlled trial was undertaken, in which 40 Guillain Barre Syndrome (GBS) patients with a GBS disability score of grade four and five were enrolled. A societal perspective was adopted for the analysis and assessment of both the health system cost and out-of-pocket expenditures. Cost-minimization analysis was undertaken as both the treatments were equally effective at the end of 12 weeks. RESULTS: No statistically significant differences were observed in the GBS Disability scores during overall treatment course in both treatment groups. The Out-of-pocket cost for the immunoglobulin (IVIG) group was INR 219 247 (4298 USD) and for the TPE group was INR 104 070 (2040.5 USD). Overall INR 86 685 ($1700), that is, 53% higher cost was observed in IVIG group without any concomitant health outcome benefit. CONCLUSION: In comparison with IVIG, TPE appears to be the better option for treatment of GBS in cost-constraint countries like ours to provide an economic treatment option to most average people.

Hyponatremia in Guillain-Barré Syndrome.

OBJECTIVES: To evaluate incidence, risk factors, and in-hospital outcomes associated with hyponatremia in patients hospitalized for Guillain-Barré Syndrome (GBS). METHODS: We identified adult patients with GBS in the Nationwide Inpatient Sample (2002-2011). Univariate and multivariable analyses were used. RESULTS: Among 54,778 patients hospitalized for GBS, the incidence of hyponatremia was 11.8% (compared with 4.0% in non-GBS patients) and increased from 6.9% in 2002 to 13.5% in 2011 (P < 0.0001). Risk factors associated with hyponatremia in multivariable analysis included advanced age, deficiency anemia, alcohol abuse, hypertension, and intravenous immunoglobulin (all P < 0.0001). Hyponatremia was associated with prolonged length of stay (16.07 vs. 10.41, days), increased costs (54,001 vs. 34,125, $USD), and mortality (20.5% vs. 11.6%) (all P < 0.0001). In multivariable analysis, hyponatremia was independently associated with adverse discharge disposition (odds ratio: 2.07, 95% confidence interval, 1.91-2.25, P < 0.0001). CONCLUSIONS: Hyponatremia is prevalent in GBS and is detrimental to patient-centered outcomes and health care costs. Sodium levels should be carefully monitored in high-risk patients.

Economic Cost of Campylobacter, Norovirus and Rotavirus Disease in the United Kingdom.

OBJECTIVES: To estimate the annual cost to patients, the health service and society of infectious intestinal disease (IID) from Campylobacter, norovirus and rotavirus. DESIGN: Secondary data analysis. SETTING: The United Kingdom population, 2008-9. MAIN OUTCOME MEASURES: Cases and frequency of health services usage due to these three pathogens; associated healthcare costs; direct, out-of-pocket expenses; indirect costs to patients and caregivers. RESULTS: The median estimated costs to patients and the health service at 2008-9 prices were: Campylobacter £50 million (95% CI: £33m-£75m), norovirus £81 million (95% CI: £63m-£106m), rotavirus £25m (95% CI: £18m-£35m). The costs per case were approximately £30 for norovirus and rotavirus, and £85 for Campylobacter. This was mostly borne by patients and caregivers through lost income or out-of-pocket expenditure. The cost of Campylobacter-related Guillain-Barré syndrome hospitalisation was £1.26 million (95% CI: £0.4m-£4.2m). CONCLUSIONS: Norovirus causes greater economic burden than Campylobacter and rotavirus combined. Efforts to control IID must prioritise norovirus. For Campylobacter, estimated costs should be considered in the context of expenditure to control this pathogen in agriculture, food production and retail. Our estimates, prior to routine rotavirus immunisation in the UK, provide a baseline vaccine cost-effectiveness analyses.

Hospital Admissions, Transfers and Costs of Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has a highly variable clinical course, leading to frequent transfers within and between hospitals and high associated costs. We defined the current admissions, transfers and costs in relation to disease severity of GBS. METHODS: Dutch neurologists were requested to report patients diagnosed with GBS between November 2009 and November 2010. Information regarding clinical course and transfers was obtained via neurologists and general practitioners. RESULTS: 87 GBS patients were included with maximal GBS disability score of 1 or 2 (28%), 3 or 4 (53%), 5 (18%) and 6 (1%). Four mildly affected GBS patients were not hospital admitted. Of the 83 hospitalized patients 68 (82%) were initially admitted at a neurology department, 4 (5%) at an ICU, 4 (5%) at pediatrics, 4 (5%) at pediatrics neurology and 3 (4%) at internal medicine. Median hospital stay was 17 days (IQR 11-26 days, absolute range 1-133 days). Transfers between departments or hospitals occurred in 33 (40%) patients and 25 (30%) were transferred 2 times or more. From a cost-effectiveness perspective 21 (25%) of the admissions was suboptimal. Median costs for hospital admission of GBS patients were 15,060 Euro (IQR 11,226-23,683). Maximal GBS disability score was significantly correlated with total length of stay, number of transfers, ICU admission and costs. CONCLUSIONS: Hospital admissions for GBS patients are highly heterogeneous, with frequent transfers and higher costs for those with more severe disease. Future research should aim to develop prediction models to early identify the most cost-effective allocation in individual patients.

Cost-minimization analysis of the direct costs of TPE and IVIg in the treatment of Guillain-Barré syndrome.

BACKGROUND: Controlled trials have found therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) infusion therapy to be equally efficacious in treating Guillain-Barré syndrome (GBS). Due to increases in the price of IVIg compared to human serum albumin (HSA), used as a replacement fluid in TPE, we examined direct hospital-level expenditures for TPE and IVIg for meaningful cost-differences between these treatments. METHODS: Using financial data from our two institutions, hospital cost profiles for IVIg and 5% albumin were established. Reimbursement amounts were obtained from publicly available Medicare data resources to determine payment rates for TPE, non-tunneled central catheter line placement, and drug infusion therapy. A model was developed which allows hospitals to input cost and reimbursement amounts for both IVIg and TPE with HSA that results in real-time valuations of these interventions. RESULTS: The direct cost of five IVIg infusion sessions totaling 2.0 grams per kilogram (g/kg) body weight was $10,329.85 compared to a series of five TPE procedures, which had direct costs of $4,638.16. CONCLUSIONS: In GBS patients, direct costs of IVIg therapy are more than twice that of TPE. Given equivalent efficacy and similar severity and frequencies of adverse events, TPE appears to be a less expensive first-line therapy option for treatment of patients with GBS.

Physiological changes during and outcome following 'filtration' based continuous plasma exchange in Guillain Barre Syndrome.

BACKGROUND: Therapeutic plasma exchange is an extracorporeal blood purification technique designed for the removal of large molecular weight substances from plasma. It is the first line treatment in Guillain Barre Syndrome (GBS) improving outcome. AIM: To study the outcome in GBS following therapeutic plasma exchange (TPE) utilizing a modified, cost saving, filtration based plasma exchange technique. METHODOLOGY AND FINDINGS: Consenting patients with GBS underwent TPE using a modified regime of two 48 h sessions as a cost saving strategy. The second session was conducted only if there was inadequate benefit from the first session. Nerve conduction studies confirmed the diagnosis of GBS. RESULTS: Fifteen patients were studied. One died following a cerebro-vascular accident. Of the remaining 14 patients, five showed improvement in muscle power at least by one grade in one limb within 48 h of plasma exchange. The duration of intensive care unit stay was 10 (median) days (range 4-66). Nine required mechanical ventilation for (median) 15 days (range 4-50). The mean 24h urine output increased significantly since the initiation of plasma exchange was 6262.92 ml (SD=8867.24, P=0.032) at 48 h and 6474.92 ml at 72 h (SD=6364.81, P=0.003). The pulse rates and blood pressures were not significantly different before and after plasma exchange. Complications attributable to plasma exchange were mild; a hypersensitivity reaction and a tendency to ooze from a puncture site. CONCLUSION: 'Continuous' TPE, the modified cost saving technique seems to improve the outcome of patients with Guillain Barre Syndrome with minimal complications.

Plasma exchange after initial intravenous immunoglobulin treatment in Guillain-Barré syndrome: critical reassessment of effectiveness and cost-efficiency.

OBJECTIVES: To assess whether intravenous immunoglobulin (IVIG) followed by plasma exchange (PE) is more effective for patients with Guillain-Barré syndrome compared with IVIG alone. METHODS: Retrospective chart review of 46 patients treated for Guillain-Barré syndrome between 1995 and 2005 was performed. Patients were divided into four subgroups based on treatment received (IVIG, PE, IVIG + PE, or neither). Disability grade on admission, after completion of IVIG, and on the day of discharge from hospital (DGD) were assessed. DGD was the primary outcome measure. Duration of hospitalization, costs, duration of symptoms before treatment, and interval between IVIG and initiation of PE were analyzed. RESULTS: Mean disability grade on admission was similar for all groups. DGD was significantly lower for the IVIG group (P < 0.001) than other groups. Compared with admission, patients treated with IVIG + PE had more severe impairment after completion of IVIG (P = 0.044) but did not show significant improvement after PE. Disability grade on admission and DGD scores for patients treated earlier (less than 14 days after onset of symptoms) versus later (greater than 14 days) were not significantly different. Duration of hospitalization was longer in patients receiving IVIG + PE versus IVIG alone (P < 0.001). The cost of treatment was significantly higher in the IVIG + PE subgroup (P < 0.001). No correlation between interval from IVIG to PE onset and DGD score was found. CONCLUSIONS: We found no association between PE after IVIG and improved short-term outcomes of patients with Guillain-Barré syndrome, but there was an association with an increase in cost and duration of hospitalization. There was no association between the timing of PE after IVIG and the short-term outcome. Prospective studies are needed to clarify whether the cost/benefit ratio favors the routine use of this therapeutic approach.

National trends in hospital outcomes among patients with Guillain-Barré syndrome requiring mechanical ventilation.

Several new treatments have been introduced for Guillain-Barré syndrome over the last decade. To assess the impact of these new strategies on outcomes and hospitalization charges among patients with Guillain-Barré syndrome requiring mechanical ventilation, we compared pertinent variables between nationally representative data derived from 1992 and 2002. Compared with patients admitted in 1992, the patients admitted in 2002 showed an increase in hospital charges ($168,600 versus $116,300, P = 0.007), longer hospitalization (52.6 +/- 23.3 versus 40.3 +/- 36.3 days, P = 0.017), and greater in-hospital mortality (11.1% versus 7.6%, P = 0.003). Thus, improvements in therapeutic strategies over that decade are not reflected in mortality, length of hospitalization, or hospital charges in the current study. This outcome may be more reflective of changing patterns of hospitalization rather than relatively futility of new treatments.

Economic cost of Guillain-Barré syndrome in the United States.

OBJECTIVE: This study estimated the annual economic cost of Guillain-Barré syndrome (GBS) in the United States in 2004, including the direct costs of medical care and the indirect costs due to lost productivity and premature death. METHODS: The cost-of-illness method was used to determine the costs of medical care and lost productivity, and a modified value of a statistical life approach was used to determine the cost of premature deaths. Data were obtained from the Nationwide Inpatient Sample, the Medical Expenditure Panel Survey, the Compressed Mortality File, a telephone survey of 180 adult patients with GBS, and other sources. RESULTS: The estimated annual cost of GBS was $1.7 billion (95% CI, $1.6 to 1.9 billion), including $0.2 billion (14%) in direct medical costs and $1.5 billion (86%) in indirect costs. Most of the medical costs were for community hospital admissions. Most of the indirect costs were due to premature deaths. The mean cost per patient with GBS was $318,966 (95% CI, $278,378 to 359,554). CONCLUSIONS: The economic cost of Guillain-Barré syndrome (GBS) was substantial, and largely due to disability and death. The cost estimate summarizes the lifetime health burden due to GBS in monetary terms, and provides some of the information needed to assess the cost-effectiveness of health measures that affect GBS.

Pharmacoeconomics of therapy for Guillain-Barré syndrome: plasma exchange and intravenous immunoglobulin.

Guillain-Barré syndrome (GBS) is an acute neuropathy and a clinical syndrome that includes a number of pathological and electrophysiological subtypes. Intravenous immunoglobulin (IVIG) and plasma exchange (PE) are both equally efficacious for the treatment of GBS; however, the cost of IVIG may be lower for both the patient and the healthcare system. To compare the pharmacoeconomics of PE and IVIG in GBS, a retrospective study was done from 1999 to 2004, which included a total of 24 patients with GBS who were admitted to Taipei Veterans General Hospital. This showed that except for the costs of the drugs used in IVIG, treatment of GBS with IVIG was more cost-effective (p=0.057) than that with PE in total length of hospitalization and the cost of procedures and hospitalization. The study also showed that the total costs were higher for patients on ventilators than those not requiring ventilators (p=0.008, t-test) and the length of hospitalization showed a very strong linear relationship to total costs (Pearson correlation coefficient=0.907). The regression analysis showed that each additional day of hospitalization increased the hospitalization costs by an average of 5599 New Taiwan Dollars (NT) (US$1.00=NT$33.50 in 2005).

Exchange transfusion: a low-cost alternative for severe childhood Guillain-Barré syndrome.

The high cost and nonavailability of plasmapheresis and intravenous immunoglobulin are prohibitive for the treatment of Guillain-Barré syndrome in resource-poor settings. Exchange transfusion can be an alternative therapy for severe disease in children. The effectiveness of exchange transfusion was evaluated in nine children (median age 6 years) with severe Guillain-Barré syndrome (functional disability score >/= 4). All patients had lower limb weakness for a median duration of 4 days (range 2-16 days). Upper limb weakness (n = 8), respiratory involvement (n = 7), pooling of oral secretions (n = 3), and facial palsy (n = 1) were other motor signs. Four children developed respiratory failure; three were ventilated. Other clinical features included leg pains, meningismus and Lasàgue's sign, backache, excessive sweating, and hemodynamic instability. Two children had albuminocytologic dissociation on cerebrospinal fluid analysis. Nerve conduction velocity testing was done in three patients; two had suggestive findings. One course of exchange transfusion could be performed in seven patients. Six children (86%) responded well with one or more of the following: a halt in progressive motor weakness, improvement in leg pains, meningismus, and straight-leg raising within 24 to 48 hours; one could be weaned off the ventilator by 60 hours. All had improvement in motor power of at least one muscle group by one grade within 3 to 7 days. Two patients died, whereas five (71% of the treatment group) were discharged and could walk independently by 4 months. Two untreated ones had died. Exchange transfusion seems to be a safe and effective alternative for severe Guillain-Barré syndrome. It should be offered whenever intravenous immunoglobulin or plasmapheresis is not available or affordable. Replacement of immunosaturated red cells, removal of activated T cells and monocytes, and transient thrombocytopenia are possible explanations for its effectiveness in addition to removal of pathogenic autoantibodies, immune complexes, cytokines, and complements.

Values for preventing influenza-related morbidity and vaccine adverse events in children.

BACKGROUND: Influenza vaccination recently has been recommended for children 6-23 months old, but is not currently recommended for routine use in non-high-risk older children. Information on disease impact, costs, benefits, risks, and community preferences could help guide decisions about which age and risk groups should be vaccinated and strategies for improving coverage. The objective of this study was to measure preferences and willingness-to-pay for changes in health-related quality of life associated with uncomplicated influenza and two rarely-occurring vaccination-related adverse events (anaphylaxis and Guillain-Barré syndrome) in children. METHODS: We conducted telephone interviews with adult members selected at random from a large New England HMO (n = 112). Respondents were given descriptions of four health outcomes: uncomplicated influenza in a hypothetical 1-year-old child of their own, uncomplicated influenza in a hypothetical 14-year-old child of their own, anaphylaxis following vaccination, and Guillain-Barré syndrome. "Uncomplicated influenza" did not require a physician's visit or hospitalization. Preferences (values) for these health outcomes were measured using time-tradeoff and willingness-to-pay questions. Time-tradeoff questions asked the adult to assume they had a child and to consider how much time from the end of their own life they would be willing to surrender to avoid the health outcome in the child. RESULTS: Respondents said they would give a median of zero days of their lives to prevent an episode of uncomplicated influenza in either their (hypothetical) 1-year-old or 14-year-old, 30 days to prevent an episode of vaccination-related anaphylaxis, and 3 years to prevent a vaccination-related case of Guillain-Barré syndrome. Median willingness-to-pay to prevent uncomplicated influenza in a 1-year-old was $175, uncomplicated influenza in a 14-year-old was $100, anaphylaxis $400, and Guillain-Barré syndrome $4000. The median willingness-to-pay for an influenza vaccination for their children with no risk of anaphylaxis or Guillain-Barré syndrome was $50 and $100, respectively. CONCLUSION: Most respondents said they would not be willing to trade any time from their own lives to prevent uncomplicated influenza in a child of their own, and the time traded did not vary by the age of the hypothetical affected child. However, adults did indicate a willingness-to-pay to prevent uncomplicated influenza in children, and that they would give more money to prevent the illness in a 1-year-old than in a 14-year-old. Respondents also indicated a willingness to pay a premium for a vaccine without any risk of severe complications.

Health burden in the Netherlands due to infection with thermophilic Campylobacter spp.

Infection with thermophilic Campylobacter spp. usually leads to an episode of acute gastroenteritis. Occasionally, more severe diseases may be induced, notably Guillain Barré syndrome and reactive arthritis. For some, the disease may be fatal. We have integrated available data in one public health measure, the Disability Adjusted Life Year (DALY). DALYs are the sum of Years of Life Lost by premature mortality and Years Lived with Disability, weighted with a factor between 0 and 1 for the severity of illness. The mean health burden of campylobacter-associated illness in the Dutch population in the period 1990-5 is estimated as 1400 (90% CI 900-2000) DALY per year. The main determinants of health burden are acute gastroenteritis (440 DALY), gastroenteritis related mortality (310 DALY) and residual symptoms of Guillain-Barré syndrome (340 DALY). Sensitivity analysis demonstrated that alternative model assumptions produced results in the above-mentioned range.

Treatment of Guillain-Barré syndrome: a cost-effectiveness analysis.

Acute Guillain-Barré syndrome is the most common cause of neuromuscular paralysis. Plasma exchange and intravenous immune globulin (IV IgG) are both effective treatments for this condition and the purpose of this report was to compare the cost-effectiveness of these two modalities. A MEDLINE search was performed to identify randomized studies that compared the use of IV IgG and plasma exchange for treatment of acute Guillain-Barré syndrome to determine if one modality was more effective and/or safer for the management of this condition. A decision analysis was structured around the alternatives facing neurologists who must choose a treatment regimen for patients diagnosed with acute Guillain-Barré syndrome who require active therapy. Cost information was obtained directly from product manufacturers and hospital sources. Two head-to-head trials comparing the effectiveness of plasma exchange and IV IgG for treatment of acute Guillain-Barré syndrome determined that there was insufficient evidence to suggest one therapy was more effective than the other; therefore, a cost minimization analysis was performed. The costs per patient of plasma exchange and IV IgG for the treatment of acute Guillain-Barré syndrome were $6,204 and $10,165, respectively. A sensitivity analysis determined the model was sensitive to the cost of IV IgG. The cost savings per patient treatment for the use of plasma exchange varied from $304 to $6,625 depending on the IV IgG product selected. Plasma exchange and IV IgG are both effective treatments for Guillain-Barré syndrome. However, our analysis determined plasma exchange on average was almost $4,000 less costly per patient than IV IgG. Further research is required to determine the impact of patient and physician preferences on the treatment of this disorder.