Assessing patient information needs for new antidiabetic medications to inform shared decision-making: A best-worst scaling experiment in China.

BACKGROUND: Shared decision-making (SDM) is a patient-centred approach to improve the quality of care. An essential requirement for the SDM process is to be fully aware of patient information needs. OBJECTIVES: Our study aimed to assess patient information needs for new antidiabetic medications using the best-worst scaling (BWS) experiment. METHODS: BWS tasks were developed according to a literature review and the focus group discussion. We used a balanced incomplete block design and blocking techniques to generate choice sets. The final BWS contains 11 attributes, with 6-choice scenarios in each block. The one-to-one, face-to-face BWS survey was conducted among type 2 diabetic patients in Jiangsu Province. Results were analyzed using count-based analysis and modelling approaches. We also conducted a subgroup analysis to observe preference heterogeneity. RESULTS: Data from 539 patients were available for analysis. The most desired information domain was the comparative effectiveness of new antidiabetic medications. It consists of the incidence of macrovascular complications, the length of extended life years, changes in health-related quality of life, the incidence of microvascular complications, and the control of glycated haemoglobin. Of all the attributes, the incidence of macrovascular complications was the primary concern. Patients' glycemic control and whether they had diabetes complications exerted a significant influence on their information needs. CONCLUSIONS: Information on health benefits is of critical significance for diabetic patients. Patients have different information needs as their disease progresses. Personalized patient decision aids that integrate patient information needs and provide evidence of new antidiabetic medications are worthy of being established. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, a pilot survey was carried out among diabetic patients to provide feedback on the acceptability and intelligibility of the attributes.

Felbamate add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

Investigating patients' preferences for new anti-diabetic drugs to inform public health insurance coverage decisions: a discrete choice experiment in China.

BACKGROUND: Diabetes is a major public health concern with a considerable impact on healthcare expenditures. Deciding on health insurance coverage for new drugs that meet patient needs is a challenge facing policymakers. Our study aimed to assess patients' preferences for public health insurance coverage of new anti-diabetic drugs in China. METHODS: We identified six attributes of new anti-diabetic drugs and used the Bayesian-efficient design to generate choice sets for a discrete choice experiment (DCE). The DCE was conducted in consecutive samples of type 2 diabetes patients in Jiangsu Province. The mixed logit regression model was applied to estimate patient-reported preferences for each attribute. The interaction model was used to investigate preference heterogeneity. RESULTS: Data from 639 patients were available for analysis. On average, the most valued attribute was the improvement in health-related quality of life (HRQoL) (ß = 1.383, p < 0.001), followed by positive effects on extending life years (ß = 0.787, p < 0.001), and well-controlled glycated haemoglobin (ß = 0.724, p < 0.001). The out-of-pocket cost was a negative predictor of their preferences (ß = -0.138, p < 0.001). Elderly patients showed stronger preferences for drugs with a lower incidence of serious side effects (p < 0.01) and less out-of-pocket costs (p < 0.01). Patients with diabetes complications favored more in the length of extended life (p < 0.01), improvement in HRQoL (p < 0.05), and less out-of-pocket costs (p < 0.001). CONCLUSION: The new anti-diabetic drugs with significant clinical effectiveness and long-term health benefits should become the priority for public health insurance. The findings also highlight the value of accounting for preference heterogeneity in insurance policy-making.

Assessment of the satisfaction with public health insurance programs by patients with chronic diseases in China: a structural equation modeling approach.

BACKGROUND: China has successfully sustained its universal health insurance coverage over the past decade. Although patient satisfaction has been recognized as an important indicator to measure the performance of insurance programs in China, there is a lack of evidence on how patients with chronic diseases are satisfied with China's public health insurance programs and whether their satisfaction differs by type of insurance. We aimed to fill the evidence gap. METHODS: We established a hypothetical model that comprised patients' awareness of insurance policies, the fulfillment of patients' expectations of insurance benefits, patients' perceived value of health insurance coverage, patients' satisfaction with health insurance programs, patients' complaints, and trust in health insurance programs. We performed a confirmatory factor analysis by using a structural equation modeling (SEM) approach to examine the hypothesized model. A model-testing survey in 10 tertiary hospitals was conducted between June and October 2018, with a valid sample of 922 insured patients with chronic diseases. RESULTS: The SEM model, with good fit indices, showed that patients' awareness of health insurance policies, insurance program's fulfillment of expectations, and patients' perceived value of insurance coverage, positively predicted patient satisfaction (P < 0.01). The fulfillment of patients' expectations of insurance benefits was the major predictor of satisfaction with health insurance (coefficient = 0.593, P < 0.001), while the patients' perceived value of insurance coverage had the largest impact on their trust in health insurance (coefficient = 0.409, P < 0.01). Compared to patients with Urban-Rural Resident Basic Medical Insurance, Urban Employee Basic Medical Insurance enrollees had a higher degree of satisfaction with insurance on average (P < 0.01). Despite differences in the degree of satisfaction, the main findings from the SEM were also proved by the multi-group analysis. CONCLUSIONS: Our findings highlight the importance of incorporating patients' perceived value as part of the ongoing efforts to increase satisfaction with health insurance by patients, especially those who have chronic diseases. Policymakers are also suggested to formulate evidence-informed reimbursement policies that meet patients' expectations.

Intravenous immunoglobulins for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum immunoglobulin A (IgA) levels, lack of the immunoglobulin G (IgG) subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. This is an update of a Cochrane review first published in 2011 and last updated in 2017. OBJECTIVES: To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects when used as monotherapy or as add-on treatment for people with epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) (20 December 2018), MEDLINE (Ovid, 1946 to 20 December 2018), Web of Science (1898 to 20 December 2018), ISRCTN registry (20 December 2018), WHO International Clinical Trials Registry Platform (ICTRP, 20 December 2018), the US National Institutes of Health ClinicalTrials.gov (20 December 2018), and reference lists of articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life. MAIN RESULTS: We included one study (61 participants). The included study was a randomised, double-blind, placebo-controlled, multicentre trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with drug-resistant epilepsy. Seizure freedom was not reported in the study. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency (RR 1.89, 95% CI 0.85 to 4.21; one study, 58 participants; low-certainty evidence). The study reported a statistically significant effect for global assessment in favour of IVIg (RR 3.29, 95% CI 1.13 to 9.57; one study, 60 participants; low-certainty evidence). No adverse effects were demonstrated. We found no randomised controlled trials that investigated the effects of IVIg monotherapy for epilepsy. Overall, the included study was rated at low to unclear risk of bias. Using GRADE methodology, the certainty of the evidence was rated as low. AUTHORS' CONCLUSIONS: We cannot draw any reliable conclusions regarding the efficacy of IVIg as a treatment for epilepsy. Further randomised controlled trials are needed.

Felbamate add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2017.Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy. SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web), MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), on 18 December 2018. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, the third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data.Only one study reported the outcome, 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate while another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were: headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants.We assessed the evidence for all outcomes using GRADE and found it as being very-low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

Disparities in mental health care utilization among inpatients in various types of health institutions: a cross-sectional study based on EHR data in Shanghai, China.

BACKGROUND: Reform of the health care system in China has prompted concerns about the utilization of mental health services. This study aims to compare the utilization of mental health services among inpatients in various types of health institutions in Shanghai (community health care centres, secondary general hospitals, tertiary general hospitals, and specialty hospitals). METHODS: Based on electronic health record (EHR) data, we extracted all of the mental hospitalization data from various types of public health institutions in Pudong New Area, Shanghai, China, from 2013 to 2016. The distribution of mentally ill inpatients and the possible factors contributing to the observed differences in these institutions were analysed. RESULTS: Specialty psychiatric hospitals in Pudong New Area, Shanghai, admitted more inpatients and treated in patients with more severe disorders (49.73%). However, those who were male (OR = 0.545), were elderly (OR = 20.133), had inferior insurance (urban social insurance for citizens: OR = 4.013; paying themselves, OR = 29.489), had a longer length of stay (OR = 1.001) and had lower costs (OR = 0.910) were more likely to choose community health centres than specialty hospitals. Those who preferred the secondary and tertiary hospitals to the specialty ones were more likely to be in the male, elderly, married, shorter length of stay and higher-cost groups. Notably, compared to those with urban social insurance for workers, those who had urban social insurance for citizens (OR = 3.136) or paid out-of-pocket (OR = 9.822) were significantly clustered in the tertiary hospitals rather than the specialty hospitals. CONCLUSIONS: Inpatients who were male, were older, had inferior insurance, had a longer length of stay and had lower costs preferred the elementary health services. However, the utilization of mental health care in high-tier institutions reflected defects, especially the fact that the current health insurance system does not adequately restrict patients' choices, and those who paid more tended to choose tertiary hospitals instead of professional specialty ones. We suggest that psychiatric services should be enhanced by instituting reforms, including public education, improved health insurance, a forceful referral system, and competency reinforcement for primary care physicians, to provide a more integrated mental health system.

Status of evidence-based chronic diseases prevention implementation in Shanghai, China: A qualitative study.

BACKGROUND: Given the rapid increase in chronic disease epidemics in developing countries and the lagging research and practice in evidence-based chronic diseases prevention (EBCDP), we evaluated the status of public health practitioners' implementation of EBCDP and its impeding factors in China, as well as made a comparison between China and the developed countries to encourage better utilisation of this new field of science in China. METHODS: We interviewed health practitioners and patients from various health institutions in China and conducted a literature review to assess the current status of EBCDP practice in developed countries and identify the contextual driving factors. RESULTS: China is in its initial stage of EBCDP practice, as it lacks evidence-based interventions. Moreover, health practitioners' awareness of EBCDP is inadequate. The lack of policy support, especially funding, has restricted the efficiency and quality of EBCDP in terms of its adoption, implementation, and maintenance. Currently, EBCDP practice is limited to the practitioners' spontaneous behaviours. The literature review showed that developed countries practising EBCDP did well in evidence development and awareness; however, much has yet to be explored regarding practitioners' adoption and implementation and the maintenance of evidence-based practice. The impeding factors in developed countries were related to individual (patients and physicians) and organisational factors (such as resources, leaders, and climate). CONCLUSION: To promote EBCDP practice in China, more evidence for effective chronic disease prevention programmes is needed, and multiple and flexible measures should be implemented for a successful transition to evidence-based practice.

Felbamate as an add-on therapy for refractory partial epilepsy.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2014) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and we have assessed its effects as an add-on therapy to standard drugs in this review. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with refractory partial-onset epilepsy. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, up to 20 October 2016. There were no language and time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomised placebo-controlled add-on studies of people of any age with refractory partial-onset seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. We resolved disagreements by discussion. If disagreements persisted, the third review author arbitrated. We assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: We included four randomised controlled trials with a total of 236 participants. Two trials were parallel design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. Two studies were at an unclear risk of bias for random sequence generation and allocation concealment. These two studies did not include any description of their methods for outcome assessment and performance blinding (i.e. participants or doctors). Two studies were at high risk of bias for incomplete outcome data. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the results. Only one study reported 50% or greater reduction in seizure frequency. One study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. One study reported percentage reduction in seizure frequency compared to placebo, but there were no P values. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, limited number of individual studies and differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with refractory partial-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

Intravenous immunoglobulins for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum immunoglobulin A (IgA) levels, lack of the immunoglobulin G (IgG) subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. This is an updated version of the original Cochrane review published in Issue 1, 2011. OBJECTIVES: To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects when used as monotherapy or as add-on treatment for people with epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Epilepsy Group Specialized Register (2 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (2 February 2017), MEDLINE (Ovid, 1946 to 2 February 2017), Web of Science (1898 to 2 February 2017), ISRCTN registry (2 February 2017), WHO International Clinical Trials Registry Platform (ICTRP, 2 February 2017), the US National Institutes of Health ClinicalTrials.gov (2 February 2017), and reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life. MAIN RESULTS: We included one study (61 participants). The included study was a randomized, double-blind, placebo-controlled, multi-centre trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with refractory epilepsy. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency. The study reported a statistically significant effect for global assessment in favour of IVIg. No adverse effects were demonstrated. We found no randomized controlled trials that investigated the effects of IVIg monotherapy for epilepsy. Overall, the included study was rated as low/unclear risk of bias. Using GRADE methodology, the quality of the evidence was rated as low. AUTHORS' CONCLUSIONS: We cannot draw any reliable conclusions regarding the efficacy of IVIg as a treatment for epilepsy. Further randomized controlled trials are needed.

Preparing for the introduction of hospital autonomy in Laos: an assessment of current situation and suggestions for policy-making.

The National Assembly of Lao People's Democratic Republic (Laos) approved the Health Sector Reform Strategy in 2012, which called for an assessment as to whether Laos should introduce hospital autonomy, and if so, in which ways. The purpose of this study is to assess the status quo of hospital governance in Laos and propose policy suggestions for hospital autonomy in the country. We formulated an analytic framework for hospital autonomy based on previous work by other researchers, collected qualitative data through key informant interviews and focus group discussions, and also performed secondary data analysis. Public hospitals in Laos enjoyed some informal autonomy with little accountability and Laos is facing key challenges of hospital governance. As a result, introducing hospital autonomy in Laos could bring risks, benefits and debates. Before Laos decides on granting autonomy to its public hospitals, we strongly suggest that the government do pilot in selected public hospitals with well-regulated governance framework first and conduct rigorous evaluations to examine whether the granted autonomy leads to the intended social goals of equity, quality, efficiency and sustainability. We recommend residual claimants should be monitored by the government and by the society with open and transparent approach, and active measures should be taken to improve performance and ensure social functions. The study findings may also provide some suggestions for low- and middle-income countries, which are contemplating the introduction of hospital autonomy in the public sector. Copyright © 2015 John Wiley & Sons, Ltd.

Felbamate as an add-on therapy for refractory epilepsy.

BACKGROUND: This review is an update of a previously published review in The Cochrane Database of Systematic Reviews (Issue 1, 2011) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and its effects as an add-on therapy to standard drugs are assessed in this review. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with refractory partial-onset epilepsy. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (24 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), and PubMed (24 July 2013). This search was run for the original review on 20 May 2010. There were no language and time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo-controlled add-on studies of people of any age with refractory partial-onset seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel or crossover design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. We resolved disagreements by discussion. If disagreements persisted, the third review author arbitrated. We assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: Three randomised controlled trials with a total of 153 participants were included. The first was a parallel design, the second had a two-period crossover design, and the third had a three-period crossover design. One study was at unclear risk of bias for random sequence generation and allocation concealment. And in the same study, there was no description of how to blind outcome assessment, performance blinding was for participants, might not be for doctors. Two studies were at high risk of bias for incomplete outcome data. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the results. None of the three studies reported 50% or greater reduction in seizure frequency. Only one study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, limited number of individual studies and differences in outcome measure, we have found no reliable evidence to support the use of felbamate as an add-on therapy in patients with refractory partial-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.Since the last version of this review no new studies have been found.

The role of Toll-like receptor 4 on inflammation and Aß formation in cortex astrocytes.

To investigate the role and possible molecular mechanism of astrocytes in inflammation and amyloid ß-protein (Aß) formation, in this research, by using LPS to stimulate cultured rat astrocytes in vitro with or without anti-Toll-like receptor 4 (TLR4) antibody pretreatment, we first detected the TLR4, TNF-α, IL-1ß, ß-amyloid precursor protein (ß-APP) and ß-site APP clearing enzyme 1 (BACE1) mRNA with real-time PCR, and TLR4, NF-κB/P65 protein in cultured astrocytes by Western blot, and then further probed the translocation of NF-κB/P65 using immunofluorescence and the contents of TNF-α, IL-1ß and Aß in culture supernatant through ELISA. We found that all of these indexes increased at different degrees after LPS-stimulation. However, if pretreatment with anti- TLR4 antibody, such stimulating effects of LPS on the nuclear translocation of NF-κB/P65 and TNF-α, IL-1ß, Aß contents in astrocytic culture supernatant were reduced significantly or disappeared in comparison with the group with only LPS-administration. Our results suggest that TLR4 in astrocytes might play an important role in the inflammation and Aß formation through the TLR4/NF-κB signaling pathway, thus providing new knowledge and understanding of the inflammatory hypothesis of AD pathogenesis.

Awareness of diabetic retinopathy among patients with type 2 diabetes mellitus attending Donga Clinic in Francistown, Botswana.

Context: Diabetic retinopathy (DR) prevalence is steadily increasing in the country and by raising patient awareness, health providers can educate on regular eye exams, stimulate collaboration with experts, enhance monitoring and follow-up, and improve the patient's overall condition. Aim: To assess the awareness of diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM) during their new/follow-up visit in a diabetes clinic. Settings and Design: Patients were given a questionnaire for 4 weeks. Methods and Material: A facility-based cross-sectional study was conducted, and data were analyzed with SPSS. Results: A total of 160 patients were enrolled (59.08 study was conductedents wite females. 42% had DM duration of less than 5 years. Hypertension was a comorbidity at 83%. Blood sugar control was good among 53%. 96.3% were nonsmokers, 1.9% quit smoking, and 1.9% smoked. 100% believed diabetes may affect their eyes, 83.1% stated eye exams were necessary even when diabetes was well managed, 96.9% believed eye exams were necessary when diabetes was poorly controlled. Majority (43%) felt they should go for eye checkups every 6 months. 75% were unaware of the treatments available for DR. Patients were aware of blindness, cataract, glaucoma, DR, at 63%, 14%, 10%, and 13%, respectively. The primary reason for undergoing eye examination was doctor's referral at 94%. Healthcare provider was the common source of information on DM complications (79%). Conclusion: The need arises to raise DR awareness to increase case detection thus reduce the strain of DR's sight-threatening complications.

Assessment of patients' preferences for new anticancer drugs in China: a best-worst discrete choice experiment on three common cancer types.

OBJECTIVES: Despite the advancement in anticancer drug therapies, cancer treatment decisions are often complex and preference-sensitive, making them well suited for studying shared decision-making (SDM). Our study aimed to assess preferences for new anticancer drugs among three common types of patients with cancer to inform SDM. DESIGN: We identified five attributes of new anticancer drugs and used a Bayesian-efficient design to generate choice sets for a best-worst discrete choice experiment (BWDCE). The mixed logit regression model was applied to estimate patient-reported preferences for each attribute. The interaction model was used to investigate preference heterogeneity. SETTING: The BWDCE was conducted in Jiangsu province and Hebei province in China. PARTICIPANTS: Patients aged 18 years or older, who had a definite diagnosis of lung cancer, breast cancer or colorectal cancer were recruited. RESULTS: Data from 468 patients were available for analysis. On average, the most valued attribute was the improvement in health-related quality of life (HRQoL) (p<0.001). The low incidence of severe to life-threatening side effects, prolonged progression-free survival and the low incidence of mild to moderate side effects were also positive predictors of patients' preferences (p<0.001). Out-of-pocket cost was a negative predictor of their preferences (p<0.001). According to subgroup analysis by type of cancer, the improvement in HRQoL remained the most valuable attribute. However, the relative importance of other attributes varied by type of cancer. Whether patients were newly diagnosed or previously diagnosed cancer cases played a dominant role in the preference heterogeneity within each subgroup. CONCLUSIONS: Our study can assist in the implementation of SDM by providing evidence on patients' preferences for new anticancer drugs. Patients should be informed of the multiattribute values of new drugs and encouraged to make decisions reflecting their values.

Effectiveness of Panretinal Photocoagulation Plus Intravitreal Anti-VEGF Treatment Against PRP Alone for Diabetic Retinopathy: A Systematic Review With Meta-Analysis.

Objective: To compare the efficacy and safety of panretinal photocoagulation (PRP) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) against PRP monotherapy for diabetic retinopathy (DR). Methods: We searched Pubmed, Cochrane Library, Web of Science, Embase, and Science Direct Register of Controlled Trials from April 2011 to January 2021 to identify the randomized trials that compared the efficacy and safety between PRP combined with intravitreal anti-VEGF and PRP monotherapy for DR. We searched in the following databases between April 2011 and January 2021: Pubmed, Cochrane Library, Web of Science, Embase, and Science Direct without any restriction of countries or article type. The outcome measures were the best-corrected visual acuity (BCVA), neovascularization on the disc (NVD), neovascularization elsewhere (NVE), central macula thickness (CMT), and total retinal volume over time (FAS), and we also observed the adverse events (AEs) between the two groups. Results: A total of 351 studies were identified, of which 11 studies were included in this meta-analysis (N = 1,182 eyes). Compared with PRP monotherapy, PRP plus anti-VEGF combination treatment produced a mean reduction in BCVA in units of logMAR of -0.23 [95% CI -0.32, -0.15] or a mean improvement in BCVA in units of letters of 4.99 [95% CI 3.79, 6.19], and also yielded a mean reduction in NVD of -28.41 [95% CI -30.30, -26.52], in NVE of -1.33 [95% CI -1.52, -1.14], in CMT of -1.33 [95% CI -1.52, -1.14], or in total FAS. No significant difference was observed on the risk of AEs as vitreous hemorrhage, elevation in intraocular pressure, and cataract between the two different treatments. Conclusion: PRP with anti-VEGF combination treatment can achieve the ideal efficacy on DR by improving BCVA and NV regression, with no potential increased incidence of AEs, which proves that the combination therapy is an efficient therapeutic strategy that could improve the management of patients with DR.

Evaluating the risk of hypertension in residents in primary care in Shanghai, China with machine learning algorithms.

Objective: The prevention of hypertension in primary care requires an effective and suitable hypertension risk assessment model. The aim of this study was to develop and compare the performances of three machine learning algorithms in predicting the risk of hypertension for residents in primary care in Shanghai, China. Methods: A dataset of 40,261 subjects over the age of 35 years was extracted from Electronic Healthcare Records of 47 community health centers from 2017 to 2019 in the Pudong district of Shanghai. Embedded methods were applied for feature selection. Machine learning algorithms, XGBoost, random forest, and logistic regression analyses were adopted in the process of model construction. The performance of models was evaluated by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, accuracy and F1-score. Results: The XGBoost model outperformed the other two models and achieved an AUC of 0.765 in the testing set. Twenty features were selected to construct the model, including age, diabetes status, urinary protein level, BMI, elderly health self-assessment, creatinine level, systolic blood pressure measured on the upper right arm, waist circumference, smoking status, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, frequency of drinking, glucose level, urea nitrogen level, total cholesterol level, diastolic blood pressure measured on the upper right arm, exercise frequency, time spent engaged in exercise, high salt consumption, and triglyceride level. Conclusions: XGBoost outperformed random forest and logistic regression in predicting the risk of hypertension in primary care. The integration of this risk assessment model into primary care facilities may improve the prevention and management of hypertension in residents.

Felbamate as an add-on therapy for refractory epilepsy.

BACKGROUND: Epilepsy is a chronic and disabling neurologic disorder, affecting approximately one per cent of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second generation antiepileptic drugs and its effects as an add-on therapy to standard drugs are assessed in this review. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with refractory partial-onset epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialized Register (6 December 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 6 December 2010), and PubMed (6 December 2010). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo-controlled add-on studies of people of any age with refractory partial-onset seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel or crossover design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. Disagreements were resolved by discussion. If disagreements persisted, the third review author arbitrated. The following outcomes were assessed: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: Three randomized controlled trials were included. The first was a parallel design, the second was a two-period crossover design, and the third was a three-period crossover design. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the results. None of the three studies reported 50% or greater reduction in seizure frequency. Only one study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, limited number of individual studies and differences in outcome measure, we have found no reliable evidence to support the use of felbamate as an add-on therapy in patients with refractory partial-onset epilepsy. A large scale, randomized controlled trial conducted over a greater period of time is required to inform clinical practice.

Intravenous immunoglobulins for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum IgA level, lack of IgG subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. OBJECTIVES: To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects, when used as monotherapy or as add-on treatment for people with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialized Register (14 June 2010), the Cochrane Central Register of Controlled Trials (Issue 2 of 4, The Cochrane Library, 2010), MEDLINE (1950 to June 2010), Web of Science (14 June 2010), Current Controlled Trials (11 June 2010), the National Research Register (NRR) archive (11 June 2010), the US National Institutes of Health (Clinicaltrials.gov) (11 June 2010) and reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life. MAIN RESULTS: We included one study (61 patients). We found no randomized controlled trials that investigated the effects of IVIg monotherapy for epilepsy. The included study was a randomized, double-blind, placebo-controlled, multi-center trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with refractory epilepsy. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency. The study reported a statistically significant effect for global assessment in favor of IVIg. No adverse effects were demonstrated. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding the efficacy of IVIg as a treatment for epilepsy. Further randomized controlled trials are needed.

Comparative Effectiveness and Safety of High-Intensity Focused Ultrasound for Uterine Fibroids: A Systematic Review and Meta-Analysis.

Background: Uterine fibroids are common benign tumors among premenopausal women. High- intensity focused ultrasound (HIFU) is an emerging non-invasive intervention which uses the high-intensity ultrasound waves from ultrasound probes to focus on the targeted fibroids. However, the efficacy of HIFU in comparison with that of other common treatment types in clinical procedure remains unclear. Objective: To investigate the comparative effectiveness and safety of HIFU with other techniques which have been widely used in clinical settings. Methods: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Cumulative Index to Nursing & Allied Health Literature, Web of Science, ProQuest Nursing & Allied Health Database, and three Chinese academic databases, including randomized controlled trials (RCTs), non-RCTs, and cohort studies. The primary outcome was the rate of re-intervention, and the GRADE approach was used to interpret the findings. Results: About 18 studies met the inclusion criteria. HIFU was associated with an increased risk of re-intervention rate in comparison with myomectomy (MYO) [pooled odds ratio (OR): 4.05, 95% confidence interval (CI): 1.82-8.9]. The results favored HIFU in comparison with hysterectomy (HYS) on the change of follicle-stimulating hormone [pooled mean difference (MD): -7.95, 95% CI: -8.92-6.98), luteinizing hormone (MD: -4.38, 95% CI: -5.17-3.59), and estradiol (pooled MD: 43.82, 95% CI: 36.92-50.72)]. HIFU had a shorter duration of hospital stay in comparison with MYO (pooled MD: -4.70, 95% CI: -7.46-1.94, p < 0.01). It had a lower incidence of fever (pooled OR: 0.15, 95% CI: 0.06-0.39, p < 0.01) and a lower incidence of major adverse events (pooled OR: 0.04, 95% CI: 0.00-0.30, p < 0.01) in comparison with HYS. Conclusions: High-intensity focused ultrasound may help maintain feminity and shorten the duration of hospital stay. High-quality clinical studies with a large sample size, a long-term follow-up, and the newest HIFU treatment protocol for evaluating the re-intervention rate are suggested to be carried out. Clinical decision should be based on the specific situation of the patients and individual values.