An exploration of service use pattern changes and cost analysis following implementation of community perinatal mental health teams in pregnant women with a history of specialist mental healthcare in England: a national population-based cohort study.

BACKGROUND: The National Health Service in England pledged >£365 million to improve access to mental healthcare services via Community Perinatal Mental Health Teams (CPMHTs) and reduce the rate of perinatal relapse in women with severe mental illness. This study aimed to explore changes in service use patterns following the implementation of CPMHTs in pregnant women with a history of specialist mental healthcare in England, and conduct a cost-analysis on these changes. METHODS: This study used a longitudinal cohort design based on existing routine administrative data. The study population was all women residing in England with an onset of pregnancy on or after 1st April 2016 and who gave birth on or before 31st March 2018 with pre-existing mental illness (N = 70,323). Resource use and costs were compared before and after the implementation of CPMHTs. The economic perspective was limited to secondary mental health services, and the time horizon was the perinatal period (from the start of pregnancy to 1-year post-birth, ~ 21 months). RESULTS: The percentage of women using community mental healthcare services over the perinatal period was higher for areas with CPMHTs (30.96%, n=9,653) compared to areas without CPMHTs (24.72%, n=9,615). The overall percentage of women using acute care services (inpatient and crisis resolution teams) over the perinatal period was lower for areas with CPMHTs (4.94%, n=1,540 vs. 5.58%, n=2,171), comprising reduced crisis resolution team contacts (4.41%, n=1,375 vs. 5.23%, n=2,035) but increased psychiatric admissions (1.43%, n=445 vs. 1.13%, n=441). Total mental healthcare costs over the perinatal period were significantly higher for areas with CPMHTs (fully adjusted incremental cost £111, 95% CI £29 to £192, p-value 0.008). CONCLUSIONS: Following implementation of CPMHTs, the percentage of women using acute care decreased while the percentage of women using community care increased. However, the greater use of inpatient admissions alongside greater use of community care resulted in a significantly higher mean cost of secondary mental health service use for women in the CPMHT group compared with no CPMHT. Increased costs must be considered with caution as no data was available on relevant outcomes such as quality of life or satisfaction with services.

The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine the magnitude of infection risk in patients with SLE and evaluate the effect of general and SLE-related factors on infection risk. METHODS: We searched MEDLINE and Embase from inception to July 2018, screening for observational studies that evaluated infection risk in patients with SLE compared with the general population/healthy controls. Outcomes of interest included overall severe infection, herpes zoster infection/reactivation, opportunistic infections, pneumonia and tuberculosis. Random-effects models were used to calculate pooled risk ratios (RRs) for each type of infection. Sensitivity analysis assessed the impact of removing studies with high risk of bias. RESULTS: Eleven retrospective or prospective cohort studies were included in the meta-analysis: overall severe infection (n = 4), pneumonia (n = 6), tuberculosis (n = 3) and herpes zoster (n = 2). Pooled RRs for overall severe infection significantly increased for patients with SLE compared with the general population/healthy controls [RR 2.96 (95% CI 1.28, 6.83)]. Pooled RRs for pneumonia, herpes zoster and tuberculosis showed significantly increased risk compared with the general population/healthy controls [RR 2.58 (1.80, 3.70), 2.50 (2.36, 2.65) and 6.11 (3.61, 10.33), respectively]. Heterogeneity and evidence of publication bias were present for all analyses, except herpes zoster. Sensitivity analyses confirmed robustness of the results. CONCLUSION: Patients with SLE have significantly higher risk of infection compared with the general population/healthy controls. Efforts to strengthen strategies aimed at preventing infections in SLE are needed. PROTOCOL REGISTRATION: PROSPERO number: CRD42018109425.

Single-inhaler triple therapy in patients with chronic obstructive pulmonary disease: a systematic review.

BACKGROUND: Guidelines recommend that treatment with a long-acting ß2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base. METHODS: We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations. RESULTS: We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15-52% compared with LAMA/LABA, 15-35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25-50 (preventing one patient from having an event) and the event-based number needed to treat of around 3-11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons. CONCLUSION: The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials. TRIAL REGISTRATION: PROSPERO #CRD42018102125 .

Automated Mass Extraction of Over 680,000 PICOs from Clinical Study Abstracts Using Generative AI: A Proof-of-Concept Study.

BACKGROUND: Generative artificial intelligence (GenAI) shows promise in automating key tasks involved in conducting systematic literature reviews (SLRs), including screening, bias assessment and data extraction. This potential automation is increasingly relevant as pharmaceutical developers face challenging requirements for timely and precise SLRs using the population, intervention, comparator and outcome (PICO) framework, such as those under the impending European Union (EU) Health Technology Assessment Regulation 2021/2282 (HTAR). This proof-of-concept study aimed to evaluate the feasibility, accuracy and efficiency of using GenAI for mass extraction of PICOs from PubMed abstracts. METHODS: Abstracts were retrieved from PubMed using a search string targeting randomised controlled trials. A PubMed clinical study 'specific/narrow' filter was also applied. Retrieved abstracts were processed using the OpenAI Batch application programming interface (API), which allowed parallel processing and interaction with Generative Pre-trained Transformer 4 Omni (GPT-4o) via custom Python scripts. PICO elements were extracted using a zero-shot prompting strategy. Results were stored in CSV files and subsequently imported into a PostgreSQL database. RESULTS: The PubMed search returned 682,667 abstracts. PICOs from all abstracts were extracted in < 3 h, with an average processing time of 200 s per 1000 abstracts. A total of 395,992,770 tokens were processed, with an average of 580 tokens per abstract. The total cost was $3390. On the basis of a random sample of 350 abstracts, human verification confirmed that GPT-4o accurately and comprehensively extracted 342 (98%) of all PICOs, with only outcome elements rarely missed. CONCLUSIONS: Using GenAI to extract PICOs from clinical study abstracts could fundamentally transform the way SLRs are conducted. By enabling pharmaceutical developers to anticipate PICO requirements, this approach allows for proactive preparation for the EU HTAR process, or other health technology assessments (HTAs), streamlining efficiency and reducing the burden of meeting these requirements.

This study explored how artificial intelligence (AI) can help automate a key part of systematic literature reviews (SLRs), which are used to summarise research in healthcare. AI was used to extract specific information referred to as population, intervention, comparator and outcome (PICOs) from nearly 700,000 abstracts of clinical studies from the PubMed database. AI extracted the PICO information from all the abstracts in under 3 h, which is significantly faster than a human could do. This demonstrates that AI could save a lot of time and effort compared with using human reviewers to do the same task. The study also found that AI performed accurately in identifying the PICO elements in the abstracts, although further human verification is still required. The use of AI in this way could help pharmaceutical developers meet upcoming requirements from the European Union, which require timely and thorough reviews of clinical evidence. AI can speed up the process, reducing the burden on pharmaceutical developers and allowing them to prepare more efficiently for these assessments. However, further testing and validation is needed before using AI in this way becomes common.

Artificial Intelligence to Automate Health Economic Modelling: A Case Study to Evaluate the Potential Application of Large Language Models.

BACKGROUND: Current generation large language models (LLMs) such as Generative Pre-Trained Transformer 4 (GPT-4) have achieved human-level performance on many tasks including the generation of computer code based on textual input. This study aimed to assess whether GPT-4 could be used to automatically programme two published health economic analyses. METHODS: The two analyses were partitioned survival models evaluating interventions in non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). We developed prompts which instructed GPT-4 to programme the NSCLC and RCC models in R, and which provided descriptions of each model's methods, assumptions and parameter values. The results of the generated scripts were compared to the published values from the original, human-programmed models. The models were replicated 15 times to capture variability in GPT-4's output. RESULTS: GPT-4 fully replicated the NSCLC model with high accuracy: 100% (15/15) of the artificial intelligence (AI)-generated NSCLC models were error-free or contained a single minor error, and 93% (14/15) were completely error-free. GPT-4 closely replicated the RCC model, although human intervention was required to simplify an element of the model design (one of the model's fifteen input calculations) because it used too many sequential steps to be implemented in a single prompt. With this simplification, 87% (13/15) of the AI-generated RCC models were error-free or contained a single minor error, and 60% (9/15) were completely error-free. Error-free model scripts replicated the published incremental cost-effectiveness ratios to within 1%. CONCLUSION: This study provides a promising indication that GPT-4 can have practical applications in the automation of health economic model construction. Potential benefits include accelerated model development timelines and reduced costs of development. Further research is necessary to explore the generalisability of LLM-based automation across a larger sample of models.

Artificial Intelligence to Automate Network Meta-Analyses: Four Case Studies to Evaluate the Potential Application of Large Language Models.

BACKGROUND: The emergence of artificial intelligence, capable of human-level performance on some tasks, presents an opportunity to revolutionise development of systematic reviews and network meta-analyses (NMAs). In this pilot study, we aim to assess use of a large-language model (LLM, Generative Pre-trained Transformer 4 [GPT-4]) to automatically extract data from publications, write an R script to conduct an NMA and interpret the results. METHODS: We considered four case studies involving binary and time-to-event outcomes in two disease areas, for which an NMA had previously been conducted manually. For each case study, a Python script was developed that communicated with the LLM via application programming interface (API) calls. The LLM was prompted to extract relevant data from publications, to create an R script to be used to run the NMA and then to produce a small report describing the analysis. RESULTS: The LLM had a > 99% success rate of accurately extracting data across 20 runs for each case study and could generate R scripts that could be run end-to-end without human input. It also produced good quality reports describing the disease area, analysis conducted, results obtained and a correct interpretation of the results. CONCLUSIONS: This study provides a promising indication of the feasibility of using current generation LLMs to automate data extraction, code generation and NMA result interpretation, which could result in significant time savings and reduce human error. This is provided that routine technical checks are performed, as recommend for human-conducted analyses. Whilst not currently 100% consistent, LLMs are likely to improve with time.

Community perinatal mental health teams and associations with perinatal mental health and obstetric and neonatal outcomes in pregnant women with a history of secondary mental health care in England: a national population-based cohort study.

BACKGROUND: Women with a pre-existing severe mental disorder have an increased risk of relapse after giving birth. We aimed to evaluate associations of the gradual regional implementation of community perinatal mental health teams in England from April, 2016, with access to mental health care and with mental health, obstetric, and neonatal outcomes. METHODS: For this cohort study, we used the national dataset of secondary mental health care provided by National Health Service England, including mental health-care episodes from April 1, 2006, to March 31, 2019, linked at patient level to the Hospital Episode Statistics, and birth notifications from the Personal Demographic Service. We included women (aged ≥18 years) with an onset of pregnancy from April 1, 2016, who had given birth to a singleton baby up to March 31, 2018, and who had a pre-existing mental disorder, defined as contacts with secondary mental health care in the 10 years immediately before pregnancy. The primary outcome was acute relapse, defined as psychiatric hospital admission or crisis resolution team contact in the postnatal period (first year after birth). Secondary outcomes included any secondary mental health care in the perinatal period (pregnancy and postnatal period) and obstetric and neonatal outcomes. Outcomes were compared according to whether a community perinatal mental health team was available before pregnancy, with odds ratios (ORs) adjusted for time trends and maternal characteristics (adjORs). FINDINGS: Of 807 798 maternity episodes in England, we identified 780 026 eligible women with a singleton birth, of whom 70 323 (9·0%) had a pre-existing mental disorder. A postnatal acute relapse was found in 1117 (3·6%) of 31 276 women where a community perinatal mental health team was available and in 1745 (4·5%) of 39 047 women where one was unavailable (adjOR 0·77, 95% CI 0·64-0·92; p=0·0038). Perinatal access to any secondary mental health care was found in 9888 (31·6%) of 31 276 women where a community perinatal mental health team was available and 10 033 (25·7%) of 39 047 women where one was not (adjOR 1·35, 95% CI 1·23-1·49; p<0·0001). Risk of stillbirth and neonatal death was higher where a community perinatal mental health team was available (165 [0·5%] of 30 980 women) than where it was not (151 [0·4%] of 38 693 women; adjOR 1·34, 95% CI 1·09-1·66; p=0·0063), as was the risk of a baby small for gestational age (2227 [7·2%] of 31 030 women vs 2542 [6·6%] of 38 762 women; adjOR 1·10, 1·02-1·20; p=0·016), whereas preterm birth risk was lower (3167 [10·1%] of 31 206 women vs 4341 [11·1%] of 38 961; adjOR 0·86, 0·74-0·99; p=0·032). INTERPRETATION: The regional availability of community perinatal mental health teams reduced the postnatal risk of acute relapse and increased the overall use of secondary mental health care. Community perinatal mental health teams should have close links with maternity services to avoid intensive psychiatric support overshadowing obstetric and neonatal risks. FUNDING: The National Institute for Health and Care Research.

Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. METHODS: We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. RESULTS: Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90 days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5 mg/day), patients on high-dose SCS (≥ 7.5 mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. CONCLUSIONS: Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Healthcare Resource Use and Costs Associated with Organ Damage in Newly Diagnosed Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis compared healthcare resource use (HCRU) and costs associated with incident organ damage in a cohort of adult patients with systemic lupus erythematosus (SLE). METHODS: Incident SLE cases were identified (Clinical Practice Research Datalink [CPRD] and Hospital Episode Statistics-linked healthcare databases; January 1, 2005-June 30, 2019). Annual incidence of 13 organ damage domains was calculated from SLE diagnosis through follow-up. Annualized HCRU and costs were compared between organ damage and non-organ damage patient groups using generalized estimating equations. RESULTS: A total of 936 patients met the inclusion criteria for SLE. Mean age was 48.0 (standard deviation [SD] 15.7) years and 88% were female. Over a median follow-up period of 4.3 (interquartile range [IQR] 1.9-7.0) years, 59% (315/533) had evidence of post-SLE diagnosis incident organ damage (≥ 1 type), which was greatest for musculoskeletal (146/819 [18%]), cardiovascular (149/842 [18%]), and skin (148/856 [17%]) domains. Patients with organ damage had greater resource use for all organ systems, excluding gonadal, versus those without it. Overall, mean (SD) annualized all-cause HCRU was greater in patients with organ damage versus those without it (inpatient, 1.0 versus 0.2; outpatient, 7.3 versus 3.5; accident and emergency, 0.5 versus 0.2 days; primary care contacts, 28.7 versus 16.5; prescription medications, 62.3 versus 22.9). Adjusted mean annualized all-cause costs were significantly greater in both post- and pre-organ damage index periods for patients with organ damage versus those without it (all P < 0.05, excluding gonadal). Overall organ damage was associated with significantly increased adjusted mean annualized per-patient cost (£4442 greater [P < 0.0001]) ranging between £2709 and £7150 greater depending on the organ damage type. CONCLUSION: Organ damage was associated with higher HCRU and healthcare costs, before and after SLE diagnosis. More effective SLE management may slow disease progression, prevent organ damage onset, improve clinical outcomes, and reduce healthcare costs.

Obstetric and neonatal outcomes in pregnant women with and without a history of specialist mental health care: a national population-based cohort study using linked routinely collected data in England.

BACKGROUND: Pregnant women with pre-existing mental illnesses have increased risks of adverse obstetric and neonatal outcomes compared with pregnant women without pre-existing mental illnesses. We aimed to estimate these differences in risks according to the highest level of pre-pregnancy specialist mental health care, defined as psychiatric hospital admission, crisis resolution team (CRT) contact, or specialist community care only, and the timing of the most recent care episode in the 7 years before pregnancy. METHODS: Hospital and birth registration records of women with singleton births between April 1, 2014, and March 31, 2018 in England were linked to records of babies and records from specialist mental health services provided by the England National Health Service, a publicly funded health-care system. We compared the risks of adverse pregnancy outcomes, including fetal and neonatal death, preterm birth, and babies being born small for gestational age (SGA; birthweight <10th percentile), and composite indicators for neonatal adverse outcomes and maternal morbidity, between women with and without a history of contact with specialist mental health care. We calculated odds ratios adjusted for maternal characteristics (aORs), using logistic regression. FINDINGS: Of 2 081 043 included women (mean age 30·0 years; range 18-55 years; 77·7% White, 11·4% South Asian, 4·7% Black, and 6·2% mixed or other ethnic background), 151 770 (7·3%) had at least one pre-pregnancy specialist mental health-care contact. 7247 (0·3%) had been admitted to a psychiatric hospital, 29 770 (1·4%) had CRT contact, and 114 753 (5·5%) had community care only. With a pre-pregnancy mental health-care contact, risk of stillbirth or neonatal death within 7 days of birth was not significantly increased (0·45-0·49%; aOR 1·11, 95% CI 0·99-1·24): risk of preterm birth (<37 weeks) increased (6·5-9·8%; aOR 1·53, 1·35-1·73), as did risk of SGA (6·2- 7·5%; aOR 1·34, 1·30-1·37) and neonatal adverse outcomes (6·4-8·4%; aOR 1·37, 1·21-1·55). With a pre-pregnancy mental health-care contact, risk of maternal morbidity increased slightly from 0·9% to 1·0% (aOR 1·18, 1·12-1·25). Overall, risks were highest for women who had a psychiatric hospital admission any time or a mental health-care contact in the year before pregnancy. INTERPRETATION: Information about the level and timing of pre-pregnancy specialist mental health-care contacts helps to identify women at increased risk of adverse obstetric and neonatal outcomes. These women are most likely to benefit from dedicated community perinatal mental health teams working closely with maternity services to provide integrated care. FUNDING: National Institute for Health Research.

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review.

BACKGROUND: Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality. METHODS: We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted. RESULTS: Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group. CONCLUSION: The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.

Health-care utilization and costs in adults with systemic lupus erythematosus in the United Kingdom: a real-world observational retrospective cohort analysis.

OBJECTIVE: The aim was to describe direct health-care costs for adults with SLE in the UK over time and by disease severity and encounter type. METHODS: Patients aged ≥18 years with SLE were identified using the linked Clinical Practice Research Datalink-Hospital Episode Statistics database from January 2005 to December 2017. Patients were classified as having mild, moderate or severe disease using an adapted claims-based algorithm based on prescriptions and co-morbid conditions. We estimated all-cause health-care costs and incremental costs associated with each year of follow-up compared with a baseline year, adjusting for age, sex, disease severity and co-morbid conditions (2017 UK pounds). RESULTS: We identified 802 patients; 369 (46.0%) with mild, 345 (43.0%) moderate and 88 (11.0%) severe disease. The mean all-cause cost increased in the 3 years before diagnosis, peaked in the first year after diagnosis and remained high. The adjusted total mean annual increase in costs per patient was £4476 (95% CI: £3809, £5143) greater in the year of diagnosis compared with the baseline year (P < 0.0001). The increase in costs per year was 4.7- and 1.6-fold higher among patients with severe SLE compared with those with mild and moderate SLE, respectively. Primary care utilization was the leading component of costs during the first year after diagnosis. CONCLUSION: The health-care costs for patients with SLE in the UK are substantial, remain high after diagnosis and increase with increasing severity. Future research should assess whether earlier diagnosis and treatment might reduce disease severity and associated high health-care costs.

Disease severity, flares and treatment patterns in adults with systemic lupus erythematosus in the UK: a real-world observational retrospective cohort analysis.

OBJECTIVES: The aim was to characterize disease severity, clinical manifestations, treatment patterns and flares in a longitudinal cohort of adults with SLE in the UK. METHODS: Adults with SLE were identified in the Clinical Practice Research Datalink-Hospital Episode Statistics database (1 January 2005-31 December 2017). Patients were required to have ≥12 months of data before and after the index date (earliest SLE diagnosis date available). SLE disease severity and flares were classified using adapted claims-based algorithms, which are based on SLE-related conditions, medications and health-service use. RESULTS: Of 802 patients, 369 had mild, 345 moderate and 88 severe SLE at baseline. A total of 692 initiated treatment in the first year after diagnosis. Five hundred and fifty-seven received antimalarials, 203 immunosuppressants and 416 oral CSs. Information on biologic use in hospitals was unavailable. The mean (S.d.) time to initiating any medication was 177 (385.3) days. The median time to first flare was 63 days (95% CI: 57, 71). At least one flare was experienced by 750 of 802 patients during follow-up; the first flare was mild for 549 of 750, moderate for 116 of 750 and severe for 85 of 750. The mean (S.d.) annual overall flare rate (year 1) was 3.5 (2.5). A shorter median time to first flare was significantly associated with moderate/severe disease (P < 0.001) and clinical manifestations (P < 0.001). CONCLUSION: Our findings suggest some delay in the initiation of SLE treatment. Most patients experience a flare within 2 months of diagnosis. Early treatment might delay or reduce the severity of the first SLE flare and might translate to slower disease progression, lower accrual of organ damage and better outcomes.

Risk of malignancy in patients with systemic lupus erythematosus: Systematic review and meta-analysis.

BACKGROUND: Malignancy is a potential comorbidity in patients with systemic lupus erythematosus (SLE). However, risk by malignancy type remains to be fully elucidated. We evaluated the risk of malignancy type in SLE patients in a systematic review and meta-analysis. METHODS: MEDLINE and EMBASE were searched from inception to July 2018 to identify observational studies that evaluated malignancy risk in adult SLE patients compared with the general population. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I2 test. FINDINGS: Forty-one studies reporting on 40 malignancies (one overall, 39 site-specific) were included in the meta-analysis. The pooled RR for all malignancies from 3694 events across 80 833 patients was 1.18 (95% CI: 1.00-1.38). The risk of 24 site-specific malignancies (62%) was increased in SLE patients. For malignancies with ≥6 studies, non-Hodgkin lymphoma and Hodgkin lymphoma risk was increased >3-fold; myeloma and liver >2-fold; cervical, lung, bladder, and thyroid ≥1.5-fold; stomach and brain >1.3-fold. The risk of four malignancies (breast, uterine, melanoma, prostate) was decreased, whereas risk of 11 other malignancies did not differ between SLE patients and the general population. Heterogeneity ranged between 0% and 96%, and 63% were non-significant. INTERPRETATION: The risk of overall and some site-specific malignancies is increased in SLE compared with the general population. However, the risk for some site-specific malignancies is decreased or did not differ. Further examination of risk profiles and SLE patient phenotypes may support guidelines aimed at reducing malignancy risk. FUNDING: AstraZeneca. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42018110433.

Systemic lupus erythematosus; stroke and myocardial infarction risk: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the risk of stroke and myocardial infarction (MI) in adult patients with systemic lupus erythematosus (SLE) through a systematic review and meta-analysis. METHODS: We searched MEDLINE and EMBASE from inception to May 2020 to identify observational studies (cohort and cross-sectional) that evaluated risk of stroke and MI in adult patients with SLE compared with the general population or healthy controls. Studies were included if they reported effect-size estimates that could be used for calculating pooled-effect estimates. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% CIs for stroke and MI. Heterogeneity quantified by the I2 test and sensitivity analyses assessed bias. RESULTS: In total, 26 studies were included in this meta-analysis: 14, 5 and 7 studies on stroke, MI and both stroke and MI, respectively. The pooled RR for ischaemic stroke was 2.18 (95% CI 1.78 to 2.67; I2 75%), intracerebral haemorrhage 1.84 (95% CI 1.16 to 2.90; I2 67%), subarachnoid haemorrhage 1.95 (95% CI 0.69 to 5.52; I2 94%), composite stroke 2.13 (95% CI 1.73 to 2.61; I2 88%) and MI 2.99 (95% CI 2.34 to 3.82; I2 85%). There was no evidence for publication bias, and sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Overall, patients with SLE were identified to have a twofold to threefold higher risk of stroke and MI. Future research on the interaction between known SLE-specific modifiable risk factors and risk of stroke and MI to support development of prevention and treatment strategies are needed. PROSPERO REGISTRATION NUMBER: CRD42018098690.

Variation in outcome after subarachnoid hemorrhage: a study of neurosurgical units in UK and Ireland.

BACKGROUNDS AND PURPOSE: The purpose of the study was to describe the characteristics, management, and outcomes of patients with confirmed aneurysmal subarachnoid hemorrhage and to compare outcomes across neurosurgical units (NSUs) in the UK and Ireland. METHODS: A cohort of patients admitted to NSUs with subarachnoid hemorrhage between September 14, 2001 and September 13, 2002 was studied longitudinally. Information was collected to characterize clinical condition on admission and treatment. Death or severe disability, defined by the Glasgow Outcome Score-Extended, was ascertained at 6 months. RESULTS: Data for 2397 patients with a confirmed aneurysm and no coexisting neurological pathology were collected by all 34 NSUs in the UK and Ireland. Aneurysm repair was attempted in 2198 (91.7%) patients (surgical clipping, 57.7%; endovascular coiling, 41.2%; other repair, 1.0%). Most patients (65.0%) were admitted to the NSU on the same day or the day after their hemorrhage; 32.0% of treated patients had the aneurysm repaired on the day of admission to the NSU (day 0), day 1 or day 2 and a further 39.3% by day 7. Glasgow Outcome Score-Extended at 6 months was obtained for 90.6% of patients (2172), of whom 38.5% had an unfavorable outcome. The median risk of an unfavorable outcome for all patients was 31% (5(th) and 95(th) percentiles, 12% and 83%), depending on prerepair prognostic factors. After adjustment for case-mix, the percentage of patients with an unfavorable outcome in each NSU did not differ significantly from the overall mean. CONCLUSIONS: In this study that collected representative data from the UK and Ireland, there was no evidence that the performance of any NSU differed from the average.

Verteporfin photodynamic therapy cohort study: report 3: cost effectiveness and lessons for future evaluations.

PURPOSE: To report (1) the costs of verteporfin photodynamic therapy (VPDT) in routine treatment of neovascular age-related macular degeneration (nAMD), (2) the relationship between health and social service costs and best-corrected visual acuity (BCVA), (3) the cost-effectiveness of VPDT versus a best supportive care (BSC) group who were assumed to have no active treatment, and (4) lessons for future cost-effectiveness analyses (CEAs). DESIGN: The CEA of VPDT versus BSC that uses health-related quality of life (HrQoL), resource use, and visual acuity data from the United Kingdom (UK) VPDT Cohort Study. PARTICIPANTS: Data on VPDT use were collected from patients attending 45 ophthalmology provider units in the UK National Health Service, 15 units collected data on self-reported use of services. METHODS: Incremental costs of VPDT versus BSC were calculated from treatment costs, change in cost associated with declining BCVA, and difference in BCVA previously attributed to VPDT. Similarly, incremental quality-adjusted life years (QALYs) were calculated from change in HRQoL associated with declining BCVA, giving an incremental cost per QALY of VPDT versus BSC over 2 years. MAIN OUTCOME MEASURES: Incremental costs (UK pounds [ pound]; United States dollars [$]); incremental QALYs; costs per QALY. RESULTS: The treatment costs of VDPT were pound 3026 ($4544) in year 1 and pound 845 ($1269) in year 2. For patients who used services, a 5-letter decrease in BCVA was associated with an increase in annual costs of approximately pound 110 ($165; 95% confidence intervals, approximately pound 48 [$72] to pound 174 [$261]). The incremental costs and QALYs for VPDT were pound 3514 ($5276) and 0.021, respectively, giving incremental costs per QALY gained of pound 170000 ($255000). CONCLUSIONS: Verteporfin photodynamic therapy is unlikely to be cost effective for patients with nAMD. This article provides realistic estimates of VPDT costs and the costs associated with declining vision. Future studies can follow this approach to assess accurately the cost effectiveness of new interventions for nAMD.

Verteporfin photodynamic therapy cohort study: report 2: clinical measures of vision and health-related quality of life.

PURPOSE: To quantify decreases in health-related quality of life (HRQoL) for given deterioration in clinical measures of vision; to describe the shape of these relationships; and to test whether the gradients of these relationships change with duration of visual loss. DESIGN: A prospective, longitudinal study of patients treated with verteporfin photodynamic therapy in the United Kingdom National Health Service. PARTICIPANTS: Patients with neovascular age-related macular degeneration (AMD) treated in 18 ophthalmology departments in the United Kingdom with expertise in management of neovascular AMD. METHODS: Responses to HRQoL questionnaires (Short Form 36 [SF-36] and National Eye Institute Visual Functioning Questionnaire [NEIVFQ]) and clinical measures of vision were recorded at baseline and at follow-up visits. Mixed regression models were used to characterize the relationships of interest. MAIN OUTCOME MEASURES: Measures of vision were best-corrected visual acuity (BCVA) and contrast sensitivity (CS). The SF-36 physical and mental component scores (PCS and MCS), SF-6D utility, and distance, near, and composite NEIVFQ scores were derived to characterize HRQoL. RESULTS: The SF-6D, PCS, and MCS were linearly associated with BCVA; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 0.0058, 0.245, and 0.546, respectively (all P<0.0001). Gradients were not influenced by duration of follow-up. Models predicting distance, near, and composite NEIVFQ scores from BCVA were quadratic; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 5.08, 5.48, and 3.90, respectively (all P<0.0001). The BCVA predicted HRQoL scores more strongly than CS. CONCLUSIONS: Clinically significant deterioration in clinical measures of vision is associated with small decreases in generic and vision-specific HRQoL. Our findings are important for further research modeling the cost effectiveness of current and future interventions for neovascular AMD.

Verteporfin photodynamic therapy cohort study: report 1: effectiveness and factors influencing outcomes.

PURPOSE: To compare the visual outcomes after verteporfin photodynamic therapy (VPDT) administered in routine clinical practice with those observed in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) trials and to quantify the effects of clinically important baseline covariates on outcome. DESIGN: A prospective longitudinal study of patients treated with VPDT in 45 ophthalmology departments in the United Kingdom with expertise in the management of neovascular age-related macular degeneration (nAMD). PARTICIPANTS: Patients with wholly or predominantly classic choroidal neovascularization (CNV) of any cause with a visual acuity >or=20/200 in the eye to be treated. METHODS: Refracted best-corrected visual acuity (BCVA) and contrast sensitivity were measured in VPDT-treated eyes at baseline and subsequent visits. Eyes were retreated at 3 months if CNV was judged to be active. Baseline angiograms were graded to quantify the percentages of classic and occult CNV. Treated eyes were categorized as eligible or ineligible for TAP, or unclassifiable. MAIN OUTCOME MEASURES: Best-corrected visual acuity and contrast sensitivity during 1 year of follow-up after initial treatment. RESULTS: A total of 7748 treated patients were recruited. Data from 4043 patients with a diagnosis of nAMD were used in the present analysis. Reading center determination of lesion type showed that 87% were predominantly classic CNV. Eyes received 2.4 treatments in year 1 and 0.4 treatments in year 2. Deterioration of BCVA over 1 year was similar to that observed in the VPDT arms of the TAP trials and was not influenced by TAP eligibility classification. Best-corrected visual acuity deteriorated more quickly in current smokers; with increasing proportion of classic CNV, increasing age, and better baseline BCVA; and when the fellow eye was the better eye. CONCLUSIONS: Patients in the cohort who would have been eligible for the TAP trials demonstrated deterioration in BCVA similar to VPDT-treated TAP participants but with fewer treatments. Clinical covariates with a significant impact on BCVA outcomes were identified.

Navigational cue effects in Alzheimer's disease and posterior cortical atrophy.

OBJECTIVE: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. METHODS: The effect of visual cues on visually guided navigation was assessed within a simplified real-world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated-measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion-based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. RESULTS: Results illustrate marked deficits in patients' navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast-cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. INTERPRETATION: The study evaluated navigation to destinations within a real-world environment. There is evidence that introducing perceptual changes to the environment may improve patients' navigational ability.