Belimumab : a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis

Objectives: To undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies. Methods: We searched eight electronic databases and reference lists for randomised controlled trials (RCTs) of belimumab against placebo or best supportive care. Quality assessment and random effects meta-analysis were undertaken. Design: A meta-analysis of RCTs. Participants: 2133 SLE patients. Primary and secondary outcome measures: SLE Responder Index (SRI) at week 52. Results: Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76) investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab effectiveness for the SRI at week 52. Ethnicity and geographical location of participants varied considerably between BLISS trials. Although tests for statistical heterogeneity were negative, BLISS-52 results were systematically more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By week 76, the primary SRI outcome in BLISS-76 was not statistically significant (OR 1.31, 95% CI 0.919 to 1.855)

Impact of Moderate to Severe Renal Impairment on Mortality and Appropriate Shocks in Patients with Implantable Cardioverter Defibrillators

Background. Due to underrepresentation of patients with chronic kidney disease (CKD) in large Implantable-Cardioverter Defibrillator (ICD) clinical trials, the impact of ICD remains uncertain in this population. Methods. Consecutive patients who received ICD at Creighton university medical center between years 2000–2004 were included in a retrospective cohort after excluding those on maintenance dialysis. Based on baseline Glomerular filtration rate (GFR), patients were classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30–59 mL/min; and mild or no CKD: GFR ≥ 60 mL/min. The impact of GFR on appropriate shocks and survival was assessed using Kaplan-Meier method and Generalized Linear Models (GLM) with log-link function. Results. There were 509 patients with a mean follow-up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated GFR: 2 fold higher risk with GFR between 30–59 mL/min and 5 fold higher risk with GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate shock(s); appropriate shock-free survival was lower in patients with severe CKD (GFR < 30) compared to mild or no CKD group (2.8 versus 4.2 yrs). Conclusion. Even moderate renal dysfunction increases all cause mortality in CKD patients with ICD. Severe but not moderate CKD is an independent predictor for time to first appropriate shock

Effectiveness of 10-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in Pakistan

Objective: To assess the effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) against invasive pneumococcal disease (IPD) due to vaccine serotypes of Streptococcus pneumoniae post introduction of the vaccine into the routine immunization program in Pakistan.Methods: A matched case-control study was conducted at 16 hospitals in Sindh Province, Pakistan. Children aged (eligible to receive PCV10) who presented with radiographically confirmed pneumonia and/or meningitis were enrolled as cases. PCR for the lytA gene was conducted on blood (for radiographic pneumonia) and cerebrospinal fluid (for meningitis) samples to detect S. pneumoniae. The proportion of IPD due to vaccine serotypes (including vaccine-related serogroups) was determined through serial multiplex PCR. For each case, at least five controls were enrolled from children hospitalized at the same institution, matched for age, district, and season.Results: Of 92 IPD patients enrolled during July 2013 to March 2017, 24 (26.0%) had disease caused by vaccine serotypes. Most case (87.5% of 24) and control (66.4% of 134) children had not received any PCV10 doses. The estimated effectiveness of PCV10 against vaccine-type IPD was 72.7% (95% confidence interval (CI) -7.2% to 92.6%) with at least one dose, 78.8% (95% CI -11.9% to 96.0%) for at least two doses, and 81.9% (95% CI -55.7% to 97.9%) for all three doses of vaccine.Conclusion: The vaccine effectiveness point estimates for PCV10 were high and increased with increasing number of doses. However, vaccine effectiveness estimates did not reach statistical significance, possibly due to low power. The findings indicate the likely impact of vaccine in reducing the burden of vaccine-type IPD if vaccine uptake can be improved

Intraoperative ultrasound-guided iodine-125 seed implantation for unresectable pancreatic carcinoma

<p>Abstract</p> <p>Background</p> <p>To assess the feasibility and efficacy of using ¹²⁵I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma.</p> <p>Methods</p> <p>Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with ¹²⁵I seed implantation guided by intraoperative ultrasound and received D₉₀of ¹²⁵I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy.</p> <p>Results</p> <p>87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3).</p> <p>Conclusion</p> <p>There were no deaths related to ¹²⁵I seed implant. In this preliminary investigation, ¹²⁵I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.</p

Protocol for a national cohort study to explore the long-term clinical and patient-reported outcomes and cost-effectiveness of implant-based and autologous breast reconstruction after mastectomy for breast cancer: The Brighter Study

Introduction Breast reconstruction (BR) is offered to improve quality of life for women with breast cancer undergoing mastectomy. As most women will be long-Term breast cancer survivors, high-quality information regarding the long-Term outcomes of different BR procedures is essential to support informed decision-making. As different techniques vary considerably in cost, policymakers also require high-quality cost-effectiveness evidence to inform care. The Brighter study aims to explore the long-Term clinical and patient-reported outcomes (PROs) of implant-based and autologous BR and use health economic modelling to compare the long-Term cost-effectiveness of different reconstructive techniques. Methods and analysis Women undergoing mastectomy and/or BR following a diagnosis of breast cancer between 1 January 2008 and 31 March 2009 will be identified from hospital episode statistics (HES). Surviving women will be contacted and invited to complete validated PRO measures including the BREAST-Q, EQ-5D-5L and ICECAP-A, or opt out of having their data included in the HES analysis. Long-Term clinical outcomes will be explored using HES data. The primary outcome will be rates of revisional surgery between implant-based and autologous procedures. Secondary outcomes will include rates of secondary reconstruction and reconstruction failure. The long-Term PROs of implant-based and autologous reconstruction will be compared using BREAST-Q, EQ-5D-5L and ICECAP-A scores. Multivariable regression will be used to examine the relationship between long-Term outcomes, patient comorbidities, sociodemographic and treatment factors. A Markov model will be developed using HES and PRO data and published literature to compare the relative long-Term cost-effectiveness of implant-based and autologous BR. Ethics and dissemination The Brighter study has been approved by the South-West-Central Bristol Research Ethics Committee (20/SW/0020), and the Confidentiality Advisory Group (20/CAG/0021). Results will be published in peer-reviewed journals and presented at national meetings. We will work with the professional associations, charities and patient groups to disseminate the results

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

Background and Aim: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. Methods: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. Results: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5–30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. Conclusions: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI

Panel 7: otitis media:treatment and complications

Objective: We aimed to summarize key articles published between 2011 and 2015 on the treatment of (recurrent) acute otitis media, otitis media with effusion, tympanostomy tube otorrhea, chronic suppurative otitis media and complications of otitis media, and their implications for clinical practice. Data Sources: PubMed, Ovid Medline, the Cochrane Library, and Clinical Evidence (BMJ Publishing). Review Methods: All types of articles related to otitis media treatment and complications between June 2011 and March 2015 were identified. A total of 1122 potential related articles were reviewed by the panel members; 118 relevant articles were ultimately included in this summary. Conclusions: Recent literature and guidelines emphasize accurate diagnosis of acute otitis media and optimal management of ear pain. Watchful waiting is optional in mild to moderate acute otitis media; antibiotics do shorten symptoms and duration of middle ear effusion. The additive benefit of adenoidectomy to tympanostomy tubes in recurrent acute otitis media and otitis media with effusion is controversial and age dependent. Topical antibiotic is the treatment of choice in acute tube otorrhea. Symptomatic hearing loss due to persistent otitis media with effusion is best treated with tympanostomy tubes. Novel molecular and biomaterial treatments as adjuvants to surgical closure of eardrum perforations seem promising. There is insufficient evidence to support the use of complementary and alternative treatments. Implications for Practice: Emphasis on accurate diagnosis of otitis media, in its various forms, is important to reduce overdiagnosis, overtreatment, and antibiotic resistance. Children at risk for otitis media and its complications deserve special attention

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future