Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease ...burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.
In an outpatient, home-use, random-order, controlled trial we compared automated glycemic control with the iLet bionic pancreas in the insulin-only (IOBP) vs. the bihormonal (BHBP) configurations for ...one week each in adult subjects (n=10) with type 1 diabetes. Subjects used their typical insulin analog (lispro or aspart) during both arms of the study. During the BHBP period the iLet delivered micro-doses of dasiglucagon, a glucagon analog stable in aqueous solution (Zealand Pharma). The insulin control algorithm was identical in both configurations, was initiated solely based on each subjects’ body mass without any information regarding patients’ baseline insulin needs, and used a glucose target of 110 mg/dl. The mean CGM glucose was lower in the BHBP arm vs. the IOBP arm (139±11 vs. 149±13 mg/dl, p=0.004) while the % of time with CGMG <54 mg/dl was nominally reduced (0.2%, IQR 0-0.4 vs. 0.6%, IQR 0.2-1.1%, p=0.11). We used an autoregressive time series model to determine statistical significance for differences between arms for each individual subject. Eight subjects had a significantly lower mean CGMG during the BHBP arm (p<0.05, mean improvement 12±7 mg/dl), while in the remaining two subjects there was no significant difference (nominal absolute difference 2±1 mg/dl). Eight of the ten subjects had a nominal reduction of the % of time <54 mg/dL in the BHBP arm (mean nominal difference -0.5%, range -0.1 to -1.0%), none of which were statistically significant. Here we demonstrated significant benefit of adding dasiglucagon in eight of ten subjects, allowing them to achieve a lower mean glucose without increased rates of hypoglycemia, in a trial comparing the BHBP and IOBP configurations of the iLet.
Disclosure
J. Sherwood: None. C.A. Balliro: None. R.Z. Jafri: None. L.E. Castellanos: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Greaux: None. H. Zheng: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
Funding
Beta Bionics, Inc.
Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary manifestation of cystic fibrosis. The current standard of care for CFRD involves treatment with insulin, typically via ...multiple daily injections. We conducted a small pilot study comparing usual care with automated glycemic control using the bihormonal (insulin and glucagon) and insulin-only configurations of the bionic pancreas. Both configurations of the bionic pancreas achieved good glycemic control, with mean glucose levels <150 mg/dl and minimal hypoglycemia. Subjects reported improved treatment satisfaction and reduced burden of diabetes management with the bionic pancreas. Further investigation of automated glycemic control in the treatment of CFRD is warranted.
The Gen3 iLet (iLet) is a purpose-built, fully integrated, bionic pancreas (BP) platform that can operate in a bihormonal, insulin-only, or glucagon-only mode and can receive data from the Dexcom G5 ...or the Senseonics Eversense implanted CGM. We performed a random-order, cross-over, outpatient study comparing the insulin-only mode of the iLet to usual care (UC) for 7 days each as a bridge from past studies using the BP algorithm on an iPhone connected wirelessly to an insulin pump. The study enrolled adults with T1D who used either MDI (n=12) or CSII (n=22) for their UC. Participants enrolled at Massachusetts General Hospital (n=17) used the Eversense while those at Stanford (n=17) used the G5 as the input CGM signal for the iLet. There was no statistically significant difference between the iLet and UC in % time <54 mg/dl (0.6 0.2,1.1 vs. 0.6 0.1,1.2, p=0.87) or mean CGM glucose (155±12 vs. 162±26 mg/dl, p=0.097). The iLet significantly increased % time within 70-180 mg/dl vs. UC (70.1% vs. 61.5%, p=0.006). The mean insulin TDD was not significantly different between iLet and UC (44±20 vs. 42±20 u/day). No serious adverse events occurred during either arm. Several device issues occurred that led to changes in the Gen4 iLet under development to improve safety and usability in pivotal trials. These results suggest that the iLet, using either the Eversense or G5 CGMs, may provide safe and effective glucose control to users with MDI or CSII as their UC.
Disclosure
R.Z. Jafri: None. C.A. Balliro: None. J. Sherwood: None. M. Hillard: None. L. Ekhlaspour: None. L. Hsu: None. R. Selagamsetty: Employee; Self; Beta Bionics. Other Relationship; Self; Boston University. J.R. Costik: Board Member; Self; Nightscout Foundation. Employee; Self; Beta Bionics. Employee; Spouse/Partner; Ortho Clinical Diagnostics. J. Sloane: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics.
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK108612)
Introduction
We investigated the safety of, and glucose control by, the insulin-only configuration of the iLet
®
bionic pancreas delivering fast-acting insulin aspart (faster aspart), using the same ...insulin-dosing algorithm but different time to maximal serum drug concentration (
t
max
) settings, in adults with type 1 diabetes.
Methods
We performed a single-center, single-blinded, crossover (two 7-day treatment periods) escalation trial over three sequential cohorts. Participants from each cohort were randomized to a default
t
max
setting (
t
65
t
max
= 65 min) followed by a non-default
t
max
setting (
t
50
t
max
= 50 min; cohort 1,
t
40
t
max
= 40 min; cohort 2,
t
30
t
max
= 30 min; cohort 3), or vice versa, all with faster aspart. Each cohort randomized eight new participants if escalation-stopping criteria were not met in the previous cohort.
Results
Overall, 24 participants were randomized into three cohorts. Two participants discontinued treatment, one due to reported ‘low blood glucose’ during the first treatment period of cohort 3 (
t
30
). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all
t
max
settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default
t
max
settings, with comparable insulin dosing. The mean time sensor glucose was in range (70–180 mg/dl) was > 70% for all cohorts, except the default
t
max
setting in cohort 1. No severe hypoglycemic episodes were reported. Furthermore, there were no clinically significant differences in adverse events between the groups.
Conclusion
There were no safety concerns with faster aspart in the iLet at non-default
t
max
settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default
t
max
settings.
Trial Registration
ClinicalTrials.gov, NCT03816761.
Plain Language Summary
One way to give insulin is to use an insulin delivery system. The iLet
®
is a new type of insulin delivery system that works together with a continuous sugar monitoring tool (CGM). The CGM shows the blood sugar level in the body throughout the day. Based on this, the iLet automatically gives the insulin that is needed to control the blood sugar. Fast-acting insulin aspart (faster aspart) is a type of insulin that doctors can prescribe for use with insulin pens and insulin pumps. The researchers wanted to test the safety of faster aspart when given to people at different delivery settings in the iLet. Twenty-four men and women with type 1 diabetes from the USA took part. The different insulin delivery settings were the standard setting (
t
max
65 = 65 min) and new settings (
t
max
50 = 50 min;
t
max
40 = 40 min;
t
max
30 = 30 min). The shorter the
t
max
setting, the faster the insulin was assumed to be absorbed into the body by the iLet. People had good blood sugar control with faster aspart delivered using the iLet. The time with low blood sugar (i.e., < 54 mg/dl) was low for both the standard setting and the new settings. The average blood sugar was lower with the shorter, non-standard
t
max
settings. No people had serious side effects. No severe hypoglycemic episodes were reported. In this study, researchers found that it was safe to use faster aspart with the different settings in the iLet.
A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs ...across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs.
There is growing evidence to suggest that the brain is an important target for insulin action, and that states of insulin resistance may extend to the CNS with detrimental effects on cognitive ...functioning. Although the effect of systemic insulin resistance on peripheral organs is well-studied, the degree to which insulin impacts brain function in vivo remains unclear.
This randomized, single-blinded, 2-way-crossover, sham-controlled, pilot study determined the effects of hyperinsulinemia on fMRI brain activation during a 2-back working memory task in 9 healthy older adults (aged 57-79 years). Each participant underwent two clamp procedures (an insulin infusion and a saline placebo infusion, with normoglycemia maintained during both conditions), to examine the effects of hyperinsulinemia on task performance and associated blood-oxygen-level dependent (BOLD) signal using fMRI.
Hyperinsulinemia (compared to saline control) was associated with an increase in both the spatial extent and relative strength of task-related BOLD signal during the 2-back task. Further, the degree of increased task-related activation in select brain regions correlated with greater systemic insulin sensitivity, as well as decreased reaction times and performance accuracy between experimental conditions.
Together, these findings provide evidence of insulin action in the CNS among older adults during periods of sustained cognitive demand, with the greatest effects noted for individuals with highest systemic insulin sensitivity.
This work was funded by the National Institutes of Health (5R21AG051958, 2016).
Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.
This cross sectional study was ...carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.
Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02) and surgical margin status (p = 0.001) were statistically significant for determination of relapse of disease.
The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.
Abstract Background Infants and young children are particularly susceptible to developing tuberculosis (TB) following exposure and infection, and isoniazid preventive therapy can substantially reduce ...this risk. This evidence-base provides the rationale for the policy and guidelines to screen and manage children that are household contacts of TB cases, prioritizing those with sputum smear-positive TB. The guidelines have been in place for decades, but are rarely implemented. IPT programs in high-TB burden countries are rare and fraught with low uptake and low rates of therapy completion. Methods This study describes the demographics and outcomes of contact management and the IPT program for <5 years old at the Indus Hospital in Karachi, Pakistan from 2011 to 2014. Children <5 years old in contact with newly diagnosed sputum smear-positive pulmonary TB patients were referred by the counselor for contact evaluation. All children underwent a history, physical, CXR and TST. All contacts were started on IPT based on WHO recommendations after confirming that they had no TB disease. Outcomes were defined as children who were enrolled, started on IPT but never returned for follow-up (primary default), children who had one or more follow-up visits but did not complete treatment (default) and children who completed IPT (treatment completed). Results A total of 240 children were enrolled in the Indus IPT program from 2011 to 2014. Of these, data from 184 contacts was analyzed in detail as the remainder were still on IPT. All children enrolled were less than 5 years of age (mean age 3 years) and 96 (52%) were males. Of all the enrolled children, 76/240 (31.6%) were <5% weight for their age (underweight), of these 52% were female children. A symptom of either cough or fever was reported by 29/184 (15.7%) children; however, all responded to routine antibiotics and did not have CXR findings suggestive of TB disease. Of the enrolled who had a TST done, 12/209 (5.8%) had a positive result. Analysis of outcomes revealed that only 60/184 (32.6%) completed 6 months of IPT (with no gender predisposition). Among those who completed therapy, none developed TB disease during follow-up. Outcome trends revealed an increase in completion rate (40% in 2013 compared with 26% in 2012), which may reflect improvement in counseling services in 2013. Children who had an initial symptom or were underweight at the start of IPT were more likely to complete treatment ( p < 0.01). Conclusion Despite a large cohort of TB patients in the Indus TB program-5487 SS+ patients registered during the study period – this IPT program enrollment has been low. A high rate of patient default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness enhancing efforts by community field teams will help improve outcomes. It is vital that the National TB Program strengthens and expands contact management with a community-based approach and incentives.
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