A new calculator developed by the University of Exeter will help clinicians classify whether a patient has type 1 or type 2 diabetes, ensuring they get the best treatment and reducing complications.

The calculator uses a model that takes into account available data about the patient, as well as blood test results. It can be used to identify if a person is likely to have type 1 diabetes, to reduce misdiagnosis. Former Prime Minister Theresa May was initially diagnosed with type 2 diabetes. Only when tablet treatment failed to work was she re-diagnosed with type 1.

It is often difficult for clinicians to diagnose which type of diabetes a patient has. While blood tests such as antibodies against the cells that make insulin, or a person’s genetic risk of type 1 diabetes may help diagnosis,  these tests do not give a diagnosis on their own, and may be interpreted very differently depending on whether or not a person has other features of type 1 diabetes. The new calculator, currently available in beta format, combines available information from blood tests with a person’s age of diagnosis and BMI for a personalised medicine approach. The calculator was developed by researchers at the universities of Exeter, Oxford and Dundee.

The new calculator will build on the success of a similar calculator previously developed at Exeter, to help clinicians determine whether a patient has the diabetes subtype MODY, caused by a single gene. The online calculator has been used by more than 100,000 people, with more than 9,000 people downloading the calculator phone app Diabetes Diagnostics, which will be updated to include the new calculator. New research recently presented at the European Association for the Study of Diabetes conference in Barcelona has shown that almost half of all referrals sent to the UK diagnostic laboratory for MODY now report using the calculator, and those that report using the calculator have a higher detection rate compared with those that do not.
Dr Angus Jones, of the University of Exeter Medical School, who led the research, said: “The right diagnosis in diabetes is absolutely crucial to getting the best outcomes for patients, as treatment is very different in different types of diabetes. However in some people it can be very difficult to know what type of diabetes they have. Our new calculator can help clinicians by combining different features to give them the probability a person will have type 1 diabetes, and assess whether additional tests are likely to be helpful.”
The new beta format calculator can be accessed here: www.diabetesgenes.org/t1dt2d-prediction-model/
University of Exeterwww.exeter.ac.uk/news/research/title_754422_en.html

A recently published study examines the evolutionary and epidemiologic history of an epidemic strain of extensively drug-resistant tuberculosis (XDR-TB) – called LAM4/KZN – in KwaZulu-Natal, South Africa. This strain was first reported in a 2005 outbreak in Tugela Ferry, KwaZulu-Natal, where it was associated with 90 % mortality among predominantly HIV infected individuals, and has since become widespread throughout the province. A new study identifies key host, pathogen and environmental factors that facilitated the success of this XDR-TB strain and steps that can be taken for early identification and containment of future epidemics.

The study, led by Columbia University, involved a multi-institutional team of researchers from South Africa, the United States, and Norway, used genomic, spatial and protein modelling to answer when and where this strain emerged, and how and why it became widespread. The study utilized data and TB strains collected in the prospective XDR-TB transmission study (TRAX) from 2011 to 2014 led by Emory University, the University of KwaZulu-Natal, and the U.S. Centers for Disease Control and Prevention.

Researchers localized the geographic origin of the strain to a rural district, bordering Mozambique and eSwatini, with high pre-existing rates of drug-resistant TB located 400 hundred kilometres away from where the first outbreak of LAM4/KZN was reported. Results also indicate that the strain emerged in the early 1990s, acquiring key advantageous mutations prior to undergoing marked expansion concurrent with the onset of the generalized HIV epidemic. In addition, the study suggests cyclical rural-urban migration in the rapid and widespread dissemination of this strain.
"Our results indicate that this strain of  XDR-TB emerged approximately 12 years before it was identified by public health activities," said lead researcher Barun Mathema, PhD, assistant professor of epidemiology at Columbia University Mailman School of Public Health. "Our research highlights multiple environmental and pathogen-specific factors must align in order for these pathogens to establish sustained transmission and disperse into geographically separated populations. These processes take place in the so-called ‘pre-detection’ period, years before the pathogens are first noticed as public health threats," said Mathema.

"From our findings, we learned the importance of HIV coinfection, high pre-existing rates of drug-resistant TB, human migration, and adaptive evolution in the emergence and dispersal of this critical public health threat," noted first author Tyler S. Brown, MD, research fellow in the Infectious Diseases Division at Massachusetts General Hosptial.

"Routine integration of whole-genome sequencing into public health surveillance can address any knowledge gaps and enable us to better understand the pre-detection period and inform strategies for early identification and local containment of AMR pathogens," observed Mathema. "Surveillance, enabled by the rapidly decreasing cost of pathogen sequencing, can provide a powerful strategy for public health practitioners."

ScienceDaily

www.sciencedaily.com/releases/2019/10/191028175153.htm

Byondis B.V. (formerly Synthon Biopharmaceuticals) announced that Quantum Leap Healthcare Collaborative (Quantum Leap) selected the company’s investigational antibody-drug conjugate (ADC) SYD985 ([vic-]trastuzumab duocarmazine) for a new investigational treatment arm in its ongoing I-SPY 2 TRIAL for neoadjuvant treatment of locally advanced breast cancer. This treatment arm will focus on treatment for HER2-low early-stage breast cancer.
The I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis) is a standing Phase II randomized, controlled, multicentre study aimed at rapidly screening and identifying promising treatments in specific subgroups of women with newly-diagnosed, high-risk, locally advanced breast cancer (Stage II/III). Quantum Leap, sponsor of the I-SPY 2 TRIAL, leads a pre-competitive consortium that includes the U.S. Food & Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 16 major U.S. cancer research centres.
The new I-SPY 2 treatment arm will evaluate SYD985 against standard of care therapy in Stage II/III early-stage, high-risk breast cancer patients, with a focus on tumours with heterogeneous and low HER2 expression. Byondis will supply the investigational drug and provide financial and regulatory support. Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.
SYD985 is Byondis’ most advanced ADC, targeting a range of HER2-positive cancers such as metastatic breast cancer (MBC) and endometrial cancer. The company is currently conducting a Phase III study of SYD985 (TULIP or SYD985.002) to compare its efficacy and safety to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Previously, the FDA granted fast track designation for SYD985 based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001).
SYD985 uses Byondis’ unique, proprietary linker-drug (LD) technology. Although marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
SYD985 is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD985 binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumour cell death. SYD985 can be considered a form of targeted chemotherapy.