Antibiotics versus surgery in acute appendicitis

A systemic review of research literature by scientists at the University of Southampton shows that antibiotics may be an effective treatment for acute non-complicated appendicitis in children, instead of surgery. The research paper is published in Pediatrics.

The condition, which causes the appendix – a small organ attached to the large intestine – to become inflamed due to a blockage or infection, affects mainly children and teenagers. Appendicitis is currently treated through an operation to remove the appendix, known as an appendicectomy, and it is the most common cause of emergency surgery in children.

The review, led by Nigel Hall, Associate Professor of Pediatric Surgery at the University of Southampton, assessed existing literature published over the past 10 years that included 10 studies reporting on 413 children who received non-operative treatment rather than an appendectomy. It shows that no study reported any safety concern or specific adverse events related to non-surgical treatment, although the rate of recurrent appendicitis was 14 per cent.

The review says that longer term clinical outcomes and cost effectiveness of antibiotics compared to appendicectomy require further evaluation, preferably as large randomized trials to reliably inform decision making.

To further this research Mr. Hall and his team in Southampton, along with colleagues at St George’s Hospital in Tooting, Alder Hey Children’s Hospital in Liverpool and Great Ormond Street Hospital, are currently carrying out a year-long feasibility trial which will see children with appendicitis randomly allocated to have either surgery or antibiotic treatment.

Reference: Georgiou, Roxani, Simon Eaton, Michael P. Stanton, Agostino Pierro, and Nigel J. Hall. “Efficacy and Safety of Nonoperative Treatment for Acute Appendicitis: A Meta-analysis.” Pediatrics, 2017.
Research funding: National Institute for Health Research Health Technology Assessment Programme (UK).
Adapted from press release by University of Southampton.

Systemic review of literature finds no evidence of increased risk of fatal stomach bleed following use of aspirin

Stomach bleeds caused by aspirin are considerably less serious than the spontaneous bleeds that can occur in people not taking the drug, concludes a study led by Cardiff University. Published in the journal Public Library of Science, the extensive study of literature on aspirin reveals that while regular use of the drug increases the risk of stomach bleeds by about a half, there is no valid evidence that any of these bleeds are fatal.

Professor Peter Elwood from Cardiff University’s School of Medicine said: “Although many people use aspirin daily to reduce the risk of health problems such as cancer and heart disease, the wider use of the drug is severely limited because of the side effect of bleeding from the stomach. With our study showing that there is no increased risk of death from stomach bleeding in people who take regular aspirin, we hope there will be better confidence in the drug and wider use of it by older people, leading to important reductions in deaths and disablement from heart disease and cancer across the community.”

Heart disease and cancer are the leading causes of death and disability across the world, and research has shown that a small daily dose of aspirin can reduce the occurrence of both diseases by around 20-30%.

Recent research has also shown that low doses of aspirin given to patients with cancer, alongside chemotherapy and/or radiotherapy, is an effective additional treatment, reducing the deaths of patients with bowel, and possibly other cancers, by a further 15%.

The study ‘Systematic review and meta-analysis of randomized trials to ascertain fatal gastrointestinal bleeding events attributable to preventive low-dose aspirin: No evidence of increased risk’ can be found in Public Library of Science.

This study was a systematic review and meta-analysis of randomized trials. This type of research provides the strongest evidence for drawing causal conclusions because it draws together all of the best evidence.

Citation: “Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk”. Peter C. Elwood , Gareth Morgan  , Julieta Galante , John W. K. Chia , Sunil Dolwani , J. Michael Graziano , Mark Kelson , Angel Lanas , Marcus Longley , Ceri J. Phillips , Janet Pickering , Stephen E. Roberts , Swee S. Soon , Will Steward , Delyth Morris & Alison L. Weightman. PLOS ONE 2016 vol: 11 (11) pp: e0166166.
Adapted from press release by the University of Cardiff.

Therapeutic Antibody conjugates proven clinically effective with acceptable toxicity

Antibody Drug Conjugates (ADCs) have shown a clearly documented efficacy and acceptable toxicity and can be easily implemented in oncology departments where chemotherapy administration is a routine practice. A similar efficacy with acceptable toxicity has been documented with Antibody Radionuclide Conjugates (ARCs) which need to be injected with the help of a nuclear medicine department which can be a limitation for referral from an oncologist.

In a review collecting the clinical results of 11 studies including 598 patients treated with 6 Antibody Drug Conjugates and 9 studies (including 377 patients treated with 5 Antibody Radionuclide Conjugates), toxicity was generally less frequent with Antibody Drug Conjugates than with Antibody Radionuclide Conjugates but often led to more uncomfortable side effects. Both conjugates have shown some clinical efficacy in terms of survival (progression free survival or overall survival) depending on the tumor type, radiosensitive or not.

The good results of both conjugates could be significantly improved in the future. Targeting Cancer Stem Cells (CSC) using both cytotoxic payloads (drugs or radionuclides) could delay tumor relapse. Preclinical studies have shown a promising therapeutic index with long-term tumor regression warranting a clinical application.

Efficacy of Antibody Radionuclide Conjugates could be improved with the use of alpha-emitting radionuclides which deliver a high fraction of their energy inside the targeted tumor cell leading to highly efficient killing especially for isolated tumor cells or clusters of malignant cells in the body.

The efficacy of both Antibody Drug Conjugates and Antibody Radionuclide Conjugates could be enhanced by parallel treatment with immune checkpoint inhibitors thus providing synergistic immunogenic cell death.

In conclusion therapeutic immunoconjugates using chemotherapeutic drug or radionuclides as cytotoxic payloads have clearly shown clinical efficacy, which could be significantly improved in the near future.

Citation: Chatal, Jean-François, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, and Caroline Rousseau. “Therapeutic Immunoconjugates. Which Cytotoxic Payload: Chemotherapeutic Drug (ADC) or Radionuclide (ARC)?.” Current Cancer Therapy Reviews 12, no. 1 (2016): 54-65.
Adapted from press release by Bentham Science Publishers.

Review of literature suggests that brain imaging scans can predict psychotherapy outcome in depression and anxiety

Brain imaging scans may one day provide useful information on the response to psychotherapy in patients with depression or anxiety, according to a systamic review of current research. The results of the systamic review are reported in Harvard Review of Psychiatry, published by Wolters Kluwer.

Studies show promising initial evidence that specific “neuroimaging markers” might help in predicting the chances of a good response to psychotherapy, or choosing between psychotherapy or medications, in patients with major depressive disorder (MDD) and other diagnoses. “While some brain areas have emerged as potential candidate markers, there are still many barriers that preclude their clinical use,” comments lead author Dr. Trisha Chakrabarty of University of British Columbia, Vancouver.

The researchers analyzed previous research evaluating brain imaging scans to predict the outcomes of psychotherapy for major depressive and anxiety disorders. Psychiatrists are interested in identifying brain imaging markers of response to psychotherapy–comparable to electrocardiograms and laboratory tests used to decide on treatments for myocardial infarction.

The review found 40 studies including patients with major depressive disorder (MDD), obsessive-compulsive disorder, posttraumatic stress disorder, and other diagnoses. Some studies used structural brain imaging studies, which show brain anatomy; others used functional scans, which demonstrate brain activity.

Although no single brain area was consistently associated with response to psychotherapy, the results did identify some “candidate markers.” Studies suggested that psychotherapy responses might be related to activity in two deep brain areas: the amygdala, involved in mood responses and emotional memories; and the anterior insula, involved in awareness of the body’s physiologic state, anxiety responses, and feelings of disgust.

In major depressive disorder (MDD) studies, patients with higher activity in the amygdala were more likely to respond to psychotherapy. In contrast, in some studies of anxiety disorders, lower activity in the amygdala was associated with better psychotherapy outcomes. Studies of anterior insula activity showed the converse: psychotherapy response was associated with higher pretreatment activity in anxiety disorders and lower activity in major depressive disorder (MDD).

Other studies linked psychotherapy responses to a frontal brain area called the anterior cingulate cortex, which plays a critical role in regulating emotions. Most of the evidence suggested that major depressive disorder (MDD) patients with lower activity in some parts of the ACC (ventral and subgenual) were more likely to have good outcomes with psychotherapy.

The researchers emphasize the limitations of current evidence on neuroimaging markers of psychotherapy response–the studies were highly variable in terms of their methodology and results. Further studies are needed to assess how the potential neuroimaging markers perform over time, whether they can predict which patients will respond better to medications versus psychotherapy, and how they might be integrated with clinical features in order to improve outcomes for patients with depression and anxiety disorders.

Citation: Chakrabarty, Trisha; Ogrodniczuk, John; Hadjipavlou, George. “Predictive Neuroimaging Markers of Psychotherapy Response: A Systematic Review”. Harvard Review of Psychiatry 2016 vol: 24 (6) pp: 396-405
Adapted from press release by Wolters Kluwer Health