Anti-VEGF intervention in neovascular AMD: benefits and risks restated as natural frequencies.

OBJECTIVE: Clear information is essential to properly determine preference in medical intervention. In neovascular age-related macular degeneration, patients need to understand the balance of risk and benefit of anti-vascular endothelial growth factor (VEGF) treatment. This balance is altered by the number of injections administered. METHODS: Natural frequencies, displayed as pictographically as icon arrays, are used to show material outcomes from the MARINA and HARBOR (12 months) trials. We also calculated the number needed to treat (NNT) and number needed to harm (NNH). RESULTS: MARINA 24-month data show the absolute risk reduction is 37% and the NNT is 3; meaning for one patient to benefit three need to be treated.12 months' HARBOR data show that compared with as-needed treatment, scheduled monthly injection treatment increases the number of patients achieving a better visual outcome. The number of patients suffering harm is also increased by the additional injections. CONCLUSION: Displaying MARINA and HARBOR trial data as natural frequencies, with numbers needed to treat and harm, communicates complimentary information on the positive and negative aspects of anti-VEGF treatment

Is "No test is better than a bad test"? Impact of diagnostic uncertainty in mass testing on the spread of Covid-19

Testing is viewed as a critical aspect of any strategy to tackle epidemics. Much of the dialogue around testing has concentrated on how countries can scale up capacity, but the uncertainty in testing has not received nearly as much attention beyond asking if a test is accurate enough to be used. Even for highly accurate tests, false positives and false negatives will accumulate as mass testing strategies are employed under pressure, and these misdiagnoses could have major implications on the ability of governments to suppress the virus. The present analysis uses a modified SIR model to understand the implication and magnitude of misdiagnosis in the context of ending lockdown measures. The results indicate that increased testing capacity alone will not provide a solution to lockdown measures. The progression of the epidemic and peak infections is shown to depend heavily on test characteristics, test targeting, and prevalence of the infection. Antibody based immunity passports are rejected as a solution to ending lockdown, as they can put the population at risk if poorly targeted. Similarly, mass screening for active viral infection may only be beneficial if it can be sufficiently well targeted, otherwise reliance on this approach for protection of the population can again put them at risk. A well targeted active viral test combined with a slow release rate is a viable strategy for continuous suppression of the virus.</jats:p

Intravascular Papillary Endothelial Hyperplasia (Masson's Hemangioma) of the Liver: A New Hepatic Lesion

Intravascular papillary endothelial hyperplasia (Masson's hemangioma) is a disease characterized by exuberant endothelial proliferation within the lumen of medium-sized veins. In 1923, Masson regarded this disease as a neoplasm inducing endothelial proliferation, however, now it is considered to be a reactive vascular proliferation following traumatic vascular stasis. The lesion has a propensity to occur in the head, neck, fingers, and trunk. Occurrence within the abdominal cavity is known to be very rare, and especially in the liver, there has been no reported case up to date. The authors have experienced intravascular papillary endothelial hyperplasia of the liver in a 69-yr-old woman, and report the case with a review of the literature

Is no test better than a bad test: Impact of diagnostic uncertainty on the spread of COVID-19 (vol 15, e0240775, 2020)

[This corrects the article DOI: 10.1371/journal.pone.0240775.]

Factors influencing accuracy of referral and the likelihood of false positive referral by optometrists in Bradford, United Kingdom

YesAims: Levels of false positive referral to ophthalmology departments can be high. This study aimed to evaluate commonality between false positive referrals in order to find the factors which may influence referral accuracy. Methods: In 2007/08, a sample of 431 new Ophthalmology referrals from the catchment area of Bradford Royal Infirmary were retrospectively analysed. Results: The proportion of false positive referrals generated by optometrists decreases with experience at a rate of 6.2% per year since registration (p < 0.0001). Community services which involved further investigation done by the optometrist before directly referring to the hospital were 2.7 times less likely to refer false positively than other referral formats (p = 0.007). Male optometrists were about half as likely to generate a false positive referral than females (OR = 0.51, p = 0.008) and as multiple/corporate practices in the Bradford area employ less experienced and more female staff, independent practices generate about half the number of false positive referrals (OR = 0.52, p = 0.005). Conclusions: Clinician experience has the greatest effect on referral accuracy although there is also a significant effect of gender with women tending to refer more false positives. This may be due to a different approach to patient care and possibly a greater sensitivity to litigation. The improved accuracy of community services (which often refer directly after further investigation) supports further growth of these schemes.This study was funded by the University of Bradford

Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19

AbstractTesting is viewed as a critical aspect of any strategy to tackle epidemics. Much of the dialogue around testing has concentrated on how countries can scale up capacity, but the uncertainty in testing has not received nearly as much attention beyond asking if a test is accurate enough to be used. Even for highly accurate tests, false positives and false negatives will accumulate as mass testing strategies are employed under pressure, and these misdiagnoses could have major implications on the ability of governments to suppress the virus. The present analysis uses a modified SIR model to understand the implication and magnitude of misdiagnosis in the context of ending lockdown measures. The results indicate that increased testing capacity alone will not provide a solution to lockdown measures. The progression of the epidemic and peak infections is shown to depend heavily on test characteristics, test targeting, and prevalence of the infection. Antibody based immunity passports are rejected as a solution to ending lockdown, as they can put the population at risk if poorly targeted. Similarly, mass screening for active viral infection may only be beneficial if it can be sufficiently well targeted, otherwise reliance on this approach for protection of the population can again put them at risk. A well targeted active viral test combined with a slow release rate is a viable strategy for continuous suppression of the virus.</jats:p

In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug

The anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg–1, intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg–1, i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and β-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action. © 1999 Cancer Research Campaig