Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR).

OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP?

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used.

REVIEW METHODS: Systematic review and economic modelling.

RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO.

LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR.

CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

Placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes: The effect of vitamin C and E supplementation

AIM: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae.

METHODS: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood.

RESULTS: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation.

CONCLUSION: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation.

The effect of preferential paw usage on dogs' (Canis familiaris) performance in a manipulative problem-solving task

In a number of species, individuals showing lateralized hand/paw usage (i.e. the preferential use of either the right or left paw) compared to ambilateral individuals have been shown to be more proactive in novel situations. In the current study we used an established test to assess preferential paw usage in dogs (the Kong test) and then compared the performance of ambilateral and lateralized dogs as well as left- vs. right-pawed dogs in a novel manipulative problem solving task. Results showed an equal proportion of ambilateral and lateralized dogs but contrary to predictions non-lateralized dogs were faster at accessing the apparatus in test trials. No differences emerged between right- and left-pawed dogs. Results are discussed in relation to previous studies on lateralization. © 2013 Elsevier B.V.

Non-invasive ventilation for cystic fibrosis.

Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis. To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 22 February 2013. Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation in people with acute or chronic respiratory failure in cystic fibrosis. Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Fifteen trials were identified; seven trials met the inclusion criteria with a total of 106 participants. Six trials evaluated single treatment sessions and one evaluated a six-week intervention.Four trials (79 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method and showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that NIV increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support, measuring lung function, validated quality of life scores and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks. Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.

Modeling the Rossiter-McLaughlin Effect: Impact of the Convective Center-to-limb Variations in the Stellar Photosphere

bservations of the Rossiter–McLaughlin (RM) effect provide information on star–planet alignments, which can inform planetary migration and evolution theories. Here, we go beyond the classical RM modeling and explore the impact of a convective blueshift that varies across the stellar disk and non-Gaussian stellar photospheric profiles. We simulated an aligned hot Jupiter with a four-day orbit about a Sun-like star and injected center-to-limb velocity (and profile shape) variations based on radiative 3D magnetohydrodynamic simulations of solar surface convection. The residuals between our modeling and classical RM modeling were dependent on the intrinsic profile width and v sin i; the amplitude of the residuals increased with increasing v sin i and with decreasing intrinsic profile width. For slowly rotating stars the center-to-limb convective variation dominated the residuals (with amplitudes of 10 s of cm s−1 to ~1 m s−1); however, for faster rotating stars the dominant residual signature was due a non-Gaussian intrinsic profile (with amplitudes from 0.5 to 9 m s−1). When the impact factor was 0, neglecting to account for the convective center-to-limb variation led to an uncertainty in the obliquity of ~10°–20°, even though the true v sin i was known. Additionally, neglecting to properly model an asymmetric intrinsic profile had a greater impact for more rapidly rotating stars (e.g., v sin i = 6 km s−1) and caused systematic errors on the order of ~20° in the measured obliquities. Hence, neglecting the impact of stellar surface convection may bias star–planet alignment measurements and consequently theories on planetary migration and evolution.

Collective synchrony increases prosociality towards non-performers and out-group members

Previous research has found that behavioural synchrony between people leads to greater prosocial tendencies towards co-performers. In this study we investigated the scope of this prosocial effect: does it extend beyond the performance group to an extended in-group (extended parochial prosociality) or even to other people in general (generalized prosociality)? Participants performed a simple rhythmic movement either in time (synchrony condition) or out of time (asynchrony condition) with each other. Before and during the rhythmic movement, participants were exposed to a prime that made salient an extended in-group identity. After the task, half the participants had the opportunity to help an extended in-group member; the other half had the opportunity to help an out-group member. We found a main effect of our synchrony manipulation across both help targets suggesting that the prosocial effects of synchrony extend to non-performers. Furthermore, there was a significantly higher proportion of participants willing to help an out-group member after moving collectively in synchrony. This study shows that under certain intergroup contexts synchrony can lead to generalized prosociality with performers displaying greater prosociality even towards out-group members.