An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

Thin-client medical devices.

Designing as little functionality as possible on the device, and placing the processing burden on the server, can reduce the cost of medical devices and provide other benefits.

The effects of 8-OH-DPAT and (+/-)-pindolol on isolation-induced ultrasonic vocalizations in 3-, 10-, and 14-day-old rats.

It has been established that administration of 5-HT1A agonists attenuates the rate of isolation-induced ultrasonic vocalizations (USV) in 10-day-old rat pups. In this study we extended these findings by examining the effects of administration of the serotonergic 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and mixed 5-HT1A antagonist/beta adrenergic antagonist, (+/-)-pindolol, in 3-, 10-, and 14-day-old rat pups in order to assess the effect of these drugs from a developmental perspective. At all three ages, 8-OH-DPAT significantly reduced the rate of isolation-induced USV. While only the highest dose (1.0 mg/kg) of 8-OH-DPAT administered to the 10- and 14-day-olds significantly reduced the rate of vocalization, both the 0.1- and 1.0-mg/kg doses significantly attenuated the vocalization rate in the 3-day-olds. Pindolol administration did not alter the rate of USV at any age nor did it block the quieting effect that generally occurs when an anesthetized littermate is placed with the isolated pup. We conclude that 8-OH-DPAT is effective as early as 3 days of age in the quieting of isolation-induced USV and that the regional age-dependent development of 5-HT1A receptors and projections are important factors in the observed differential sensitivity to 8-OH-DPAT administration during development.

Evaluating photoscreeners II: MTI and fortune videorefractor.

BACKGROUND: Amblyopia is a public health problem, usually amenable to treatment if detected early. Photoscreeners are camera-based instruments which can detect risk factors for amblyopia such as squint, refractive errors and media opacities. OBJECTIVE: To evaluate two commercially available photoscreeners, namely the MTI photoscreener (Medical Technology, Iowa City, IA, USA) and the Fortune Optical VRB-100 (Fortune Optical, Padova, Italy) videophotorefractor, in a selected childhood population, having a high prevalence of amblyopia, before undertaking a full-scale trial in the general population. SUBJECTS AND METHODS: The study design was a double-masked study. One-hundred and five children aged between 12 and 44 months with either normal vision or known visual disorders were photoscreened without cycloplegia using the Fortune and the MTI photoscreeners. Each child had a full ophthalmic examination either on the day of screening or in the preceding 6 months. Risk factors were: any manifest strabismus (squint), hypermetropia >3.5 D, anisometropia > or =1 D sphere, myopia > or =2 D sphere, astigmatism > or =2 D, media opacity or fundus abnormality affecting vision. The prevalence of risk factors for amblyopia was 60%. Photoscreen images were reviewed by two independent masked observers for indicators of amblyopiogenic risk factors and compared to the full ophthalmological examination to determine sensitivity and specificity for each instrument. RESULTS: Sensitivities and specificities for the detection of risk factors for amblyopia were as follows. Fortune photoscreener: reader 1, sensitivity 60%, specificity 75%; reader 2, sensitivity 68% specificity 86%. MTI photoscreener: reader 1, sensitivity 56%, specificity 79%; reader 2, sensitivity 61%, sensitivity 86%. The results for reader 1 and 2 showed no significant differences for either instrument. CONCLUSION: Both instruments performed unsatisfactorily in a study population aged 1-4 years with a high prevalence of amblyopiogenic risk factors. Accordingly, we do not believe that either instrument can be recommended to screen for eye disorders in children between the ages of 1 and 4 years because the low prevalence of amblyopia in this population demands very high sensitivity and specificity in order to avoid inappropriate over- or under-referral.

Adjunctive intra-operative local anaesthesia in paediatric strabismus surgery: a randomized controlled trial.

PURPOSE: The aim of the present study was to test the hypothesis that adjunctive local anaesthesia decreases postoperative pain, vomiting or length of stay in children having strabismus repair METHOD: A prospective, randomized, triple-armed clinical trial involving a treatment comparison between topical amethocaine, sub-conjunctival bupivacaine and, as a placebo, topical normal saline was performed. All treatments were given at the end of surgery before emergence from the anaesthetic. RESULTS: Overall, there was no statistically significant difference between outcome measures in the three trial groups. Using post hoc analysis there was a statistically significant difference between the groups receiving amethocaine and bupivacaine compared with the saline group in terms of the pain score at 120 min postoperatively. This difference has little clinical significance. CONCLUSIONS: Neither topical amethocaine nor subconjunctival bupivacaine makes a clinically significant difference to postoperative pain, emesis or length of stay. Moderate dose paracetamol per rectum alone appears to be effective analgesia for strabismus surgery, although it probably masked any small adjunctive effect of the topical anaesthesia used in the present trial.

Macular folds and poor vision associated with zone III retinopathy of prematurity.

PURPOSE: To describe two cases of zone III retinopathy of prematurity associated with macular folds and poor vision. METHOD: Case reports. RESULTS: Two premature infants with zone III retinopathy of prematurity developed clinically notable elevation of the neovascular ridge with macular folds and poor vision. CONCLUSIONS: Retinopathy of prematurity in zone III may lead to compromised anatomic and functional outcomes. Notable elevation of the neovascular ridge may be an important risk factor for an adverse outcome.

Impact of bicycle helmet safety legislation on children admitted to a regional pediatric trauma center.

PURPOSE: The regional pediatric trauma center in Buffalo, NY, has been active in pediatric injury prevention programs, including community education and distribution of bicycle helmets, since 1990. Since June 1, 1994, the use of bicycle safety helmets for children under 14 years of age has been mandated by a state law in New York. The authors undertook this study to assess the impact of this legislation on the frequency of helmet use in children involved in bicycle crashes presenting to the regional pediatric trauma center, and to assess the impact of helmet use on the number and severity of head injuries. METHODS: Bicycle crash victims (n = 208) admitted to a regional pediatric trauma center from 1993 to 1995 were studied retrospectively. Head injuries were classified as concussion alone, skull fractures, intracranial hemorrhages (ie, epidural, subdural, and subarachnoid), cerebral contusions, or diffuse cerebral edema alone (without any other intracranial injury). Helmeted children (HC) were compared with nonhelmeted children (NHC) using chi2 and Fisher's Exact test. P value less than .05 was considered significant. RESULTS: Only 31 children (15%) wore helmets at the time of the crash. Helmet use increased from 2%, during the period of education alone, to 26% after the legislation went into effect (P < .00001). The proportion of children suffering head injuries was similar in both groups (HC, 68%; NHC, 61%; P = NS). However, the type of head injury was different. HC were more likely to sustain concussion alone (HC, 65%; NHC, 44%; P < .03). HC were less likely to have skull fractures (HC, 0%; NHC, 13%; P < .02), and exhibited a trend toward less intracranial hemorrhages (HC, 0%; NHC, 9%; P = NS), cerebral contusions (HC, 3%; NHC, 5%; P = NS), and cerebral edema (HC, 0%; NHC, 0.6%; P = NS). Excluding the isolated concussions, head injuries were noted in only one HC, compared with 30 NHC (P < .04). None of the three children who died wore helmets at the time of the crash, and all died of multiple head injuries. CONCLUSIONS: The bicycle helmet safety law resulted in a 13-fold increase in the use of bicycle helmets among the children admitted to a regional pediatric trauma center after bicycle crashes, but the helmet use remains inadequate. Helmet use reduced the severity of head injuries, and might have prevented deaths caused by head injuries.

Risk of hemorrhage and appropriate use of blood transfusions in pediatric blunt splenic injuries.

OBJECTIVE: To define changes in hematocrit (Hct) and the indications for blood transfusion in pediatric blunt splenic injury. DESIGN: Retrospective case series MATERIALS AND METHODS: All children with blunt splenic injuries from 1990 to 1995 were studied (n = 74). Transfusion practices were reviewed for the whole group. Thirty children with isolated splenic injuries who were not transfused were analyzed to document Hct changes (mean +/- 95% confidence intervals). MEASUREMENTS AND RESULTS: The Hct at presentation was 37 +/- 2%, which rapidly dropped to 31 +/- 2% (p < 0.05) within 24 hours. After remaining stable at that level for the next 5 days, the Hct rose to 33 +/- 4% on day 6 (p = not significant), 35 +/- 4% on day 7 (p = not significant), and 38 +/- 2% (p = not significant) on day 13 +/- 3. Fifteen children received transfusions, all but one of whom had suffered multiple injuries. The transfusion rate declined from 38% of children in 1990 to 10% in 1995. CONCLUSIONS: After the initial drop within the first 24 hours, the Hct remains stable and rises with time to reach the baseline by day 6. Transfusion rates have declined over time, and transfusions are now used almost exclusively in severely injured children with multiple injuries.

Isolation alters striatal met-enkephalin immunoreactivity in rat pups.

Isolated preweanling rats emit ultrasonic vocalizations. Mu- and delta-opioid agonists quiet isolated pups; naltrexone, an opioid receptor blocker, prevents this quieting. A littermate companion is as effective as morphine in quieting vocalizations, and naltrexone also blocks companion quieting. We have now quantified methionine enkephalin (Met-ENK) immunoreactivity in the brains of 10-day-old Wistar rat pups taken directly from the home cage or kept either alone or with a companion for a brief or prolonged period. Met-ENK is an endogenous ligand that binds to the mu- and delta-opioid receptors. Striatal peptide levels were higher when pups were with a companion than when they were kept alone; the peptide level of pups in the home cage did not differ from either. Comparisons of pups in the brief (5 min) and prolonged (60 min) separation conditions showed significantly higher peptide levels following a brief period out of the nest than at the end of an hour. In hypothalamus, hippocampus, and frontal cortex neither social condition nor duration of separation significantly altered peptide quantity. Larger amounts of Met-ENK in pups provided with a companion could reflect an increase in posttranslational cleavage of the precursor molecule leading to stimulation of receptors that act to diminish USV. Reduced levels following 60 min out of the home cage might reflect depletion of the peptide following an initial release during the period when the pup's vocal response is most vociferous.

The isolation and companion comfort responses of 7- and 3-day-old rat pups are modulated by drugs active at the opioid receptor.

Rat pups emit ultrasonic vocalizations (USVs) when isolated in a novel environment. In 10-day-olds, USV has been shown to be reduced by either the administration of 0.125 mg/kg morphine (MOR) or the presence of a littermate; these effects were both reversed by naltrexone (NLX), an opioid receptor blocker. The present study reports that the same dose of MOR produced NLX-antagonized quieting without sedation in 7- and 3-day-old pups; higher doses of MOR decreased USV but produced motor deficits as well. The 0.125 mg/kg dose of MOR is less effective in reducing USV in 3- and 7-day-olds; calling rates declined by no more than 42%, compared with 65% at 10 days of age. The presence of a companion also lowered the USV of 3- and 7-day-olds by a lesser amount (55-57%) than the 67% seen in 10-day-olds or the 90% decline when pups are 2 weeks old. This suggests that age-related changes in the opioid system may be relevant to the increased salience of a social companion that comes with maturity.

U50,488 increases ultrasonic vocalizations in 3-, 10-, and 18-day-old rat pups in isolation and the home cage.

Separation-induced calling in the young of many species can be modulated by the opioid system. Morphine reduces ultrasonic vocalizations (USVs) produced by isolated rat pups, an effect blocked by naltrexone. Central administration of the mu and delta opiate receptor agonists DAMGO and DPDPE reduce USV; kappa receptor agonist U50,488 increases them. We now find that peripheral U50,488 not only boosted calling rates in isolated 3-, 10-, and 18-day-old rat pups, but also induced calling in pups of these ages tested in the home cage with their littermates, where USVs are seldom heard in nature. U50,488 lowered rectal temperature, although temperature loss and USV were not correlated within drug treatment groups.

Aversive properties of the kappa opioid agonist U50,488 in the week-old rat pup.

mu Opioids have been shown to produce analgesia and to be reinforcing during the first week of life in the rat. kappa Opioids also have analgesic actions in both the infant and adult, but can be aversive in the mature animal. We examined the aversive effects of the kappa opioid agonist U50,488 during the first postnatal week in the rat pup in three ways. In the first experiment, U50,488, injected peripherally (1.0-30.0 mg/kg), was paired with an odor and pups were tested 8 h later for positional preference for avoidance of that odor. This task is similar to conditioned preference/aversion tests used with adult animals. Both 3- and 7-day-old pups learned to avoid the odor adulterated side at the two higher doses. When exposed to odors previously associated with U50,488, pups at both ages decreased locomotor activity. In a second experiment, acute treatment with U50,488 increased ultrasonic distress vocalizations (USV) equally at 3 and 7 days of age, increased locomotor activity, and decreased rectal temperature. Neither of the latter two effects was correlated with the increase in USV production. The third experiment showed that conditioned odor cues increased USV 8 h later in 3- and 7-day-old pups at 1.0-10.0 mg/kg without changes in activity or rectal temperature. The results from these studies suggest that U50,488 can produce aversions in the neonatal rat pup as it does in the adult.

Ultrasonic vocalizations are elicited from rat pups in the home cage by pentylenetetrazol and U50,488, but not naltrexone.

Although isolated rat pups emit ultrasonic vocalizations (USVs), those kept warm and undisturbed in the home cage with their littermates seldom do. Drugs were administered to 10-day-old pups in the home cage to determine whether pharmacological agents can elicit USV in this familiar environment. Ten-day-old Wistar rats were injected with U50,488, a highly selective kappa opioid agonist; pentylenetetrazol (PTZ), an anxiogenic drug that binds at the GABA-benzodiazepine receptor complex; or naltrexone (NLX), an opiate receptor blocker, and then were returned to their littermates in the home cage. U50,488 increased USV and activity levels, lowered body temperature, and disrupted contact with littermates. PTZ raised activity levels but had a smaller effect on vocalization rates and did not alter temperature or contact with littermates. Behavioral measures and body temperature were unchanged by NLX.

Effect of a social companion on the ultrasonic vocalizations and contact responses of 3-day-old rat pups.

Rat pups that are isolated in a novel environment emit ultrasonic calls. Vocalization in 3-day-old pups has been thought to be predominantly under thermal control (Allin & Banks, 1971). By the 2nd week of life, ultrasonic vocalizations are reduced when pups are tested in the company of a single anesthetized littermate (Carden & Hofer, 1990a; Hofer & Shair, 1978). In the present study, it was demonstrated that the vocalization rate of 3-day-old pups is also decreased when an anesthetized littermate is present in the isolation chamber. To determine whether this quieting was a function of the body heat of the companion, in a 2nd experiment, the axillary temperature of the companion was lowered until it was the same as the ambient temperature of the test chamber, 22 degrees C. In the presence of a cool companion, ultrasonic vocalizations were also reduced. For the last experiment, a textured plastic surrogate was substituted for the littermate. Calls were not diminished in the presence of the surrogate.

Differential effects of specific opioid receptor agonists on rat pup isolation calls.

The possibility was investigated that specific opioid receptor types might selectively alter the production of isolation-induced ultrasonic vocalizations. Intracisternal injections of mu, delta and kappa opioid receptor agonists were administered to isolated 10-day-old rat pups. The mu receptor agonist [D-Ala2-NMe-Phe4-Gly-ol]-enkephalin (DAMGO) and delta receptor agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) both reduced the rate of isolation-induced ultrasonic calling in the absence of sedation. The kappa receptor agonist U50,488 had the opposite effect, significantly raising the rate of vocalization. Fourteen-day-old pups, with a larger delta receptor population, showed a greater sensitivity to DPDPE than was seen in the younger animals.