Hours In Stage Research Articles

Serial Urinary C-C Motif Chemokine Ligand 14 and Risk of Persistent Severe Acute Kidney Injury

Retrospective observational study. Data derived from two multinational ICU studies (Ruby and Sapphire). Critically ill patients with early stage 2-3 AKI. None. We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08-0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46; p = 0.001). In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay. A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received renal replacement therapy (RRT) or died before achieving 72 hours in stage 3 AKI were also considered to have reached the end point. A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%; 95% CI, 84% to 96%), and 13 ng/ml achieved high specificity (93%; 95% CI, 89% to 96%). The cutoff of 1.3 ng/ml identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/ml had an adjusted odds ratio (aOR) of 3.82 (95% CI, 1.73 to 9.12; P=0.001) for the development of persistent severe AKI compared with those with a CCL14 ≤1.3 ng/ml, whereas a CCL14 >13 ng/ml had an aOR of 10.4 (95% CI, 3.89 to 29.9; P<0.001). Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/ml) allow for the identification of patients at high risk for the development of persistent severe AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.Clinical Trial registry name and registration number: Identification and Validation of Biomarkers of Acute Kidney Injury Recovery, NCT01868724.

Effect of Pharmacist-Led Interventions on (Non)Motor Symptoms, Medication-Related Problems, and Quality of Life in Parkinson Disease Patients: A Pilot Study.

Patients with Parkinson disease (PD) use multiple drugs. This pill burden with consequent poor adherence may cause worsening of motor symptoms and drug-related problems. Therefore, a multifaceted pharmacist-led intervention program was designed to improve adherence, motor-functioning, and quality of life (QoL) in PD patients. This prospective pilot study was performed in an outpatient PD clinic, where usual care was compared with stepwise introduction of 3 interventions: unit dose packaging (UDP), Parkinson KinetiGraph (PKG), and pharmacist-led medication review (MR).The study analyzed endpoints at 6 weeks (stage 1, usual care), 10 weeks (stage 2, UDP), 14 weeks (stage 3, UDP + PKG), and 26 weeks (UDP + PKG + MR) on motor symptoms, medication adherence, and QoL. Medication adherence improved significantly after the combined UDP, PKG, and MR intervention in nonadherent patients. On time significantly increased from 56% (±30) at stage 1, to 64% (±25) at stage 3, and to 68% (±27) at stage 4, which correlated with an increase of 1.4 and 2.2 hours in stage 3 and 4, respectively. Quality of life only improved significantly after MR (Parkinson's Disease Questionnaire with 8 domains, 21.0 ± 3.5 in stage 3 vs 19.5 ± 5.3 in stage 4, P = 0.01). Our data did not support the added value of UDP alone or in combination with PKG. Only the combined intervention of UDP, PKG, and MR showed significant improvements in medication adherence, on time, and QoL. This supports the effectiveness of MR by a clinical pharmacist for PD patients in an outpatient setting. Therefore, this small scale study should be followed by larger-scale trials on this topic.

Investigating the development of double‐peak subauroral ion drift (DSAID)

AbstractThis study focuses on the newly described ionospheric feature, called double‐peak subauroral ion drift (DSAID), which is a subclass of the well‐known single‐peak SAID. Double‐layer Region 2 (R2) field aligned currents (FACs) could be the main driver of DSAID. Our aim is to gain new insights into the development of DSAID during its two‐stage progression. Observational results are provided by five scenarios, each demonstrating a certain progression sequence of DSAID. Results show that SAID/DSAID occurred during flux transfer events and was accompanied by flow channels (FCs) associated with dayside magnetopause (FC‐2) and nightside magnetotail (FC‐3) reconnections, with westward electrojet (eastward FC), and with auroral streamers (FC‐4). In the premidnight magnetic local time (MLT) sector of stage 2, DSAID development was due to the short‐circuiting of the reconnection‐injected plasma jets during substorms or pseudobreakups. Thus, the related ring current pressure buildup enhanced the downward R2 FACs leading to double/multiple circuits forming double‐layer R2 FACs. During the midnight MLT hours of stage 2, DSAID development was closely related to the westward traveling surge (WTS)/substorm current wedge (SCW). WTS/SCW‐related strong upward R1 FACs closed with meriodional currents producing eastward and downward (i.e., downward R2 FAC‐style) return currents enhancing the downward R2 FACs and thus leading to double/multiple circuits forming double‐layer R2 FACs. Auroral streamers/FC‐4 represent a substorm substructure and their occurrence with DSAID after stage 2 demonstrates that this substructure occasionally includes DSAID. Our results demonstrate also that the short‐circuited system underlying SAID/DSAID acted sometimes as a current generator and sometimes as a voltage generator.

Sleep in children with high functioning autism: polysomnography, questionnaires and diaries in a non-complaining sample

Sleep disorders in children with autism are frequently reported on questionnaires filled by parents. The aim of this study was to characterize sleep using objective and subjective measures in the same sample of autistic children without comorbidities and no primary complaints of sleep disorders. Eleven autistic children (10.3 ± 2.2 years) diagnosed with ADI-R and ADOS criteria and 13 typically-developing children (10.2 ± 2.0 years) were recruited. Exclusion criteria comprised the use of psychotropic medication, a full IQ lower than 75, a history of epilepsy and spontaneous complaints of sleep disorders from the parents. After their children were recruited, parents filled a sleep diary for 2 weeks and the Child Sleep Habit Questionnaire (CSHQ); children were then recorded for 2 consecutive nights in a sleep laboratory. Sleep stages of night 2 were scored according to Rechtschaffen and Kales (1968) using 20 s. epochs. Stage 2 sleep spindles and K-complexes were visually scored on bilateral prefrontal and central electrodes; REM sleep rapid eye movements were also scored. Variables were log transformed when abnormally distributed. Groups were compared using t -tests for independent samples. Sleep diaries showed a longer sleep latency in autistic children (43.6 ± 39.0 mn vs. 17.2 ± 17.5 mn, p = .037). The CSHQ showed no significant group differences. Polysomnographically recorded sleep latency was longer in autistic children (33.0 ± 8.3 min vs. 14.4 ± 4.6 min, p = .023), the duration of stages 3 and 4 (slow-wave sleep: SWS) was shorter (18.2 ± 3.2% vs 23.6 ± 5.7%; p = .009) but total sleep time was similar (539.7 ± 54.3 vs. 560.8 ± 60.2; p = .94). Sleep spindle density (per hour of Stage 2) was similar in both groups at central electrodes and Fp1 but it was lower at Fp2 (119.2 ± 97.7 vs. 225.5 ± 122.2, p = .03). The density of K-complexes was lower at the four electrodes (.0001 < p < .01). REM sleep parameters (latency, duration, distribution, eye movement density) were not different between groups. These results show that autistic children without subjectively reported sleep difficulties according to the CSHQ show signs of poor sleep on sleep diaries and polysomnography. Sleep diaries disclosed longer sleep latencies. Most polysomnographic differences were in nonREM sleep, raising the hypothesis of a difficulty for autistics to synchronize their cortical activity, possibly leading to impaired cortical sleep protective mechanisms such as sleep spindles and K-complexes. Canadian Institute for Health Research; ”Fonds de recherche du Québec – Santé”.

Laser photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a prospective randomized pilot study of treatment to ridge and avascular retina versus avascular retina alone

The purpose of this study was to compare the structural outcome of laser treatment to avascular retina and ridge versus laser treatment to avascular retina alone in cases with threshold retinopathy of prematurity (ROP). A prospective, randomized, interventional, comparative study of consecutive cases referred to a single tertiary center was considered here. 50 infants with bilateral symmetrical threshold ROP were recruited into this study over a period of 3 years. Threshold ROP was defined as per CRYO-ROP study. Perinatal history details for all patients including significant maternal history were recorded. One eye of each patient was randomized (Microsoft Excel 2000) to one of the two treatment groups--laser treatment to avascular retina (Group A) or laser treatment to avascular retina and ridge (Group B). Laser treatment was performed with a 810 nm diode laser (Iris Medical Instruments, Inc. Mountain View, CA, USA). Treatment was continued until regression of ROP. Structural outcome was assessed at a minimum follow-up of 6 months and was considered favorable or unfavorable as per the CRYO-ROP study criteria. An unfavorable outcome consisted of either (1) a retinal fold involving the macula; (2) any retinal detachment involving zone 1; or (3) a retrolental mass that obscured visualization of the posterior pole. Secondary outcome measures included the difference in time to regression of ROP and complications of treatment between the two treatment groups. 100 eyes of 50 infants received laser photocoagulation for threshold ROP after randomization (50 eyes in each group). Of these 50 infants, 20 (40%) were female and 30 (60%) were male. A significant proportion of the children (46%) were conceived as twins. The average birth weight was 1360 ± 326 g (range 750-2200 g). The mean gestational age at birth was 30.72 ± 1.6 weeks (range 26-36 weeks). Zone I disease was present in 14 (14%) eyes and zone II in the remaining 86 eyes (86%). Threshold stage retinopathy (CRYO-ROP criteria) extending 360° (12 clock hours) was present in 21 infants (42%), 5 contiguous clock hours of stage 3+ in 14 infants (28%) and intermediate range in the remaining 15 infants (30%). At 6 months follow-up, 3 eyes (6%) in group A and 1 eye (2%) in group B had an adverse structural outcome; however, the time to regression of retinopathy 2.98 ± 1.5 weeks in group A and 3.12 ± 1.1 in group B (P = 0.889) and the rate of complications such as retinal hemorrhage, 3 eyes in group A and 4 eyes in group B, was comparable. Zone I eyes showed equal incidence of favorable anatomical outcome (85.7%) in each group. Laser treatment to ridge was found to be safe and effective in the treatment of threshold ROP in this short-term pilot study; however, it needs to be ascertained whether this treatment has long-term advantages over conventional laser treatment to avascular retina, as well as the long-term benefits of treatment to ridge.

Sleep after mobile phone exposure in subjects with mobile phone‐related symptoms

Several studies show increases in activity for certain frequency bands (10-14 Hz) and visually scored parameters during sleep after exposure to radiofrequency electromagnetic fields. A shortened REM latency has also been reported. We investigated the effects of a double-blind radiofrequency exposure (884 MHz, GSM signaling standard including non-DTX and DTX mode, time-averaged 10 g psSAR of 1.4 W/kg) on self-evaluated sleepiness and objective EEG measures during sleep. Forty-eight subjects (mean age 28 years) underwent 3 h of controlled exposure (7:30-10:30 PM; active or sham) prior to sleep, followed by a full-night polysomnographic recording in a sleep laboratory. The results demonstrated that following exposure, time in Stages 3 and 4 sleep (SWS, slow-wave sleep) decreased by 9.5 min (12%) out of a total of 78.6 min, and time in Stage 2 sleep increased by 8.3 min (4%) out of a total of 196.3 min compared to sham. The latency to Stage 3 sleep was also prolonged by 4.8 min after exposure. Power density analysis indicated an enhanced activation in the frequency ranges 0.5-1.5 and 5.75-10.5 Hz during the first 30 min of Stage 2 sleep, with 7.5-11.75 Hz being elevated within the first hour of Stage 2 sleep, and bands 4.75-8.25 Hz elevated during the second hour of Stage 2 sleep. No pronounced power changes were observed in SWS or for the third hour of scored Stage 2 sleep. No differences were found between controls and subjects with prior complaints of mobile phone-related symptoms. The results confirm previous findings that RF exposure increased the EEG alpha range in the sleep EEG, and indicated moderate impairment of SWS. Furthermore, reported differences in sensitivity to mobile phone use were not reflected in sleep parameters.

Estratégia de detecção precoce e redução de mortalidade na sepse grave

To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock. Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality. We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003). The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Idyllic Little Bali

Idyllic Little Bali Lori Ostlund (bio) Calvin goes first, telling them about the time he was in Florida and decided to attend a Beach Boys concert, not really knowing anything about the Beach Boys except that they played music for basking in the sun to, which—Calvin being from Michigan—might explain why he knew so little about them. He hitched a ride up to Fort Lauderdale, which was where the concert was being held, with a guy in a convertible who dropped him off right at the stadium, and it wasn’t until the band came on stage hours later that he realized the convertible guy, the guy with whom he’d scored the ride, was actually one of the Beach Boys, the drummer, whose name he couldn’t recall. This is exactly how Calvin tells the story, his clauses like tired acrobats that can’t quite stick their landings, and though the others at the table have known Calvin only a day, they are disappointed. Joe goes next, then Martin, and after them Noreen and Sylvie begin a long story about their first date, on which they went to a rundown bar on the west side of Albuquerque, the kind of place, Sylvie explains, where Hispanic butch-femme couples show up in wedding gear on Saturday nights to hold their receptions, the butches playing pool in their tuxedos, the femmes taking over the bathrooms, where, in a never-ending cycle, they fix their makeup and cry with happiness. “So,” Sylvie says in a voice thick with drama. “There we are on our first date, and Noreen invites this woman Deb to play pool with us.” Noreen cuts in, explaining that this Deb woman had actually struck up a conversation with her while Sylvie was off in the bathroom. She describes Deb as a massive-thighed Amazon who raised horses and engaged in competitive weightlifting, details that, in her mind, make clear that Deb had posed no threat to their date. She even tells them how Deb, who was wearing shorts, had [End Page 5] said, “Go ahead. Feel it,” flexing her very large thigh for Noreen, and how she, Noreen, had of course refused. “I didn’t even know her,” she reports earnestly. “So why would I feel her thigh?” She actually seems to be soliciting their input, though it is not clear whether she is seeking plausible reasons that she (or anyone in that position) might have opted to feel the thigh or their approval for not having done so. “It’s irrelevant anyway,” announces Sylvie, but Noreen doesn’t reply because she is thinking about Deb’s thigh, about the way that Deb had first extended her foot delicately, like someone testing the water in a pool, but then had ground her toes hard into the floor, making the leg muscles leap to the surface. There is absolutely nothing sexual about the memory. On the contrary, the thigh had been far too large, too freakish, to find appealing. Noreen had felt the way she did the first time that she saw the penis of an aroused farm animal, fascinated and repulsed, actually unable to look away, but with no sense that what she was seeing had anything to do with her. “She gave me the creeps. Immediately,” continues Sylvie, by way of letting these relative strangers know that her instincts are keener than Noreen’s. “But Noreen invited her to play pool with us, so what could I say? Then, halfway through the game, this really blonde, granola-y type walks in and sits down at the bar. She’s watching us play, so finally I go over and invite her to join the next game, and it turns out that she’s Australian.” She pauses as though she has revealed something significant. “Olivia Newton-John?” suggests Calvin dryly, and the others laugh because, boring Beach Boys story aside, Calvin is funny. “What?” says Sylvie nervously, bewildered by the laughter but still joining in, assuming that if others are laughing, then something must be funny. Perhaps because they have spent so much time around strangers on this trip, Noreen has begun to notice just how often...

Soil podzolization induced by reforestation as shown by sequential and kinetic extractions of Fe and Al

SummaryThe impact of 60‐year‐old reforestation on soil evolution was studied by following the evolution of Fe and Al distribution as an indicator of early podzolization. We determined the distribution of Al and Fe in soils by combining sequential and kinetic extractions. We extracted the soil sequentially with: 1 mol litre−1 sodium acetate at pH 5.5 (stage 1); twice with 0.1 mol litre−1 sodium pyrophosphate at pH 10 (stage 2 and 2b); and with 1 mol litre−1 hydroxylamine in 4.3 mol litre−1 acetic acid solution at 90°C (stage 3). For each, we drew a kinetic‐extraction curve. We show that no re‐adsorption, precipitation or complexation with dissolved organic matter occurred for the reaction times recommended in this procedure, that is 6 hours for stage 1, 1.5 hours for stage 2 and 2b and 3 hours for stage 3. For a given extraction, the kinetic curves have the same shape for all samples, that is their behaviour is similar for a given reagent. Sequential extraction can therefore be used to compare the speciation of metals in different samples taken from the same soil. In addition, 60 years after reforestation by beech, a decrease of 12 and 17% is noted in the total Fe and Al contents, respectively, in the 0–10 cm layer, accompanied by a re‐distribution of these elements within the different soil compartments: a decrease of the Fe and Al bound to oxy‐hydroxide in favour of organic complexes and more soluble forms. Sequential extraction is therefore a good indicator of the first pedogenetic modifications induced by human intervention through reforestation.

Relationship of Epileptic Seizures to Sleep Stage and Sleep Depth

Interictal epileptiform discharges (IEDs) are facilitated by NREM stages 3 and 4 sleep and as sleep is deepening. To determine whether sleep influences seizures in a similar way to IEDs, we examined seizure rates in various stages of sleep in epilepsy patients undergoing overnight video-EEG-polysomnography (VPSG). Cross-sectional study. Neurology Department. PATIENTS, MEASUREMENTS, AND INTERVENTIONS: We reviewed VPSGs from our Sleep and Epilepsy Laboratories to identify patients with recorded seizures during sleep. A total of 55 patients having 117 seizures were identified. Ninety-five percent of seizures occurred in NREM sleep (61% in stage 2, 20% in stage 1, 14% in stages 3 and 4 combined), and 5% in REM sleep. Adjusting for time spent in each stage of sleep, patients had 0.34 seizures per hour in stage 1, 0.38 seizures per hour in stage 2, 0.29 seizures/hr in stage 3 and 4 combined, and 0.09 seizures per hour in REM sleep. Seizures/hour was higher in NREM sleep (0.35 for NREM and 0.09 for REM; p=0.0001). For single seizures occurring in 1 night, seizure rate was significantly higher in NREM stages 1 and 2 as compared to NREM stages 3 and 4 sleep. A significant increase in log delta power, an automated measure of sleep depth, was observed in the 10 minutes prior to seizures. Both seizures and IEDs are facilitated by NREM sleep. While deeper stages of NREM sleep activate IEDs, lighter stages of NREM sleep promote seizures, at least for single seizures occurring in 1 night.

Lower number of K-complexes and K-alphas in sleep bruxism: a controlled quantitative study

Objectives: Although patients with sleep bruxism (SB) show a higher incidence of rhythmic masticatory muscle activity (RMMA) during sleep than matched normal controls, they are good sleepers. Sleep macrostructure (e.g. total sleep time, sleep latency, number of awakenings or sleep stage shifts and sleep stage duration) is similar between groups. Differences in sleep microstructure between SB patients and normals have been investigated only in few studies. The aim of the present study was to quantify number of microarousals, K-complexes, K-alphas, EEG spindles, and the density of slow wave activity, in both groups, in order to better understand the pathophysiology of SB.Methods: Ten normal sleepers were matched for age and gender with 10 patients who exhibited frequent tooth-grinding during sleep. Using quantitative polysomnographic measures, we compared the above-mentioned sleep variables in both groups. Data are presented as indices for total sleep and for consecutive non-rapid eye movement (non-REM) episodes over non-REM to rapid eye movement (REM) cycles and per hour of sleep.Results: SB patients showed 6 times more RMMA episodes per hour of sleep than normals (P<0.001), with a higher frequency in the second and third non-REM to REM cycles. SB patients presented 42.7% fewer K-complexes per hour of stage 2 sleep, but only normals showed a decline from the first to fourth non-REM episode. Only 24% of SB-RMMA episodes were associated with K-complexes in 60s. The number of K-alphas was 61% lower in SB patients, no change across non-REM episodes was noted. While no difference in electroencephalographic (EEG) spindles or slow wave activity (SWA) was observed between groups, EEG spindles increased and SWA decreased linearly over consecutive non-REM to REM cycles.Conclusions: According to our observations, good sleep in SB patients is characterized by a low incidence of K-complexes or K-alphas and by the absence of any difference in other sleep microstructure variables or SWA.

Retinal detachment associated with subthreshold retinopathy of prematurity.

To report a series of infants who progressed from mild retinopathy of prematurity (ROP) to severe ROP with retinal detachment without demonstrating detectable threshold disease. Between January 1993 and August 1998, seven infants at Oregon Health Sciences University, followed in accordance with the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP) protocol, progressed to retinal detachment despite documentation that threshold had not been reached. This outlying subset of patients was analyzed and compared to the cohort in the CRYO-ROP study. Six of 7 patients were male, 6 (86%) patients had symmetric disease, and all patients were born outside the study hospital. Mean birth-weight was 877 g and mean gestational age was 26 weeks. Mean postconceptual age at the time of retinal detachment was 41 weeks. Because of bilateral detachment in 3 patients, the total number of study eyes is 10. Failure to achieve threshold resulted from insufficient clock hours or insufficient stage in 2 eyes and lack of plus in 8 eyes. Zone I disease was present in 1 eye. Rarely, despite adhering to ROP examination protocol, the retina may detach without demonstrating antecedent threshold disease. Very low birthweight is a factor that may lead to a less predictable course. This study found a lack of plus disease results in failure to reach threshold more often than the occurrence of insufficient clock hours of stage 3 disease. Further study is needed to determine if selected cases of subthreshold ROP may benefit from ablative therapy.

Retinopathy of Prematurity: History, Classification, and Pathophysiology

After completing this article, readers should be able to: 1. Describe the onset of retinopathy of prematurity (ROP). 2. Explain the role of oxygen in ROP. 3. Compare and contrast zones I, II, and III disease. 4. Describe the stages of ROP. 5. Characterize “plus” disease. 6. Describe the infants in whom severe ROP leading to the need for surgery is common. 7. Describe the timeframe at which ROP is visible in the eye. ### The First ROP In 1942, Terry described the first infant who had grey, blood vessel-covered membranes behind the pupil. As more cases were described, the name retrolental fibroplasia (RLF) was coined (Fig. 1⇓ ). Distressingly, it became common around the world in special units for preterm infants. Pathologic specimens were rare (Fig. 2⇓ ) , but serial examinations of preterm infants following birth revealed that infants were not born with RLF; they developed it after birth. By the end of the 1940s, many innovations in the new preterm infant nurseries had been implicated, some were exonerated, and it was time to examine the role of oxygen. Figure 1. End-stage ROP. The white pupils (leukocoria) of stage 5 ROP result from total retinal detachment, with the mass of fibrous neovascularization and the retina pushing up against the lens from behind. This is the source of the historical name retrolental fibroplasia. Photograph courtesy of A. Patz, MD, used with permission. Reprinted with permission from Pediatrics . 1957;19:502–504. Figure 2. A. Artist’s rendering of stage 5 retinal detachment. B. Pathologic specimen of an eye with stage 5 ROP. In this cross section, the lens is displaced into the anterior chamber by the mass of tissue in the vitreous composed of the detached retina and the large number of extraretinal vessels and accompanying scar tissue (fibroplasia). The retina remains attached at the posterior pole at the optic disc and around the rim …

Outcome-based management of retinopathy of prematurity

Purpose: A system is presented for sequentially computing the risk of progression of retinopathy of prematurity (ROP) for infants born weighing not more than 1250 gm. A personal computer program is used to monitor infants' risk of threshold ROP from first appearance of ROP, and the progression in severity is tracked with multiple logistic risk models developed from data in the Multicenter Trial of Cryotherapyfor Retinopathy of Prematurity. Methods: After entry of the infant's birth weight, gestational age, ethnicity, birth in the current hospital or elsewhere, single or multiple birth, and maturity zone of retinal vessels, risk of progression to threshold severity is calculated. New estimates of risk are computed at onset of ROP and prethreshold ROP (any zone I ROP, zone II stage 2+ or 3) according to the extent of retinal vascularization when ROP first appears, how rapidly ROP progresses, and how severe it is. When threshold ROP (8 total or 5 contiguous clock hours of stage 3+ in zone I or II) is reached,the system provides separate estimates of risk that the eye will have an unfavorable 3-month outcome if treated or not. Results: Estimates of risk of progression to threshold disease among the 4099 patients in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history study varied from less than 1% to more than 70%. For eyes with threshold disease, the risk of an unfavorable outcome at 3 months without treatment varied from less than 10% to more than 90%. Conclusion: This method of tracking identifies infants at high riskforsevere ROP and poor structural outcome. It provides information about prognosis with a specificity heretofore impossible.

Is a 'Favorable' Outcome Acceptable?-Reply

In reply For years, the Multicenter Trial of Cryotherapy for ROP investigators have devoted countless hours to studying the relation between stage 3 ROP and eventual outcome. The risk for an unfavorable outcome depends on multiple variables, only one of which is the extent of stage 3 disease. A more posterior location (zone) of ROP and the presence of plus disease are important indexes of ROP severity. Rapidity of disease progression is also significant. 1 The requested subgrouping of fundus outcome data shows no significant difference in the rate of occurrence of unfavorable outcome (P=. 65) across the 4 clock hours of ROP. The lowest rate of unfavorable fundus outcome, 6.1%, was for eyes with 4 clock hours of stage 3 ROP, and the highest rate, 15.7%, was for eyes with 3 clock hours. In response to Dr Hindle, there is probably no perfect way to ensure against adverse outcomes

Results of cryotherapy at different locations for retinopathy of prematurity.

Fifty eyes with stage 3 plus retinopathy of prematurity (ROP) were treated with cryotherapy. The avascular retina (AR) only was treated in 15 eyes with a mean extent of 8.3 hours of stage 3 ROP; the ridge extraretinal fibrovascular proliferation complex (REFP) was treated in 17 eyes with a mean extent of 7.5 hours; and both locations (BL) were treated in 18 eyes with a mean extent of 7.7 hours. Ninety-three percent to 94% of eyes in each group had less than grade III retrolental fibroplasia (RLF-Reese). However, 87% of the AR treated eyes, 59% of the REFP treated eyes, and 44% of the BL treated eyes had less than grade II RLF. Whether more than or less than 8 hours of stage 3 ROP was treated, significantly better results occurred in the AR group than the BL group (.02 < P < .05) and a statistical trend suggests that treating the AR is more effective than treating the REFP (.1 < P < .2).

Limiting Applications of Cryotherapy for Severe Retinopathy of Prematurity

In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.

Laser Photocoagulation for Threshold Retinopathy of Prematurity

To the Editor. —Threshold stage III (TS III) has been defined as 5 contiguous clock hours of stage III retinopathy of prematurity (ROP) in zone 1 or 2 in the presence of disease. The Multicenter Trial of Cryotherapy for ROP (CRYO-ROP) has shown that treatment of TS III reduces the incidence of unfavorable outcome by 46%. 1 Other investigators suggested that laser photocoagulation is effective in the treatment of ROP, although these studies used different delivery systems, treated at different stages, and varied in their outcome criteria. 2 McNamara et al 3 presented evidence of successful treatment of TS III ROP with the binocular indirect laser delivery system at the 1990 Annual Scientific Meeting of The Retina Society. Landers et al 4 reported a regressive response of TS III ROP with indirect laser photocoagulation in an eye considered at risk for complications from cryotherapy. We report preliminary results on 12 eyes

Sighs during sleep in adult humans.

We analyzed sighs (breaths with a tidal volume at least twice that of baseline breaths) during sleep in 12 normal adults. We found a total of 124 sighs in the group, with an average of 1.66 sighs/h of sleep, but with great intersubject variation (range: 1-25 sighs/night). There were sighs in all sleep stages, but there were more per hour in stage 1. 64.4% of the sighs were associated with an increase in EMG activity or EEG frequency, starting either before or immediately after the sigh. The remainder of the sighs were not associated with any arousal or sleep stage changes. The normal variability of heart rate with breathing is exaggerated during sighs, probably because of the greater inflation and the associated arousal. Sighs have larger mean inspiratory flows (Vt/Ti), expiratory flows (Vt/Te), and a larger fraction of respiratory cycle spent in inspiration (Ti/Ttot) than the previous breaths, all evidence of a change in respiratory control. Sighs during sleep may occasionally be followed by central apneas, hypoventilation, or considerable slowing of respiratory rate. Although it has been shown that a sigh renders the respiratory centers refractory to another sigh, we found that sighs sometimes occur in pairs.