Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.

Intranasal atomized dexmedetomidine for sedation during third molar extraction.

The purpose of this study was to evaluate the intranasal use of 1.5 µg/kg atomized dexmedetomidine for sedation in patients undergoing mandibular third molar removal. Eighteen patients underwent third molar removal in two surgical sessions. Patients were randomly assigned to receive intranasal water (placebo group) or 1.5 µg/kg atomized dexmedetomidine (group D) at the first session. The alternate regimen was used during the second session. Local anaesthesia was injected 30 min after placebo/sedative administration. Pain from local anaesthesia infiltration was rated on a scale from zero (no pain) to 10 (worst pain imaginable). Sedation status was measured every 10 min by a blinded observer with a modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and the bispectral index (BIS). Adverse reactions and analgesic consumption were recorded. Sedation values in group D were significantly different from placebo at 20-30 min, peaked at 40-50 min, and returned to placebo levels at 70-80 min after intranasal drug administration. Group D displayed decreased heart rate and systolic blood pressure, but the decreases did not exceed 20% of the baseline values. Intranasal administration of 1.5 µg/kg atomized dexmedetomidine is effective, convenient, and safe as a sedative for patients undergoing third molar extraction.

Effect of remifentanil on the hemodynamic responses and recovery profile of patients undergoing single jaw orthognathic surgery.

The aim of this study was to compare fentanyl-based versus remifentanil-based anesthesia with regards to the intraoperative hemodynamic stress response and recovery profiles in patients undergoing Le Fort I osteotomy. Seventeen patients were randomly divided into two groups: patients in the F-group received 2 µg/kg fentanyl intravenously followed by an infusion of 0.03-0.06 µg/kg/min, while patients in the R-group received a 0.5 µg/kg bolus of remifentanil followed by an infusion of 0.0625-0.250 µg/kg/min. Mean arterial pressure and heart rate were recorded at the following points: before anesthetic induction, at endotracheal intubation, 5 min after intubation, at incision, just before the osteotomy, during the osteotomy, during the maxillary fracturing, at suturing, at extubation, 5 min after extubation, and then 15 and 30 min postoperatively. Heart rate and mean arterial pressure were significantly lower in the R-group in comparison to the F-group from t1 to t9 (P<0.05). All measured recovery times were significantly shorter in the R-group (P<0.05). The incidence of postoperative side effects was comparable between groups. Remifentanil-based anesthesia is an appropriate alternative to fentanyl during Le Fort I orthognathic surgery; it promotes hemodynamic stability, blunts the stress response to noxious stimuli, and provides a better recovery profile.

Inhaled methoxyflurane (Penthrox) sedation for third molar extraction: a comparison to nitrous oxide sedation.

BACKGROUND: The aim of this study was to evaluate the use of inhaled methoxyflurane (Penthrox) in the reduction of dental anxiety in patients undergoing mandibular third molar removal in a specialist surgical suite and compare it to the conventional nitrous oxide sedation. METHODS: A prospective randomized, non-blinded crossover design study of 20 patients receiving two types of sedation for their third molar extraction who participated in 40 treatment sessions. At first appointment, a patient was randomly assigned to receive either nitrous oxide sedation or intermittent Penthrox inhaler sedation, with the alternate regimen administered during the second appointment. Peri-procedural vital signs (heart rate and blood pressure) were recorded and any deviations from 20% from the baseline values, as well as any drop in oxygen saturation below 92% were documented. The Ramsay Sedation Scale (RSS) score was recorded every five minutes. Patient cooperation during the procedure, patients' general opinion about the sedation technique, surgeon satisfaction and the occurrence of side effects were all recorded. After the second procedure, the patient was also asked if he or she had any preference of one sedation technique over the other. RESULTS: Levels of sedation were comparable in nitrous oxide and Penthrox sedation sessions. However, at 15 minutes of sedation it was significantly lighter (p < 0.05) in Penthrox. No patient in both regimens reached a RSS deeper than a score of 4. Parameters measured for assessment of sedation (patient cooperation, surgeon satisfaction and patient general opinion about sedation technique) were all similarly comparable for both nitrous oxide and Penthrox. In both sedation sessions, the odour of the inhalational agent was accepted by the patients; half of the patients (10 patients) who received methoxyflurane thought its odour was pleasant. Patients preferred methoxyflurane (Penthrox) inhalation over nitrous oxide sedation (Fisher's Exact test, p < 0.05). Adverse events were minimal. No patient was either deeply sedated or agitated. Blood pressure was within ± 20% from the baseline values. No patient had oxygen saturation less than 92%. Dizziness was the most frequently encountered side effect in both regimens (four patients each). Two patients had bradycardia (HR < 60 beats/minute) when nitrous oxide was used in comparison to one patient with Penthrox sedation. Paraesthesia of fingers and heaviness of the chest was encountered only with nitrous oxide sedation (four patients). Mild self-limited shivering occurred in one patient with Penthrox sedation. CONCLUSIONS: The Penthrox Inhaler can produce a comparable sedation to that of nitrous oxide for the surgical extraction of third molars under local anaesthesia.

Comparison of oral midazolam with combination of oral midazolam and nitrous oxide inhalation in relation to safety of dental sedation in young children.

The objective of the study was to compare the safety of 0.6 mg/kg oral midazolam sedation alone with a combination of 0.6 mg/kg oral midazolam and nitrous oxide-oxygen sedation during dental treatment of young children. The study had a crossover design where every patient received two different sedation regimens i.e. oral midazolam 0.6 mg/kg alone and oral midazolam 0.6 mg/kg with nitrous oxide-oxygen inhalation during two dental treatment visits. Thirty children (17 males and 13 females) were selected for the study with mean age of 55.07 (+/- 9.29) months. Safety of the two regimens was evaluated by monitoring hemodynamic parameters (heart rate, blood pressure & oxygen saturation) and through observing the child for 24 hours post-sedation for any side effects such as nausea and vomiting. Very few changes in hemodynamics were noted from baseline during both the visits. However, the mean oxygen saturation level with oral midazolam and nitrous oxide-oxygen was significantly (p < 0.05) higher than oral midazolam alone. Postoperative side effects were very few and mainly remained limited to post-sedation drowsiness. It can be concluded that oral midazolam (0.6 mg/kg) alone and oral midazolam (0.6 mg/kg) plus nitrous oxide (30%-50%) sedation are both safe while providing dental treatment to children with behavior problems.

Comparison of oral midazolam with a combination of oral midazolam and nitrous oxide-oxygen inhalation in the effectiveness of dental sedation for young children.

AIM: To compare the effectiveness of 0.6 mg/kg oral midazolam sedation alone and a combination of 0.6 mg/kg oral midazolam plus nitrous oxide-oxygen inhalation sedation, in controlling the behavior of uncooperative children during dental treatment. STUDY DESIGN: The study had a crossover design where the same patient received two different sedation regimens, that is, oral midazolam 0.6 mg/kg and oral midazolam 0.6 mg/kg with nitrous oxide-oxygen inhalation during two dental treatment visits. MATERIALS AND METHODS: Thirty children (17 males and 13 females) were randomly selected for the study, with a mean age of 55.07 (+/- 9.29) months, ranging from 48 - 72 months. A scoring system suggested by Houpt et al. (1985) was utilized for assessment of the children's behavior. RESULTS: There was no significant (p > 0.05) difference in the overall behavior assessment between the two sedation regimens, that is, oral midazolam alone and oral midazolam plus nitrous oxide-oxygen. However, the combination of midazolam and nitrous oxide-oxygen showed significantly (p < 0.05) superior results as compared to midazolam alone, in terms of controlling movement and crying during local anesthesia administration and restorative procedures. CONCLUSION: Compared to oral midazolam alone, a combination of oral midazolam and nitrous oxide inhalation sedation appears to provide more comfort to pediatric dental patients and operators during critical stages of dental treatment.

Optic nerve glioma and colonic polyposis: report of a new association.

AIM: The authors describe the clinical, radiological and histopathological features of an optic nerve glioma associated with colonic polyposis. The association between colonic polyposis and neuroepithelial tumours of the central nervous system has been previously described, but no association with optic nerve gliomas has ever been reported. METHODS: We report a 14-y-old girl with colonic polyposis and unilateral proptosis for whom an excisional biopsy of the orbital lesion was performed. RESULTS: Histopathological evidence of juvenile pilocytic astrocytoma grade 1 was detected. Correlation with criteria for Turcot's syndrome was established. CONCLUSION: Optic nerve tumours should be included in the spectrum of central nervous system lesions associated with colonic polyposis.

Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery.

BACKGROUND: Prostaglandins modulate cytokine release though increases in cAMP, regulating interleukin (IL) 6 and IL-10. Diclofenac inhibits cyclo-oxygenase activity and hence prostaglandin production. We hypothesized that diclofenac would affect release of IL-6 and IL-10 and modulate the immune response. METHODS: In a randomized, double-blind, placebo-controlled study, we investigated the effect of diclofenac in patients undergoing major urological surgery. Patients were randomized to receive either diclofenac (50 mg orally every 8 h the day before surgery and 75 mg i.m. every 12 h on the day of surgery, n = 23) or placebo (n = 23). Standardized combined general anaesthesia and epidural analgesia was administered. Serum IL-6, IL-10 and cortisol were measured before surgery and 30 min and 2, 6, 12 and 24 h after skin incision. Temperature, leucocyte count and C-reactive protein concentration were measured before surgery and after 24 h. RESULTS: IL-6 and IL-10 concentrations increased, reaching peak levels at 12 and 6 h respectively in both groups. At 12 h, the IL-6 concentration was significantly lower in patients receiving diclofenac than in those receiving placebo (P = 0.003). In contrast, IL-10 concentration at 6 h was higher in diclofenac-treated patients (P = 0.008), and this was associated with less pyrexia (P = 0.03), a lower leucocyte count (P = 0.0002) and a lower C-reactive protein concentration (P = 0.0039). Serum cortisol concentration was similar in the two groups of patients until 24 h, when the concentration was lower in patients who received diclofenac (P = 0.002). Cortisol concentration correlated with IL-6 concentration at 24 h. CONCLUSIONS: Administration of diclofenac was associated with lower IL-6 and higher IL-10 concentrations, and lower leucocyte count, C-reactive protein concentration and temperature. Diclofenac may have an anti-inflammatory role in major surgery.

Cyanoacrylate tissue adhesive in the management of recurrent retinal detachment caused by macular hole.

Nine eyes of nine patients with rhegmatogenous retinal detachment caused by a macular hole were treated by the transvitreal application of cyanoacrylate tissue adhesive to the macular hole. Eight of the nine eyes had previously failed conventional vitreous surgery with gas tamponade and laser photocoagulation. Eight eyes (89%) were completely reattached with a minimum follow-up of three months. In the successfully treated eyes, post-operative visual acuity was 20/200 in two eyes, 20/400 to 5/200 in five eyes, and less than 5/200 in one eye. Direct sealing of macular holes in difficult cases may obviate the need for extended intraocular tamponade or macular buckling with their associated complications.

Evaluation of the functional results after different techniques for treatment of retinal detachment due to macular holes.

A total of 50 eyes with retinal detachment due to macular holes were treated in the period from July 1986 to December 1987. In all, 10 eyes underwent pneumatic retinopexy using plain room air. A total of 30 eyes were treated by pars plana vitrectomy, followed by fluid/air exchange, with no treatment of the macular break; in 9 of these the detachment recurred, reflattening of the retina by air tamponade followed by laser photo-coagulation. The other 10 eyes underwent pars plana vitrectomy followed by silicone oil tamponading because of proliferative vitreoretinopathy (PVR). This paper compares the functional results for each group. The parameters used included visual acuity, color vision and visual fields.

Quantification of cellular proliferation in experimental proliferative vitreoretinopathy.

Proliferation of host cells from around the optic nerve head has recently been implicated in the development of experimental proliferative vitreoretinopathy in rabbit eyes injected with homologous fibroblasts. We used liquid scintillation spectrometry to quantitate the tritiated thymidine incorporation into cells in the vitreous, retina, and optic nerve head following intravitreal injection of 250,000 homologous dermal fibroblasts. Cellular proliferation peaked three days after injection of the fibroblasts. The amount of tritiated thymidine incorporation that occurred three days following injection of irradiated homologous fibroblasts (incapable of cellular division) was not significantly different than that following injection of normal homologous fibroblasts, indicating that host cells were responsible for most of the cellular proliferation. Treatment with fluorouracil or triamcinolone acetonide completely arrested cellular proliferation following injection of normal fibroblasts.

Retinal toxicity of cyanoacrylate tissue adhesive in the rabbit.

N-butyl-2-cyanoacrylate tissue adhesive was injected into the preretinal space of rabbit eyes to study potential toxicity to the retina. Application of 3.3-10.0 ul of cyanoacrylate tissue adhesive showed localized but definite retinal toxicity. White halos appeared surrounding the preretinal cyanoacrylate immediately after injection with a gradual evolution of the white areas into pigmentary scars by 1 month. Histological examination confirmed severe focal necrosis of the retina. No identifiable distant toxic effects or electrophysiologic changes were observed during the 6-month follow-up period.

Transvitreal cyanoacrylate retinopexy in the management of complicated retinal detachment.

We used transvitreally delivered cyanoacrylate tissue adhesive to seal retinal breaks in 25 selected patients undergoing vitreous surgery for complicated retinal detachment. With a minimum follow-up period of six months, all but one retinal hole remained closed. Complete retinal reattachment posterior to the encircling buckle was achieved in 18 of 25 eyes (72%). In ten of 25 eyes (40%) the final visual acuity was 5/200 or better.

Experimental transvitreal cyanoacrylate retinopexy in a primate model.

We evaluated the use of transvitreal cyanoacrylate retinopexy in the treatment of experimental rhegmatogenous retinal detachment during vitreous surgery in the cynomolgus monkey. The chorioretinal adhesions produced with cyanoacrylate tissue adhesive as compared with those produced by transscleral retinal cryopexy were more rapid in onset as well as stronger. To test the efficacy of cyanoacrylate retinopexy further, a 360-degree peripheral retinectomy was created in five eyes with circumferential cyanoacrylate application to the posterior retinal edge. The cyanoacrylate retinopexy did not prevent the development of proliferative vitreoretinopathy with traction retinal detachment, but in three of the eyes the tissue adhesive continued to maintain retinal apposition to the retinal pigment epithelium at the retinotomy edge. Histologic examination of the retinas disclosed a foreign body reaction adjacent to the cyanoacrylate sites, but there was no evidence of any distant effects caused by the tissue adhesive.

Improvement in efficacy of corticosteroid therapy in an animal model of proliferative vitreoretinopathy by pretreatment.

Intraocular injection of the corticosteroid triamcinolone acetonide reduces the incidence of retinal detachment in rabbit eyes injected with tissue-cultured fibroblasts. When the steroid was injected simultaneously with the cells, a reduction of retinal detachment from 93% (control) to 75% (treated) was achieved on day 28. When the steroid was injected 24 h preceding cell injection, the reduction of retinal detachment was from 85% (control) to 43% (treated). The development of retinal detachment is caused by proliferation of injected fibroblasts. Reduction of this proliferation is probably achieved partially through direct inhibition of mitosis, but more important may be the reduction of the reactive inflammatory process.

Classification of the stages of proliferative vitreoretinopathy in a refined experimental model in the rabbit eye.

Eighty-four rabbit eyes injected intravitreously with tissue-cultured fibroblasts following gas compression of the vitreous were examined clinically over a period of 1 month. Detailed clinical descriptions of the extent of retinal changes were recorded. Clinical landmarks were determined and arranged into a new classification of this model of proliferative vitreoretinopathy (PVR). The proposed classification will allow easier communication between research groups using this model to study the treatment and prevention of PVR.

Transvitreal cyanoacrylate retinopexy in the management of complicated retinal detachment.

Failures in vitreous surgery for complex vitreoretinal disorders are frequently due to an inability to keep preexisting or iatrogenic retinal breaks permanently closed. We have used transvitreally delivered cyanoacrylate tissue adhesive to seal retinal breaks in selected patients undergoing vitreous surgery for complicated retinal detachment. With a minimum follow-up period of 6 months, all but one retinal hole have remained closed and complete retinal reattachment posterior to the encircling buckle was achieved in 18 of 25 eyes (72%). In 10 of the 25 eyes (40%) the final visual acuity was 5/200 or better.

Experimental transvitreal cyanoacrylate retinopexy through silicone oil.

We evaluated the use of transvitreal cyanoacrylate retinopexy in the treatment of experimental rhegmatogenous retinal detachment during vitreous surgery in rabbit eyes filled with silicone oil. The view to the fundus was superior to that obtained in our previous model of cyanoacrylate retinopexy in the air-filled eye. Glue delivery was consequently both easier and more precise through silicone oil relative to air. The chorioretinal adhesions produced with cyanoacrylate tissue adhesive were compared with those produced by transscleral retinal cryopexy and were found to be more rapid in onset as well as stronger. An exaggerated tissue response adjacent to the cyanoacrylate site suggested a potential toxic chemical or thermal reaction, or both, to the tissue adhesive, but there was no evidence of any distant ocular effects.

Experimental transvitreal cyanoacrylate retinopexy.

We used an experimental rabbit model of rhegmatogenous retinal detachment to compare the onset, quality, and duration of chorioretinal adhesions obtained by transvitreal application of N-butyl-2-cyanoacrylate mixed with iophendylate with those obtained by transscleral retinal cryopexy. The chorioretinal adhesions produced by the cyanoacrylate tissue adhesive were immediate in onset, stronger, and long lasting.