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At least 19 recordsLinked to original sources

Laparoscopic renal cryotherapy in swine: comparison of puncture cryotherapy preceded by arterial embolization and contact cryotherapy.

Variable results of open, percutaneous, and laparoscopic cryosurgery of the kidney have been reported. Minimally invasive approaches to lower-pole renal ablation were prospectively compared in swine: laparoscopic puncture cryoablation preceded by arterial embolization, laparoscopic contact cryosurgery, and arterial embolization alone. Eighteen kidneys in nine domestic pigs were randomized to one of three treatment groups of six organs each: (1) puncture cryotherapy preceded by selective lower-pole arterial embolization; (2) contact cryotherapy alone; and (3) arterial embolization alone. Under general anesthesia, appropriate animals underwent selective arterial embolization of the lower pole via femoral cutdown using Gelfoam pledgets. Animals randomized to cryotherapy underwent dissection of the lower pole of the kidney using a single 12-mm umbilical and two midclavicular-line ports in the lateral position. Under external ultrasound guidance, two 3-mm cryoprobes (Cryomedical Sciences, Rockville, MD) were positioned in the lower pole of the kidney, and double-freeze technique to -190 degrees C was performed using puncture or contact application. Ultrasonography was used to guide probe insertion during puncture cryotherapy only. Kidneys were harvested 11 to 14 days after the procedure. Both puncture and contact kidneys demonstrated cell death and subsequent necrosis by light microscopy and electron micrography. On average, puncture lesions were heavier than contact lesions, 19.3 g v 10.1 g (P = 0.02; unpaired t-test), whereas the kidneys were equivalent in weight: 74.1 g v 74.1 g. Puncture lesions represented 26.4% of total kidney weight v 13.5% in the contact group (P = 0.002; unpaired t-test). Only focal infarcts were identified in the embolization group. No evidence of adjacent visceral injury was identified in any of the groups, and no animal required conversion to open laparotomy. One kidney bled after contact cryotherapy, and hemostasis was achieved laparoscopically. Laparoscopic cryotherapy is reproducible and effective using either the puncture technique preceded by arterial embolization or the contact technique, without evidence of damage to adjacent structures. Contact lesions were less voluminous and more peripheral than puncture lesions. Embolization alone produces focal infarcts and focal zones of cell death.

Animals↗

A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.

OBJECTIVE: To examine biopsy specimens of tissue immediately adjacent to anogenital (AG) warts which had been treated with either cryotherapy plus subcutaneous interferon (IFN) alpha 2a or cryotherapy alone, for histological features of (a) human papilloma virus (HPV) infection (b) localised cellular immune responses, to further characterise any cellular immune infiltrates with tissue immunocytochemistry, and to relate any histological, immunocytochemical findings to the treatment response of nearby AG warts. DESIGN: A randomised placebo controlled observer blind study. SETTING: Genitourinary Medicine clinic, Department of Immunopathology, Royal Victoria Hospital, Belfast, N. Ireland. SUBJECTS: Thirty patients with AG warts; 16 treated with IFN alpha 2a plus cryotherapy, and 14 treated with cryotherapy alone. OUTCOME MEASURES: (1) Light microscopic features associated with HPV infection and local cellular immune responses. (2) Indirect immunofluorescence detection of the following cell surface markers: HLA DR, alpha one antitrypsin, CD1, CD3, CD4, CD8, CD22. (3) Clinical response of AG warts to treatment. RESULTS: In pre-treatment biopsies only non specific indicators of HPV infection (acanthosis, 29/30 biopsies, and hyperkeratosis, 7/30 biopsies) were seen on light microscopy. Mononuclear cells were seen both throughout the upper dermis and centred around dermal blood vessels in 19/30 (63.3%) biopsies, and infiltrating into the epidermis in 12/30 (40%) biopsies. On indirect immunofluorescence CD3, CD8, CD4 antigen was detected on the surface of cells throughout the upper dermis in 24/29 (82.7%), 15/29 (51.7%), and 3/29 (10.3%), of biopsy specimens respectively. CD3 antigen, CD8 antigen and CD4 antigen was detected on the surface of cells infiltrating into the epidermis in 18/29 (62%), 7/29 (24.1%), and 6/29 (20.7%) of biopsy specimens respectively. CD1 antigen was seen on the surface of dendritic cells throughout the epidermis in all specimens; CD1 positive cells infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS: (1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts.

Adolescent↗

Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

We report the results of the national multicenter trial of cryotherapy for retinopathy of prematurity, as determined 3 months after randomization. The threshold severity of retinopathy required for entry into the clinical trial was defined as five or more contiguous or eight cumulative 30 degree sectors (clock hours) of stage 3+ retinopathy of prematurity in zone 1 or 2. Transscleral cryotherapy to the avascular retina was applied in one eye when there was threshold retinopathy in both eyes, or in half the eyes when the threshold severity existed in only one eye (18% of patients). Of the 279 infants who survived 3 months following randomization, 273 returned for outcome examination at that time. Of these infants, 260 had fundus photographs taken that could be graded for anatomic outcome. An unfavorable outcome was defined as posterior retinal detachment, posterior retinal fold (usually involving the macula), or retrolental tissue that obscured the view of the posterior pole. Whereas 51.4% of control eyes had an unfavorable outcome, this was significantly less frequent in the eyes that received cryotherapy (31.1%). No deaths were attributed to the cryotherapy procedure. These data, together with numerous additional ocular findings and preliminary 12-month postrandomization outcome results reported herein, support the efficacy of cryotherapy in reducing the risk of unfavorable ocular outcome from threshold retinopathy of prematurity. We have previously recommended cryotherapy for at least one eye in all patients with threshold retinopathy of prematurity. Now we add the recommendation cryotherapy be considered for both eyes whenever stage 3+ retinopathy of prematurity involves the posterior retina (zone 1) of both eyes.

Analysis of Variance↗

A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: a controlled study.

BACKGROUND: Treatment modalities for keloids, which are commonly found in Asians, include intralesional corticosteroid injections and cryotherapy as well as a combination of these two modalities. Few studies have been performed in a controlled fashion to evaluate the efficacy of these treatments. OBJECTIVE: A controlled study, to evaluate the combined effect of intralesional corticosteroid injection with cryotherapy vs. intralesional corticosteroid or cryotherapy alone. METHODS: Ten patients completed the study: eight patients had at least three keloids and two had two keloids. Patients were treated for at least three sessions 4 weeks apart. The outcome of the lesions was compared between the treatments regarding the thickness of the lesion using a caliper and photographic assessment, and the presence of itch and pain before and after treatment using a visual analogue scale. RESULTS: In terms of thickness, the keloids responded significantly better to combined cryotherapy and triamcinolone vs. triamcinolone alone or cryotherapy alone (P < 0.001). Pain intensity was significantly lowered with all treatment modalities; however, itch was lowered only with the combined treatment and intralesional corticosteroid alone. No significant side effects were noted with any of the treatments and no re-occurrence of keloids was noted with the combined therapy. CONCLUSION: Combined injection of intralesional steroids with cryotherapy appears to be superior to other current modalities.

Adolescent↗

Scleral indentation following cryotherapy and repeat cryotherapy enhance release of viable retinal pigment epithelial cells.

Retinal pigment epithelial (RPE) cells are an important component of intravitreal and epiretinal membranes in proliferative vitreoretinopathy (PVR) that contract and cause recurrent retinal detachment. Cryotherapy has been shown to enhance release of viable RPE cells into the vitreous cavity. This study demonstrates that repeat cryotherapy (refreezing) releases viable RPE cells in even larger numbers. Repeated indentation of the sclera after transscleral cryotherapy also releases more viable RPE cells than does cryotherapy alone or scleral indentation preceding cryotherapy. These findings suggest that refreezing should be avoided, and repeated indentation of the sclera should be minimized after cryotherapy.

Animals↗

Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study.

OBJECTIVE: To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. DESIGN: Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. PATIENTS: 60 patients with newly diagnosed AG warts. INTERVENTION: 29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. MAIN OUTCOME MEASURES: Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re-attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. RESULTS: At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. CONCLUSIONS: Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators.

Anus Diseases↗

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Astigmatism↗

Comparative study of the efficacy of combined cryotherapy and intralesional meglumine antimoniate (Glucantime) vs. cryotherapy and intralesional meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is a parasitic disease caused by Leishmania species. There is a need for more effective and less time-consuming therapeutic methods for this condition. AIM: To evaluate the efficacy of combined cryotherapy and intralesional meglumine antimoniate (MA) (Glucantime, Specia, Paris, France) for the treatment of CL. METHODS: Patients were divided into three groups: Group 1, 100 patients with 149 lesions were treated with cryotherapy plus intralesional MA; Group 2, 200 patients with 230 lesions were treated with cryotherapy; Group 3, 100 patients with 160 lesions were treated with intralesional MA. These groups were followed for 6 months after the end of treatment. RESULTS: The results showed complete cure in 90.9% of cases in Group 1, 57.15% of cases in Group 2, and 55.63% of cases in Group 3. The difference between Group 1 and the other groups was statistically significant (P < 0.05). CONCLUSIONS: Combined cryotherapy and intralesional MA is more effective than either cryotherapy or intralesional MA alone for the treatment of CL.

Adult↗

Cryotherapy and sequential exercise bouts following cryotherapy on concentric and eccentric strength in the quadriceps.

We investigated the effects of cryotherapy followed by sequential exercise bouts on concentric and eccentric strength of the quadriceps. Nineteen males (18-27 years) participated in a two-stage design involving four sequences: ice and exercise, ice and rest, no ice and exercise, and no ice and rest. We gathered concentric and eccentric strength measures (torque) using a kinetic communicator (KIN-COM) prior to exercise, immediately following treatment, and 20- and 40-minutes post-treatment. There were significant decreases in concentric and eccentric strength immediately following the 25-minute cryotherapy treatment. This suggests that applying ice immediately prior to participation or returning an athlete to competition immediately following cryotherapy treatment may adversely affect his/her ability to perform. It appears that the reduction in strength following cryotherapy is of short duration (less than 20 minutes). The delayed effect of the ice treatment and sequential exercise appears to affect concentric and eccentric strength differently. Ice did not have a delayed effect on concentric strength, but there was a significant difference in eccentric values. This difference was a failure to improve during post-tests at the rate of those not treated with ice. Exercise did not have a significant effect on eccentric strength recovery, but there was a significant difference in concentric values. Moderate exercise following cryotherapy appears to help the recovery of concentric strength.

Journal Article↗

Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

We report the preliminary three-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied in one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degrees sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined three months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.

Clinical Trials as Topic↗

Non-specific immunity in patients with primary anogenital warts treated with interferon alpha plus cryotherapy or cryotherapy alone.

Combination treatment of primary anogenital warts with subcutaneous interferon alpha 2a plus cryotherapy was no more efficacious than cryotherapy alone. Patients with primary AG warts showed no in vitro or in vivo suppression of non-specific immunity. In patients treated with interferon plus cryotherapy non-specific cellular immunity was stimulated, both in vitro and in vivo compared with patients treated with cryotherapy alone.

Adolescent↗

Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

This study of the safety and efficacy of cryotherapy in treating severe retinopathy of prematurity registered 9751 infants with birth weights less than 1251 g at 23 study centers. Two hundred ninety-one infants developed a defined threshold retinopathy of prematurity, and cryotherapy was performed in approximately half of the eyes through a randomization protocol. Twelve months after randomization, results of masked grading of fundus photographs of the posterior pole were similar to results obtained 3 months after randomization, and indicated an unfavorable outcome in 25.7% of the eyes that received cryotherapy compared with 47.4% of the control eyes (P less than .0001). For the first time, masked Teller Acuity Card assessment of grating acuity was performed in this study group and indicated an unfavorable functional outcome in 35.0% of the treated eyes compared with 56.3% of the control eyes (P less than .0001). These results indicate that cryotherapy reduces the risk of unfavorable retinal and functional outcome from threshold retinopathy of prematurity.

Cohort Studies↗

Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

We report the preliminary 3-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied to one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degree sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined 3 months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.

Clinical Trials as Topic↗

Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

Cryotherapy for Retinopathy of Prematurity Cooperative Group Reports from the 3- and 12-month follow-up examinations in the Multicenter Cryotherapy for Retinopathy of Prematurity trial indicated a beneficial effect of cryotherapy in the treatment of severe retinopathy of prematurity. This report provides results from the 3 1/2-year follow-up examination on 92% of the 256 survivors from the original cohort of 291 infants in the randomized trial. Functional outcome was evaluated by masked assessment of letter acuity using the HOTV crowded letter test and grating acuity using the Teller Acuity Card procedure. Structural outcome was evaluated by physician's assessment of retinopathy of prematurity residua in the posterior pole. All three outcome measures showed a reduction in unfavorable outcomes in treated vs control eyes: 46.6% vs 57.5% (P < .01) for letter acuity, 52.4% vs 65.6% (P < .001) for grating acuity, and 26.1% vs 45.4% (P < .001) for posterior pole status. These results support the long-term efficacy and safety of cryotherapy in the treatment of severe retinopathy of prematurity.

Cryosurgery↗

Postoperative cryotherapy: risks versus benefits of continuous-flow cryotherapy units.

Continuous-flow cryotherapy units have been proved to decrease pain, inflammation, swelling, blood loss, and narcotic usage in the postoperative setting. Complications related to cryotherapy are extremely rare (estimated at 0.00225%) but can be devastating. Complications include frostbite, chronic pain, and loss of digits. Caution should be exercised when prescribing continuous-flow cryotherapy units to patients with known risk factors for cold injury. All members involved with care of the patient, including the physician, nursing staff, patient, and patient's family and caregivers, should take an active roll in monitoring the foot for signs and symptoms of cold injury. Continuous-flow cold therapy should be discontinued when capillary refill time is greater than 5 seconds.

Adult↗

Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was a randomized trial designed to test whether cryotherapy applied to the retina significantly decreased the incidence of retinal detachment, retinal fold, or retrolental "mass." Randomization into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled end of the intake period. At the time of the decision, a favorable outcome at 3 months posttreatment occurred more frequently in eyes treated with cryotherapy (78%) as compared to untreated eyes (57%) (chi 2 = 20.5). The basic statistical method used in monitoring the results was conditional power (or stochastic curtailment). Several other issues were considered in deciding to terminate the trial, including the examination of results across subgroups and clinical centers, the completeness of follow-up, clinical assessment of outcome, and long-term consequences of the treatment.

Bias↗

Correlation of retinopathy of prematurity in fellow eyes in the cryotherapy for retinopathy of prematurity study. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: To examine the similarity of extent (sectors) and severity (stage) of acute-phase retinopathy of prematurity (ROP) between fellow eyes and the concordance of cicatricial outcomes at age 1 year of eyes that did not develop threshold disease. METHODS: Four thousand ninety-nine infants with birth weights of less than 1251 g who participated in a natural history segment of the Cryotherapy for Retinopathy study underwent biweekly eye examinations from 4 to 6 weeks after birth until retinal vasculature was complete or until ROP regressed or reached threshold severity. Eyes were categorized as follows: (1) no ROP, (2) less than prethreshold ROP, (3) prethreshold ROP, (4) threshold ROP, and (5) unable to determine. The presence and stage of ROP residua in fellow eyes were evaluated at 12 months. RESULTS: Acute-phase ROP status between 32 and 42 weeks postconceptional age showed a high degree of correspondence between fellow eyes in severity (stage) and location (zone) of ROP, presence of plus disease, and sectors of stage 3 retinopathy. More variability between eyes was seen when cicatricial status at age 1 year was examined. This higher variability was evident even though results from patients with threshold ROP (many of whom underwent cryotherapy) were excluded. CONCLUSION: The usual course of ROP during its acute phase is for fellow eyes to be very similar in ROP status. However, asymmetry between eyes is not unusual in eyes with posterior pole residua of ROP.

Acute Disease↗

Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) is a randomized clinical trial sponsored by the National Eye Institute (NEI) designed to test whether cryotherapy applied to eyes of premature infants with a specified extent of stage 3+ ROP significantly decreases the incidence of an unfavorable outcome. An unfavorable outcome is defined as either retinal detachment or a retinal fold and was determined at 3 months posttreatment by the use of a masked photographic system. Enrollment into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled closing date for enrollment because of demonstrated treatment benefit. The purpose of this article is to discuss the operations involved in the orderly termination of enrollment and dissemination of results from this trial. These activities included preparation of trial participants and staff, release of trial information, continuing patient care, data collection and coding, and publication of trial results.

Blindness↗