There were no severe AEs (95% CI: 0.00% to 0.71%), and all AEs were resolved and documented with their severity, relation to device/procedure, intervention, and final outcome. All AEs occurred between days 0 and 7.
Adverse Event 1 and 2
The subject arrived on day 7 for the scheduled removal. The PrePex device was already removed, and the subject had no foreskin. There was mild bleeding from his MC wound, which stopped after 30 seconds of direct pressure. He admitted to removing the device with a razor on the night of day 6 after feeling intense pain accompanied by compression by the inner ring (AE1; Table 3). Although removing the device by himself, he created a wound caused by cutting his foreskin with the razor. The subject felt no pain after the removal, and there was no bleeding. Mild bleeding began when he rode a motorbike to the hospital for the scheduled removal. The pain was related to the device. The bleeding was not related to the PrePex device but to the fact that the subject cut his own foreskin (AE2). The AE was resolved with application of the standard postremoval dressing according to the standard postremoval procedure. No special follow-up other than the regular follow-up plan was required.
Adverse Event 3
The subject arrived to the hospital for an unscheduled visit 1 day after placement complaining that although he could urinate, the flow was disturbed. During examination, it was discovered that the inner ring was placed improperly causing the foreskin to stretch and partially disturb urine flow.
This AE was related to the device. Replacement was performed with a new device. The new elastic ring was placed over the same circumcision line of the original elastic ring, so the previous compressed foreskin was included. The removal on day 7 of the second device went well, and the regular follow-up plan proceeded.
Adverse Event 4
The subject arrived 2 days after placement for an unscheduled visit and explained he showered, had an erection, and touched the device. He felt a slight pain. He noticed that the elastic ring was partially moved out of the inner ring groove. The movement occurred while the subject had an erection and was probably masturbating. The subject was examined to confirm that only the elastic ring partially moved. Localized edema and initial necrotic tissue were observed.
This AE was related to the device. A coinvestigator released the elastic ring completely and replaced it on the previous observed circumcision line to let the process continue until day 7. The inner ring was not replaced or moved from its original location. A new placement ring was used to perform the standard PrePex placement. The subject returned for his scheduled removal visit.
Adverse Event 5
After the device was removed on day 7, the subject called the hospital that night and complained of bleeding from the penis, which began after urinating. The subject went to a local clinic for dressing, but the bleeding did not stop. He returned to the hospital to be examined, which revealed active mild bleeding from a small artery 90-degree angle from the frenulum. One suture was used to stop the bleeding and resolve the AE.
This AE is possibly related to the device. The subject returned the following morning for his next scheduled visit and continued with the regular follow-up plan.
It was assumed that a trained PrePex team should perform the PrePex procedure in a reasonable timeframe, which would improve with experience. Duration of PrePex preparation and procedure were taken from the last 125 subjects., after a nurse had gained experience. The mean placement preparation time was 1 minute 37 seconds (SD: 21 seconds, median: 1 minute 38 seconds), and removal preparation was 1 minute 11 seconds (SD: 8 seconds, median: 9 seconds). The mean placement procedure took 1 minute 8 seconds (SD: 26 seconds, median: 1 minute 2 seconds). The mean removal procedure took 1 minute 43 seconds (SD 47 seconds, median: 1 minute 25 seconds). The mean total procedure time, including preparation, was 4 minutes, 39 seconds (SD: 4 minutes 39 seconds; 1 minute 2 seconds), almost 2 minutes less than the average physician time and 5 times faster than the average time it took a surgical MC procedure in the RTC (Table 4).
Expected Side Effects
Expected side effects are clinical findings which are expected in a normal circumcision procedure. They are not considered an AE because they are within the normal range of a well-healing wound of a circumcision procedure as reported in all circumcision-related literature.
There were 76 expected side effects observed (14.6% of the 518 subjects), which included 18 cases of oozing (3.4% of side effects), 50 cases of localized edema (9.6%), and 8 clear exudates (1.5%). The majority of side effects (57.3%) were observed on day 9, preceded by 18.6% of cases on day 7. The last side effects were observed on day 49. There were none when wearing the device. All side effects resolved naturally in short time.
A possible additional side effect noticed in 57 subjects (11.0%) on day 9 was that the wound had a white caramel-like cover over the exposed granulating tissue. There was no sign of infection, local increase in skin heat next to the wound, pain, or change in color around the wound or deviation from average time to complete healing. The slough was cleaned, but not removed, with simple sterile gauze to absorb clear exudates. The subjects were asked to wash the wound with water and soap at home, as was already requested with follow-ups. The problem was resolved in all subjects in 1–2 weeks. All 57 cases had no additional side effect or AE, and it was believed that the white slough observed in the 57 subjects was a result of the necrotizing tissue process.
None of the expected side effects delayed or complicated the normal MC healing process.
Pain measurements reported by 496 of 518 subjects during placement were an average of 1 on a VAS scale of 10. Thirty minutes postplacement, 123 subjects’ measurements averaged 0.5.
Subjects were given 2 tablets of ibuprofen to use if necessary at home to control possible pain or discomfort. When they came back for the removal, 387 subjects were questioned on pill usage. Three hundred and forty-seven (89.6%) used the pills at home, which effectively reduced their pain.
When subjects returned for device removal, they were asked if they had an erection although wearing the device; 446 (86.1%) reported that they had an erection, and 72 (13.9%) did not reply. Therefore, all subjects who reported on whether they had an erection, indeed, had an erection. The average pain during erection was 2.68, and 42.6% of subjects indicated that they felt pain of 2 at erection.
The average time to complete healing was 33 days postdevice removal on day 40. In the RCT, average healing time was 38 days.14 Healing was calculated for 334 of 518 subjects; 147 subjects (28.3%) did not return for their final visit, and, therefore, cannot be included in the analysis. Two phone calls, 1 week apart, were made to the subjects’ mobile phones to remind them of their final visit. Then, a third call was made to their friend/relative contact they provided at the time of enrollment. In any case, it should be noted that these subjects lost-to-follow-up who missed the final visit were all observed and followed through almost complete healing and showed very good healing progress for several weeks. This leaves no doubt in the investigators’ opinion that they achieved complete healing 5 days after the last visit attended by these subjects.
Confidence in Procedure and Nurses
For the last group of subjects to undergo the PrePex procedure, a questionnaire was filled out by these subjects and by all the nurses to assess the PrePex placement and removal. It should be noted that it was the investigators’ prestudy decision to collect data that best represented the view of the subjects and nurses on the procedure in an optimal manner that eliminated bias from less experience in conducting the procedure. Thus, by surveying the final procedures, the investigators felt it would best represent the procedure being conducted on a regular basis by regular staff. After placement, 123 subjects responded to a procedure questionnaire, 87% found the procedure easy, and 97.5% found painless. Almost all thought that the nurse was confident in the procedure with 68.3% saying very good and 28.4% good. Almost all thought the procedure went quickly (65.9% very fast, 25.2% fast).
After removal, 92.2% of 103 subjects thought the removal was easy (7.7% difficult), and all of them found it painless. Nurses were thought to have been more confident with the removal (78.6% very good, 16.5% good, and 3.9% medium). Only 1% thought the removal was slow. At the end of the study, 96.9% of 130 subjects would recommend a PrePex circumcision.
The nurses responded to similar questionnaires for the final group of procedures. No one thought the placement or removal procedure went badly or was unsafe. Among the operators, 89.1% felt they did well in performing the placement procedure, and 85.6% of the assistants thought they did well. Their confidence increased after the removal; 98.5% of the operators thought they performed the removal well and 97.8% of the assistants.
The primary objective of this study was to assess the safety and efficacy of the nonsurgical circumcision PrePex procedure when performed by nurses. Device safety was assessed by the rate of clinical AEs and device-related incidents attributed to the PrePex device and its procedures. Other measures such as procedure time, expected side effects rate, pain assessment, and time to complete healing were considered for the nurses’ performance.
None of the nurses who participated in this study had previously seen or performed a PrePex procedure. The results demonstrate that the PrePex training course is effective in training nurses who have no experience with PrePex MC in becoming PrePex MC experts. The short total procedure time posttraining (4 minutes and 39 seconds), low AE rate (0.96%), and successful circumcision of the 518 subjects further demonstrate that the training course was effective in training nurses to perform safe, effective, and scalable PrePex MC procedures.
The overall AE rate in the study was 0.96% (95% CI: 0.31% to 2.24%), which is lower than the study hypothesis AE rate of 2% and lower than the RCT—reported 11% AE rate of surgical MC. It should be noted that the investigators believe that the AE results of this study are so much lower than the reported surgical AE rate for Rwanda because there is a lack of standardization of the exact definition of what constitutes an AE. The reported 11% rate (which is 9.5% if you omit 1 unrelated AE) is taken from a comparison study between the PrePex and surgical MC using the dorsal-slit method, in which the AE threshold was very low for both procedures.14 It is possible, therefore, that certain clinical occurrences were defined as AEs in that study, which may not be considered AEs in other studies.
In this current study, only 1 AE related to the device was also associated with the performance of nurse—the erroneous placement of the device that partially disturbed urine flow. Two AEs were related to subject behavior while wearing the device, although 1 was directly device related. The AE rate related to subject behavior could be further reduced with proper counseling and education after the placement procedure. There were no serious AEs, and all AEs resolved with minimal intervention and without any harmful outcome to subjects. It is therefore concluded that the PrePex procedure when performed by nurses is very safe and is safer than adult surgical MC performed by physicians, which strongly supports task-shifting MC from Physicians to nurses.
After gaining experience, the nurses performed the procedure on average at 1 minute and 56 seconds faster than the physicians performing PrePex in the RTC. The PrePex procedure of nurse was also much faster than surgical MC (by 5 times). This further attests to the successful nurse PrePex training program.
Pain was minimal, mainly during erection. Over-the-counter pain medication relieved pain the subjects felt.
The expected side effects did not delay or complicate the normal MC healing process. It was believed that the white slough observed in 57 subjects was a result of the necrotizing tissue process and should not be confused with wound infection because it does not have any accompanying signs of wound infection,16 such as change of skin color, sweet bacterial odor, increase in skin temperature, edema/erythema, exudates, etc. This side effect healed without any intervention, such as antibiotics.
Average healing time was 33 days from removal, as compared with 38 days from removal in the RTC, which further demonstrates that there is no difference in time to complete healing when PrePex MC is done by nurses or physicians and further validates the efficacy of the study.
A possible limitation of the study was not having the performance data of physicians as comparison. That said, the nurses had very good training and with experience were increasingly efficient and confident with the procedure. Another limitation may be that as many as one-third of the subjects did not return for their final follow-up visit, which would have determined their complete healing. Because they made no further contact with the hospital, it was assumed that their healing was complete. The low response rate on the questionnaires by the number of subjects and the number of procedures the nurses reported on is a final limitation of the study which bears impact on the strength of the conclusion without a broader overview of the progress and improvement of nurses and subject satisfaction over time. However, as previously explained with the results of the study, the investigators did not want to subject the nurses performance to subject bias over time.
It should be further clarified that narrow foreskin was included in the rigorous exclusion criteria to ensure a more efficient study flow because of the risk of potential pain from inserting the ring through a narrow foreskin. Nearly 11% of candidates were excluded due to their narrow foreskin, but it is assumed many could have still had the procedure done. A future study is needed to confirm the eligibility of subjects with narrow foreskin.
This study validates the safety and efficacy of task-shifting PrePex MC from physicians to nurses in Rwanda where physicians are limited, not necessarily available to perform surgical MC, and the demand for MC is very high. The procedure was minimally invasive and did not require injected anesthesia, sutures, or sterile settings. PrePex has the potential to facilitate rapid, safe, nonphysician MC scale-up programs for HIV prevention, an imminent need in Sub Saharan Africa where physicians are limited. The recommendation, pending approval by WHO, is that the Government of Rwanda move forward with scaling up the adult MC program in Rwanda and use the Prepex device and nonsurgical procedure where physicians are limited.
Kristen Eckert and Dr Marissa Carter (Strategic Solutions, Inc, Cody, WY) edited the article, and they have also given permission to have their name and information included in the acknowledgment.
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Keywords:© 2013 Lippincott Williams & Wilkins, Inc.
Africa; male circumcision; nonsurgical; safety; nurses; HIV prevention