A Novel Use of Cyclobenzaprine and Hyoscyamine (BLAVACARE TM) Impregnated Vaginal Suppositories for the Symptomatic Treatment of Interstitial Cystitis, Bladder Spasms, and Painful Bladder Syndrome
, Kirby Smith 2, Woodwin Weeks 2, Arian Baker 2, Stephen Yarbrough 2, Samantha Leggio 3,4 and Ummar Jamal 3Round 1
Reviewer 1 Report
The manuscript is interesting, considering the poor response to traditional treatments of patients with Interstitial Cystitis and the need, therefore, for better therapeutic strategies. The text is made in a fairly fluid English, which however needs corrections in some points (in order to improve its shape and make it more appreciated by the reader), which will be reported below. However, three points deserve to be further explored: 1) The authors state “We combined 10 mg of Flexeril and 0.125 mg of hyoscyamine into a vaginal suppository with glycerin for use every 12 hours as needed. The medication combination relaxes the bladder muscle while decreasing bladder and urethral spasms”. I believe that more details on the possible mechanisms of action of these drugs and why they have been successful are needed. 2) The authors state “Since initiation, KG has been able to achieve the level of analgesia she desired”. Please the authors clarify why they did not use validated one-dimensional scales (such as NRS, VAS or VRS) to assess pain objectively after each type of treatment. 3) Similarly, the authors state “There has been a remarkable improvement in her quality of life and her ability to function. She has also had a notable increase in her job productivity as she is no longer taking time off secondary to her discomfort”. Please the authors clarify why they did not use quality of life scales. In this way, it would have been possible to objectively assess the impact of the innovative treatment on improving the quality of life. Furthermore, a comparison between the two treatments on their impact on quality of life would also have been possible (the same way could be done for pain assessment). Here are some minor revisions: - The authors write “IC / PBS can greatly affects ones quality of life in a magnitude of ways. In this report, we look at a case of a patient with longstanding interstitial cystitis symptoms who was successfully treated with a novel approach after failing treatment with the current guidelines in the management of IC / PBS”. Please the authors modify the sentence as follows: “IC/PBS can greatly affects the quality of life in several ways. In this report, we present the case of a patient with longstanding interstitial cystitis symptoms who was successfully treated with a novel approach after failing treatment established by the current guidelines in the management of IC/PBS”. - The authors write: “Treatment options range from behavioral to pharmacological to surgical and still a majority are left with unsatisfactory treatment results”. Please the authors modify the sentence as follows: “Treatment options range from behavioral to pharmacological to surgical but still the majority of patients remain with unsatisfactory treatment results”. - The authors, on line 43, refer to the instillation of DMSO in the bladder. Please the authors write the acronym in brackets and report the sentence as follows: “...... of sacral neuromodulation with bladder installations of Dimethylsulfoxide”. - On line 58, please the authors modify the sentence as follows: “Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) affect up to 5% of females in the U.S. and incurs, on average, twice the health care costs as compared to women without IC/BPS”; - On line 61, please the authors modify the sentence as follows: “While the underlying etiology is poorly understood, IC/PBS differ significantly in the following aspect: interstitial cystitis is a chronic inflammatory disease while Bladder Pain Syndrome lacks the inflammatory component”. - On line 64, please the authors modify the sentence as follows: “Several theories attempt to explain the condition, indicating as causal factors inflammation and mast cell activation, urothelial dysfunction/GAG layer defects, increased levels of nitric oxide in the urine, depletion of Tamm-Horsfall Protein (THP) in the urine and genetic/autoimmune causes”; - On line 67 please the authors modify the sentence as follows: “The lack of clear understanding of IC/PBS makes diagnosis challenging”.Author Response
- Mechanism of action of flexeril and hyoscyamine is now addressed in lines 59-64.
- Originally, when treating this patient we were not thinking of writing a case report. We were just treating our patient and when the patient self-reported a significant improvement in her symptoms it was then when the decision was made to write it up to share this combination. Therefore, no scales or surveys were used with this patient. This can show insight into doing a larger scale study and incorporating scales and surveys to further advance the treatment of IC.
- Same response as #2. I think the next step would be to conduct a case series and incorporate scales and surveys to further assess this combination.
Suggested corrections were made to lines: 15-18, 29, 64, 84, 87-91
Thank you for your suggestions and feedback
Reviewer 2 Report
Please improve introduction section describing treatment options according guidelines.
Do not use first person in academic writing.
The suppository is your creation? Is the use of suppository approved by ethic committee?
How did you calculate the improvement of quality of life? What about the use of some questionnaires?
Author Response
Introduction section was improved by describing treatment options according guidelines in lines 30-41
The suppository is your creation? Is the use of suppository approved by ethic committee? Yes our creation and yes approved by ethics committee
How did you calculate the improvement of quality of life? What about the use of some questionnaires? improvement was self-reported. We were just focusing on the treatment of our patient we were not planning on writing up a report until after she self-reported such an increase in her quality of life.
Reviewer 3 Report
Interstitial cystitis and painful bladder spasms (IC/PBS) are some of the most difficult disorders to treat in the field of Urology. A number of options have been described for its management. I have been using TENS and sacral neuromodulation in refractory cases. However, this report provides me additional insights.
I would like to congratulate the authors for the successful management of a chronic patient via non-operative means.
My comments are below:
Abstract: is well-written and includes all the important information.
Introduction: the relevant information about the IC/PBS disorder is adequately presented in this section.
Case description: is optimal with a focus on the brief history, previous treatments, present condition. Also, patient anonymity is maintained during the case report. The details about the present treatment are adequate. I would like the authors to mention the follow-up duration after initiation of the suppository.
Discussion: The discussion about the IC/PBS, its presentation, treatment options, etc. is adequate. However, my advice to the authors is to discuss your new treatment option (10 mg of Flexeril and 0.125 49 mg of hyoscyamine into a vaginal suppository) in 2-3 lines. In this, you can highlight the mechanism of action of these drugs and the possibility of any synergism between the two drugs.
Author Response
The mechanism of action of the drugs has been added to lines 80-85.
Patient follow up was at 4 weeks 8 weeks and 12 weeks, this was added to the report.
Thank you for your comments and suggestions.
