混合型尿失禁同時包含應力性尿失禁與急迫性尿失禁。當保守治療、骨盆底肌訓練及口服藥物效果不佳時，臨床上仍缺乏足夠證據決定應先處理哪一種成分。MUSA 試驗以多中心、隨機、優越性設計，直接比較兩種作用目標不同的侵入性治療：膀胱內注射 onabotulinumtoxinA 100 U，主要針對急迫性尿失禁；中段尿道吊帶則主要針對應力性尿失禁。研究納入 21 歲以上、兩種症狀皆造成中度至重度困擾、咳嗽壓力測試陽性、三日排尿日誌至少記錄 4 次急迫性漏尿，且先前保守治療與口服藥物失敗的女性。150 人接受隨機分派，137 人具有治療後資料並納入主要分析；其中 82.5% 的患者屬應力性與急迫性症狀相對均衡，而非單一症狀明顯占優勢。

主要終點為六個月時 Urogenital Distress Inventory（UDI）總分相較基線的變化。肉毒桿菌素組平均改善 66.8 分，吊帶組改善 84.9 分，組間平均差異為 18.1 分（95% CI，−4.6 至 40.7；p＝0.12）。因此，本篇研究未能證實肉毒桿菌素優於中段尿道吊帶。由於研究採優越性設計，這項陰性結果不應解讀為兩種治療已被證明等效，而應表述為六個月整體混合型尿失禁症狀的改善未觀察到顯著組間差異。兩組的改善幅度均超過研究預先採用的 UDI 總分最小臨床重要差異 26.1 分，顯示兩種處置皆可帶來具有臨床意義的症狀改善。

次要終點進一步呈現兩種治療的差異。六個月時，吊帶組的 UDI 應力性分量表改善較大，與肉毒桿菌素組的組間差異為 20.1 分（95% CI，8.4 至 31.9；p＜0.001），高於該分量表的最小臨床重要差異 5.4 分。相較之下，UDI 刺激性分量表在六個月時兩組無顯著差異（p＝0.27）。三個月時肉毒桿菌素組的刺激性症狀改善較多，但此差異至六個月已不存在。排尿日誌亦呈現相同方向：吊帶組對應力性漏尿次數的減少較明顯，但兩組急迫性漏尿次數的改善無顯著差異。作者據此指出，中段尿道吊帶治療應力性成分後，部分患者的急迫性症狀同樣可改善；然而研究結果並未證明吊帶直接治療膀胱過動，也不能推論所有混合型尿失禁患者都應優先接受吊帶。

這篇研究另一項重要資訊是單一治療未必足以長期控制兩種症狀。肉毒桿菌素組有 12.7% 於六個月內接受第二次注射，至十二個月增加為 28.2%。六個月後研究允許追加或交叉治療；至十二個月，吊帶組有 30.3% 接受肉毒桿菌素，肉毒桿菌素組有 15.5% 接受吊帶，整體共有 22.6% 的患者曾接受兩種治療。因此，十二個月結果已受到交叉治療影響，較適合用來反映實務上追加治療的需求，而非單純比較最初隨機分派治療的持續效果。

安全性方面，兩組整體不良事件無顯著差異，且無與研究治療相關的嚴重不良事件。吊帶組有 11.8% 於術後帶導尿管返家，2.9% 發生陰道網膜暴露，1.5% 接受吊帶移除或修整；肉毒桿菌素組無人於治療後立即需留置導尿，但 2.8% 在術後兩週仍需間歇性自我導尿。十二個月內泌尿道感染在兩組皆常見，發生率分別為 27.8% 與 29.4%。這些風險資料可作為共享決策的一部分，但研究並未證明某一治療在安全性上優於另一治療。

本篇列出的優點包括隨機設計、使用經驗證的患者報告結果，以及負責施測問卷與排尿日誌的人員維持盲態。研究前六個月僅允許隨機分派的治療，使主要終點能較清楚比較兩種策略；後六個月則允許實務上的追加治療。限制包括患者與手術醫師無法盲化、患者事先知道六個月後可能接受另一種治療而可能影響交叉治療率、追蹤時間不足以評估慢性疾病的長期追加治療需求，以及研究族群的種族與族裔分布不能代表美國整體人口。另外，多數受試者的兩種症狀相對均衡，結果不宜直接外推至明顯以應力性或急迫性症狀為主的患者。

綜合而言，MUSA 試驗的結論不是兩種治療完全相同，也不是中段尿道吊帶必然優於肉毒桿菌素，而是對保守治療與口服藥物失敗、且兩種症狀皆明顯困擾的女性，六個月時兩種處置均能改善整體症狀，且未觀察到主要終點的顯著組間差異。吊帶對應力性症狀的改善較明確，而急迫性症狀在六個月時兩組相近。臨床選擇應依患者最重視的症狀、對手術與人工網膜的接受度、對重複注射及可能導尿的接受度，並說明部分患者最終仍可能需要兩種治療。這正是本文所支持的共享決策重點。

Importance: Mixed urinary incontinence, which includes both stress and urgency urinary incontinence, adversely affects quality of life and can be difficult to manage. Studies comparing procedural-based treatments for mixed urinary incontinence are lacking.

Objective: To determine whether intradetrusor onabotulinumtoxinA is more effective than midurethral sling for the treatment of mixed urinary incontinence in females.

Design, setting, and participants: Randomized, superiority trial involving females (aged ≥21 years) with moderate to severe bother from both stress and urgency urinary incontinence who had unsuccessful conservative treatments and oral medications. The study was conducted at 7 US sites with enrollment between July 2020 and September 2022; the last date of follow-up was December 29, 2023.

Interventions: Intradetrusor injection of onabotulinumtoxinA, 100 U (treatment focused on the urgency component), vs surgical synthetic mesh midurethral sling (treatment focused on the stress component). Recipients of onabotulinumtoxinA could receive an additional injection between 3 and 6 months. All participants could receive additional treatment (including crossover to the alternative treatment) between 6 and 12 months.

Main outcomes and measures: The primary outcome was change at 6 months in mixed incontinence symptoms as measured by the Urogenital Distress Inventory (UDI) total score (0-300 points; higher scores indicate worse symptoms; minimal clinically important difference, 26.1). Secondary outcomes included stress and irritative UDI subscores.

Results: Among 150 females randomized, 137 were treated, had postbaseline outcome data, and were included in the primary analysis (mean [SD] age, 59.0 [11.5] years). Both groups demonstrated mean improvement in UDI total score at 6 months with no significant difference between groups (onabotulinumtoxinA: -66.8 points [95% CI, -84.9 to -48.8]; sling: -84.9 [95% CI, -100.5 to -69.3]; mean difference, 18.1 points [95% CI, -4.6 to 40.7]; P = .12). For secondary outcomes, greater UDI stress score improvement was seen with the sling (-45.2 [95% CI, -53.7 to -36.8]) compared with onabotulinumtoxinA (-25.1 [95% CI, -34.1 to -16.1]) (P < .001); however, no significant difference was seen between groups in UDI irritative score (onabotulinumtoxinA: -32.9 [95% CI, -40.3 to -25.6] vs sling: -27.4 [95% CI, -34.6 to -20.3]; P = .27). In the onabotulinumtoxinA group, 12.7% and 28.2% received a second injection by 6 and 12 months, respectively. By 12 months, 30.3% in the sling group received onabotulinumtoxinA, and 15.5% in the onabotulinumtoxinA group received a sling. Overall, adverse events were not different between groups.

Conclusions and relevance: There was no observed difference in UDI total score improvement at 6 months between the onabotulinumtoxinA and midurethral sling groups in females with moderate to severe mixed urinary incontinence who previously did not respond to conservative treatments. These findings may help inform treatment decisions based on patient preference in partnership with clinician recommendations.