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      // ── TITLE ──────────────────────────────────────────────────────────
      para([
        new TextRun({
          text: "Comparison of mean peak flow rate in holmium laser versus cold knife treatment in patients with urethral strictures",
          font: "Times New Roman", size: 26, bold: true
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      ], { alignment: AlignmentType.CENTER, spacing: { after: 240 } }),

      // ── INTRODUCTION ───────────────────────────────────────────────────
      heading("Introduction", HeadingLevel.HEADING_1),

      para([
        n("One of the oldest known urological disorders, urethral stricture, is still common and difficult to treat today."),
        cite("1"),
        n(" It is a prevalent ailment with a prominent rate of morbidity; in industrialized regions, its estimated prevalence is approximately 0.6%, and in poor countries, it may be greater."),
        cite("2"),
        n(" The stricture's depth, location, and length of scarring all affect the available treatment choices. These consist of cold-knife urethrotomy, electrocautery, and several kinds of laser therapies."),
        cite("3")
      ]),

      para([
        n("In the past 20 years, these have become especially popular. While avoiding thermal injury to the surrounding tissues, a cold-knife incision may result in mechanical injuries that could induce recurrence."),
        cite("4"),
        n(" In contrast, electrocautery may result in severe heat injury and repeated strictures."),
        cite("5"),
        n(" Because of its accuracy and effectiveness, the Holmium:YAG (Ho:YAG) laser has emerged as the most popular option among laser treatments in recent years. The Sachse Urethrotome "),
        err(", "),
        fix("[no comma needed] "),
        n("is carefully advanced to the stricture site and the stricture is then incised using a 12 o'clock position technique until adequately treated."),
        cite("6"),
        n(" Additionally, the urethral strictures are treated with a variety of lasers, including argon, carbon dioxide, potassium titanyl phosphate (KTP), neodymium (Nd), yttrium aluminum-garnet (YAG), and holmium (Ho):YAG."),
        cite("7"),
        n(" Because of its great precision and low heat impact on nearby tissues, the Ho:YAG laser is becoming a popular technique for endourology."),
        cite("8")
      ]),

      para([
        n("One hundred and thirty patients with urethral strictures were recruited by Shaikh MI et al. and split equally into two groups. A cold knife was used to open the patients in Group A, while a holmium laser was employed in Group B. On "),
        err("third"),
        n(" "),
        fix("the third"),
        n(" day, the average peak flow rates for groups A and B were 26.66\u00b13.69\u00a0ml/s and 28.72\u00b14.63\u00a0ml/s, respectively. On day 30, the maximum flow rates in groups A and B "),
        err("are"),
        n(" "),
        fix("were"),
        n(" 24.00\u00b13.44\u00a0ml/s and 20.84\u00b12.77\u00a0ml/s, respectively (p\u202f=\u202f0.000)."),
        cite("9"),
        n(" Group A (holmium group, n\u202f=\u202f10) and Group B (cold knife group, n\u202f=\u202f10) each had internal urethrotomy using a holmium laser and a cold knife, respectively, in a study by Maged WA et al. At the end of the third month, the holmium group experienced a greater post-operative drop in peak flow rate than the cold knife group."),
        cite("10")
      ]),

      para([
        n("The purpose of this study is to evaluate the effectiveness of optical internal urethrotomy, which uses a holmium laser in comparison to a cold knife, in treating short-segment urethral strictures in our local setting. The study will help standardize treatment protocols for urethral stricture based on functional results. The local findings will encourage adoption of minimally invasive laser techniques in public hospitals, improving access to modern urologic care. The study will help in informed decision making, enabling patients to understand treatment options and their expected outcomes based on evidence.")
      ]),

      // ── OBJECTIVE ──────────────────────────────────────────────────────
      para([
        new TextRun({ text: "Objective: ", font: "Times New Roman", size: 24, bold: true }),
        n("To compare mean peak flow rate in holmium laser versus cold knife treatment in patients with urethral strictures.")
      ]),

      // ── OPERATIONAL DEFINITIONS ────────────────────────────────────────
      heading("Operational Definitions", HeadingLevel.HEADING_1),

      para([
        new TextRun({ text: "Urethral stricture: ", font: "Times New Roman", size: 24, bold: true }),
        n("Patients with urinary obstructive symptoms, urinary flow\u202f<\u202f15\u00a0ml/sec on uroflowmetry and micturating cystourethrography showing narrowed urethral segment (abrupt change in urethral caliber) with absent or reduced contrast filling and proximal urethral dilatation will be labelled as having urethral stricture.")
      ]),

      para([
        new TextRun({ text: "Peak urinary flow rate: ", font: "Times New Roman", size: 24, bold: true }),
        n("Urinary flow in ml/sec will be measured on uroflowmetry on enrollment and 30-days post-operatively.")
      ]),

      para([
        new TextRun({ text: "Obesity: ", font: "Times New Roman", size: 24, bold: true }),
        n("Obesity will be assessed through body mass index (BMI). BMI will be calculated by formula \u2013 weight in kg/height in meter"),
        new TextRun({ text: "2", font: "Times New Roman", size: 24, superScript: true }),
        n(". Weight will be measured on a weighing scale and height on stadiometer. A BMI of \u226527.5\u00a0kg/m"),
        new TextRun({ text: "2", font: "Times New Roman", size: 24, superScript: true }),
        n(" will be taken as obese.")
      ]),

      para([
        new TextRun({ text: "Diabetes mellitus (DM): ", font: "Times New Roman", size: 24, bold: true }),
        n("DM will be deemed positive if known case of diabetes mellitus on hypoglycemic therapy for \u226501-year \u2013 assessed on history and medical record.")
      ]),

      para([
        new TextRun({ text: "Smoker: ", font: "Times New Roman", size: 24, bold: true }),
        n("Current smoker who has smoked \u226510 cigarettes/day for two years will be labelled as smoker.")
      ]),

      para([
        new TextRun({ text: "Hypertension: ", font: "Times New Roman", size: 24, bold: true }),
        n("Hypertension will be deemed positive if known case of hypertension on antihypertensive therapy for \u22651-year \u2013 assessed on history and medical record.")
      ]),

      // ── HYPOTHESIS ─────────────────────────────────────────────────────
      para([
        new TextRun({ text: "Hypothesis: ", font: "Times New Roman", size: 24, bold: true }),
        n("Urinary flow rate 30-days post-operatively will be higher in cold-knife compared to holmium laser internal urethrotomy for urethral strictures.")
      ]),

      // ── MATERIAL & METHODS ─────────────────────────────────────────────
      heading("Material & Methods", HeadingLevel.HEADING_1),

      para([
        new TextRun({ text: "Setting: ", font: "Times New Roman", size: 24, bold: true }),
        n("Department of Urology, Sahiwal Teaching Hospital")
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      para([
        new TextRun({ text: "Study design: ", font: "Times New Roman", size: 24, bold: true }),
        n("Randomized Controlled Trial")
      ]),

      para([
        new TextRun({ text: "Duration: ", font: "Times New Roman", size: 24, bold: true }),
        n("Six months after approval of synopsis")
      ]),

      para([
        new TextRun({ text: "Sample size", font: "Times New Roman", size: 24, bold: true }),
        cite("9"),
        new TextRun({ text: ": ", font: "Times New Roman", size: 24, bold: true }),
        n("Sample size is calculated through OpenEpi online software using mean difference formula. Where,")
      ]),

      para([
        n("Peak flow rate in cold-knife\u202f=\u202f24.00\u00b13.44\u00a0ml/s\u2003\u2003Power of the study\u202f=\u202f80%")
      ]),
      para([
        n("Peak flow rate in Holmium laser\u202f=\u202f20.84\u00b12.77\u00a0ml/s\u2003\u2003Confidence level\u202f=\u202f95%")
      ]),
      para([
        n("Sample size\u202f=\u202f30 in each group, Total sample size\u202f=\u202f"),
        new TextRun({ text: "60", font: "Times New Roman", size: 24, bold: true })
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      para([
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        n("Non-probability consecutive sampling")
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      para([
        new TextRun({ text: "Inclusion Criteria: ", font: "Times New Roman", size: 24, bold: true }),
        n("Males aged 18 to 70 years with short segment urethral strictures (length\u202f<\u202f2\u00a0cm), planned to undergo internal urethrotomy")
      ]),

      para([
        new TextRun({ text: "Exclusion Criteria: ", font: "Times New Roman", size: 24, bold: true }),
        n("Patients with multiple or recurrent strictures, those with active urinary tract infections, complete urethral obliteration on urethroscopy, with pan-anterior strictures, posterior stenosis, failed prior interventions, or lichen sclerotic changes.")
      ]),

      // ── DATA COLLECTION ────────────────────────────────────────────────
      heading("Data Collection Procedure", HeadingLevel.HEADING_1),

      para([
        n("The study will be conducted after approval of the Institutional Ethics Committee and CPSP. A total of 60 patients presenting to the Department of Urology, fulfilling the inclusion criteria, will be enrolled in the study after informed consent. Baseline characteristics like age, obesity, diabetes mellitus, hypertension, smoking and stricture etiology (e.g., iatrogenic, post-infectious, trauma) will be recorded. All patients will undergo confirmatory micturating cystourethrography (MCUG) from the radiology department and reported by consultant radiologist for location (bulbar, penile, membranous) and length (mm) of stricture. Baseline peak urinary flow rate (Qmax\u202f<\u202f15\u00a0ml/sec) will be recorded. Patients will be randomly assigned to Group A (cold-knife) and Group B (holmium laser) through lottery method using sealed opaque envelopes.")
      ]),

      para([
        n("In cold-knife urethrotomy procedure, a cystoscope is passed into the urethra, and a cold knife is used to incise the stricture at the 12 o'clock position to widen the narrowed lumen to restore normal urine flow. While in holmium laser urethrotomy procedure, a laser fiber is passed through a cystoscope, and precise incisions are made in the stricture, usually at the 12 o'clock position, to widen the lumen. Duration of procedure (minutes) will be recorded in both the groups. Post-procedure 20Fr Foley catheter will be placed in all patients. All patients will be discharged after 24\u201348 hours after the procedure, once they are stable. They are advised catheter care, antibiotic course completion, avoidance of heavy exercise and maintenance of good hydration. Post-procedure uroflowmetry will be performed after 30 days and assessor will not be aware of procedures performed. All the data will be recorded on proforma.")
      ]),

      // ── DATA ANALYSIS ──────────────────────────────────────────────────
      heading("Data Analysis", HeadingLevel.HEADING_1),

      para([
        err("SPP"),
        n(" "),
        fix("SPSS"),
        n(" version 23 will be used for data analysis. Normality of numerical data will be assessed through Shapiro-Wilk test. Age, symptom duration, stricture length, and peak urinary flow (Qmax) will be presented as mean and standard deviation (median and IQR if not normally distributed). Obesity, diabetes mellitus, hypertension, smoking and stricture etiology will be presented as frequency and percentages. "),
        err("Post operative"),
        n(" "),
        fix("Post-operative"),
        n(" Qmax between the groups will be compared through independent sample t-test and p-value\u202f<\u202f0.05 will be considered significant. Data will be stratified on age, obesity, diabetes mellitus, hypertension, smoking and stricture etiology. Post-stratification independent sample t-test will be applied to compare Qmax between the treatment groups and p-value\u202f<\u202f0.05 will be taken as significant.")
      ]),

      // ── REFERENCES ─────────────────────────────────────────────────────
      heading("References", HeadingLevel.HEADING_1),

      refPara(1, [n("Payne SR, Anderson P, Spasojević N, Demilow TL, Teferi G, Dickerson D. Male urethral stricture disease: why management guidelines are challenging in low-income countries. BJU Int. 2022;130(2):157-65.")]),
      refPara(2, [n("Bugeja S, Payne SR, Eardley I, Mundy AR. The standard for the management of male urethral strictures in the UK: a consensus document. J Clin Urol. 2021;14(1):10-20.")]),
      refPara(3, [n("Chen C, Qin J, Wang C, Huang H, Li H, Wen Z, et al. Comparison of laser versus cold knife visual internal urethrotomy in the treatment of urethral stricture (stricture length\u202f<\u202f2\u00a0cm): A systematic review and meta-analysis. Medicine. 2024;103(18):e37524.")]),
      refPara(4, [n("Faizan M, Mahboob E, Samad MA, Fatima L, Fatima A, Iqbal A, et al. Safety and efficacy of lasers compared to cold knife in direct visual internal urethrotomy: a systematic review and Meta-analysis. Lasers Med Sci. 2024;39(1):209.")]),
      refPara(5, [n("Cebeci OO. Is endourological intervention a suitable treatment option in the management of iatrogenic thermal ureteral injury? A contemporary case series. BMC Urol. 2022;22(1):137.")]),
      refPara(6, [n("Srilakshmi V, Sasanka KSST. Cold knife urethrotomy vs. laser urethrotomy: a comparative study of outcome in short segment urethral strictures. Int Surg J. 2020;7(4):1047-51.")]),
      refPara(7, [n("Lumen N, Campos-Juanatey F, Dimitropoulos K, Greenwell T, Martins FE, Osman NI, et al. European Association of Urology guidelines on urethral stricture disease (part 1): management of male urethral stricture disease. Eur Urol. 2021;80(2):190-200.")]),
      refPara(8, [n("Aldaqadossi HA, Shaker H, Kotb Y, Abo-Farha M. Efficacy and safety of holmium laser urethrotomy in the management of urethral strictures. Arab J Urol. 2020;18(1):28-33.")]),
      refPara(9, [n("Shaikh MI, Siddiqui A, Rehman A, Hussain I, Memon AR. Comparison of mean peak flow rate among patients undergoing direct visual internal urethrotomy. Pak J Med Health Sci. 2023;17(06):535-7.")]),
      refPara(10, [n("Ali Maged W, Gamal MA, Tawfeles SF. Evaluation of holmium laser versus cold knife in optical internal urethrotomy for the management of urethral stricture. QJM Int J Med. 2021;114(Supplement_1):hcab110-014.")]),

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      para([n("2. \u201cOn third day\u201d \u2192 \u201cOn the third day\u201d (Introduction) \u2013 missing definite article.")]),
      para([n("3. \u201care 24.00\u2026\u201d \u2192 \u201cwere 24.00\u2026\u201d (Introduction) \u2013 tense inconsistency; past tense required for reported study results.")]),
      para([n("4. \u201cThe Sachse Urethrotome, is carefully\u2026\u201d \u2192 comma removed (Introduction) \u2013 erroneous comma between subject and verb.")]),
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