Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians

Bir grup antifungal etkin maddenin tayinine yönelik sıvı kromatografik yöntemlerin geliştirilmesi ve analitik yöntem geçerliliği çalışmaları

Metronidazol (MTR), klotrimazol (CLT), ekonazol (ECO), mikonazol (MCO) ve itrakonazol'ün (ITR) yapay vücut sıvılarında tayinine yönelik HPLC-PDA yöntemi geliştirilmiş ve ICH Q2(R1) kılavuzuna göre yöntem geçerliliği çalışmaları yürütülmüştür. Sırasıyla 1,58; 2,38; 3,16; 4,04 ve 5,58 dakikalık alıkonma zamanlı pikler yüksek çözünürlükle (yaklaşık R>2) ayrılmıştır. Doğrusal derişim aralığı tüm etkin maddeler için 1-50 ppm olarak (R2= 0,9999) sağlanmıştır. MTR, CLT, ECO, MCO ve ITR için kalibrasyon grafiklerine ait denklemler sırasıyla y=0,1119x+0,0066, y=0,6217x–0,067, y=0,3282x–0,0785, y=0,398x–0,0656 ve y=0,359x–0,0913 şeklindedir. Kesinlik parametresi için tüm standartların çoklu enjeksiyonları (n=3) ile 1; 2,5; 5; 10; 25 ve 50 ppm derişimleri için yapılarak sonuçların %RSD değeri hesaplanmıştır. Hesaplanan %RSD değerlerine göre yöntemimiz tüm standartlar için %2,5 şartını sağlamaktadır. MTR, CLT, ECO, MCO ve ITR için belirleme sınırı (LOD) değerleri sırasıyla 0,0107 ppm (6,25x10-8M), 3,22x10-3 ppm (9,34x10-9M), 0,092 ppm (2,07x10-7M), 0,144 ppm (3,01x10-7M) ve 0,105 ppm (1,49x10-7M) düzeylerinde hesaplanmıştır. Aynı etkin maddeler için tayin sınırı (LOQ) değerleri ise sırasıyla 0,173 ppm (1,01x10-6M), 0,262 ppm (7,60x10-7M), 0,863 ppm (1,94x10-6M), 0,865 ppm (1,81x10-6M) ve 0,944 ppm (1,34x10-6M) olarak saptanmıştır. Yapay vücut sıvıları olarak yapay idrar 1 ve 2 (U1 ve U2), tükrük 1 ve 2 (S1 ve S2), mide vasatı (G), barsak vasatı (I), suni barsak vasatı (AI) yapay vücut sıvılarına 40'ar ppm'lik standart ve ayrıca müstahzar karışımları ekilmiş ve geri kazanımları için HPLC-PDA analizleri yapılmıştır. MTR haricinde diğer standartların geri kazanımında en yüksek yüzde değerleri U2, S1 ve S2 yapay vücut sıvılarında gözlemlenmiştir. Görece en düşük geri kazanımlar ise I ve AI yapay vücut sıvılarında görülmektedir. Doğruluk parametresi için yapay vücut sıvılarına 40 ppm standart karışımı ekimi yapılarak (n=3) HPLC ile tayinleri gerçekleştirilmiştir. Tayinler sonrası saptanan düzeylerin ortalaması, standart sapması ve bağıl hata (%) değerleri hesaplanmıştır. Elde edilen sonuçlara göre, AI barsak vasatı haricinde genel olarak diğer yapay vücut sıvılarında kabul edilebilir eksi veya artı yönde yapılmış bağıl hata oranları ile doğruluk parametresi sağlanmıştır. Literatürde triazol yapılı antifungal ilaç etkin maddelerinin tayini için geliştirilmiş yeterli sayıda HPLC-PDA yöntemi olmakla birlikte tezimizde çalışılan antifungal etkin maddeler olan MTR, CLT, ECO, MCO ve ITR'nin eş-zamanlı tayin edildiği bir HPLC-PDA yöntemine rastlanılmamıştır.HPLC-PDA method, for the determination of metronidazole (MTR), clotrimazole (CLT), econazole (ECO), miconazole (MCO) and itraconazole (ITR) in simulated artificial body fluids, is developed and method validation studies were performed in accordance to ICH Q2(R1) guideline. Peaks with the retention times of 1.58, 2.38, 3.16, 4.04 and 5.58 minutes, respectively were separated with high resolution (approximate R2>2). Linear concentration range was obtained as 1-50 ppm (R2= 0,9999) for entire drug substances. Equations of the calibration graphs for MTR, CLT, ECO, MCO and ITR were as y=0.1119x+0.0066, y=0.6217x–0.067, y=0.3282x–0.0785, y=0.398x–0.0656 and y=0.359x–0.0913, respectively. For the precision parameter, multiinjections (n=3) of entire standards at 1, 2.5, 5, 10, 25 and 50 ppm concentrations were performed and RSD% values of the findings were calculated. According to calculated RSD% values, our method provides 2.5% requirement for entire standards. Limit of detection (LOD) values for MTR, CLT, ECO, MCO and ITR were calculated as 0.0107 ppm (6.25x10-8M), 3.22x10-3 ppm (9.34x10-9M), 0.092 ppm (2.07x10-7M), 0.144 ppm (3.01x10-7M) and 0.105 ppm (1.49x10-7M) levels, respectively. For the same drug substances limit of quantification (LOQ) values were determined as 0.173 ppm (1.01x10-6M), 0.262 ppm (7.60x10-7M), 0.863 ppm (1.94x10-6M), 0.865 ppm (1.81x10-6M) and 0.944 ppm (1.34x10-6M), respectively. Standards and separately commercial drugs mixture of 40 ppm were spiked into artificial urine 1 and 2 (U1 and U2), saliva 1 and 2 (S1 and S2), gastric juice (G), intestinal juice (I), artificial intestinal juice (AI) as artificial body fluids, and HPLC-PDA analysis were conducted for the recoveries. Highest recovery percentages of standards except MTR were observed in U2, S1 and S2 artificial body fluids. Relatively the lowest recoveries were observed in I and AI artificial body fluids. For the accuracy parameter 40 ppm standards mixture was spiked into artifiacial body fluids (n=3) and determined by HPLC. After determinations averages, standart deviations and relative errors (%) of the determined levels were calculated. In accordance to obtained results, for entire artificial body fluids except AI, accuracy parameter was achieved with reasonable negative and positive relative errors Even though sufficient amount of HPLC-PDA methods, developed for the determination of triazole stuctured antifungal drug substances, are present in literature no HPLC-PDA method was met for the simultaneous determination of MTR, CLT, ECO, MCO and ITR as the antifungal drug substances studied in our thesis