Non-randomized Observational Study Research Articles

Metformin and Cancer: Solutions to a Real-World Evidence Failure.

The quest to repurpose metformin, an antidiabetes drug, as an agent for cancer prevention and treatment, which began in 2005 with an observational study that reported a reduction in cancer incidence among metformin users, generated extensive experimental, observational, and clinical research. Experimental studies revealed that metformin has anticancer effects via various pathways, potentially inhibiting cancer cell proliferation. Concurrently, multiple nonrandomized observational studies reported remarkable reductions in cancer incidence and outcomes with metformin use. However, these studies were shown, in 2012, to be affected by time-related biases, such as immortal time bias, which tend to greatly exaggerate the benefit of a drug. The observational studies that avoided these biases did not find an association. Subsequently, the randomized trials of metformin for the treatment of type 2 diabetes and as adjuvant therapy for the treatment of various cancers, advanced or metastatic, did not find reductions in cancer incidence or outcomes. Most recently, the largest phase 3 randomized trial of metformin as adjuvant therapy for breast cancer, which enrolled 3,649 women with a 5-year follow-up, found no benefit for disease-free survival or overall survival with metformin. This major failure of observational real-world evidence studies in correctly assessing the effects of metformin on cancer incidence and outcomes was caused by preventable biases which, surprisingly, are still prominent in 2022. Rigorous approaches for observational studies that emulate randomized trials, such as the incident and prevalent new-user designs along with propensity scores, avoid these biases and can provide more accurate real-world evidence for the repurposing of drugs such as metformin.

Dosimetric Comparison of Hypofractionated Regimen in Breast Cancer Using Two Different Techniques: Intensity-Modulated Radiation Therapy (IMRT) and Volumetric-Modulated Arc Therapy (VMAT).

Breast cancer treated with adjuvant hypofractionation radiotherapy with two different techniques, i.e., volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) and their effects in terms of loco-regional control and adverse effects in terms of cutaneous, pulmonary, and cardiac outcomes are compared. This is a prospective non-randomized observational study. VMAT and IMRT plan for 30 breast cancer patients who were supposed to receive adjuvant radiotherapy were prepared using a hypofractionation schedule. The plans were dosimetrically evaluated. Dosimetric comparative analysis of IMRT and VMAT in hypofractionated radiotherapy in breast cancer is done and tested whether VMAT has a dosimetric advantage over IMRT. These patients were recruited for a clinical assessment of toxicities. They were followed up for at least three months. On dosimetric analysis, planning target volume (PTV) coverage (PTV_ V95) of both VMAT (96.41 ± 1.31) and IMRT (96.63 ± 1.56) were similar with significantly lower monitor units required with VMAT plans (1,084.36 ± 270.82 vs 1,181.55 ± 244.50, p = 0.043). Clinically, all patients tolerated hypofractionation through VMAT (n = 8) and IMRT (n = 8) satisfactorily in the short term. No cardiotoxicity or appreciable falls in pulmonary function test parameters were observed. Acute radiation dermatitis poses challenges similar to standard fractionation or any other delivery technique. PVT dose, homogeneity, and conformity indices were similar in both VMAT and IMRT groups. In VMAT, there was high-dose sparing of some critical organs like the heart and lungs at the cost of the low-dose baths to these organs. Increased risk of secondary cancer will require a decade-long follow-up study to indict the VMAT technique. As we move toward precision in oncology, "one-size-fits-all" can never be an acceptable dictum. Each patient is unique and therefore we must offer, and the patient must "choose wisely."

Accuracy of pilot balloon palpation for cuff pressure assessment in small versus large sized tubes: a prospective non-randomized observational study

Pilot balloon palpation is still a commonly used method to evaluate cuff pressure of the endotracheal tube after intubation. This study determined whether the size of the tracheal tube influenced the accuracy of pilot balloon palpation. A prospective observational analysis of 208 patients intubated with an endotracheal tube of internal diameter (ID) 6.0 or 8.0 was conducted. An anesthesiologist judged the cuff pressure by manual pilot balloon palpation, and then measured the cuff pressure with a pressure gauge. Cuff pressure exceeding 20–30 cmH2O was defined as false recognition. The intracuff pressure was significantly higher in ID 6.0 tube than in the ID 8.0 tube (41.9 ± 18.8 cmH2O vs. 30.3 ± 11.9 cmH2O, p < 0.001). The number of patients that were mistakenly perceived to have appropriate cuff pressure by pilot balloon palpation was significantly higher in the ID 6.0 group compared to the ID 8.0 group (85 (81.7%) vs. 64 (61.5%), p = 0.001). Therefore, a smaller tube size may further increase risk of inaccurate measurement by pilot balloon palpation and although pressure gauge is recommended for all sizes to maximize accuracy, groups with increased risk factors should be targeted for standardized use of the pressure gauge.

Primary observations of EVO ICL implantation for high myopia with concave iris

PurposeTo investigate the morphological changes of concave iris in myopic patients after EVO implantable collamer lens (ICL) implantation.MethodsEVO ICL candidates with posterior bowing iris were observed using ultrasound biometric microscopy (UBM) in this prospective nonrandomized observational study. Forty patients were enrolled, with 20 patients in the concave iris group and the other 20 patients in the control group. None of the patients underwent laser peripheral iridotomy. All patients received preoperative and postoperative examinations, which included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), subjective manifest refraction and intraocular pressure. UBM was used to observe iris curvature (IC), irido-corneal angle (ICA), posterior chamber angle (PCA), iris-lens contact distance (ILCD), iris-zonule distance (IZD) and ciliary process length (CPL). Anterior chamber angle pigment was observed by gonioscopy. The preoperative and postoperative data were analyzed using SPSS.ResultsThe average follow-up period was 13.3 ± 5.3 months. The mean efficacy indices were 1.10 ± 0.13 and 1.07 ± 0.11 (P = 0.58), and the safety indices were 1.19 ± 0.09 and 1.18 ± 0.17 in the control group and the concave iris group (P = 0.93), respectively. The IOP postoperatively were 14.13 ± 2.02 mmHg and 14.69 ± 1.59 mmHg in control and concave iris groups (P = 0.37). Preoperatively, the concave iris group was presented with greater IC (P < 0.0001), longer ILCD (P < 0.0001), wider ICA (P = 0.004), narrower PCA (P = 0.01), and shorter IZD (P = 0.03) than the control group. In the concave iris group, IC, ILCD and ICA were significantly decreased after ICL implantation (P < 0.0001), while PCA and IZD were significantly increased (P = 0.03 and P = 0.04, respectively). Postoperative IC, ILCD, ICA, PCA and IZD were not statistically different between groups (P > 0.05). There was no significant difference in pigment deposition grades between the two groups (P = 0.37).ConclusionAfter EVO ICL implantation, the morphology of concave iris was significantly improved, which may reduce the risk of intraocular pigment dissemination caused by iris concavity. The concave iris has no impact on the safety of EVO ICL surgery during the follow-up.

State-of-the-art of miliary tuberculosis in children: protocol for a scoping review of the literature

Background: Miliary Tuberculosis (TB) is a rare manifestation of TB described in both adults and children. Pediatirc reports are rare and therefore evidence about diagnostics and management is scarce. Methods: We will start our research in March 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS. The main review question will be “What are the main clinical characteristics and outcomes of pediatric miliary TB reported in the literature?” We will include randomized and non-randomized controlled trials, prospective and retrospective observational studies, performed on children and adolescents (younger than 18 years), hospitalized or not, with a confirmed diagnosis of miliary TB. To report our findings, we will follow Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. Dissemination: The findings of this review will be published in international peer-reviewed journals and presented in pediatric infectious diseases national and international conferences.

Safety and Efficacy of MCA‐M2 Thrombectomy in Delayed Time Window: A Propensity Score Analysis From the STAR Registry

Background Mechanical thrombectomy of middle cerebral artery M2 segment occlusion of the middle cerebral artery has reported safety and efficacy in recent post‐hoc and observational studies. However, there is no known benefit of mechanical thrombectomy for patients with M2 segment occlusions in the delayed time window (&gt;6 hours). Methods The Stroke Thrombectomy and Aneurysm Registry (STAR) is a prospective, multicenter, nonrandomized observational study registry for acute ischemic stroke thrombectomy and aneurysm treatment. We analyzed all patients who underwent mechanical thrombectomy within the late time window (&gt;6 hours from symptom onset) involving isolated M2 occlusions. We used propensity score matching to select a comparison group of patients who underwent mechanical thrombectomy for M1 occlusion in the same time window. Results Of 1083 consecutive patients analyzed, propensity matching yielded 180 well matched M1 and M2 pairs. Baseline demographics were well balanced between the groups (M1 and M2). Alberta stroke program early CT score (7.6±1.7 versus 8.3±1.5; P &lt;0.001) was higher in the M2 group. There was a trend towards less complete recanalization (Thrombolysis in Cerebral Infarction 3) 46.1% versus 39.9% ( P =0.053) in the middle cerebral artery M2 segment cohort. However, successful recanalization (Thrombolysis in Cerebral Infarction 2b‐3) was better in middle cerebral artery M2 segment cohort (85% versus 90.5%; P =0.053). Postprocedural asymptomatic hemorrhage rates were similar (29.4% versus 27.8%; P =0.816), but symptomatic hemorrhage rates were higher in the M1 group (7.2% versus 2.2%; P =0.047). Rates of good clinical outcome (modified Rankin scale 0–2) were similar at final follow‐up (43.9% versus 46.7%; P =0.672). The overall mortality was also similar between the cohorts (12.8% versus 13.9%; P =0.877). Conclusion In our analysis of the Stroke Thrombectomy and Aneurysm Registry, M2 occlusions not only achieved similar rates of recanalization and good functional outcome compared with M1 occlusions in a delayed time window (6–24 hours from last normal) but also had less symptomatic intracranial hemorrhage.

Presepsin and procalcitonin as markers of infectious respiratory diseases in children: a protocol for a scoping review of the literature

Background: Presepsin is a new inflammatory marker used in clinical practice for the diagnosis of severe bacterial infections, which might be used in combination or substitution of other classical indexes such as procalcitonin. Presepsin has been studied mainly in specific categories of patients (generally adults, critically ill patients or neutropenic children) to identify severe bacterial infections and to predict the mortality risk, while the role of this marker in discriminating bacterial from viral infections in otherwise healthy children of different age groups is less examined. This scoping review aims to better explore available evidence around the potential role of presepsin in pediatric respiratory infectious diseases, analyzing its ability to distinguish the severity and type of respiratory pathology and comparing it with a classic inflammation index such as procalcitonin. Methods: We started our research in February 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS. The main review question will be “What is known about the diagnostic role of presepsin and/or procalcitoninin the differential diagnosis of respiratory tract infection’s severity and etiology?” We will include randomized and non-randomized controlled trials, prospective and retrospective observational studies, performed on children and adolescents (younger than 18 years), hospitalized or not, with a confirmed diagnosis of upper and/or lower respiratory infectious disease. We will include children diagnosed with pneumonia, bronchiolitis, bronchitis, croup, and other types of infectious respiratory diseases. To report our findings, we will follow Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. Dissemination: The findings of this review will be published in a peer-reviewed journal and presented in national and international conferences.

Outcomes of Salvage Procedures for Failed Total Ankle Arthroplasty.

The number of total ankle arthroplasty (TAA) procedures increased rapidly in the last years and so have its complications. The main pillars in treating failed TAA are revision total ankle arthroplasty (RTAA), revision total ankle arthrodesis (RAA), or revision tibiotalocalcaneal fusion (RTTC). To evaluate these options, we compared clinical, radiologic, and patient-reported outcomes. A single-center, retrospective review of 111 cases of revision procedures of failed TAA from 2006 to 2020 was performed. Patients undergoing polyethylene exchange and revision of one metallic component were excluded. Demographic data, failure, and survival rates were analyzed. The European Foot and Ankle Society (EFAS) score and radiographic changes in the subtalar joint were evaluated. The average follow-up was 67.89 ± 40.51 months. One hundred eleven patients underwent removal of TAA. The procedures included 40 revisions of both metallic components, 46 revision total ankle arthrodesis and 25 revision tibiotalocalcaneal fusion. The overall failure rate in the cohort was 5.41% (6/111). The failure rate after RAA was 4.35 times higher than that of RTAA, whereas RTTC did not show failures. RTAA and RTTC lead to a 1-year and 5-year survival rate of 100%. RAA resulted in a 1-year survival rate of 90% and a 5-year survival rate of 85%. The mean EFAS score in the cohort was 12.02 ± 5.83. Analysis of the EFAS score showed that RTTC provided the most reliable pain reduction, and RTAA achieved the best gait pattern. RAA resulted in poorer clinical results. Subtalar joint degeneration occurred significantly less in the RTAA group (P = .01). This retrospective study suggests lower failure rates, increased short-term survival and a better clinical outcomes of revision arthroplasty and tibiotalocalcaneal fusion than ankle arthrodesis. Revision arthroplasty is a promising solution in treating failed total ankle arthroplasty considering lower rate of subsequent adjacent joint degeneration. Level III, non-randomized observational study.

Abstract P5-08-11: Objective Comparison of Post-operative Activity after Sentinel Lymph Node Biopsy versus Axillary Lymph Node Dissection Using Wearable Activity Monitors – The ‘BRACELET’ Study

Abstract Introduction Axillary de-escalation is driven by both a desire to minimize injury and a growing awareness of the oncological safety of axillary conservation. However, the evidence of the impact of axillary procedures is largely subjective and based on patient questionnaires. Sensing technologies such as Wearable Activity Monitors (WAM) can acquire functional postoperative data, enabling objective analysis of patients’ physical activity (PA) levels. This technology implementation would help surgeons better comprehend the post-operative recovery phase and provide individualized interventions for patients. We aimed to use WAMs in order to investigate differences in physical recovery between axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) – with a hypothesis that the ALND group has slower recovery compared to SLNB. Methods A single centre, prospective non-randomized observational study was conducted from September 2019 to May 2022. Consecutive patients undergoing breast and axillary surgery were identified from theatre lists. Patients with movement disorders or upper limb impairment and those using mobility devices or aids were excluded. Eligible consented patients wore WAMs (AX3, Axivity, UK – triaxial accelerometer) on both wrists at least one day pre- and up to two weeks post-operatively. The Mann-Whitney U test and the Wilcoxon Signed Rank Test were performed to analyze the PA levels between arms and surgeries. Patient demographics and potential confounders such as concomitant breast/reconstruction surgery were recorded. Results A total of 53 patients were recruited. Greater PA level was observed in the control arm compared to the surgically treated side in both SLNB and ALND groups in week 1 (SLNB: 69.6% vs 61.1%, p=0.006; ALND: 75.3% vs 60.4%, p&amp;lt; 0.001) and 2 (SLNB: 77.6% vs 71.1%, p=0.113; ALND: 81.9% vs 70.2%, p&amp;lt; 0.001) respectively. When comparing activities of the surgically treated side only, the ALND patients had significantly lower PA level compared to SLNB group in post-operative day 7-9 (65.4% vs 72.5%, p=0.035). Subgroup analysis was performed to compare surgically treated side of ‘Mastectomy Only and SLNB’ versus ‘Mastectomy Only and ALND’. PA level was significantly lower in the latter than the former in week 2 (78.5% vs 83.5%, p=0.027). There were no significant differences in demographics between the 2 groups. Conclusion ALND consistently results in decreased PA level compared to SLNB. The findings also demonstrate the longitudinal impact of SLNB, which impacts PA levels, even up to 2 weeks after surgery. Monitoring recovery objectively after breast cancer surgery provides patients and surgeons with more information about the likely outcomes of their treatment and may help them choose the best option, particularly where oncological outcomes are equivocal. This information could also be used to improve outcomes by identifying vulnerable patients who would benefit from early exercise intervention, encouraging physical activity, and keeping track of individualised PA that could be added to the feedback rehabilitation care plan. Citation Format: Nur Amalina Che Bakri, Richard Kwasnicki, Luqman Tenang, Emmanuel Giannas, Kieran Dhillon, Ara Darzi, Daniel Leff. Objective Comparison of Post-operative Activity after Sentinel Lymph Node Biopsy versus Axillary Lymph Node Dissection Using Wearable Activity Monitors – The ‘BRACELET’ Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-11.

Incidence of sacroiliac joint pain after lumbosacral spine fusion: A systematic review

ObjectivesTo determine the incidence of sacroiliac joint (SIJ) pain after lumbosacral spinal fusion. BackgroundPersistent low back pain is a potential source of disability and poor outcomes following lumbar spine fusion. The SIJ has been described as a potential source. However, there is a paucity of data concerning its importance. MethodsThis is a PROSPERO registered systematic review. A systematic search of the English literature was performed in Medline, Embase and Cochrane Library databases. MeSH terms such as Lumbar vertebrae, Sacrum, Spinal Fusion, Pain, Sacrum, Ligaments, Sacroiliac Joint were utilized for the search. Key words such as “sacroiliac dysfunction.mp.” and “sacroiliac complex.mp.” were utilized for the search. Two independent reviewers reviewed articles to determine eligibility for final review and analysis. The Newcastle-Ottawa Scale was used to appraise the quality of all nonrandomized observational studies. Inverse variance weighting with random effects was used to pool data. The GRADE approach, PRISMA workflow and checklists was performed. ResultsTwelve studies were included. All studies were observational and of moderate to low quality. The pooled incidence of sacroiliac joint pain was 15.8%. The pooled incidence of SIJ pain for patients without fusion extending to the sacrum was 15.8%. The pooled incidence of SIJ pain for patients with fusion extending to the sacrum was 32.9%. There was high heterogeneity. ConclusionSIJ pain is a potential cause of persistent pain after lumbar spine surgery. The current literature of poor quality. Patients presenting with pain after lumbosacral spine fusion should be evaluated for SIJ related pain.

No Placebo Effect beyond Regression to the Mean on the Six Minute Walk Test in Pulmonary Arterial Hypertension Trials.

In drug studies, patients are often included when the disease activity is high. This will make any treatment appear to lessen disease activity, although the improvement is biased by selection. This effect is known as regression towards the mean (RTM). We aimed at investigating drug trials in Pulmonary Arterial Hypertension (PAH) using the 6-minute walking distance test (6MWD) as a primary outcome for the phenomenon of RTM. An existing registry of 43 open label studies and 23 randomized controlled trials conducted between 1990 and 2009 was used as the data source. Data analysis was carried out for 18 randomized controlled trials (RCTs) and 24 open label studies out of this registry. Data were analyzed for verum and placebo arms of the RCTs separately, as well as for the open label arms. In the verum arms, the overall effect given as 33.2 m (95% CI: 25.7; 40.6]); 6MWD was slightly lower than the effect in the observational studies, with 44.6 m (95% CI: [25.4; 63.8]). After studying and interpreting the data, we found that regression towards the mean plays only a minor role in PAH studies. In particular, placebo effects in the RCTs were negligibly small, with a mean 6MWD of -2.5 m (95% CI: [-9.8; 4.7]) in the placebo arm. Therefore, our analysis indicates that results of non-randomized observational studies can be regarded as valid tools for gaining valid clinical effects in patients with PAH.

Analgesic Efficacy and Outcomes of Ultrasound-guided Erector Spinae Plane Block in Patients Undergoing Bariatric and Metabolic Surgeries: A Systematic Review.

Erector spinae plane block (ESPB) has been used as an intervention for providing postoperative analgesia in patients undergoing bariatric and metabolic surgeries. After registering the protocol in PROSPERO, randomized controlled trials and nonrandomized observational studies were searched in various databases till July 2022. The primary outcome was 24-h opioid consumption; the secondary outcomes were intraoperative opioid use, pain scores, time to rescue analgesia, and complications. The risk of bias and Newcastle-Ottawa scale were used to assess the quality of evidence. From the 695 studies identified, 6 studies were selected for analysis. The 24-h opioid consumption was significantly lesser in ESPB group when compared to control (mean difference [MD]: -10.67; 95% confidence interval [CI]: -21.03, -0.31, I² = 99%). The intraoperative opioid consumption was significantly less in the ESPB group (MD: -17.75; 95% CI: -20.36, -15.13, I² = 31%). The time to rescue analgesia was significantly more in the ESPB group (MD: 114.36; CI: 90.42, 138.30, I² = 99%). Although pain scores were significantly less at 6 and 24 h in ESPB group (MD: -2.00, 95% CI: -2.49, -1.51; I² = 0% and MD: -0.48; 95% CI: -0.72, -0.24; I² = 48%), at zero and 12 h, the pain scores were comparable (MD: -1.53, 95% CI: -3.06, -0.00, I² = 97% and MD: -0.80; 95% CI: -1.80, 0.20, I² = 88%). Bilateral ESPB provides opioid-sparing analgesia and better pain scores when compared to control. These results should be interpreted with caution due to high heterogeneity among the included studies.

Efficacy and safety of oral tizanidine premedication as pre-emptive analgesia in adult patients undergoing elective surgeries- A systematic review.

Tizanidine is a centrally acting α2 agonist which has been used as a premedication due to its opioid-sparing and sympatholytic properties. This systematic review assessed the safety and feasibility of oral tizanidine. After registering the protocol with PROSPERO (CRD42022368546), randomized controlled trials and non-randomized observational studies were searched in various databases. The primary outcome was intraoperative opioid use; the secondary outcomes were 24-hr opioid consumption, pain scores, time to rescue analgesia, and adverse events. The risk of bias scale was used to assess the quality of evidence. Out of 202 studies identified, five studies fulfilled the inclusion criteria. Intraoperative opioid consumption was significantly less in the tizanidine group (MD: -2.40; 95% CI: -4.22, -0.59; P = 0.010; I2 = 0 %). The 24-hr opioid consumption was comparable between both groups (MD: -42.53, 95% CI: -91.45, 6.39; P = 0.09; I2 = 99%). Time to rescue analgesia was comparable between both groups (MD: 308.22; 95% CI: -263.67, 880.11, P = 0.29, I2 = 100%). Pain scores at 6 and 12 hours were comparable (MD: -1.37; 95% CI: -3.68, 0.94; P = 0.24; I2 = 97%) and (MD: -1.76; 95% CI: -4.06, 0.53; P = 0.13; I2 = 95%); however, at 24 hours the scores were better in the tizanidine group (MD: -1.10; 95% CI: -1.50, -0.69; P < 0.0001 I2 = 0%). Although dry mouth was significantly more in the tizanidine group (MD: 5.35; 95% CI: 1.72, 16.62; P = 0.004; I2 = 0%), postoperative nausea/vomiting and dizziness were comparable. Tizanidine reduces intraoperative opioid consumption without significant adverse events. However, it does not provide effective opioid-sparing analgesia or reduced opioid requirement in the first 24 hours after surgery.

Comparative Study on Short-Term Outcome in Patients Undergoing Pilonidal Sinus Surgery in Tertiary Care

ABSTRACT Background: Pilonidal sinus is a disease that affects young men commonly arising from the hair follicles of the sacrococcygeal area. At present, there is no standardized surgical management available for chronic pilonidal sinus. The purpose of this study is to evaluate wound healing and short-term outcomes in pilonidal sinus patients undergoing modified Limberg flap surgery and lay open for secondary healing after excision in a tertiary care hospital. Patients and Methods: This is a nonrandomized comparative observational study performed at Apollo Hospitals, Chennai, during January 2021 to August 2021. Group A included 25 participants who opted off-midline primary closure using modified Limberg rhomboid flap procedure. Group B included 25 participants who underwent excision of pilonidal sinus and laying the wound open for secondary healing. All patients, in both groups, were seen on the 3rd, 5th, 7th, 15th, and 30th post-operative day. They were followed until complete wound healing. Results: The study showed that the modified Limberg flap closure group had a shorter period of complete wound healing in comparison to the excision and lay-open group but at a cost of prolonged duration of hospitalization. This study shows the significant difference in the period to return to daily activity between Group A and Group B. Postoperative wound complications such as infection and recurrence were seen in Group A. Conclusions: Conventional wide excision of pilonidal sinus and laying it open for secondary healing is advisable in pilonidal sinus disease and be performed as a day-case surgery. For the success of modified Limberg flap closure, prone nursing is recommended.

Performance of Bayesian Propensity Score Adjustment for Estimating Causal Effects in Small Clinical Trials

Propensity score (PS) adjustment can control confounding effects and reduce bias when estimating treatment effects in non-randomized trials or observational studies. PS methods are becoming increasingly used to estimate causal effects, including when the sample size is small compared to the number of confounders. With numerous confounders, quasi-complete separation can easily occur in logistic regression used for estimating the PS, but this has not been addressed. We focused on a Bayesian PS method to address the limitations of quasi-complete separation faced by small trials. Bayesian methods are useful because they estimate the PS and causal effects simultaneously while considering the uncertainty of the PS by modelling it as a latent variable. In this study, we conducted simulations to evaluate the performance of Bayesian simultaneous PS estimation by considering the specification of prior distributions for model comparison. We propose a method to improve predictive performance with discrete outcomes in small trials. We found that the specification of prior distributions assigned to logistic regression coefficients was more important in the second step than in the first step, even when there was a quasi-complete separation in the first step. Assigning Cauchy (0, 2.5) to coefficients improved the predictive performance for estimating causal effects and improving the balancing properties of the confounder.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study

Introduction: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). Methods: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 22^0/7 and 31^6/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. Results: 113 VPI with a mean gestational age of 27 weeks (+/− 2.3 weeks) and mean birth weight of 946 g (+/− 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 22⁰–26⁶ weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 27⁰–32⁰ weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. Conclusion: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

A survey on dairy and dairy products influence on early menarche: A non-randomized analytical cross sectional observational study

Menarche is first menstrual period which is phase of transition from childhood to adulthood. Many studies revealed decline in age of menarche. Background: There is large concern over early puberty. Dairy products are considered as one of the reason for decline in age of puberty due to presence of steroid hormones. Objective: Main objective of this study is to identify whether Dairy & dairy products has any role for early puberty. Methods: An online cross-sectional study has been conducted (between September 2022 to nov-2022) at MNR Homoeopathic medical college & hospital, Sangareddy, Telangana, India using NHANES Diet questionnaire. Results: Weak negative relationship between intake of dairy products consumption for early menarche. Conclusion: Further detailed study with large sample survey is needed to draw the statement whether dairy products has directly proportional ratio in declining the age of puberty.

Systematic Review and Meta-Analysis of Sciatic Nerve Injury in Acetabular Fractures

Background: Acetabular fracture is a challenging orthopaedic injury, usually associated with post-traumatic arthritis, deep vein thrombosis, and sciatic nerve injury (SNI). Therefore, we assess the incidence and outcome of SNI associated with acetabular fractures in this study. Methodology: We applied search keywords across PubMed, clinicaltrail.gov, Scopus, and Cochrane library database from 2002 to March 2022 with the studies reporting SNI associated with acetabular fracture. Patient's demographic details, acetabular fracture type, recoveries rate and time, number of patients with acetabular fracture reporting SNI, and follow-up. Methodological Index for Observational Non-Randomized Studies (MINORS) criteria assessed the quality appraisal of each identified study. Results: This study includes twenty-one studies with a total of 682 patients, 19 iatrogenic SNI, and 44 post-traumatic injuries. Overall incidence of post-traumatic and iatrogenic SNI associated with acetabular fractures was 9% [95% CI: 6%-11%] and 5% [95% CI: 3%-7%] respectively. The overall recoveries rate from iatrogenic SNI and post-traumatic SNI associated with acetabular fracture were 55% (95% CI: 22%-83%) and 68% (95% CI: 53% -81%), respectively. The overall quality score of all included studies was 64.28± 7.43% (R: 56.25 % -81.25%), with seven studies below 60%. In most cases, Recoveries of sciatic nerve injury occur within 2-24 months after any open reduction and internal fixation (ORIF). Conclusion: This review estimates SNI incidence with acetabular fracture and recoveries rates. However, this study fails to report the association of SNI with specific acetabular fracture types due to insufficient reported data across eligible studies

Comparison of above elbow and below elbow immobilisation for conservative treatment of distal end radius fracture in adults: A systematic review and meta-analysis of randomized clinical trials

PurposeThe aim of this study was to analyze if any difference exists on the type of immobilisation (above elbow vs. below elbow) in the conservative treatment of distal end radius fractures in adults. MethodsThe study was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic literature search was performed up to 1st October 2021 in Medline, Embase, Ovid and Cochrane database using the search terms, “distal end radius fractures OR fracture of distal radius”, “conservative treatment OR non-surgical treatment”, “above elbow immobilisation” and “below elbow immobilisation”. Randomized clinical trials written in English, describing outcome of distal end radius fractures in adults by conservative or non-surgical means using above elbow immobilisation or below elbow immobilisation were included and assessed according to the risk of bias assessment (RoB2) tool by Cochrane collaboration. Non-randomized clinical trials, observational studies, retrospective studies, review articles, commentaries, editorials, conference presentations, operative techniques and articles without availability of full text were excluded from this review. The meta-analysis was performed using Review Manager version 5.4.1 (The Cochrane Collaboration, Copenhagen, Denmark). ResultsSix randomized clinical trials were included for quantitative review. High heterogeneity (I2 > 75%) was noted among all the studies. The standard mean difference (MD) between the disability of the arm, shoulder and hand scores in both the groups was 0.52 (95% CI: −0.28 to 1.32) which was statistically non-significant. There was no statistical difference in the radial height (MD = 0.10, 95% CI: −0.91 to 1.12), radial inclination (MD = 0.5, 95% CI: −1.88 to 2.87, palmar tilt (MD =1.06, 95% CI: −0.31 to 2.43) and ulnar variance (MD = 0.05, 95% CI: −0.74 to 0.64). It was observed that shoulder pain occurred more commonly as a complication in above elbow immobilisation and the values were statistically significant (above elbow: 38/92, 41.3%; below elbow: 19/94, 20.2%). ConclusionThis two-armed systematic review on the above elbow or below elbow immobilisation to be used for conservative treatment of the distal end radius fracture in adults resulted in non-significant differences in terms of functional and radiological scores among the 2 groups but significant increase in the complication rates in the above elbow group.

HTA110 The Value of Real-World Evidence (RWE) in Melanoma in Health Technology Assessment (HTA) Appraisals

Increasingly real-world evidence (RWE) is also appraised to support the value of new health technologies that ensures timely patient access. RWE is considered as evidence gathered outside of RCTs and derived from data obtained from non-randomized trials, observational studies, or databases amongst others. This analysis aims to assess the value of RWE in recent HTA appraisals for melanoma drugs in England, France, Canada, Australia, Germany, Scotland, and the Netherlands.