Nevin Manimala

Hum Reprod. 2021 Apr 30:deab093. doi: 10.1093/humrep/deab093. Online ahead of print.

ABSTRACT

STUDY QUESTION: Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone?

SUMMARY ANSWER: Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone.

WHAT IS KNOWN ALREADY: Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET.

STUDY DESIGN, SIZE, DURATION: Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks’ gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints.

MAIN RESULTS AND THE ROLE OF CHANCE: The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99-1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01-1.68), P = 0.042), with a statistically significant lower rate of miscarriage at <12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32-0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group.

LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice.

STUDY FUNDING/COMPETING INTERESTS: This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant.

TRIAL REGISTRATION NUMBER: NCT0399876.

PMID:33930124 | DOI:10.1093/humrep/deab093

Europace. 2021 Apr 30:euab022. doi: 10.1093/europace/euab022. Online ahead of print.

ABSTRACT

AIMS: Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). Data on the efficacy of catheter ablation of AF in HCM patients are sparse.

METHODS AND RESULTS: Observational multicentre study in 137 HCM patients (mean age 55.0 ± 13.4, 29.1% female; 225 ablation procedures). We investigated (i) the efficacy of catheter ablation for AF beyond the initial 12 months; (ii) the available risk scores, stratification schemes and genotype as potential predictors of arrhythmia relapse, and (iii) the impact of cryoballoon vs. radiofrequency in procedural outcomes. Mean follow-up was 43.8 ± 37.0 months. Recurrences after the initial 12-month period post-ablation were frequent, and 24 months after the index procedure, nearly all patients with persistent AF had relapsed, and only 40% of those with paroxysmal AF remained free from arrhythmia recurrence. The APPLE score demonstrated a modest discriminative capacity for AF relapse post-ablation (c-statistic 0.63, 95% CI 0.52-0.75; P = 0.022), while the risk stratification schemes for sudden death did not. On multivariable analysis, left atrium diameter and LV apical aneurysm were independent predictors of recurrence. Fifty-eight patients were genotyped; arrhythmia-free survival was similar among subjects with different gene mutations. Rate of procedural complications was high (9.3%), although reducing over time. Outcome for cryoballoon and radiofrequency ablation was comparable.

CONCLUSION: Very late AF relapses post-ablation is common in HCM patients, especially in those with persistent AF. Left atrium size, LV apical aneurysm, and the APPLE score might contribute to identify subjects at higher risk of arrhythmia recurrence. First-time cryoballoon is comparable with radiofrequency ablation.

PMID:33930121 | DOI:10.1093/europace/euab022

Anesthesiology. 2021 Apr 30. doi: 10.1097/ALN.0000000000003797. Online ahead of print.

ABSTRACT

BACKGROUND: Evoked potential monitoring is believed to prevent neurologic injury in various surgical settings; however, its clinical effect has not been scrutinized. It was hypothesized that an automated nerve monitor can minimize intraoperative nerve injury and thereby improve clinical outcomes in patients undergoing shoulder arthroplasty.

METHODS: A prospective, blinded, parallel group, superiority design, single-center, randomized controlled study was conducted. Study participants were equally randomized into either the automated nerve-monitored or the blinded monitored groups. The primary outcome was intraoperative nerve injury burden as assessed by the cumulative duration of nerve alerts. Secondary outcomes were neurologic deficits and functional scores of the operative arm, and the quality of life index (Euro Quality of life-5 domain-5 level score) at postoperative weeks 2, 6, and 12.

RESULTS: From September 2018 to July 2019, 213 patients were screened, of whom 200 were randomized. There was no statistically significant difference in the duration of nerve alerts between the automated nerve-monitored and control groups (median [25th, 75th interquartile range]: 1 [0, 18] and 5 [0, 26.5]; Hodges-Lehman difference [95% CI]: 0 [0 to 1] min; P = 0.526). There were no statistically significant differences in secondary outcomes between groups. However, in the ancillary analysis, there were reductions in neurologic deficits and improvements in quality of life index occurring in both groups over the course of the study period.

CONCLUSIONS: Protection from nerve injury is a shared responsibility between surgeons and anesthesiologists. Although a progressive improvement of clinical outcomes were observed over the course of the study in both groups as a consequence of the real-time feedback provided by the automated nerve monitor, this trial did not demonstrate that automated nerve monitoring by itself changes important clinical outcomes compared with no monitoring.

PMID:33930115 | DOI:10.1097/ALN.0000000000003797

PLoS One. 2021 Apr 30;16(4):e0251084. doi: 10.1371/journal.pone.0251084. eCollection 2021.

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) kills millions of people globally; it is worse in pregnant women. HBV and Human Immune Virus (HIV) co-infection is associated with increased liver diseases such as cirrhosis and hepatocellular carcinoma. This study aimed at identifying the determinants of HBV infection among HIV-positive pregnant women.

METHODS: A multicentre unmatched case-control study was conducted among 109 cases (HBV/HIV co-infected) and 327 controls (HIV positive) pregnant women in seven hospitals of the Eastern Amhara region. Interview and chart review data collection techniques were employed by trained personnel. A binary logistic regression model was used to identify independent predictors of hepatitis B virus infection. Variables with a p-value of <0.05 and 95% confidence interval for odds ratio not containing 1 considered independent predictors of HBV infection.

RESULTS: The findings of this study revealed that history of STI [AOR, 1.97, 95%CI, 1.09-3.56], hospital admission [AOR, 3.08, 95%CI, 1.69-5.61], traditional delivery care [AOR, 3.31, 95%CI, 1.72-6.37], family history of HBV [AOR, 3.33, 95%CI, 1.72-6.37], presence of opportunistic infections [AOR, 0.23, 95%CI, 0.12-0.58], viral load [AOR, 7.58, 95%CI, 3.18-8.01], CD4 count [AOR, 2.15, 95% CI, 1.01-4.59], anaemia [AOR, 3.07, 95% CI, 1.71-5.51] and unsafe sex [AOR, 1.98, 95%CI, 1.09-3.61] had a statistically significant association with HBV infection.

CONCLUSIONS: Several exposure variables had statistically significant association with HBV infection. High Viral Load appeared to be the largest predictor of HBV infection in HIV patients. Therefore, targeted interventions such as behavioral change intervention for unsafe sex and STI should be in place, and screening tests and treatment at the early stage of conception for both partners is necessary.

PMID:33930097 | DOI:10.1371/journal.pone.0251084

PLoS One. 2021 Apr 30;16(4):e0251030. doi: 10.1371/journal.pone.0251030. eCollection 2021.

ABSTRACT

A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤ 6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤ 6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.

PMID:33930089 | DOI:10.1371/journal.pone.0251030

PLoS Pathog. 2021 Apr 30;17(4):e1009560. doi: 10.1371/journal.ppat.1009560. Online ahead of print.

ABSTRACT

Herpes-Simplex Virus 1 (HSV-1) infects most humans when they are young, sometimes with fatal consequences. Gene expression occurs in a temporal order upon lytic HSV-1 infection: immediate early (IE) genes are expressed, then early (E) genes, followed by late (L) genes. During this infection cycle, the HSV-1 genome has the potential for exposure to APOBEC3 (A3) proteins, a family of cytidine deaminases that cause C>U mutations on single-stranded DNA (ssDNA), often resulting in a C>T transition. We developed a computational model for the mutational pressure of A3 on the lytic cycle of HSV-1 to determine which viral kinetic gene class is most vulnerable to A3 mutations. Using in silico stochastic methods, we simulated the infectious cycle under varying intensities of A3 mutational pressure. We found that the IE and E genes are more vulnerable to A3 than L genes. We validated this model by analyzing the A3 evolutionary footprints in 25 HSV-1 isolates. We find that IE and E genes have evolved to underrepresent A3 hotspot motifs more so than L genes, consistent with greater selection pressure on IE and E genes. We extend this model to two-step infections, such as those of polyomavirus, and find that the same pattern holds for over 25 human Polyomavirus (HPyVs) genomes. Genes expressed earlier during infection are more vulnerable to mutations than those expressed later.

PMID:33930088 | DOI:10.1371/journal.ppat.1009560

PLoS One. 2021 Apr 30;16(4):e0250860. doi: 10.1371/journal.pone.0250860. eCollection 2021.

ABSTRACT

In this laboratory study, we assessed the resistance to microvacuole (glistening) formation in hydrophobic intraocular lenses (IOLs). Glistenings were induced in five lenses each of five different hydrophobic acrylic IOL models, using an established in vitro laboratory model: 800C (Rayner, Worthing, UK), AcrySof SN60WF (Alcon, Fort Worth, USA), Tecnis ZCB00 (Johnson & Johnson Vision, Santa Ana, USA), Vivinex XY1 (Hoya, Tokyo, Japan) and CT Lucia 611P (Zeiss, Oberkochen, Germany). We evaluated the number of microvacuoles per square millimeter (MV/mm2) in the central part of each IOL. Results were analyzed statistically, and mean glistening numbers were ranked, with the highest in the SN60WF which had 66.0 (±45.5) MVs/mm, followed by the 611P with 30.7 (±8.4) MVs/mm2. The 800C and XY1 showed comparable values of 2.0 (±3.6) and 2.7 (±2.4) MVs/mm2, respectively. ZCB00 had the lowest number with 0.9 (±0.6) MVs/mm2. This study shows that the resistance to glistening formation differs depending on the hydrophobic acrylic copolymer composition of the IOL material. Some IOLs from current clinical use are still prone to develop glistenings whereas others, including the ZCB00, 800C and XY1 show high resistance to microvacuole formation.

PMID:33930084 | DOI:10.1371/journal.pone.0250860

PLoS One. 2021 Apr 30;16(4):e0250941. doi: 10.1371/journal.pone.0250941. eCollection 2021.

ABSTRACT

BACKGROUND: Central venous access (CVA) is a frequent procedure taught in medical residencies. However, since CVA is a high-risk procedure requiring a detailed teaching and learning process to ensure trainee proficiency, it is necessary to determine objective differences between the expert’s and the novice’s performance to guide novice practitioners during their training process. This study compares experts’ and novices’ biomechanical variables during a simulated CVA performance.

METHODS: Seven experts and seven novices were part of this study. The participants’ motion data during a CVA simulation procedure was collected using the Vicon Motion System. The procedure was divided into four stages for analysis, and each hand’s speed, acceleration, and jerk were obtained. Also, the procedural time was analyzed. Descriptive analysis and multilevel linear models with random intercept and interaction were used to analyze group, hand, and stage differences.

RESULTS: There were statistically significant differences between experts and novices regarding time, speed, acceleration, and jerk during a simulated CVA performance. These differences vary significantly by the procedure stage for right-hand acceleration and left-hand jerk.

CONCLUSIONS: Experts take less time to perform the CVA procedure, which is reflected in higher speed, acceleration, and jerk values. This difference varies according to the procedure’s stage, depending on the hand and variable studied, demonstrating that these variables could play an essential role in differentiating between experts and novices, and could be used when designing training strategies.

PMID:33930076 | DOI:10.1371/journal.pone.0250941

J Cataract Refract Surg. 2021 Apr 5. doi: 10.1097/j.jcrs.0000000000000668. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the difference in anterior chamber depth (ACD) after uneventful cataract surgery between two hydrophobic acrylic single-piece intraocular lenses (IOLs) with different material properties.

SETTING: Hanusch Hospital, Vienna, Austria DESIGN:: Single-center, bilateral randomized paired-eye controlled study METHODS:: Patients scheduled for bilateral cataract surgery were randomized to receive the Clareon IOL in one eye and the AcrySof IQ IOL (both Alcon Laboratories Inc.) in the contralateral eye. Preoperatively a slit lamp examination, optical biometry (IOLMaster 700, Carl Zeiss Meditec AG), refraction and visual acuity measurements were performed. ACD was assessed 1 hour and 1 week after surgery as well as with additional measurement of uncorrected (UDVA) and corrected distance visual acuity (CDVA) 6 months postoperatively.

RESULTS: Eighty eyes of 40 patients were analyzed in this study. ACD at the 6-month follow-up was 3.94 ± 0.30 mm for the Clareon IOL and 3.91 ± 0.32 mm for the AcrySof IQ IOL (P=.08). Statistically significant differences in the ACD shift between both IOLs were detected between 1 week and 6 months (P=.04) and 1 hour to 6 months (P=.04). There were no significant differences between both IOLs in UDVA (P=.78), in CDVA (P=.59) and in spherical equivalent (SE, P=.39) at the 6-month visit. The mean absolute error between the measured and the aimed SE was not significant (P=.97).

CONCLUSIONS: There was no clinically relevant difference in ACD between the Clareon IOL and the AcrySof IQ IOL in patients after uneventful cataract surgery. Both IOLs yielded good refraction and visual acuity outcomes.

PMID:33929807 | DOI:10.1097/j.jcrs.0000000000000668

J Cataract Refract Surg. 2021 Apr 5. doi: 10.1097/j.jcrs.0000000000000669. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to determine the prevalence of keratoconus (KC) in the students and faculty members (aged ≥18 and ≤30 years) studying/working at the Medical and Health Sciences faculties of Eskişehir Osmangazi University.

SETTING: Eskişehir Osmangazi University DESIGN:: Prevalence study METHODS:: Subjects were randomly selected to undergo KC screening using a proportional stratified sampling method. Out of the 648 invited subjects, 585 (90.3%) responded to the invitation. The demographic data, medical/family history and habits of the subjects were collected using a standardized questionnaire. Subjects were classified as KC, ectasia susceptibility, and normal based on the corneal tomography. The chi-square and Kruskal-Wallis tests were used for the analysis of categorical variables and parametric values, respectively. Risk factors for KC were determined using logistic regression analysis.

RESULTS: The prevalence of KC was 2,393/100,000 (2.4%, 95% CI: 1.3%-4%), whereas that of ectasia susceptibility was 1,538/100,000 (1.5%, 95% CI: 0.7%-2.9%). Although the prevalence was much higher in male (4%, 95% CI: 1.7%-7.7%) than in female (1.6%, 95% CI: 1.1%-4.4%) the difference was not statistically significant (p=0.09). The majority (78.6%, n=11) of KC patients were unaware of their disease. Eye rubbing (OR:3.53, p=0.024) and consanguineous marriage (OR:12.87, p=0.032) were independent risk factors for KC.

CONCLUSION: This is the first population-based KC prevalence study in a randomized sample conducted in Turkey. The prevalence of KC in Turkey was much higher than in European countries but similar to neighboring countries in the Middle East. Eye rubbing and history of consanguineous marriage were significant risk factors.

PMID:33929805 | DOI:10.1097/j.jcrs.0000000000000669