OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in SCD-related proliferative retinopathy.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched the following resources (26 June 2022): Latin American and Caribbean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.
SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults with SCD.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and risk of bias of the included trials; we extracted and analysed data, contacting trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria.
MAIN RESULTS: We included three trials (414 eyes of 339 children and adults) comparing the efficacy and safety of laser photocoagulation to no therapy in people with PSR. There were 160 males and 179 females ranging in age from 13 to 67 years. The trials used different laser photocoagulation techniques; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; a two-centre trial employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre; while a third trial employed focal scatter laser photocoagulation using argon laser. The mean follow-up periods were 21 to 32 months in one trial, 42 to 47 months in a second, and 48 months in the third. Two trials had a high risk of allocation bias due to the randomisation method for participants with bilateral disease; the third trial had an unclear risk of selection bias. One trial was at risk of reporting bias. Given the unit of analysis is the eye rather than the individual, we chose to report the data narratively. Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported no difference between groups for complete regression of PSR: 30.2% in the laser group and 22.4% in the control group. The same trial also reported no difference between groups in the development of new PSR: 34.3% of lasered eyes and 41.3% of control eyes (very low-certainty evidence). The two-centre trial using feeder vessel coagulation, only presented data at follow-up for one centre (mean period of nine years) and reported the development of new sea fan in 48.0% in the treated and 45.0% in the control group; no statistical significance (P = 0.64). A third trial reported regression in 55% of the laser group versus 28.6% of controls and progression of PSR in 10.5% of treated versus 25.7% of control eyes. We graded the evidence for these two primary outcomes as very low-certainty evidence. The sectoral scatter laser photocoagulation trial reported visual loss in 3.0% of treated eyes (mean follow-up 47 months) versus 12.0% of controlled eyes (mean follow-up 42 months) (P = 0.019). The feeder vessel coagulation trial reported visual loss in 1.14% of the laser group and 7.5% of the control group (mean follow-up 26 months at one site and 32 months in another) (P = 0.07). The focal scatter laser photocoagulation trial (mean follow-up of four years) reported that 72/73 eyes had the same visual acuity, while visual loss was seen in only one eye from the control group. We graded the certainty of the evidence as very low. The sectoral scatter laser trial detected vitreous haemorrhage in 12.0% of the laser group and 25.3% of control with a mean follow-up of 42 (control) to 47 months (treated) (P ≤ 0.5). The two-centre feeder vessel coagulation trial observed vitreous haemorrhage in 3.4% treated eyes (mean follow-up 26 months) versus 27.5% control eyes (mean follow-up 32 months); one centre (mean follow-up nine years) reported vitreous haemorrhage in 1/25 eyes (4.0%) in the treatment group and 9/20 eyes (45.0%) in the control group (P = 0.002). The scatter laser photocoagulation trial reported that vitreous haemorrhage was not seen in the treated group compared to 6/35 (17.1%) eyes in the control group and appeared only in the grades B and (PSR) stage III) (P < 0.05). We graded evidence for this outcome as low-certainty. Regarding adverse effects, only one occurrence of retinal tear was reported. All three trials reported on retinal detachment, with no significance across the treatment and control groups (low-certainty evidence). One trial reported on choroidal neovascularization, with treatment with xenon arc found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow-up of three years or more. The included trials did not report on other adverse effects or quality of life.
AUTHORS' CONCLUSIONS: Our conclusions are based on the data from three trials (two of which were conducted over 30 years ago). Given the limited evidence available, which we assessed to be of low- or very low-certainty, we are uncertain whether laser therapy for sickle cell retinopathy improves the outcomes measured in this review. This treatment does not appear to have an effect on clinical outcomes such as regression of PSR and development of new incidences. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors (VEGFs) . Patient-important outcomes as well as cost-effectiveness should be addressed.
Methods: Pseudopregnancy (pc) was induced in cyclic Sprague-Dawley rats by sterile mating. Subcutaneous injection of nicotine tartrate (7.5 mg/kg/day) was scheduled from day 1 through day 5, day 5 through day 9 or day 1 through day 9 of pc. In another group of pseudopregnant rats, concomitant treatment of nicotine tartrate concurrently with progesterone (2 mg/day) was scheduled from day 1 through day 9 pc. Control groups received subcutaneous injections of vehicle only. Endometrial decidualization was induced on day 5 pc. On day 10 pc, animals were sacrificed.The degree of decidual growth and circulating levels of estrogen and progesterone were measured.
Results: The decidual growth in all the first three nicotine-treated groups of animals was significantly reduced, particularly in the animals treated with nicotine from day 1 through day 9 pc. Plasma estrogen levels were significantly elevated in animals treated with nicotine from day 1 through day 9 pc. Conversely, levels of plasma progesterone were found to be significantly attenuated in the same group of nicotine-treated animals compared to controls. Exogenous replacement of progesterone, however, caused a higher degree of endometrial decidualization compared to the nicotine-treated group but it was slightly less than when compared to control.
Conclusions: In conclusion, nicotine-induced progesterone deficiency with a corresponding elevation of estrogen may possibly attenuate the degree of endometrial decidualization in pseudopregnant rats.
METHODS: A cross-sectional study was conducted from September 2020 to March 2021 in Ophthalmology Clinic Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM). Subjects diagnosed with center-involved DME aged between 20 to 80 years who experienced delayed anti-VEGF injection were recruited. Level of depression, anxiety and stress were assessed using DASS-21 questionnaire. Statistical analysis using non-parametric tests were performed to determine the relationship between the DASS-21 score and duration of last injection, in those whose vision was affected by delayed injection and the relationship to the impact of COVID-19 pandemic. Statistical significance was denoted as p < 0.05.
RESULTS: A total of 86 respondents with median age of 69 years old participated in this study. Most respondents were Malays (n = 47,54.7%) males (n = 51, 59.3%), had education up to secondary level (n = 37, 43%), unemployed (n = 78, 90.7%), married (n = 72, 83.7%) and living with their family (n = 82, 95.3%). The number of intravitreal injections received was at least three times among the respondents (n = 81, 94.2%). More than half of the respondents (n = 46, 53.5%) had been postponed for more than 12 weeks and felt that their vision was affected after delayed intravitreal injection (n = 47, 54.7%). Most of the subjects did not experience depression, anxiety, or stress. However, there was a significant level of stress scores among those with delayed injection of 9 to 12 weeks (p = 0.004), and significant anxiety (p = 0.029) and stress (p = 0.014) scores found in subjects with vision affected due to delayed treatment.
CONCLUSION: The level of anxiety and stress can be significant in DME patients who experienced delay in intravitreal anti-VEGF treatment. Assessment of psychosocial impacts is important to identify early mental health issues potentially leading to the onset of psychiatry illness, thus early intervention is indispensable.
OBJECTIVE: The aim of this study was to determine the optimal injection site for botulinum neurotoxin injections in the submandibular gland.
MATERIALS AND METHODS: Anatomical considerations when injecting botulinum neurotoxin into the submandibular gland were determined using ultrasonography. The thickness of the submandibular gland, its depth from the skin surface, and the location of the vascular bundle were observed bilaterally in 42 participants. Two cadavers were dissected to measure the location of the submandibular gland corresponding to the ultrasonographic observation.
RESULTS: The thickest part of the submandibular gland measured 11.12 ± 2.46 in width with a depth of 4.63 ± 0.76. At the point where it crosses the line of the lateral canthus, it measured 5.53 ± 1.83 in width and 8.73 ± 1.64 in depth.
CONCLUSION: The authors suggest optimal injection sites based on external anatomical landmarks. These guidelines aim to maximize the effects of botulinum neurotoxin therapy by minimizing its deleterious effects, which can be useful in clinical settings.
OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults.
SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence.
MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics.
AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.
METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes.
RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.
METHODOLOGY: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique.
RESULTS: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p
MATERIALS AND METHODS: This was a pilot study of N=50 women, who were planning for IVF treatment in University Malaya Medical Centre, Kuala Lumpur, Malaysia from July to December 2023. Women without prior nutritional treatment were consented and assigned to either the multinutrient supplementation (Omega 3, coenzyme Q10, folic acid, selenium, vitamin E, catechins) as the study group or 5mg folic acid daily as control group for at least a month prior to their IVF treatment. All women were treated using an antagonist protocol and ovarian stimulation was started with 200 -300IU of urinary HMG and or recombinant FSH. Antagonists (Ganirelix) commenced when the leading follicle reached a diameter of 11 mm. Triggering with hCG or GnRH agonist when at least 3 follicles of 17 mm in diameter were achieved. Oocyte retrieval was performed 36th hour after trigger. Conventional IVF/ICSI was used for fertilisation. All parameters recorded and analysed using SPSS.
RESULTS: The mean age (36.44 ± 3.33 vs 35.32 ± 3.47 years) and body mass index (25.28 ± 4.12 vs 24.80 ± 4.36 kg/m2) of women in multinutrient supplementation group was similar to control group. The Follicular Output Rate (FORT) in women on multinutrient supplementation showed a trend towards benefit compared to control group, although it is not statistically significant (68.12 ± 19.47 vs 64.91 ± 20.06, p=0.493). The mean number of MII oocytes retrieved from mature follicles and number of good quality embryo on day 3 after fertilisation were not statistically significant between the two groups (6.65 ±3.84 vs 6.09 ± 3.01, p=0.626 and 4.00 ± 3.10 vs 3.45 ± 2.30, p=0.549, respectively). In addition, there were no differences in endometrial thickness before embryo transfer in both groups (10.35 ± 1.32mm vs 10.36 ± 2.04mm, p=0.320). However, the total dose of follicle stimulating hormone and duration of controlled ovarian stimulation were lower in the study group compared to control group (2410 ± 656.82 IU vs 2706.82 ± 536.15 IU, p= 0.119 and 8.90 ± 2.13 days vs 9.68 ± 1.29 days, p=0.164, respectively).
CONCLUSION: A multinutrient supplementation given for a minimum of 28 days, may have a positive effect on FORT and lower use of gonadotropin. More and larger sample research is warranted to prove this effect.