Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis in fetal life. Recently, researchers have attempted to use anti-VEGF agents for the treatment of retinopathy of prematurity ...(ROP), a vasoproliferative disorder. There is currently uncertainty regarding the safety and efficacy of these agents in preterm infants with ROP.
To evaluate the efficacy and safety of anti-VEGF drugs when used either as monotherapy, i.e. without concomitant cryotherapy or laser therapy or in combination with planned cryo/laser therapy in preterm infants with type 1 ROP (defined as zone I any stage with plus disease, zone I stage 3 with or without plus disease or zone II stage 2 or 3 with plus disease).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (1966 to January 1, 2016), EMBASE (1980 to January 1, 2016), CINAHL (1982 to January 1, 2016), conference proceedings, and previous reviews.
Randomised or quasi-randomised controlled trials that evaluated the efficacy and safety of administration, or both, of anti-VEGF agents compared with conventional therapy in premature infants with ROP.
We used standard Cochrane and Cochrane Neonatal methods for data collection and analysis.
Three trials, in which 239 infants participated, fulfilled the inclusion criteria. Two trials compared intravitreal bevacizumab with conventional laser therapy (monotherapy) while the third compared intravitreal pegaptanib plus laser treatment with laser and cryotherapy (combination therapy) in infants with type 1 ROP.Of the two studies that evaluated intravitreal bevacizumab, one randomized infants while the other randomized eyes of the infants to the intervention and control groups. The former did not report any difference in the incidence of complete or partial retinal detachment between the groups (143 infants; RR 1.04, 95% CI 0.21 to 5.13; RD 0.00, 95% CI -0.06 to 0.07; very low quality evidence) but reported a significant reduction in the risk of refractive errors - very high myopia - at 30 months of age (211 eyes; RR 0.06, 95% CI 0.02 to 0.20; RD -0.40, 95% CI -0.50 to -0.30; low quality evidence) and recurrence of ROP by 54 weeks' postmenstrual age (143 infants; RR 0.22, 95% CI 0.08 to 0.62; RD -0.20, 95% CI -0.31 to -0.09; moderate quality evidence) in the bevacizumab group. The study found no difference in the risk of mortality before discharge from the hospital (150 infants; RR 1.50; 95% CI 0.26 to 8.75; RD 0.01; 95% CI -0.04 to 0.07; low quality evidence), mortality at 30 months of age (150 infants; RR 0.86, 95% CI 0.30 to 2.45; RD -0.01; 95% CI -0.10 to 0.08; low quality evidence), corneal opacity requiring corneal transplant (286 eyes; RR 0.34, 95% CI 0.01 to 8.26; RD -0.01; 95% CI -0.03 to 0.02; very low quality evidence), or lens opacity requiring cataract removal (286 eyes; RR 0.15, 95% CI 0.01 to 2.79; RD -0.02; 95% CI -0.05 to 0.01; very low quality evidence). The second trial that randomized eyes of the infants did not find any difference in the risk of complete retinal detachment between the eyes randomized to bevacizumab and those that were randomized to laser therapy (13 eyes; RR 0.33, 95% CI 0.01 to 7.50; RD -0.08, 95% CI -0.27 to 0.11).When used in combination with laser therapy, intravitreal pegaptanib was found to reduce the risk of retinal detachment when compared to laser/cryotherapy alone (152 eyes; RR 0.26, 95% CI 0.12 to 0.55; RD -0.29, 95% CI -0.42 to -0.16; low quality evidence). The incidence of recurrence of ROP by 55 weeks' postmenstrual age was also lower in the pegaptanib + laser therapy group (76 infants; RR 0.29, 95% CI 0.12 to 0.7; RD -0.35, 95% CI -0.55 to -0.16; low quality evidence). There was no difference in the risk of perioperative retinal haemorrhages between the two groups (152 eyes; RR 0.62, 95% CI 0.24 to 1.56; RD -0.05, 95% CI -0.16 to 0.05; very low quality evidence). The risk of delayed systemic adverse effects with either of the drugs is, however, not known.
Intravitreal bevacizumab reduces the risk of refractive errors during childhood when used as monotherapy while intravitreal pegaptanib reduces the risk of retinal detachment when used in conjunction with laser therapy in infants with type 1 ROP. Quality of evidence was, however, low for both the outcomes because of the risk of detection and other biases. Effect on other critical outcomes and, more importantly, the long-term systemic adverse effects of the drugs are not known. The insufficient data precludes strong conclusions favouring routine use of intravitreal anti-VEGF agents in preterm infants with type 1 ROP.
Further studies are needed to evaluate the effect of anti-VEGF agents on structural and functional outcomes in childhood and delayed systemic adverse effects such as myocardial dysfunction and adverse neurodevelopmental outcomes.
Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID‐19) pandemic begun. The objective of ...this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS‐CoV‐2 infection. All adult COVID‐19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID‐19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID‐19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio OR: 0.28; 95% confidence interval CI: 0.09–0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99–0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5–37.6; p = .01) remained significant. In this retrospective study of COVID‐19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.
Highlights
Anosmia and dysgeusia are frequent findings in SARS‐CoV2 infections.
It was noted in more than 1/5th of those infected.
Absence of rhinitis, low platelet and elevated creatinine were associated with these symptoms.
Purpose
To compare the effect of ‘intermittent’ central venous oxygen saturation (ScvO
2
) monitoring with ‘continuous’ ScvO
2
monitoring on shock resolution and mortality in children with septic ...shock.
Methods
Primary outcome was the achievement of therapeutic goals or shock resolution in the first 6 h. We randomly assigned children < 17 years’ age with septic shock to ‘intermittent ScvO
2
’ or ‘continuous ScvO
2
’ groups. All children were subjected to subclavian/internal jugular line insertion and managed as per Surviving Sepsis Campaign Guidelines. To guide resuscitation, we used ScvO
2
estimated at other clinical and laboratory parameters were monitored similarly in both groups.
Results
We enrolled 75 and 77 children median (IQR) age: 6 (1.5–10) years in the ‘intermittent’ and ‘continuous’ groups, respectively. Baseline characteristics were comparable between the groups. When compared to the ‘continuous’ group, fewer children in the ‘intermittent’ group achieved shock resolution within first 6 h 19% vs. 36%; relative risk (RR) 0.51; 95% CI 0.29–0.89; risk difference − 18.0%; 95% CI − 32.0 to − 4.0. The lower bound of confidence interval, however, crossed the pre-specified non-inferiority margin. There was no difference in the proportion of children attaining shock resolution within 24 h (63% vs. 69%; RR 0.86; 95% CI 0.68–1.08) or risk of mortality between the groups (47% vs. 43%; RR 1.06; 95% CI 0.74–1.51).
Conclusions
Given that a greater proportion of children attained therapeutic end points in the first 6 h, continuous monitoring of ScvO
2
should preferably be used to titrate therapy in the first few hours in children with septic shock. In the absence of such facility, intermittent monitoring of ScvO
2
can be used to titrate therapy in these children, given the lack of difference in the proportion of patients achieving shock resolution at 24 h or in risk of mortality between the intermittent and continuous groups.
Rationale
The extent of diaphragmatic atrophy and dysfunction in critically ill children from developing countries is not established.
Objectives
To estimate changes in ultrasound measurements of ...diaphragmatic thickness over the first week of mechanical ventilation. To assess magnitude and risk factors of diaphragmatic atrophy.
Methods
In an observational cohort study, children aged 1–18 years, requiring mechanical ventilation were included. Ultrasound measurements of diaphragmatic thickness at end‐expiration (DTe) and end‐inspiration (DTi), and diaphragmatic thickening fraction (DTF) were performed daily during the first week of admission, and pre‐ and post‐extubation. Diaphragmatic atrophy (%) and atrophy rate (rate of decline in DTe, % per day) were calculated.
Measurements and Main Results
Of 55 children (74.6% boys) enrolled, 20 (36.4%) died. Of 35 children with planned extubation, 5 (14.3%) required reintubation. Baseline median (interquartile range IQR) DTe, DTi, and DTF were 1.27 mm (1, 1.6), 1.76 mm (1.35, 2.10), and 33.75% (26.90, 44.60), respectively. There was a significant reduction in DTe over the first week of mechanical ventilation (p < .001), median (IQR) diaphragmatic atrophy and atrophy rate of 9.91% (5.26, 17.35) and 2.01% (1.08, 3.04) per day, respectively. Diaphragmatic atrophy rate was lower in pressure targeted ventilation (n = 44; 1.79% 1.03, 2.87) than volume targeted ventilation (n = 11; 3.10% 1.31, 5.49), p = .038. There was no difference in diaphragmatic parameters (atrophy rate, and peri‐extubation DTe and DTF) in extubation success versus failure.
Conclusions
The diaphragm undergoes progressive atrophy during the first week of mechanical ventilation in critically ill children. Future studies should evaluate ventilation strategies to reduce the diaphragmatic atrophy.
To the Editor, The new pandemic COVID -19 caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a global threat. So far, more than 11 million infections and more than five ...hundred thousand deaths have been reported worldwide. In India the number of cases as of 5th July, 2020 is 6,73,165 with 19,268 deaths. Health care workers (HCWs) have been the backbone of this pandemic since the very beginning...
Background: Anti-malarial drugs inhibit coronaviruses in-vitro. Few published studies have evaluated the safety and efficacy of these drugs in the treatment of COVID-19 infection. Materials and ...Methods: This is a systematic review and meta-analysis of clinical trials and observational studies. Major database searches were carried out up until June 5, 2020. Participants admitted with RT-PCR-confirmed SARS Cov-2 (COVID-19) infection were included. The "Intervention group" received anti-malarial drugs with or without other drugs (Azithromycin) administered as an adjunct to the standard treatment/care. The "Control group" received treatment except anti-malarial drugs. The primary outcome is "all-cause mortality." Secondary outcome measures were effects on clinical and laboratory parameters and adverse events. Results: Of 3,472 citations, 17 (six clinical trials and 11 observational studies) studies provided data of 8,071 participants. Compared to the control, Hydroxy-chloroquine (HCQ) has no significant effect on mortality (OR 0.87; 95% CI 0.46-1.64); eight observational studies; N = 5,944. Data from a single, small non-randomized trial (N = 42) also reached a similar conclusion (OR 1.94; 95% CI 0.07-50.57; p = 0.69). Compared to the control, HCQ plus Azithromycin (AZM) significantly increased mortality (OR 2.84; 95% CI 2.19-3.69); four observational studies; N = 2,310. Compared to the control, risk of any adverse event was significantly increased in HCQ group (OR 3.35; 95% CI 1.58-7.13); four clinical trials; N = 263. Compared to control, risk of adverse cardiac events (abnormal ECG, arrhythmia, or QT prolongation) were not significantly increased in HCQ group (but significantly increased in the HCQ plus AZM group). The GRADE evidence generated for all the outcomes was of "very low-quality." Conclusions: As very low quality evidence suggests an increased risk of mortality and adverse event with HCQ plus Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this combination for treatment of hospitalized adults with COVID-19 infection. Good quality, multi-centric RCTs (including both hospitalized and non-hospitalized patients) are required for any firm recommendation to be made during the ongoing pandemic. OSF Protocol Registration Link: https://osf.io/6zxsu.
Pediatric sepsis is an important cause of mortality and morbidity in low- and middle-income countries (LMIC), where there is a huge burden of infectious diseases. Despite shortage of resources, ...adapting protocol-based care has reduced sepsis-related deaths but survivors of pediatric sepsis are at risk of poor functional outcomes.
To perform a scoping review of the literature on functional outcomes of pediatric sepsis survivors after discharge from the intensive care unit (ICU) and discuss the implications for patients in LMICs. The outcomes include prevalence of survival with reduced functional outcomes or quality of life (QoL) and changes over time during follow-up or recovery, and these outcomes were compared with other groups of children.
We searched major medical electronic databases for relevant literature from January 2005 until November 2021, including Medline (
PubMed), Embase, CINAHL, and Google Scholar databases. We included observational studies and follow-up data from clinical trials involving children/adolescents (≤18 years) who were admitted to pediatric intensive care unit (PICU) and got discharged finally. Major focus was on survivors of sepsis in LMIC. We followed PRISMA guidelines for scoping reviews (PRISM-ScR).
We included eight papers reporting data of functional outcomes in 2,915 children (males = 53%, and comorbidity present in 56.6%). All included studies were either a prospective or retrospective cohort study. Studies were classified as Level II evidence. Disabilities affecting physical, cognitive, psychological, and social function were reported in children following discharge. Overall disability reported ranged between 23 and 50% at hospital discharge or 28 days. Residual disability was reported at 1, 3, 6, and 12 months of follow-up with an overall improving trend. Failure to recover from a baseline HRQL on follow-up was seen in one-third of survivors. Organ dysfunction scores such as pSOFA, PeLOD, vasoactive inotrope score, neurological events, immunocompromised status, need for CPR, and ECMO were associated with poor functional outcome.
The research on functional outcomes in pediatric sepsis survivors is scarce in LMIC. Measuring baseline and follow-up functional status, low-cost interventions to improve management of sepsis, and multidisciplinary teams to identify and treat disabilities may improve functional outcomes.
Our primary objective was to evaluate the effect of peer counselling by mother support groups (MSG's) in improving the infant and young child feeding (IYCF) practices in the community.
We conducted ...this repeated-measure before and after study in the Lalitpur district of Uttar Pradesh, India between 2006 and 2011. We assessed the IYCF practices before and after creating MSG's within the community. The feeding practices were reassessed at two time points-2 (T1) and 5 years (T2) after the intervention and compared with that of the pre-intervention phase (T0).
The total population covered by the project from the time of its initiation was 105000. A total of 425 (T0), 480 (T1) and 521 (T2) mother infant pairs were selected from this population. There was significant improvement in the following IYCF practices in the community (represented as %; adjOR (95% CI, p) such as initiation of breast feeding within 1 hour at both T1 (71% vs. 11%); 19.6 (13.6, 28.2, p = <0.0001)and T2 (62% vs. 11%); 13.3 (9.4, 18.9, p = <0.0001); use of prelacteal feeds at both T1 (67% vs. 15%); 12.6 (CI: 9.0, 17.6, p<0.0001) and T2 (67% vs. 5%); 44.4 (28.8, 68.4, p = <0.0001); rates of exclusive breast feeding for 6 months at both T1 (50% vs. 7%); 13.6 (7.6, 25.0, p = <0.0001) and T2 (60% vs. 7%); 20.5 (11.3, 37.2, p = <0.0001); initiation of complementary feeding at T1 (85% vs. 54%); 5.6 (3.6, 8.7, p = <0.0001) and T2 (96% vs. 54%); 22.9 (11.8, 44.1, p = <0.0001) and complementary feeding along with continued breast feeding at both T1 (36% vs. 4.5%); 6 (1.15, 31.4, p = 0.033) and T2 (42% vs. 4.5%); 8.06 (1.96, 49.1, p = 0.005) as compared to pre-intervention period (T0) after adjusting for important social and demographic variables.
Peer counseling by MSG's improved the IYCF practices in the district and could be sustained.
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