The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in ...mechanistic terms. The multiple mechanisms discussed in this review seem to share a common element: prolonged increases in reactive oxygen species (ROS) production in diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways. ROS and poly(ADP-ribose) polymerase also reduce sirtuin, PGC-1α, and AMP-activated protein kinase activity. These changes cause decreased mitochondrial biogenesis, increased ROS production, and disturbed circadian clock synchronization of glucose and lipid metabolism. Excessive ROS production also facilitates nuclear transport of proatherogenic transcription factors, increases transcription of the neutrophil enzyme initiating NETosis, peptidylarginine deiminase 4, and activates the NOD-like receptor family, pyrin domain-containing 3 inflammasome. Insulin resistance causes excessive cardiomyocyte ROS production by increasing fatty acid flux and oxidation. This stimulates overexpression of the nuclear receptor PPARα and nuclear translocation of forkhead box O 1, which cause cardiomyopathy. ROS also shift the balance between mitochondrial fusion and fission in favor of increased fission, reducing the metabolic capacity and efficiency of the mitochondrial electron transport chain and ATP synthesis. Mitochondrial oxidative stress also plays a central role in angiotensin II-induced gap junction remodeling and arrhythmogenesis. ROS contribute to sudden death in diabetics after myocardial infarction by increasing post-translational protein modifications, which cause increased ryanodine receptor phosphorylation and downregulation of sarco-endoplasmic reticulum Ca(++)-ATPase transcription. Increased ROS also depress autonomic ganglion synaptic transmission by oxidizing the nAch receptor α3 subunit, potentially contributing to the increased risk of fatal cardiac arrhythmias associated with diabetic cardiac autonomic neuropathy.
Aims
To conduct a systematic review and meta‐analysis of observational studies in order to assess the association between Type 1 diabetes and fractures.
Background
The risk of fracture in men and ...women with Type 1 diabetes has not been studied in a large prospective well designed cohort.
Methods
Data were selected from Medline and Embase and s from annual scientific meetings of various diabetes and bone and mineral societies. Published studies that reported the fracture risk in people with Type 1 diabetes in comparison with people without diabetes between 1990 and July 2014 and s from various annual meeting (2005 onwards) were included in the present meta‐analysis. Data were extracted from the text of included publications or from s of conferences.
Results
The 14 studies that met the inclusion criteria reported 2066 fracture events among 27 300 people with Type 1 diabetes (7.6%) and 136 579 fracture events among 4 364 125 people without diabetes (3.1%). The pooled relative risk of any fracture in people with Type 1 diabetes was 3.16 (95% CI 1.51–6.63; P = 0.002). Women and men with Type 1 diabetes had a four and two times higher risk of any fractures, respectively, compared with people without diabetes. The pooled relative risks of hip fractures and spinal fractures were 3.78 (95% CI 2.05–6.98; P < 0.001) and 2.88 (95% CI 1.71–4.82; P < 0.001), respectively, among people with Type 1 diabetes.
Conclusions
Our meta‐analysis suggests that both men and women with Type 1 diabetes might have an increased risk of any fractures. A large prospective epidemiological study is needed to confirm our findings.
Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental outcomes. Studies have shown a ...reduction in changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in neonates experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for analgesia. This is an update of a review first published in 2006 and updated in 2012.
The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given.
We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries (ICTRP, ISRCTN and clinicaltrials.gov) in August 2022; searches were limited from 2011 forwards. We checked the reference lists of included studies and relevant systematic reviews.
We included randomised controlled trials (RCTs) or quasi-RCTs of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates. We included both term (≥ 37 completed weeks postmenstrual age) and preterm infants (< 37 completed weeks' postmenstrual age) up to a maximum of 44 weeks' postmenstrual age. The study must have reported on either physiological markers of pain or validated pain scores.
We assessed the methodological quality of the trials using the information provided in the studies and by personal communication with the authors. We extracted data on relevant outcomes, estimated the effect size and reported this as a mean difference (MD). We used the GRADE approach to assess the certainty of evidence.
Of the 66 included studies, 36 evaluated breastfeeding, 29 evaluated supplemental breast milk and one study compared them against each other. The procedures conducted in the studies were: heel lance (39), venipuncture (11), intramuscular vaccination (nine), eye examination for retinopathy of prematurity (four), suctioning (four) and adhesive tape removal as procedure (one). We noted marked heterogeneity in the control interventions and pain assessment measures amongst the studies. Since many studies included multiple arms with breastfeeding/supplemental breast milk as the main comparator, we were not able to synthesise all interventions together. Individual interventions are compared to breastfeeding/supplemental breast milk and reported. The numbers of studies/participants presented with the findings are not taken from pooled analyses (as is usual in Cochrane Reviews), but are the overall totals in each comparison. Overall, the included studies were at low risk of bias except for masking of intervention and outcome assessment, where nearly one-third of studies were at high risk of bias. Breastfeeding versus control Breastfeeding may reduce the increase in heart rate compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration of sucrose/glucose (20% to 33%) with skin-to-skin contact (low-certainty evidence, 8 studies, 784 participants). Breastfeeding likely reduces the duration of crying compared to no intervention, lying on table, rocking, heel warming, holding by mother, skin-to-skin contact, bottle feeding mother's milk and moderate concentration of glucose (moderate-certainty evidence, 16 studies, 1866 participants). Breastfeeding may reduce percentage time crying compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration sucrose and moderate concentration of sucrose with skin-to-skin contact (low-certainty evidence, 4 studies, 359 participants). Breastfeeding likely reduces the Neonatal Infant Pain Scale (NIPS) score compared to no intervention, holding by mother, heel warming, music, EMLA cream, moderate glucose concentration, swaddling, swaddling and holding (moderate-certainty evidence, 12 studies, 1432 participants). Breastfeeding may reduce the Neonatal Facial Coding System (NFCS) score compared to no intervention, holding, pacifier and moderate concentration of glucose (low-certainty evidence, 2 studies, 235 participants). Breastfeeding may reduce the Douleur Aigue Nouveau-né (DAN) score compared to positioning, holding or placebo (low-certainty evidence, 4 studies, 709 participants). In the majority of the other comparisons there was little or no difference between the breastfeeding and control group in any of the outcome measures. Supplemental breast milk versus control Supplemental breast milk may reduce the increase in heart rate compared to water or no intervention (low-certainty evidence, 5 studies, 336 participants). Supplemental breast milk likely reduces the duration of crying compared to positioning, massage or placebo (moderate-certainty evidence, 11 studies, 1283 participants). Supplemental breast milk results in little or no difference in percentage time crying compared to placebo or glycine (low-certainty evidence, 1 study, 70 participants). Supplemental breast milk results in little or no difference in NIPS score compared to no intervention, pacifier, moderate concentration of sucrose, eye drops, gentle touch and verbal comfort, and breast milk odour and verbal comfort (low-certainty evidence, 3 studies, 291 participants). Supplemental breast milk may reduce NFCS score compared to glycine (overall low-certainty evidence, 1 study, 40 participants). DAN scores were lower when compared to massage and water; no different when compared to no intervention, EMLA and moderate concentration of sucrose; and higher when compared to rocking or pacifier (low-certainty evidence, 2 studies, 224 participants). Due to the high number of comparator interventions, other measures of pain were assessed in a very small number of studies in both comparisons, rendering the evidence of low certainty. The majority of studies did not report on adverse events, considering the benign nature of the intervention. Those that reported on adverse events identified none in any participants. Subgroup analyses were not conducted due to the small number of studies.
Moderate-/low-certainty evidence suggests that breastfeeding or supplemental breast milk may reduce pain in neonates undergoing painful procedures compared to no intervention/positioning/holding or placebo or non-pharmacological interventions. Low-certainty evidence suggests that moderate concentration (20% to 33%) glucose/sucrose may lead to little or no difference in reducing pain compared to breastfeeding. The effectiveness of breast milk for painful procedures should be studied in the preterm population, as there are currently a limited number of studies that have assessed its effectiveness in this population.
Periventricular/intraventricular hemorrhage (PIVH) is a common short-term morbidity in preterm infants, but its long-term neurodevelopmental impact, particularly with mild PIVH, remains unclear.
To ...systematically review and meta-analyze the neurodevelopmental outcomes of preterm infants ≤34 weeks' gestation with mild and severe PIVH, compared with no PIVH.
Medline, Embase, CINAHL, and PsychINFO databases from January 2000 through June 2014.
Studies reporting long-term neurodevelopmental outcomes based on severity of PIVH were included.
Study characteristics, inclusion/exclusion criteria, exposures, and outcome assessment data extracted independently by 2 coauthors.
The pooled unadjusted odds ratios of the primary outcome of death or moderate-severe neurodevelopmental impairment (NDI) were higher with both mild (1.48, 95% CI 1.26-1.73; 2 studies) and severe PIVH (4.72, 4.21-5.31; 3 studies); no studies reported adjusted odds ratios. Among survivors, odds of moderate-severe NDI were higher with mild and severe PIVH in both unadjusted (1.75, 1.40-2.20; 3 studies; 3.36, 3.06-3.68; 5 studies) and adjusted (1.39, 1.09-1.77; 3 studies; 2.44, 1.73-3.42; 2 studies) pooled analyses. Adjusted odds of cerebral palsy and cognitive delay were higher with severe but not mild PIVH.
Only observational studies were included. Fifteen of 21 included studies had a moderate-high risk of bias.
Mild and severe PIVH are associated with progressively higher odds of death or moderate-severe NDI compared with no PIVH, but no studies adjusted for confounders. Among survivors, mild PIVH was associated with higher odds of moderate-severe NDI compared with no PIVH.
Steel pallet rack (SPR) beam-to-column connections (BCCs) are largely responsible to avoid the sway failure of frames in the down-aisle direction. The overall geometry of beam end connectors ...commercially used in SPR BCCs is different and does not allow a generalized analytic approach for all types of beam end connectors; however, identifying the effects of the configuration, profile and sizes of the connection components could be the suitable approach for the practical design engineers in order to predict the generalized behavior of any SPR BCC. This paper describes the experimental behavior of SPR BCCs tested using a double cantilever test set-up. Eight sets of specimens were identified based on the variation in column thickness, beam depth and number of tabs in the beam end connector in order to investigate the most influential factors affecting the connection performance. Four tests were repeatedly performed for each set to bring uniformity to the results taking the total number of tests to thirty-two. The moment-rotation (M-θ) behavior, load-strain relationship, major failure modes and the influence of selected parameters on connection performance were investigated. A comparative study to calculate the connection stiffness was carried out using the initial stiffness method, the slope to half-ultimate moment method and the equal area method. In order to find out the more appropriate method, the mean stiffness of all the tested connections and the variance in values of mean stiffness according to all three methods were calculated. The calculation of connection stiffness by means of the initial stiffness method is considered to overestimate the values when compared to the other two methods. The equal area method provided more consistent values of stiffness and lowest variance in the data set as compared to the other two methods.
Summary Background Acute exposure to air pollution has been linked to myocardial infarction, but its effect on heart failure is uncertain. We did a systematic review and meta-analysis to assess the ...association between air pollution and acute decompensated heart failure including hospitalisation and heart failure mortality. Methods Five databases were searched for studies investigating the association between daily increases in gaseous (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate (diameter <2·5 μm PM2·5 or <10 μm PM10 ) air pollutants, and heart failure hospitalisations or heart failure mortality. We used a random-effects model to derive overall risk estimates per pollutant. Findings Of 1146 identified articles, 195 were reviewed in-depth with 35 satisfying inclusion criteria. Heart failure hospitalisation or death was associated with increases in carbon monoxide (3·52% per 1 part per million; 95% CI 2·52–4·54), sulphur dioxide (2·36% per 10 parts per billion; 1·35–3·38), and nitrogen dioxide (1·70% per 10 parts per billion; 1·25–2·16), but not ozone (0·46% per 10 parts per billion; −0·10 to 1·02) concentrations. Increases in particulate matter concentration were associated with heart failure hospitalisation or death (PM2·5 2·12% per 10 μg/m3 , 95% CI 1·42–2·82; PM10 1·63% per 10 μg/m3 , 95% CI 1·20–2·07). Strongest associations were seen on the day of exposure, with more persistent effects for PM2·5 . In the USA, we estimate that a mean reduction in PM2·5 of 3·9 μg/m3 would prevent 7978 heart failure hospitalisations and save a third of a billion US dollars a year. Interpretation Air pollution has a close temporal association with heart failure hospitalisation and heart failure mortality. Although more studies from developing nations are required, air pollution is a pervasive public health issue with major cardiovascular and health economic consequences, and it should remain a key target for global health policy. Funding British Heart Foundation.
In December, 2019 in Wuhan city of China, a novel coronavirus (SARS-CoV-2) has garnered global attention due to its rapid transmission. World Health Organization (WHO) termed the infection as ...Coronavirus Disease 2019 (COVID-19) after phylogenic studies with SARS-CoV. The virus causes severe respiratory infections with dry cough, high fever, body ache and fatigue. The virus is primarily transmitted among people through respiratory droplets from COVID-19 infected person. WHO declared this COVID-19 outbreak a pandemic and since February, 2020 affected countries have locked down their cities, industries and restricted the movement of their citizens to minimize the spread of the virus. In spite of the negative aspects of coronavirus on the globe, the coronavirus crises brought a positive impact on the natural environment. Countries where the movement of citizens was seized to stop the spread of coronavirus infection have experienced a noticeable decline in pollution and greenhouse gases emission. Recent research also indicated that this COVID-19-induced lockdown has reduced the environmental pollution drastically worldwide. In this review, we have discussed some important positive impacts of coronavirus on environmental quality by compiling the recently published data from research articles, NASA (National Aeronautics and Space Administration) and ESA (European Space Agency).
Several studies have reported racial/ethnic variation in out-of-hospital cardiac arrest (OOHCA) characteristics, which engendered varying conclusions. We performed a systematic review and ...meta-analysed the evidence for differences in OOHCA survival when considering the patient's race and/or ethnicity.
We searched Medline and EMBASE databases up to and including 1 Oct 2011 for studies investigating racial/ethnic differences in OOHCA characteristics, supplemented by manual searches of bibliographies of relevant studies. We selected studies of any relevant design that measured OOHCA characteristics and stratified them by ethnic group. Two independent reviewers extracted information on the study population, including: race and/or ethnicity, location, age and OOHCA variables as per the Utsein template. We performed a meta-analysis of the studies comparing the black and white patients.
1701 potentially relevant articles were identified in our systematic search. Of these, 22 articles describing original studies were reviewed after fulfilling our inclusion criteria. Although 19 studies (18 within the United States (US)) compared the black and white population, only 15 fulfilled our quality assessment criteria and were meta-analysed. Compared to white patients, black patients were less likely to receive bystander cardiopulmonary resuscitation (OR = 0.66, 95%CI = 0.55-0.78), have a witnessed arrest (OR = 0.77, 95%CI = 0.72-0.83) or have an initial ventricular fibrillation/ventricular tachycardia arrest rhythm (OR = 0.66, 95%CI = 0.58-0.76). Black patients had lower rates of survival following hospital admission (OR = 0.59, 95%CI = 0.48-0.72) and discharge (OR = 0.74, 95%CI = 0.61-0.90).
Our work highlights the significant discrepancy in OOHCA characteristics and patient survival in relation to the patient's race, with the black population faring less well across all stages. Most studies compared black and white populations within the US, so research elsewhere and with other ethnic groups is needed. This review exposes an inequality that demands urgent action.
Physiological changes brought about by pain may contribute to the development of morbidity in neonates. Clinical studies have shown reduction in changes in physiological parameters and pain score ...measurements following pre-emptive analgesic administration in situations where the neonate is experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for this purpose.
The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given.
We performed a literature search using the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 10), MEDLINE (1966 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982 to February 2011), abstracts from the annual meetings of the Society for Pediatric Research (1994 to 2011), and major paediatric pain conference proceedings. We did not apply any language restrictions.
Randomised controlled trials (RCTs) or quasi-RCTs of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates were eligible for inclusion in this review. The study must have reported on either physiologic markers of pain or validated pain scores.
We assessed the methodological quality of the trials using the information provided in the studies and by personal communication with the authors. We extracted data on relevant outcomes, estimated the effect size and reported this as a risk ratio (RR), risk difference (RD) and weighted mean difference (MD) as appropriate.
Of twenty eligible studies, ten evaluated breastfeeding and ten evaluated supplemental breast milk. Sixteen studies analysed used heel lance and four used venepuncture as procedure. We noted marked heterogeneity in control intervention and pain assessment measures among the studies. Neonates in the breastfeeding group had statistically a significantly lower increase in heart rate, reduced proportion of crying time and reduced duration of first cry and total crying time compared to positioning (swaddled and placed in a crib), holding by mother, placebo, pacifier use, no intervention or oral sucrose group, or both.Premature Infant Pain Profile (PIPP) scores were significantly lower in the breastfeeding group compared to positioning, placebo or oral sucrose group, or both. However, there was no statistically significant difference in PIPP scores when compared to no intervention. Douleur Aigue Nouveau-ne scores (DAN) were significantly lower in the breastfeeding group compared to the placebo group and the group held in mother's arms, but not when compared to the glucose group. Neonatal Infant Pain Scale (NIPS) was significantly lower in the breastfeeding group compared to the no intervention group, but there was no difference when compared to the oral sucrose group. The Neonatal Facial Coding System (NFCS) was significantly lower in the breastfeeding group when compared to oral glucose, pacifier use, holding by mother and no intervention, but no difference was found when compared to formula feeding.Supplemental breast milk yielded variable results. Neonates in the supplemental breast milk group had a significantly lower increase in heart rate, a reduction in duration of crying and a lower NFCS compared to the placebo group. Neonates in the supplemental breast milk group had a significantly higher increase in heart rate changes when compared to the sucrose group. Sucrose (in any concentration, i.e. 12.5%, 20%, 25%) was found to reduce the duration of cry when compared to breast milk, as did glycine, pacifier use, rocking, or no intervention. Breast milk was found not to be effective in reducing validated and non-validated pain scores such as NIPS, NFCS, and DAN; only being significantly better when compared to placebo (water) or massage. We did not identify any study that has evaluated safety/effectiveness of repeated administration of breastfeeding or supplemental breast milk for pain relief.
If available, breastfeeding or breast milk should be used to alleviate procedural pain in neonates undergoing a single painful procedure rather than placebo, positioning or no intervention. Administration of glucose/sucrose had similar effectiveness as breastfeeding for reducing pain. The effectiveness of breast milk for painful procedure should be studied in the preterm population, as there are currently a limited number of studies in the literature that have assessed it's effectiveness in this population.
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