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BMC Medicine Dec 2014Hyponatremia is a common electrolyte disorder. Multiple organizations have published guidance documents to assist clinicians in managing hyponatremia. We aimed to... (Review)
Review
BACKGROUND
Hyponatremia is a common electrolyte disorder. Multiple organizations have published guidance documents to assist clinicians in managing hyponatremia. We aimed to explore the scope, content, and consistency of these documents.
METHODS
We searched MEDLINE, EMBASE, and websites of guideline organizations and professional societies to September 2014 without language restriction for Clinical Practice Guidelines (defined as any document providing guidance informed by systematic literature review) and Consensus Statements (any other guidance document) developed specifically to guide differential diagnosis or treatment of hyponatremia. Four reviewers appraised guideline quality using the 23-item AGREE II instrument, which rates reporting of the guidance development process across six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Total scores were calculated as standardized averages by domain.
RESULTS
We found ten guidance documents; five clinical practice guidelines and five consensus statements. Overall, quality was mixed: two clinical practice guidelines attained an average score of >50% for all of the domains, three rated the evidence in a systematic way and two graded strength of the recommendations. All five consensus statements received AGREE scores below 60% for each of the specific domains.The guidance documents varied widely in scope. All dealt with therapy and seven included recommendations on diagnosis, using serum osmolality to confirm hypotonic hyponatremia, and volume status, urinary sodium concentration, and urinary osmolality for further classification of the hyponatremia. They differed, however, in classification thresholds, what additional tests to consider, and when to initiate diagnostic work-up. Eight guidance documents advocated hypertonic NaCl in severely symptomatic, acute onset (<48 h) hyponatremia. In chronic (>48 h) or asymptomatic cases, recommended treatments were NaCl 0.9%, fluid restriction, and cause-specific therapy for hypovolemic, euvolemic, and hypervolemic hyponatremia, respectively. Eight guidance documents recommended limits for speed of increase of sodium concentration, but these varied between 8 and 12 mmol/L per 24 h. Inconsistencies also existed in the recommended dose of NaCl, its initial infusion speed, and which second line interventions to consider.
CONCLUSIONS
Current guidance documents on the assessment and treatment of hyponatremia vary in methodological rigor and recommendations are not always consistent.
Topics: Consensus; Humans; Hyponatremia; Practice Guidelines as Topic
PubMed: 25539784
DOI: 10.1186/s12916-014-0231-1 -
Sports Medicine (Auckland, N.Z.) Feb 2022Body-fluid loss during prolonged continuous exercise can impair cardiovascular function, harming performance. Delta percent plasma volume (dPV) represents the change in... (Meta-Analysis)
Meta-Analysis
The Hydrating Effects of Hypertonic, Isotonic and Hypotonic Sports Drinks and Waters on Central Hydration During Continuous Exercise: A Systematic Meta-Analysis and Perspective.
BACKGROUND
Body-fluid loss during prolonged continuous exercise can impair cardiovascular function, harming performance. Delta percent plasma volume (dPV) represents the change in central and circulatory body-water volume and therefore hydration during exercise; however, the effect of carbohydrate-electrolyte drinks and water on the dPV response is unclear.
OBJECTIVE
To determine by meta-analysis the effects of ingested hypertonic (> 300 mOsmol kg), isotonic (275-300 mOsmol kg) and hypotonic (< 275 mOsmol kg) drinks containing carbohydrate and electrolyte ([Na] < 50 mmol L), and non-carbohydrate drinks/water (< 40 mOsmol kg) on dPV during continuous exercise.
METHODS
A systematic review produced 28 qualifying studies and 68 drink treatment effects. Random-effects meta-analyses with repeated measures provided estimates of effects and probability of superiority (p) during 0-180 min of exercise, adjusted for drink osmolality, ingestion rate, metabolic rate and a weakly informative Bayesian prior.
RESULTS
Mean drink effects on dPV were: hypertonic - 7.4% [90% compatibility limits (CL) - 8.5, - 6.3], isotonic - 8.7% (90% CL - 10.1, - 7.4), hypotonic - 6.3% (90% CL - 7.4, - 5.3) and water - 7.5% (90% CL - 8.5, - 6.4). Posterior contrast estimates relative to the smallest important effect (dPV = 0.75%) were: hypertonic-isotonic 1.2% (90% CL - 0.1, 2.6; p = 0.74), hypotonic-isotonic 2.3% (90% CL 1.1, 3.5; p = 0.984), water-isotonic 1.3% (90% CL 0.0, 2.5; p = 0.76), hypotonic-hypertonic 1.1% (90% CL 0.1, 2.1; p = 0.71), hypertonic-water 0.1% (90% CL - 0.8, 1.0; p = 0.12) and hypotonic-water 1.1% (90% CL 0.1, 2.0; p = 0.72). Thus, hypotonic drinks were very likely superior to isotonic and likely superior to hypertonic and water. Metabolic rate, ingestion rate, carbohydrate characteristics and electrolyte concentration were generally substantial modifiers of dPV.
CONCLUSION
Hypotonic carbohydrate-electrolyte drinks ingested continuously during exercise provide the greatest benefit to hydration.
Topics: Bayes Theorem; Dehydration; Exercise; Humans; Osmolar Concentration; Sodium; Water-Electrolyte Balance
PubMed: 34716905
DOI: 10.1007/s40279-021-01558-y -
The Cochrane Database of Systematic... Apr 2015There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well-being are compromised.
OBJECTIVES
To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water-loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water-loss dehydration was defined primarily as including everyone with either impending or current water-loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated).
SEARCH METHODS
Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies.
SELECTION CRITERIA
Titles and abstracts were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables.
DATA COLLECTION AND ANALYSIS
Diagnostic accuracy of each test was assessed against the best available reference standard for water-loss dehydration (serum or plasma osmolality cut-off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water-loss dehydration (including either impending or current water-loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water-loss dehydration, but restricted to current dehydration in the final review.We conducted bivariate random-effects meta-analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre-specified cut-off points investigated.Pre-set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre-specifying three cut-offs for each continuous test may have led to missing a cut-off with useful sensitivity and specificity, we conducted post-hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut-off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability.
MAIN RESULTS
There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post-hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).There was sufficient evidence to suggest that several stand-alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.No tests were found consistently useful in diagnosing current water-loss dehydration.
AUTHORS' CONCLUSIONS
There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water-loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.
Topics: Aged; Dehydration; Drinking Water; Electric Impedance; Female; Humans; Male; Mouth Diseases; Osmolar Concentration; Sensitivity and Specificity; Skin Physiological Phenomena; Symptom Assessment; Urine
PubMed: 25924806
DOI: 10.1002/14651858.CD009647.pub2 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Low-intake dehydration amongst older people, caused by insufficient fluid intake, is associated with mortality, multiple long-term health conditions and hospitalisation.... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Low-intake dehydration amongst older people, caused by insufficient fluid intake, is associated with mortality, multiple long-term health conditions and hospitalisation. The prevalence of low-intake dehydration in older adults, and which groups are most at-risk, is unclear. We conducted a high-quality systematic review and meta-analysis, implementing an innovative methodology, to establish the prevalence of low-intake dehydration in older people (PROSPERO registration: CRD42021241252).
METHOD
We systematically searched Medline (Ovid), Cochrane CENTRAL, Embase (Ovid), CINAHL and Proquest from inception until April 2023 and Nutrition and Food Sciences until March 2021. We included studies that assessed hydration status for non-hospitalised participants aged ≥65 years, by directly-measured serum/plasma osmolality, calculated serum/plasma osmolarity and/or 24-h oral fluid intake. Inclusion, data extraction and risk of bias assessment was carried out independently in duplicate.
RESULTS
From 11,077 titles and abstracts, we included 61 (22,398 participants), including 44 in quality-effects meta-analysis. Meta-analysis suggested that 24% (95% CI: 0.07, 0.46) of older people were dehydrated (assessed using directly-measured osmolality >300 mOsm/kg, the most reliable measure). Subgroup analyses indicated that both long-term care residents (34%, 95% CI: 0.09, 0.61) and community-dwelling older adults (19%, 95% CI: 0.00, 0.48) were highly likely to be dehydrated. Those with more pre-existing illnesses (37%, 95% CI: 0.14, 0.62) had higher low-intake dehydration prevalence than others (15%, 95% CI: 0.00, 0.43), and there was a non-significant suggestion that those with renal impairment (42%, 95% CI: 0.23, 0.61) were more likely to be dehydrated than others (23%, 95% CI: 0.03, 0.47), but there were no clear differences in prevalence by age, sex, functional, cognitive or diabetic status. GRADE quality of evidence was low as to the exact prevalence due to high levels of heterogeneity between studies.
CONCLUSION
Quality-effects meta-analysis estimated that a quarter of non-hospitalised older people were dehydrated. Widely varying prevalence rates in individual studies, from both long-term care and community groups, highlight that dehydration is preventable amongst older people.
IMPLICATIONS
One in every 4 older adults has low-intake dehydration. As dehydration is serious and prevalent, research is needed to better understand drinking behaviour and assess effectiveness of drinking interventions for older people.
Topics: Humans; Aged; Dehydration; Prevalence; Long-Term Care; Nutritional Status; Hospitalization
PubMed: 37330324
DOI: 10.1016/j.clnu.2023.06.010 -
The Cochrane Database of Systematic... Feb 2018Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013.
OBJECTIVES
To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability.
SEARCH METHODS
We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015).
SELECTION CRITERIA
Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS
We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Combined Modality Therapy; Community-Acquired Infections; Deafness; Dexamethasone; Diuretics, Osmotic; Epilepsy; Gastrointestinal Hemorrhage; Glucose; Glycerol; Humans; Intracranial Pressure; Meningitis, Bacterial; Nervous System Diseases; Osmosis; Osmotic Pressure; Randomized Controlled Trials as Topic
PubMed: 29405037
DOI: 10.1002/14651858.CD008806.pub3 -
Archives of Disease in Childhood. Fetal... May 2019High feed osmolality (or osmolarity) is often suggested to be linked with adverse gastrointestinal events in preterm infants.
BACKGROUND
High feed osmolality (or osmolarity) is often suggested to be linked with adverse gastrointestinal events in preterm infants.
AIM
To systematically review the literature on milk feed osmolality and adverse gastrointestinal events in newborn and low birthweight infants and animals.
METHODS
MEDLINE, Embase, CAB Abstracts, Current Contents, BIOSIS Previews and SciSearch were searched from inception to May 2018 to identify potentially relevant studies.
INCLUSION CRITERIA
randomised controlled or observational studies of newborn and low birthweight infants or animals investigating the effects of milk-based feeds with different osmolalities. Only full-text, English-language papers were included.
RESULTS
Ten human and six animal studies met the inclusion criteria. Of human studies, seven reported no differences in adverse events with varying feed osmolalities; one reported delayed gastric emptying with feed osmolarity of 539 mOsm/L compared with lower levels; one reported higher necrotising enterocolitis (NEC) incidence with feed osmolarity of 650 mOsm/L compared with 359 mOsm/L; one found higher NEC incidence with the lowest feed osmolality (326 mOsm/kg compared with 385 mOsm/kg). Of animal studies, two reported delayed gastric emptying with feed osmolarity >624 mOsm/L, one reported decreased survival due to dehydration with dietary osmolarities ≥765 mOsmol/L and none reported increased NEC incidence with differing feed osmolalities. No clear mechanisms were found, and diet composition differences limited the interpretations regarding the independent impact of osmolality.
CONCLUSIONS
There is no consistent evidence that differences in feed osmolality in the range 300-500 mOsm/kg are associated with adverse gastrointestinal symptoms in neonates.
Topics: Animals; Animals, Newborn; Enterocolitis, Necrotizing; Gastric Emptying; Gastrointestinal Diseases; Humans; Infant Formula; Infant, Low Birth Weight; Infant, Newborn; Milk; Milk, Human; Osmolar Concentration
PubMed: 30523072
DOI: 10.1136/archdischild-2018-315946 -
Critical Care (London, England) Feb 2023Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically,...
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Topics: Humans; Antidotes; Fomepizole; Ethanol; Renal Dialysis; Glycolates; Ethylene Glycol; Poisoning
PubMed: 36765419
DOI: 10.1186/s13054-022-04227-2 -
Perioperative Medicine (London, England) 2018Dehydration is highly prevalent and is associated with adverse cardiovascular and renal events. Clinical assessment of dehydration lacks sensitivity. Perhaps a patient's... (Review)
Review
BACKGROUND
Dehydration is highly prevalent and is associated with adverse cardiovascular and renal events. Clinical assessment of dehydration lacks sensitivity. Perhaps a patient's thirst can provide an accurate guide to fluid therapy. This systematic review examines the sensitivity of thirst in responding to changes in plasma osmolality in participants of any age with no condition directly effecting their sense of thirst.
METHODS
Medline and EMBASE were searched up to June 2017. Inclusion criteria were all studies reporting the plasma osmolality threshold for the sensation of thirst.
RESULTS
A total of 12 trials were included that assessed thirst intensity on a visual analogue scale, as a function of plasma osmolality (pOsm), and employed linear regression to define the thirst threshold. This included 167 participants, both healthy controls and those with a range of pathologies, with a mean age of 41 (20-78) years.The value ±95% CI for the pOsm threshold for thirst sensation was found to be 285.23 ± 1.29 mOsm/kg. Above this threshold, thirst intensity as a function of pOsm had a mean ± SEM slope of 0.54 ± 0.07 cm/mOsm/kg. The mean ± 95% CI vasopressin release threshold was very similar to that of thirst, being 284.3 ± 0.71 mOsm/kg.Heterogeneity across studies can be accounted for by subtle variation in experimental protocol and data handling.
CONCLUSION
The thresholds for thirst activation and vasopressin release lie in the middle of the normal range of plasma osmolality. Thirst increases linearly as pOsm rises. Thus, osmotically balanced fluid administered as per a patient's sensation of thirst should result in a plasma osmolality within the normal range. This work received no funding.
PubMed: 29344350
DOI: 10.1186/s13741-017-0081-4 -
Clinical Nutrition ESPEN Feb 2022Advice to drink plenty of fluid is common in respiratory infections. We assessed whether low fluid intake (dehydration) altered outcomes in adults with pneumonia. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Advice to drink plenty of fluid is common in respiratory infections. We assessed whether low fluid intake (dehydration) altered outcomes in adults with pneumonia.
METHODS
We systematically reviewed trials increasing fluid intake and well-adjusted, well-powered observational studies assessing associations between markers of low-intake dehydration (fluid intake, serum osmolality, urea or blood urea nitrogen, urinary output, signs of dehydration) and mortality in adult pneumonia patients (with any type of pneumonia, including community acquired, health-care acquired, aspiration, COVID-19 and mixed types). Medline, Embase, CENTRAL, references of reviews and included studies were searched to 30/10/2020. Studies were assessed for inclusion, risk of bias and data extracted independently in duplicate. We employed random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE assessment. Prospero registration: CRD42020182599.
RESULTS
We identified one trial, 20 well-adjusted cohort studies and one case-control study. None suggested that more fluid (hydration) was associated with harm. Ten of 13 well-powered observational studies found statistically significant positive associations in adjusted analyses between dehydration and medium-term mortality. The other three studies found no significant effect. Meta-analysis suggested doubled odds of medium-term mortality in dehydrated (compared to hydrated) pneumonia patients (GRADE moderate-quality evidence, OR 2.3, 95% CI 1.8 to 2.8, 8619 deaths in 128,319 participants). Heterogeneity was explained by a dose effect (greater dehydration increased risk of mortality further), and the effect was consistent across types of pneumonia (including community-acquired, hospital-acquired, aspiration, nursing and health-care associated, and mixed pneumonia), age and setting (community or hospital). The single trial found that educating pneumonia patients to drink ≥1.5 L fluid/d alongside lifestyle advice increased fluid intake and reduced subsequent healthcare use. No studies in COVID-19 pneumonia met the inclusion criteria, but 70% of those hospitalised with COVID-19 have pneumonia. Smaller COVID-19 studies suggested that hydration is as important in COVID-19 pneumonia mortality as in other pneumonias.
CONCLUSIONS
We found consistent moderate-quality evidence mainly from observational studies that improving hydration reduces the risk of medium-term mortality in all types of pneumonia. It is remarkable that while many studies included dehydration as a potential confounder, and major pneumonia risk scores include measures of hydration, optimal fluid volume and the effect of supporting hydration have not been assessed in randomised controlled trials of people with pneumonia. Such trials, are needed as potential benefits may be large, rapid and implemented at low cost. Supporting hydration and reversing dehydration has the potential to have rapid positive impacts on pneumonia outcomes, and perhaps also COVID-19 pneumonia outcomes, in older adults.
Topics: Aged; COVID-19; Case-Control Studies; Drinking; Humans; Pneumonia; SARS-CoV-2
PubMed: 35063249
DOI: 10.1016/j.clnesp.2021.11.021 -
Frontiers in Pediatrics 2021Wolfram Syndrome is a rare autosomal recessive disease characterized by early-onset diabetes mellitus, neurodegeneration, and psychological disorders. Mutations in the...
Wolfram Syndrome is a rare autosomal recessive disease characterized by early-onset diabetes mellitus, neurodegeneration, and psychological disorders. Mutations in the gene , coding for the protein wolframin, cause Wolfram Syndrome and are associated with bipolar disorder and schizophrenia. This report aims to connect mutations to their impact on protein expression and structure, which ultimately translates to altered cell function and behavioral alterations of an individual. Published data were used to compile mutations associated with psychiatric symptoms, both in homozygous patients and heterozygous carriers of mutations. These mutations were evaluated using SNAP2, PolyPhen-2, and PROVEAN to predict the effects of sequence variants. Statistical analysis was performed to assess the correlation between the locations of the mutations and the damage prediction scores. Several mutations, clustering in the center and C-terminus of the polypeptide, such as A559T and R558C, are found in individuals with psychiatric diseases and appear particularly impactful on protein structure. Our analysis showed that mutations in all regions of wolframin were present in patients with schizophrenia whereas only cytoplasmic and ER luminal mutations were reported in patients with manic episodes and bipolar disorders. According to Poly-Phen-2 predictions, 82.4% of the ER lumen mutations and 85.7% of the membrane mutations are damaging. We propose mood disorders in Wolfram Syndrome and heterozygous carriers of mutations are the consequence of specific mutations in that alter the structure of wolframin, resulting in intracellular calcium dysregulations and impaired cell signaling, Understanding the effect of mutations on bipolar disorder and schizoprenia is integral to designing clinically targeted treatments for both diseases, which need more specialized treatments.
PubMed: 34746052
DOI: 10.3389/fped.2021.718132