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Chest Dec 2020Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.
RESEARCH QUESTION
How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?
STUDY DESIGN AND METHODS
We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.
RESULTS
We included 28 studies (13 OSA/15 CSA; N = 542; N = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHI = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).
INTERPRETATION
Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.
CLINICAL TRIAL REGISTRATION
PROSPERO (CRD42019147504).
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Humans; Sleep Apnea, Central; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 32768459
DOI: 10.1016/j.chest.2020.06.078 -
Tremor and Other Hyperkinetic Movements... 2023Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1... (Review)
Review
BACKGROUND
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in and . EA3-8 are reported in rare families. Advances in genetic testing have broadened the and phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists.
METHODS
A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized.
RESULTS
EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (), epilepsy syndromes (), GLUT-1, mitochondrial disorders (), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause.
DISCUSSION
EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
Topics: Humans; Ataxia; Cerebellar Ataxia; Acetazolamide; Mutation
PubMed: 37008993
DOI: 10.5334/tohm.747 -
JSLS : Journal of the Society of... 2022To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing postoperative referred pain.
METHODS
The following databases were searched from inception to March 1, 2020: Cochrane, PubMed, PubMed Central, Ovid, and Embase. Electronic search used: Acetazolamide AND (laparoscopy OR laparoscopic OR Celioscopy OR Celioscopies OR Peritoneoscopy OR Peritoneoscopies). No limits or filters were used. We included only studies of patients who underwent abdominal laparoscopy (LSC), had a pain assessment at approximately 24 hours postoperatively, and included a treatment with ACTZ group and a no-treatment or minimal-treatment comparison group.
RESULTS
Five studies met inclusion criteria, with a combined total of 253 participants, 116 in the ACTZ group and 137 in the control group. A Bayesian hierarchical model was assumed for the study specific treatment effects. Posterior sampling was conducted via Markov Chain Monte Carlo methods, and posterior inference carried out on the hierarchical treatment effect. ACTZ significantly decreased average pain scores compared to control group by -0.726 points (95% confidence interval -1.175-0.264). The posterior probability that ACTZ decreases mean pain scores by ≥ 0.5 was 0.846.
CONCLUSION
Current available evidence demonstrates that perioperative ACTZ may provide a modest improvement in postoperative referred pain following LSC.
Topics: Acetazolamide; Bayes Theorem; Humans; Laparoscopy; Pain, Postoperative; Pain, Referred
PubMed: 36071992
DOI: 10.4293/JSLS.2022.00032 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses. Catamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses. Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life. We judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out. Our review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Menstruation; Middle Aged; Randomized Controlled Trials as Topic; Seizures; Young Adult
PubMed: 34528245
DOI: 10.1002/14651858.CD013225.pub3 -
Neurology Nov 2023Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this...
BACKGROUND AND OBJECTIVES
Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this systematic review was to evaluate weight loss interventions in people with IIH to determine which intervention is superior in terms of weight loss, reduction in intracranial pressure (ICP), benefit to visual and headache outcomes, quality of life, and mental health.
METHODS
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42023339569). MEDLINE and CINAHL were searched for relevant literature published from inception until December 15, 2022. Screening and quality appraisal was conducted by 2 independent reviewers. Recommendations were graded using Scottish Intercollegiate Guidelines Network methodology.
RESULTS
A total of 17 studies were included. Bariatric surgery resulted in 27.2-27.8 kg weight loss at 24 months (Level 1- to 1++). Lifestyle weight management interventions resulted in between 1.4 and 15.7 kg weight loss (Level 2+ to 1++). Bariatric surgery resulted in the greatest mean reduction in ICP (-11.9 cm HO) at 24 months (Level 1++), followed by multicomponent lifestyle intervention + acetazolamide (-11.2 cm HO) at 6 months (Level 1+) and then a very low-energy diet intervention (-8.0 cm HO) at 3 months (Level 2++). The least ICP reduction was shown at 24 months after completing a 12-month multicomponent lifestyle intervention (-3.5 cm HO) (Level 1++). Reduction in body weight was shown to be highly correlated with reduction in ICP (Level 2++ to 1++).
DISCUSSION
Bariatric surgery should be considered for women with IIH and a body mass index (BMI) ≥35 kg/m since this had the most robust evidence for sustained weight management (grade A). A multicomponent lifestyle intervention (diet + physical activity + behavior) had the most robust evidence for modest weight loss with a BMI <35 kg/m (grade B). Longer-term outcomes for weight management interventions in people with IIH are required to determine whether there is a superior weight loss intervention for IIH.
Topics: Humans; Adult; Female; Pseudotumor Cerebri; Quality of Life; Obesity; Weight Loss; Bariatric Surgery; Intracranial Hypertension
PubMed: 37813577
DOI: 10.1212/WNL.0000000000207866 -
Sleep Science (Sao Paulo, Brazil) Mar 2023The aim of this systematic review is to analyze the recent scientific evidence of the clinical effects of altitude on breathing during sleep in healthy persons and... (Review)
Review
The aim of this systematic review is to analyze the recent scientific evidence of the clinical effects of altitude on breathing during sleep in healthy persons and sleep disordered patients. A search was carried out in PubMed and Scopus looking for articles published between January 1, 2010 and December 31, 2021, in English and Spanish, with the following search terms: "sleep disorders breathing and altitude". Investigations in adults and carried out at an altitude of 2000 meters above mean sea level (MAMSL) or higher were included. The correlation between altitude, apnea hypopnea index (AHI) and mean SpO2 during sleep was calculated. 18 articles of the 112 identified were included. A good correlation was found between altitude and AHI (Rs = 0.66 P = 0.001), at the expense of an increase in the central apnea index. Altitude is inversely proportional to oxygenation during sleep (Rs = -0.93 P = 0.001), and an increase in the desaturation index was observed (3% and 4%). On the treatment of respiratory disorders of sleeping at altitude, oxygen is better than servoventilation to correct oxygenation during sleep in healthy subjects and acetazolamide controlled respiratory events and oxygenation during sleep in patients with obstructive sleep apnea under treatment with CPAP. Altitude increases AHI and decreases oxygenation during sleep; oxygen and acetazolamide could be an effective treatment for sleep-disordered breathing at altitude above 2000 MAMSL.
PubMed: 37151770
DOI: 10.1055/s-0043-1767745 -
Therapeutic Advances in Respiratory... Jan 2017Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study aimed to assess the effect of acetazolamide on sleep... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study aimed to assess the effect of acetazolamide on sleep apnea at high altitude, determine the optimal therapeutic dose, and compare its effectiveness in healthy trekkers and obstructive sleep apnea (OSA) patients.
METHODS
PubMed, Embase, Scopus, Cochrane Library, and Airiti Library databases were searched up to July 2015 for randomized controlled trials (RCTs) performed above 2500 m in lowlanders and that used acetazolamide as intervention in sleep studies. Studies including participants with medical conditions other than OSA were excluded.
RESULTS
Eight studies of 190 adults were included. In healthy participants, the pooled mean effect sizes of acetazolamide on Apnea-Hypopnea Index (AHI), percentage of periodic breathing time, and nocturnal oxygenation were 34.66 [95% confidence interval (CI) 25.01-44.30] with low heterogeneity ( p = 0.7, I = 0%), 38.56% (95% CI 18.92-58.19%) with low heterogeneity ( p = 0.24, I = 28%), and 4.75% (95% CI 1.35-8.15%) with high heterogeneity ( p < 0.01, I = 87%), respectively. In OSA patients, the pooled mean effect sizes of acetazolamide on AHI and nocturnal oxygenation were 13.18 (95% CI 9.25-17.1) with low heterogeneity ( p = 0.33, I = 0%) and 1.85% (95% CI 1.08-2.62%) with low heterogeneity ( P = 0.56, I = 0%).
CONCLUSIONS
Acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of periodic breathing time and increasing nocturnal oxygenation. Acetazolamide is more beneficial in healthy participants than in OSA patients, and a 250 mg daily dose may be as effective as higher daily doses for healthy trekkers.
Topics: Acetazolamide; Adult; Altitude; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Humans; Oxygen Consumption; Randomized Controlled Trials as Topic; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
PubMed: 28043212
DOI: 10.1177/1753465816677006 -
The Cochrane Database of Systematic... Jul 2018Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge.
OBJECTIVES
To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South-East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018.
SELECTION CRITERIA
We included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV-associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random-effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10-week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta-analysis using multivariate meta-regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two-week and 10-week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node-splitting approach, and global inconsistency using design-by-treatment interaction modelling. For the network meta-analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10-week mortality.
MAIN RESULTS
We included 13 eligible studies that enrolled 2426 participants and compared 21 interventions. All studies were carried out in adults, and all but two studies were conducted in resource-limited settings, including 11 of 12 studies with 10-week mortality data.In the direct pairwise comparisons evaluating 10-week mortality, one study from four sub-Saharan African countries contributed data to several key comparisons. At 10 weeks these data showed that those on the regimen of one-week amphotericin B deoxycholate (AmBd) and flucytosine (5FC) followed by fluconazole (FLU) on days 8 to 14 had lower mortality when compared to (i) two weeks of AmBd and 5FC (RR 0.62, 95% CI 0.42 to 0.93; 228 participants, 1 study), (ii) two weeks of AmBd and FLU (RR 0.58, 95% CI 0.39 to 0.86; 227 participants, 1 study), (iii) one week of AmBd with two weeks of FLU (RR 0.49, 95% CI 0.34 to 0.72; 224 participants, 1 study), and (iv) two weeks of 5FC and FLU (RR 0.68, 95% CI 0.47 to 0.99; 338 participants, 1 study). The evidence for each of these comparisons was of moderate certainty. For other outcomes, this shortened one-week AmBd and 5FC regimen had similar fungal clearance (MD 0.05 log CFU/mL/day, 95% CI -0.02 to 0.12; 186 participants, 1 study) as well as lower risk of grade three or four anaemia (RR 0.31, 95% CI 0.16 to 0.60; 228 participants, 1 study) compared to the two-week regimen of AmBd and 5FC.For 10-week mortality, the comparison of two weeks of 5FC and FLU with two weeks of AmBd and 5FC (RR 0.92, 95% CI 0.69 to 1.23; 340 participants, 1 study) or two weeks of AmBd and FLU (RR 0.85, 95% CI 0.64 to 1.13; 339 participants, 1 study) did not show a difference in mortality, with moderate-certainty evidence for both comparisons.When two weeks of combination AmBd and 5FC was compared with AmBd alone, pooled data showed lower mortality at 10 weeks (RR 0.66, 95% CI 0.46 to 0.95; 231 participants, 2 studies, moderate-certainty evidence).When two weeks of AmBd and FLU was compared to AmBd alone, there was no difference in 10-week mortality in pooled data (RR 0.94, 95% CI 0.55 to 1.62; 371 participants, 3 studies, low-certainty evidence).One week of AmBd and 5FC followed by FLU on days 8 to 14 was the best induction therapy regimen after comparison with 11 other regimens for 10-week mortality in the network meta-analysis, with an overall SUCRA ranking of 88%.
AUTHORS' CONCLUSIONS
In resource-limited settings, one-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis. An all-oral regimen of two weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered. We found no mortality benefit of combination two weeks AmBd and FLU compared to AmBd alone. Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings.
Topics: Acetazolamide; Acute Disease; Adult; Amphotericin B; Antifungal Agents; Developing Countries; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Health Resources; Humans; Induction Chemotherapy; Intracranial Hypertension; Meningitis, Cryptococcal; Network Meta-Analysis
PubMed: 30045416
DOI: 10.1002/14651858.CD005647.pub3 -
Frontiers in Neurology 2020Reported cerebrovascular events in patients with COVID-19 are mainly ischemic, but hemorrhagic strokes and cerebral venous sinus thrombosis (CSVT), especially in...
Reported cerebrovascular events in patients with COVID-19 are mainly ischemic, but hemorrhagic strokes and cerebral venous sinus thrombosis (CSVT), especially in critically ill patients, have also been described. To date, it is still not clear whether cerebrovascular manifestations are caused by direct viral action or indirect action mediated by inflammatory hyperactivation, and in some cases, the association may be casual rather than causal. To conduct a systematic review on the cerebrovascular events in COVID-19 infection. A comprehensive literature search on PubMed was performed including articles published from January 1, 2020, to July 23, 2020, using a suitable keyword strategy. Additional sources were added by the authors by reviewing related references. The systematic review was conducted in accordance with the PRISMA guidelines. Only articles reporting individual data on stroke mechanism and etiology, sex, age, past cardiovascular risk factors, COVID symptoms, admission NIHSS, D-dimer levels, and acute stroke treatment were selected for the review. Articles that did not report the clinical description of the cases were excluded. A descriptive statistical analysis of the data collected was performed. From a total of 1,210 articles published from January 1, 2020, to July 23, 2020, 80 articles (275 patients), which satisfied the abovementioned criteria, were included in this review. A total of 226 cases of ischemic stroke (IS), 35 cases of intracranial bleeding, and 14 cases of CVST were found. Among patients with IS, the mean age was 64.16 ±14.73 years (range 27-92 years) and 53.5% were male. The mean NIHSS score reported at the onset of stroke was 15.23 ±9.72 (range 0-40). Primary endovascular thrombectomy (EVT) was performed in 24/168 patients (14.29%), intravenous thrombolysis (IVT) was performed in 17/168 patients (10.12%), and combined IVT+EVT was performed in 11/168 patients (6.55%). According to the reported presence of large vessel occlusion (LVO) (105 patients), 31 patients (29.52%) underwent primary EVT or bridging. Acute intracranial bleeding was reported in 35 patients: 24 patients (68.57%) had intracerebral hemorrhage (ICH), 4 patients (11.43%) had non-traumatic subarachnoid hemorrhage (SAH), and the remaining 7 patients (20%) had the simultaneous presence of SAH and ICH. Fourteen cases of CVST were reported in the literature (50% males), mean age 42.8 years ±15.47 (range 23-72). Treatment was reported only in nine patients; seven were treated with anticoagulant therapy; one with acetazolamide, and one underwent venous mechanical thrombectomy. Cerebrovascular events are relatively common findings in COVID-19 infection, and they could have a multifactorial etiology. More accurate and prospective data are needed to better understand the impact of cerebrovascular events in COVID-19 infection.
PubMed: 33250845
DOI: 10.3389/fneur.2020.574694 -
Journal of Clinical Sleep Medicine :... Jun 2021The recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
The recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high altitude but benefits at sea level are less well understood.
METHODS
All controlled studies of acetazolamide in obstructive sleep apnea and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index.
RESULTS
Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] -15.82, 95% CI: -21.91 to -9.74, P < .00001) in central sleep apnea (MD -22.60, 95% CI: -29.11 to -16.09, P < .00001), but not in obstructive sleep apnea (MD -10.29, 95% CI: -33.34 to 12.77, P = .38). Acetazolamide reduced the respiratory related arousal index (MD -0.82, 95% CI: -1.56 to -0.08, P = .03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13-14.11, P < .00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53-3.04, P = .005), total sleep time (MD 25.74, 95% CI: 4.10-47.38, P = .02), N2 sleep (MD 3.34, 95% CI: 0.12-6.56, P = .04) and sleep efficiency (MD 4.83, 95% CI: 0.53-9.13, P = .03).
CONCLUSIONS
Acetazolamide improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis.
SYSTEMATIC REVIEW REGISTRATION
Registry: PROSPERO; Name: The effect of acetazolamide in patients with sleep apnea at sea level: a systematic review and meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316.
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Humans; Polysomnography; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
PubMed: 33538687
DOI: 10.5664/jcsm.9116