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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 -
The Neurologist May 2021Cerebral venous sinus thrombosis (CVST) can rarely present with cranial neuropathies other than abducent nerve palsy. The authors report a case and review the literature...
INTRODUCTION
Cerebral venous sinus thrombosis (CVST) can rarely present with cranial neuropathies other than abducent nerve palsy. The authors report a case and review the literature for nonabducent cranial neuropathies in CVST.
CASE REPORT
A 22-year-old woman with a history of oral contraceptive use developed right-sided headache, blurred vision, and dizziness for 4 days. Magnetic resonance venogram showed complete thrombosis of the right transverse sinus, sigmoid sinus, and internal jugular vein, and partial thrombosis of the superior sagittal sinus, left transverse sinus, and superior part of the left internal jugular vein. Hypercoagulable workup revealed heterozygous factor V Leiden mutation. About 2 weeks after symptom onset, she developed right facial droop and left eye ptosis. Examination revealed bilateral papilledema, partial left ptosis, complete right abducent, and right peripheral facial palsies. Acetazolamide 250 mg 2 times per day was initiated for the treatment of headache. Three days after starting acetazolamide left ptosis, right facial and abducent palsies improved that continued to get better with only slight deficits at discharge 4 weeks from symptom onset. Follow-up computed tomography venogram on day 24 showed partial recanalization of CVST.
CONCLUSION
A systematic review identified 26 patients from 21 articles with nonabducent cranial neuropathies. Seven patients had lower motor neuron facial palsy, 13 patients had hearing loss or vertigo with vestibulocochlear involvement, and 6 patients had other mixed cranial nerve palsies with CVST. They are usually associated with transverse sinus and/or sigmoid sinus thrombosis. They have a good prognosis with improvement and complete resolution of cranial neuropathies in most cases usually in 1 month.
Topics: Adult; Female; Humans; Papilledema; Sinus Thrombosis, Intracranial; Superior Sagittal Sinus; Tomography, X-Ray Computed; Transverse Sinuses; Young Adult
PubMed: 33942790
DOI: 10.1097/NRL.0000000000000310 -
Cardiology in the Young May 2021Paediatric cardiac surgery on cardiopulmonary bypass induces substantial physiologic changes that contribute to post-operative morbidity and mortality. Fluid overload...
BACKGROUND
Paediatric cardiac surgery on cardiopulmonary bypass induces substantial physiologic changes that contribute to post-operative morbidity and mortality. Fluid overload and oedema are prevalent complications, routinely treated with diuretics. The optimal diuretic choice, timing of initiation, dose, and interval remain largely unknown.
METHODS
To guide clinical practice and future studies, we used PubMed and EMBASE to systematically review the existing literature of clinical trials involving diuretics following cardiac surgery from 2000 to 2020 in children aged 0-18 years. Studies were assessed by two reviewers to ensure that they met eligibility criteria.
RESULTS
We identified nine studies of 430 children across four medication classes. Five studies were retrospective, and four were prospective, two of which included randomisation. All were single centre. There were five primary endpoints - urine output, acute kidney injury, fluid balance, change in serum bicarbonate level, and required dose of diuretic. Included studies showed early post-operative diuretic resistance, suggesting higher initial doses. Two studies of ethacrynic acid showed increased urine output and lower diuretic requirement compared to furosemide. Children receiving peritoneal dialysis were less likely to develop fluid overload than those receiving furosemide. Chlorothiazide, acetazolamide, and tolvaptan demonstrated potential benefit as adjuncts to traditional diuretic regimens.
CONCLUSIONS
Early diuretic resistance is seen in children following cardiopulmonary bypass. Ethacrynic acid appears superior to furosemide. Adjunct diuretic therapies may provide additional benefit. Study populations were heterogeneous and endpoints varied. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal diuretic, timing of initiation, dose, and interval to improve post-operative outcomes.
Topics: Cardiopulmonary Bypass; Child; Diuretics; Heart Defects, Congenital; Humans; Prospective Studies; Retrospective Studies
PubMed: 33942711
DOI: 10.1017/S1047951121001451 -
The American Journal of the Medical... May 2021Acute mountain sickness (AMS) is a benign and self-limiting syndrome but can progress to life-threatening conditions if leave untreated. This study aimed to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute mountain sickness (AMS) is a benign and self-limiting syndrome but can progress to life-threatening conditions if leave untreated. This study aimed to assess the efficacy of acetazolamide for the prophylaxis of AMS and disclose potential factors that affect the treatment effect of acetazolamide.
MATERIALS AND METHODS
Randomized controlled trials comparing the use of acetazolamide versus placebo for the prevention of AMS were included. The incidence of AMS was the primary endpoint. Meta-regression analysis was conducted to explore potential factors associated with acetazolamide efficacy. Trial sequential analysis (TSA) was conducted to estimate the statistical power of the available data.
RESULTS
A total of 22 trials were included. Acetazolamide at 125, 250, and 375 mg/ twice daily (bid) significantly reduced incidence of AMS compared to placebo. TAS indicated that the current evidence was adequate confirming the efficacy of acetazolamide at 125, 250, and 375 mg/bid in lowering incidence of AMS. There was no evidence of an association between efficacy and dose of acetazolamide, timing at start of acetazolamide treatment, mode of ascent, AMS assessment score, timing of AMS assessment, baseline altitude, and endpoint altitude.
CONCLUSION
Acetazolamide is effective prophylaxis for the prevention of AMS in doses of 125, 250, and 375 mg/bid. Future investigations should focus on personal characteristics, disclosing the correlation between acetazolamide efficacy and body mass, height, degree of prior acclimatization, individual inborn susceptibility, and history of AMS.
Topics: Acetazolamide; Altitude Sickness; Carbonic Anhydrase Inhibitors; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33587912
DOI: 10.1016/j.amjms.2020.12.022 -
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 -
Journal of Neuromuscular Diseases 2021Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital...
BACKGROUND
Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP.
OBJECTIVE
This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background.
METHODS
We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process.
RESULTS
For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS
These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.
Topics: Channelopathies; Humans; Hypokalemic Periodic Paralysis; Lamotrigine; Mexiletine; Muscle, Skeletal; Mutation; Myasthenic Syndromes, Congenital; Myotonic Disorders; Precision Medicine; Randomized Controlled Trials as Topic; Sodium Channel Blockers
PubMed: 33325393
DOI: 10.3233/JND-200582 -
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 -
Revista de Neurologia Nov 2020Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low...
INTRODUCTION
Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low levels of potassium in blood. As a consequence of its low prevalence, there are still clinical and management aspects to characterize.
PATIENTS AND METHODS
A systematic review of the clinical cases published in the last decade has been developed by analyzing demographic and genetic features, the episodes' characteristics, the received treatments, the response to them and also, the differences and evolution of patients depending on the most prevalent genetic alterations: CACNA1S and SCN4A.
RESULTS
A total of 33 articles were included, allowing 40 individuals to be reviewed. The average age of onset of symptoms was 15.3 ± 9.7 years. The most frequent altered gene was CACNA1S in 20 (60.5%) cases. It was observed that subjects presenting an alteration of the gene responsible for the calcium channel, CACNA1S, presented lower serum potassium levels, own triggers and a higher proportion of subjects showing dyspnea during the crisis. Only 50% of the subjects respond to classical oral treatment with acetazolamide. Potassium-sparing diuretics and antiepileptics drugs emerge as an alternative.
CONCLUSION
Hypokalemic periodic paralysis has an heterogeneous clinical expression with phenotypic differences linked to different genetic mutations. The common preventive treatment response is suboptimal. Prospective studies are needed to discern the best therapeutic option based on genetic load.
Topics: Acetazolamide; Age of Onset; Calcium Channels, L-Type; Gene Frequency; Humans; Hypokalemic Periodic Paralysis; NAV1.4 Voltage-Gated Sodium Channel; Potassium
PubMed: 33085076
DOI: 10.33588/rn.7109.2020377 -
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 -
BMJ Open Respiratory Research Apr 2020Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our objective was to estimate the risk of commonly reported side effects based on meta-analyses. We hypothesised that these risks are dose-dependent.
METHODS
We queried MEDLINE/EMBASE (Medical Literature Analysis and Retrieval System Online/Excerpta Medica dataBASE) up until 04/10/2019, including any randomised placebo-controlled trial in which adults received oral AZM versus placebo reporting side effects. Eligibility assessment was performed by two independent reviewers. Data were abstracted by one reviewer who verified key entries at a second time point. For side effects reported by 3 studies a pooled effect estimate was calculated, and heterogeneity assessed via I; for outcomes reported by 5 studies effect modification by total daily dose (EMbyTDD; <400 mg/d, 400-600 mg/d, >600 mg/d) was assessed via meta-regression. For pre-specified, primary outcomes (paraesthesias, taste disturbances, polyuria and fatigue) additional subgroup analyses were performed using demographics, intervention details, laboratory changes and risk of bias.
RESULTS
We included 42 studies in the meta-analyses (N=1274/1211 in AZM/placebo groups). AZM increased the risk of all primary outcomes (p<0.01, I ≤16% and low-to-moderate quality of evidence for all)-the numbers needed to harm (95% CI; n) for each were: paraesthesias 2.3 (95% CI 2 to 2.7; n=39), dysgeusia 18 (95% CI 10 to 38, n=22), polyuria 17 (95% CI 9 to 49; n=22), fatigue 11 (95% CI 6 to 24; n=14). The risk for paraesthesias (beta=1.8 (95% CI 1.1 to 2.9); P=0.01) and dysgeusia (beta=3.1 (95% CI 1.2 to 8.2); P=0.02) increased with higher AZM doses; the risk of fatigue also increased with higher dose but non-significantly (beta=2.6 (95% CI 0.7 to 9.4); P=0.14).
DISCUSSION
This comprehensive meta-analysis of low-to-moderate quality evidence defines risk of common AZM side effects and corroborates dose dependence of some side effects. These results may inform clinical decision making and support efforts to establish the lowest effective dose of AZM for various conditions.
Topics: Acetazolamide; Adult; Dose-Response Relationship, Drug; Dysgeusia; Fatigue; Humans; Paresthesia; Randomized Controlled Trials as Topic
PubMed: 32332024
DOI: 10.1136/bmjresp-2020-000557