Therapeutic potential of pyruvate therapy for patients with mitochondrial diseases: a systematic review

Background: Mitochondrial disease is a term used to describe a set of heterogeneous genetic diseases caused by impaired structure or function of mitochondria. Pyruvate therapy for mitochondrial disease is promising from a clinical point of view. Methods: According to PRISMA guidelines, the following databases were searched to identify studies regarding pyruvate therapy for mitochondrial disease: PubMed, EMBASE, Cochrane Library, and Clinicaltrials. The search was up to April 2019. The endpoints were specific biomarkers (plasma level of lactate, plasma level of pyruvate, L/P ratio) and clinical rating scales [Japanese mitochondrial disease-rating scale (JMDRS), Newcastle Mitochondrial Disease Adult Scale (NMDAS), and others]. Two researchers independently screened articles, extracted data, and assessed the quality of the studies. Results: A total of six studies were included. Considerable differences were noted between studies in terms of study design, patient information, and outcome measures. The collected evidence may indicate an effective potential of pyruvate therapy on the improvement of mitochondrial disease. The majority of the common adverse events of pyruvate therapy were diarrhea and short irritation of the stomach. Conclusion: Pyruvate therapy with no serious adverse events may be a potential therapeutic candidate for patients with incurable mitochondrial diseases, such as Leigh syndrome. However, recent evidence taken from case series and case reports, and theoretical supports of basic research are not sufficient. The use of global registries to collect patient data and more adaptive trial designs with larger numbers of participants are necessary to clarify the efficacy of pyruvate therapy.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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Total Ankle Replacement in Hemophilia

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x19666191210110626 ◽

2020 ◽

Vol 20 (2) ◽

pp. 88-92

Author(s):

Emerito C. Rodriguez-Merchan

Keyword(s):

Adverse Events ◽

Daily Living ◽

Case Reports ◽

Case Series ◽

Total Ankle Replacement ◽

Cochrane Library ◽

Hemophilic Arthropathy ◽

Accessible Information ◽

Ankle Replacement

Introduction: Severe ankle hemophilic arthropathy can be a calamitous sign of severe hemophilia with important inferences for activities of daily living. Aims: To summarize the contemporary, accessible information on Total Ankle Replacement (TAR) for ankle hemophilic arthropathy. Methods: A search of Cochrane Library and PubMed (MEDLINE) regarding the role of TAR in ankle hemophilic arthropathy. Results: The insufficient information regarding the results of TAR for hemophilic arthropathy is confined to scanty case series and case reports. An evaluation of the accessible literature reveals encouraging but inconstant outcomes. The reported rate of adverse events is 33%. The reported anticipated survival of TAR is 94% at 5 years, 85% at 10 years and 70% at 15 years. Conclusion: Whereas people with advanced hemophilic arthropathy of the ankle are prone to ameliorate pain and range of motion following TAR, there is deficient knowledge to regularly recommend its use. Adverse events and infection percentages are disturbing. Moreover, the lack of survival analysis knowledge makes it difficult to assess the benefit to people with hemophilia. TAR is a demanding surgical procedure and its survival is not comparable to that after hip or knee replacement.

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Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia

CNS Spectrums ◽

10.1017/s1092852916000638 ◽

2017 ◽

Vol 22 (5) ◽

pp. 415-426 ◽

Cited By ~ 33

Author(s):

Marco Solmi ◽

Nicola Veronese ◽

Nita Thapa ◽

Silvia Facchini ◽

Brendon Stubbs ◽

...

Keyword(s):

Systematic Review ◽

Rating Scales ◽

Rating Scale ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Positive Symptom ◽

Adjunctive Treatment ◽

Tolerability Profile ◽

Efficacy And Safety

ObjectiveOur aim was to perform an updated systematic review and meta-analysis on the efficacy and safety of adjunctive minocycline as a treatment of schizophrenia.MethodsWe conducted a PubMed/Scopus database search from inception to 3 February 2016 for randomized, placebo-controlled trials (RCTs), open non-randomized studies, and case reports/series evaluating minocycline in patients with schizophrenia. Random-effects meta-analysis of positive, negative, depressive, and cognitive symptom rating scales, discontinuation and adverse effects rates calculating standardized mean difference (SMD), and risk ratios±95% confidence intervals (CI95%) were calculated.ResultsSix RCTs were eligible (minocyclinen=215, placebon=198) that demonstrated minocycline’s superiority versus placebo for reducing endpoint Positive and Negative Syndrome Scale (PANSS) total scores (SMD=–0.59;CI95%=[1.15, –0.03];p=0.04), negative (SMD=–0.76;CI95%=[–1.21, –0.31];p=0.001); general subscale scores (SMD=–0.44;CI95%=[–0.88, –0.00];p=0.05), Clinical Global Impressions scores (SMD=–0.50;CI95%=[–0.78, –0.22];p<0.001); and executive functioning (SMD=0.22;CI95%=[0.01, 0.44];p=0.04). Endpoint PANSS positive symptom scores (p=0.13), depression rating scale scores (p=0.43), attention (p=0.47), memory (p=0.52), and motor speed processing (p=0.50) did not significantly differ from placebo, before execution of a trim-and-fill procedure. Minocycline did not differ compared to placebo on all-cause discontinuation (p=0.56), discontinuation due to inefficacy (p=0.99), and intolerability (p=0.51), and due to death (p=0.32). Data from one open-label study (N=22) and three case series (N=6) were consistent with the metaanalytic results.ConclusionsMinocycline appears to be an effective adjunctive treatment option in schizophrenia, improving multiple relevant disease dimensions. Moreover, minocycline has an acceptable safety and tolerability profile. However, more methodologically sound and larger RCTs remain necessary to confirm and extend these results.

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Safety and Tolerability of Lacosamide in Patients With Epilepsy: A Systematic Review and Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.694381 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chunsong Yang ◽

Yuxuan Peng ◽

Lingli Zhang ◽

Li Zhao

Keyword(s):

Adverse Events ◽

Large Scale ◽

Randomized Clinical Trials ◽

Case Reports ◽

Meta Analysis ◽

Safety Data ◽

Case Series ◽

Cochrane Library ◽

Total Incidence ◽

Patients With Epilepsy

Background: As a third-generation antiseizure medication (ASM), lacosamide (LCM) is recommended worldwide for patients with epilepsy. We aimed to provide more conclusive evidence for the safety and tolerability of LCM in patients with epilepsy.Methods: A systematic search was performed on MEDLINE, Embase, Cochrane Library, CBM, CNKI, IDB, VIP Database, and Wanfang Database from inception to 2021 March, and all studies assessing the safety of LCM were included. A meta-analysis was performed for safety data of LCM.Results: Eighty-three studies involving 12268 populations (11 randomized clinical trials (RCTs), 16 cohort studies, 53 case series, and 3 case reports) were included in our study. Meta-analysis of the total incidence of adverse events (AEs) of LCM was 38.7% [95% CI (35.1%, 45.8%); n=75 studies]. Incidence of withdrawal due to AEs was 10.8% [95% CI (9.1%, 12.6%); n=56 studies], and incidence of serious adverse events (SAEs) was 6.5% [95% CI (4.0%, 8.9%); n=13 studies]. Most AEs were in the nervous system and digestive system. The most common AEs were sedation (15.8%), dizziness (15.7%), fatigue (9.4%), and nausea/vomiting (9.3%). For children, the total incidence of AEs of LCM was 32.8% [95% CI (21.6%, 44.0%); n=16 studies], and the most common AEs were dizziness (8.6%), nausea/vomiting (8.6%), and somnolence (6.8%).Conclusion: Lacosamide is generally safe and well tolerated in patients with epilepsy. Common AEs were sedation, dizziness, and fatigue. It is necessary to pay more attention to the prevention and management of these AEs and conduct more large-scale and high-quality studies to update safety data.

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Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835921992989 ◽

2021 ◽

Vol 13 ◽

pp. 175883592199298

Author(s):

Orthi Shahzad ◽

Nicola Thompson ◽

Gerry Clare ◽

Sarah Welsh ◽

Erika Damato ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Case Series ◽

Simple Algorithm ◽

Cancer Therapeutics ◽

Management Algorithm ◽

Ocular Symptoms ◽

Systemic Corticosteroids ◽

Permanent Loss

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

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Neurological manifestations and neuroimaging findings in patients with SARS-CoV2—a systematic review

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00322-3 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Nikita Mohan ◽

Muhammad Ali Fayyaz ◽

Christopher del Rio ◽

Navpreet Kaur Rajinder Singh Khurana ◽

Sampada Sandip Vaidya ◽

...

Keyword(s):

Neurological Diseases ◽

Case Reports ◽

Healthcare Providers ◽

Case Series ◽

Altered Mental Status ◽

Common Finding ◽

Cochrane Library ◽

Neurological Manifestations ◽

The Cochrane Library ◽

Ct And Mri

Abstract Background The COVID-19 pandemic has drastically affected everyone in a hit or miss manner. Since it began, evidence of the neuro-invasive potential of the virus has been intensifying significantly. Several pathways have been hypothesized to elucidate the neurotropic nature of SARS-CoV2. It is the need of the hour to collect vital information. Objective To evaluate and correlate the neuro-radiological and neurological manifestations in patients diagnosed with SARS-CoV2. To identify neuro-invasive pathways of COVID infection. Methods Relevant studies were identified through four databases—the Cochrane Library, PubMed, Science Direct, and Web of Science. These were searched using relevant keywords—“COVID-19,” “SARS-CoV2,” “neurological manifestations,” “neuroimaging,” “CT,” and “MRI.” Relevant articles were screened according to a pre-defined inclusion and exclusion criteria from December 2019 to August 2020. Results Our review included a total of 63 full text publications with 584 patients, composed mainly of observational studies, case reports, and case series. The most common neurological manifestations associated with COVID-19 were altered mental status, stroke, and paralysis. About 17.85% patients who underwent neuroimaging were found to be having ischemic changes suggestive of a stroke. This was followed by hemorrhagic changes as the second most common finding. The most commonly involved vessel was the Middle Cerebral Artery. Besides stroke, we found that SARS-CoV2 could be the cause for new-onset seizures, Guillain-Barre Syndrome, encephalitis, and many other severe neurological diseases. Conclusion The information that we have obtained so far will prove dynamic to healthcare providers working against the COVID-19 pandemic. It is necessary to be aware of these atypical neurological findings for the early diagnosis and treatment of COVID-19 infected patients. However, to completely understand the connection between SARS-CoV2 and the nervous system, further research is necessary.

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Real-world risk of anosmia with cancer directed systemic therapy: A pharmacovigilance assessment using FDA Adverse Events Reporting System (FAERS) database.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18790 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18790-e18790

Author(s):

Anahat Kaur ◽

Shuai Wang ◽

Arlene Yu ◽

Tarek N. Elrafei ◽

Lewis Steinberg ◽

...

Keyword(s):

Adverse Events ◽

Reporting System ◽

Case Reports ◽

Descriptive Analysis ◽

Package Insert ◽

Case Series ◽

The United States ◽

Chemotherapeutic Agents ◽

United States Food ◽

Pharmacovigilance Database

e18790 Background: Anosmia is a rare and under-reported adverse event associated with the use of several oncologic drugs. Instances of olfactory disturbances following administration of chemotherapeutic agents have been sporadically documented in case reports and case series. We aimed to conduct a more comprehensive study to generate signal for anosmia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of anosmia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 10250 cases of anosmia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 139 cases. Some of the most common suspect medications exclusively associated with more than one case of anosmia were palbociclib (n=16), enzalutamide (13), pazopanib (8), cabozantinib (8), letrozole (6), leuprolide (5), niraparib (5), rucaparib (4), tamoxifen (4), capecitabine (3), everolimus (3), anastrazole (2), exemestane (2), zoledronic acid (2), vandetanib (2) and vismodegib (2). Detailed description of medications with highest number of reported cases is listed in Table. Median age at diagnosis was 66 years (interquartile range 58-71). Anosmia was reported more commonly in females (64% ) as compared to males (33.8%). Reactions were reported to the FDA more commonly by consumers (56.8%) as compared to healthcare professionals (40.3% cases). Out of 139 patients with anosmia, 93 (66.9%) had concomitant ageusia, 8 (5.7 %) had dysgeusia and 6 (4.3%) patients had neuropathy. Conclusions: This study demonstrates a signal for anosmia as side effect in patients receiving select oncologic medications based on the FAERS database. It is worth noting that none of the suspect medications identified in this study have anosmia listed as known adverse reaction on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and olfactory function compromise. [Table: see text]

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Rituximab for Eosinophilic Granulomatosis with Polyangiitis: a Systematic Review of Observational Studies

Rheumatology ◽

10.1093/rheumatology/keab046 ◽

2021 ◽

Author(s):

Vincenzo G Menditto ◽

Giulia Rossetti ◽

Diletta Olivari ◽

Alessia Angeletti ◽

Marco Rocchi ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Granulomatosis With Polyangiitis ◽

Case Reports ◽

Case Series ◽

Biologic Agents ◽

Cochrane Library ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Extensive Literature ◽

Eosinophilic Granulomatosis

Abstract Objective to analyze the available evidence about the use of rituximab (RTX) and other biologic agents in Eosinophilic Granulomatosis with Polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. Methods A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases and an extensive literature search on other biologic agents. Results 45 papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in pANCA positive subgroup. Conclusion Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impairs a clear interpretation of results and limits their transferability in clinical practice. Differences in design, enrollment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.

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Z-drugs and Falls: A Focused Review of the Literature

The Senior Care Pharmacist ◽

10.4140/tcp.n.2020.549 ◽

2020 ◽

Vol 35 (12) ◽

pp. 549-554

Author(s):

Nicole Ryba ◽

Rebecca Rainess

Keyword(s):

Primary Outcome ◽

Case Reports ◽

Inappropriate Medication ◽

Case Series ◽

Cochrane Library ◽

Inpatient Setting ◽

Care Hospital ◽

Review Of The Literature ◽

Increased Risk ◽

Risk Of Falls

OBJECTIVE: To provide a focused review of the literature related to the association between exposure to Z-drugs and the risk of falls, especially in the older population. DATA SOURCES: A literature search was conducted using Medline, PsychInfo, and the Cochrane Library database for all clinical trials, case series, and case reports published in English up to May 2020. The search terms used consisted of each Z-drug, including "zolpidem," "zopiclone," "eszopiclone," and "zaleplon," matched with "falls." STUDY SELECTION: The search yielded 295 studies. After review of abstracts, content and references were reviewed, and duplicates removed, a total of 9 articles met inclusion of exposure to at least 1 Z-drug and a primary outcome of falls. DATA EXTRACTION: The American Geriatrics Society 2019 Beers Criteria Update for Potentially Inappropriate Medication Use in Older Adults recommends to avoid using nonbenzodiazepine hypnotics in this patient population because of the risk of adverse events. DATA SYNTHESIS: A majority of the literature suggests an increased risk of falls with exposure to Z-drug use, especially zolpidem. Eight trials examined falls as a primary outcome in non-elderly (n=3) and elderly (n=5) patients in different settings, mostly in an inpatient setting (nursing facility or acute care hospital). CONCLUSION: Exposure to Z-drugs, especially zolpidem, should be evaluated and counseled on continuously as these medications put patients at an increased risk for falls and other complications.

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