Short-term side effects of COVID-19 vaccines among healthcare workers: a multicenter study in Iran.

Since the initiation of the COVID-19 vaccination effort, there has been widespread concern regarding vaccine efficacy and potential side effects. This study aimed to explore the short-term side effects of four available COVID-19 vaccines (Sputnik V, Sinopharm, Oxford-AstraZeneca, and Covaxin) among healthcare workers (HCWs) in Iran. The multicenter study involved 1575 HCWs, with the majority received Sputnik V (74.1%), followed by Covaxin (15.6%), Sinopharm (6.4%), and Oxford-AstraZeneca (3.8%). The prevalence of at least one side effect after the first and second dose COVID-19 vaccine was 84.6% and 72.9%, respectively. The common side effects (presented in > 50% of the study participants) after the first dose of the vaccine were injection site pain (61.7%), myalgia (51.8%), and muscle pain (50.9%). The most reported side effects after the second dose of the vaccine were injection site pain (26.8%), myalgia (15.8%), fever (10.3%), headache (9.9%), and chills (9.2%). In conclusion, according to the COVID-19 vaccine type, different side effects might occur following the first and second doses of vaccination. These findings assist in addressing the ongoing problems of vaccination hesitancy which has been driven by widespread worries about the vaccine safety profile.

Efficacy and outcomes of Bempedoic acid versus placebo in patients with statin-intolerance: A pilot systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies. MATERIALS AND METHODS: An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes. RESULTS: Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in %: -25.24; 95 % CI: -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %:-21.28; 95 % CI:-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in %: -23.27; 95 % Cl: -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %:-3.37, 95 % CI:-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR:0.81; 95 % CI:0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR:0.67; 95 % CI:0.50 to 0.88; p = 0.005], and myocardial infarction [RR:0.76; 95 % CI:0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR:0.81; p = 0.15], ACM [RR:0.86; p = 0.46], cardiovascular-related mortality [RR:0.79; p = 0.44], and stroke [RR:0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR:0.80; p = 0.0002], while the risk for gout [RR:1.46; p < 0.0001] and hyperuricemia [RR:1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups. CONCLUSION: Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.

Are statins making older persons weaker? A discontinuation study of muscular side effects.

Thirteen percent of the Danish population are treated with a statin-half of these are in primary prevention, and most are > 65 years old. Statins have known muscular side effects (i.e., myalgia) correlated to reduced muscle performance. This study examines if years of statin treatment in older people introduce subclinical muscle discomfort and loss of muscle mass and strength. In total, 98 participants (71.1 ± 3.6 years (mean ± SD)), who were in primary prevention treatment for elevated plasma cholesterol with a statin, were included in this study. Statin treatment was discontinued for 2 months and then re-introduced for 2 months. Primary outcomes included muscle performance and myalgia. Secondary outcomes included lean mass and plasma cholesterol. Functional muscle capacity measured as a 6-min walk test increased after discontinuation (from 542 ± 88 to 555 ± 91 m, P < 0.05) and remained increased after re-introduction (557 ± 94 m). Similar significant results were found with a chair stand test (15.7 ± 4.3 to 16.3 ± 4.9 repetitions/30 s) and a quadriceps muscle test. Muscle discomfort during rest did not change significantly with discontinuation (visual analog scale from 0.9 ± 1.7 to 0.6 ± 1.4) but increased (P < 0.05) with the re-introduction (to 1.2 ± 2.0) and muscle discomfort during activity decreased (P < 0.05) with discontinuation (from 2.5 ± 2.6 to 1.9 ± 2.3). After 2 weeks of discontinuation, low-density lipoprotein cholesterol increased from 2.2 ± 0.5 to 3.9 ± 0.8 mM and remained elevated until the re-introduction of statins (P < 0.05). Significant and lasting improvements in muscle performance and myalgia were found at the discontinuation and re-introduction of statins. The results indicate a possible statin-related loss of muscle performance in older persons that needs further examination.

Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although statins are often discontinued when myalgia arises, a causal relationship may not always exist. How well-tolerated statins are when rechallenge is blinded and controlled is unclear. METHODS AND FINDINGS: We performed a systematic review and meta-analysis (PROSPERO CRD42023437648) to evaluate the success of statin rechallenge versus matched placebo in those who were previously statin intolerant. Our primary outcome was intolerance; our secondary outcome was the myalgia or global symptom score. Medline, Embase, CINAHL Plus, Scopus, and CENTRAL were searched from inception to May 1, 2023. Eligible trials were randomized controlled trials with parallel or crossover designs examining statin rechallenge in statin-intolerant adults. Two independent reviewers selected studies, extracted data, and assessed risk of bias (Cochrane Collaboration's risk-of-bias tool 1). Relative risk (RR) and mean difference (MD) were estimated using fixed effect Mantel-Haenszel statistics. Of 1,941 studies screened, 8 met our inclusion criteria (8 to 491 participants from Asia, Europe, North America, and Oceana). Compared to placebo, intolerance was more common in statin users [325/906 (36%) vs 233/911 (26%), RR 1.40, 95% CI, 1.23 to 1.60, I2 = 0%, 7 trials, number needed to harm 10] and there was no statistically significant difference in myalgia or global symptom score on a 100-point scale [MD 1.08, 95% CI, -1.51 to 3.67, I2 = 0%, 5 trials]. Limitations include only 1 trial asking participants about intolerable symptoms (vs inferring intolerance from discontinuation or trial withdrawal); the small number of trials; the possibility of attrition bias; and the potential for carryover effects in crossover/n-of-1 trial designs. CONCLUSIONS: Of those previously intolerant of statins who were rechallenged with a statin and compared to placebo recipients, medication intolerance was more common amongst statin recipients. However, there was no significant difference in mean myalgia or global symptom score between statin and placebo, and only one-third of those previously believed to be statin intolerant were unable to tolerate a statin on blinded rechallenge; one-quarter were intolerant of placebo.

Effects of conditioned pain modulation on Capsaicin-induced spreading muscle hyperalgesia in humans.

OBJECTIVES: Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. METHODS: Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. RESULTS: Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). CONCLUSIONS: The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits.

P2X7-NLRP3-Caspase-1 signaling mediates activity-induced muscle pain in male but not female mice.

ABSTRACT: We developed an animal model of activity-induced muscle pain that is dependent on local macrophage activation and release of interleukin-1ß (IL-1ß). Activation of purinergic type 2X (P2X) 7 receptors recruits the NOD-like receptor protein (NLRP) 3 and activates Caspase-1 to release IL-1ß. We hypothesized that pharmacological blockade of P2X7, NLRP3, and Caspase-1 would prevent development of activity-induced muscle pain in vivo and release of IL-1ß from macrophages in vitro. The decrease in muscle withdrawal thresholds in male, but not female, mice was prevented by the administration of P2X7, NLRP3, and Caspase-1 inhibitors before induction of the model, whereas blockade of IL-1ß before induction prevented muscle hyperalgesia in both male and female mice. Blockade of P2X7, NLRP3, Capsase-1, or IL-1ß 24 hours, but not 1 week, after induction of the model alleviated muscle hyperalgesia in male, but not female, mice. mRNA expression of P2X7, NLRP3, Caspase-1, and IL-1ß from muscle was increased 24 hours after induction of the model in both male and female mice. Using multiplex, increases in IL-1ß induced by combining adenosine triphosphate with pH 6.5 in lipopolysaccharide-primed male and female macrophages were significantly lower with the presence of inhibitors of P2X7 (A740003), NLRP3 (MCC950), and Caspase-1 (Z-WEHD-FMK) when compared with the vehicle. The current data suggest the P2X7/NLRP3/Caspase-1 pathway contributed to activity-induced muscle pain initiation and early maintenance phases in male but not female, and not in late maintenance phases in male mice.

Vascular endothelial growth factor-A is involved in intramuscular carrageenan-induced cutaneous mechanical hyperalgesia through the vascular endothelial growth factor-A receptor 1 and transient receptor potential vanilloid 1 pathways.

OBJECTIVES: Vascular endothelial growth factor-A (VEGF-A) plays a leading role in angiogenesis and pain hypersensitivity in cancer and chronic pain. It is not only induced by ischemic conditions but is also highly correlated with proalgesic cytokines, both of which are prominent in inflammatory muscle pain. However, the molecular basis of the involvement of VEGF-A in muscle pain remains unknown. METHODS: In the present study, we performed behavioral and pharmacological analyses to determine the possible involvement of VEGF-A in the development of inflammatory muscle pain and the associated signal transduction pathway. RESULTS: Unilateral intramuscular injection of carrageenan, a classical model of inflammatory muscle pain, increased VEGF-A gene expression in the tissues surrounding the injection site. Intramuscular administration of recombinant VEGF-A165 on the same side induced cutaneous mechanical hyperalgesia during the acute and subacute phases. The application of a specific VEGFR1 antibody on the same side significantly reduced the mechanical hyperalgesia induced by carrageenan or VEGF-A165 injection, whereas both a VEGFR2-neutralizing antibody and a VEGFR2 antagonist showed limited effects. Local preinjection of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist, also inhibited VEGF-A165-induced hyperalgesia. Finally, intramuscular VEGF-A165-induced mechanical hyperalgesia was not found in TRPV1 knockout mice during the subacute phase. CONCLUSIONS: These findings suggest that inflammatory stimuli increase interstitial VEGF-A165, which in turn induces cutaneous mechanical pain via the VEGFR1-mediated TRPV1 nociceptive pathway during inflammatory muscle pain. VEGFR1 could be a novel therapeutic target for inflammation-induced muscle pain.

Ritodrine-induced rhabdomyolysis and psychiatric symptoms: a case report and literature review.

BACKGROUND: Ritodrine hydrochloride, a ß2-adrenergic agonist, has been widely used in Asia and Europe to treat preterm labor in pregnant women. It has some typical side effects, such as palpitations, pulmonary edema, and hypokalemia. Here, we report a case of rhabdomyolysis and psychiatric symptoms might be associated with intravenous ritodrine. CASE PRESENTATION: A 32-year-old Chinese primigravida woman who was pregnant with twins by in vitro fertilization-embryo transfer was diagnosed with placenta previa and threatened abortion at 21 gestational weeks (GW). The patient was then treated with ritodrine hydrochloride. The initial dose of ritodrine was 150 µg/min, gradually increasing to 360 µg/min at 235/7 GW and 400 µg/min at 271/7 GW. Magnesium sulfate was added to the ritodrine regimen at 215/7 GW in dosage of 1-2 g/h. Psychiatric symptoms appeared at 245/7, 265/7, and 273/7 GW, manifesting as depression, anxiety, and suicidal tendencies. Severe muscle pain in her limbs and general weakness appeared after six weeks of ritodrine administration, which might have been a sign of rhabdomyolysis resulting from ritodrine administration. After ceasing the administration of ritodrine, the muscle pain and relevant data from laboratory tests on the patient were significantly improved, and her mood was stable. It is worth noting that this is the first time to report psychiatric symptoms may associated with the administration of ritodrine. In addition, we reviewed and analyzed six reported cases of rhabdomyolysis caused by ritodrine. CONCLUSION: Our results suggest that we should pay more attention to the risk of rhabdomyolysis and psychiatric symptoms induced by intravenous ritodrine hydrochloride, especially in patients with a history of neuromuscular disorder, or concomitant use of magnesium sulfate.

Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study.

BACKGROUND: The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAFV600E-mutated (BRAFV600Emut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFV600Emut mCRC patients who had progressed after 1-2 previous regimens. This analysis provides a detailed examination of the adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON study to aid gastrointestinal oncologists, given the limited experience with this combination. MATERIALS AND METHODS: AEIs, including dermatological AEs, arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia and nephrotoxicity, were examined in the doublet therapy group. Clinical characteristics associated with these AEs, AE grade, time to onset and time to resolution were also studied. RESULTS: Safety analysis included 216/220 patients randomized to doublet therapy. The most commonly occurring AEI was dermatological toxicity (75.5%), followed by arthralgia/myalgia (56.0%) and fatigue/asthenia (56.0%). Other than nephrotoxicity (7 patients; 5/7 with Grade 3 or 4), most AEs were Grade 1 or 2. Most AEs were more common in women than men (nausea/vomiting, diarrhea, abdominal pain, dermatological AEs, and arthralgia/myalgia). Nausea/vomiting, abdominal pain and fatigue/asthenia were more common in patients aged ≥70 years. Most AEs developed early, within the first 1-2 months of treatment, and resolved within 1-2 weeks. In addition, survival outcomes were better in patients experiencing arthralgia/myalgia or dermatological toxicities. CONCLUSION: This analysis indicated that, except for rare cases of nephrotoxicity, encorafenib+cetuximab is well tolerated in most patients, with most AEIs being mild-to-moderate in severity, occurring early and resolving rapidly. CLINICAL TRIAL REGISTRATION: the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35).

Statins increase muscle pain or weakness at 1 y, with an absolute excess of 11 events/1000 person-y.

SOURCE CITATION: Cholesterol Treatment Trialists' Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022;400:832-45. 36049498.

Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications.

Treatment with statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, has proven beneficial preventive effects on cardiovascular events. However, discontinuation due to intolerance and non-adherence remain two of the major gaps in both primary and secondary prevention. This leads many patients with high-risk of atherosclerotic cardiovascular disease (ASCVD) to be inadequately treated or not to achieve target lipid level goals, and as consequence they undergo an increased risk of cardiovascular events. The aim of this review is thus to give an overview of the reasons for discontinuation and on the possible mechanisms behind them. Although statins, as a class, are generally safe, they are associated with an increased risk of diabetes mellitus and hepatic transaminase elevations. Incidence of cataracts or cognitive dysfunction and others presented in the literature (e.g. proteinuria and haematuria) have been never confirmed to have a causal link. Conversely, debated remains the effect on myalgia. Muscle side effects are the most commonly reported, although myalgia is still believed by some to be the result of a nocebo/drucebo effect. Concerning mechanisms behind muscular side effects, no clear conclusions have been reached. Thus, if on one side it is important to identify individuals either at higher risk to develop a side effect, or with confirmed risk factors and conditions of statin intolerance, on the other side alternative strategies should be identified to avoid an increased ASCVD risk.

Selective androgen receptor modulator microparticle formulation reverses muscle hyperalgesia in a mouse model of widespread muscle pain.

ABSTRACT: Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. Although preclinical and clinical studies demonstrate the analgesic effects of testosterone, clinical use of testosterone is limited by adverse androgenic effects. Selective androgen receptor modulators (SARMs) activate androgen receptors and overcome treatment limitations by minimizing androgenic side effects. Thus, we tested whether daily soluble SARMs or a SARM-loaded microparticle formulation alleviated muscle hyperalgesia in a mouse-model of widespread pain (male and female C57BL/6J mice). We tested whether the analgesic effects of the SARM-loaded microparticle formulation was mediated through androgen receptors by blocking androgen receptors with flutamide pellets. In vitro and in vivo release kinetics were determined for SARM-loaded microparticles. Safety and toxicity of SARM treatment was determined using serum cardiac and liver toxicity panels, heart histology, and conditioned place preference testing. Subcutaneous daily SARM administration, and 2 injections, 1 week apart, of SARM-loaded microparticles alleviated muscle hyperalgesia in both sexes and was prevented with flutamide treatment. Sustained release of SARM, from the microparticle formulation, was observed both in vitro and in vivo for 4 weeks. Selective androgen receptor modulator treatment produced no cardiac or liver toxicity and did not produce rewarding behaviors. These studies demonstrate that SARM-loaded microparticles, which release drug for a sustained period, alleviate muscle pain, are safe, and may serve as a potential therapeutic for chronic muscle pain.

Adverse events following immunisation of COVID-19 vaccine among health care workers in the first phase of vaccination.

INTRODUCTION: The new COVID-19 vaccine was met with worldwide overwhelming uncertainties pertaining to its safety profile, effectiveness, and potential adverse reactions when it was first introduced. This led to vaccine refusal and delay in vaccine uptake in many countries including Malaysia. The objective of this study was to determine the Adverse Events Following Immunization (AEFI) to the COVID-19 vaccine. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted among healthcare workers who received the COVID-19 vaccine during the first phase of immunisation from eight public primary clinics in Johor Bahru district. Data were collected between May and September 2021 using a self-administered questionnaire. RESULTS: A total of 240 healthcare workers participated and all of them received the Pfizer Messenger RNA vaccine. Our study found that a large majority of vaccine recipients (87.5%, n=210) experienced AEFI to COVID-19 vaccine for either the first, second, or both doses. More than 80% of them experienced more than one type of AEFI. The most common AEFI reported during the first and second dose was localised symptom such as pain at injection site (60-68%), pain on the injected arm (52-61%), and swelling at injection site (32-33%). Common systemic symptoms were fever (22- 57%), myalgia (20-45%), and dizziness (24-26%). Although a large majority experienced AEFI, these reactions were mostly of mild to moderate severity (47.3-73.6%). The mean duration of AEFI onset was within 30 minutes to about 1 day (0.33-22.5 hours) of injection and lasted between 30 minutes and 2.5 days. There was no association between demographic characteristic of participants and severity of AEFI to COVID-19 vaccine. Mean duration of fever was significantly (p=0.005) longer after the second dose (34.2 hours) of vaccine compared to first (20.6 hours) CONCLUSION: This study shows that a large majority of COVID-19 vaccine recipients experienced AEFI; however, these reactions were mostly of mild to moderate severity and lasted between 30 minutes and 2.5 days. A large majority experienced more than one type of AEFI. The most common AEFI was localised reactions consisting of pain and swelling at the injection site and pain on the injected arm. The most common systemic reactions were fever, myalgia, and dizziness. Duration of fever was significantly longer after the second dose.

CV Benefits of Statins Outweigh Muscle Pain Risk.

According to this study: Statin therapy causes a small increase in reports of muscle pain, largely during the first year of treatment.The cardiovascular benefits of statins outweigh the risk of muscle pain.

Are Chronic Pain Syndromes the Reason for Statin-associated Muscle Symptoms?

BACKGROUND: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia. OBJECTIVES: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not. METHODS: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population. RESULTS: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia. CONCLUSIONS: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

Effectiveness and safety of statins on outcomes in patients with HIV infection: a systematic review and meta-analysis.

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508-0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561-1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564-1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031-2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770-2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457-2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605-4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

[Systematic review and Meta-analysis of Lianhua Qingwen preparations combined with Oseltamivir in treatment of influenza].

This study aims to explore the efficacy and safety of Lianhua Qingwen preparations combined with Oseltamivir in the treatment of influenza patients. PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang, and VIP were searched for the randomized controlled trials(RCTs) involving the comparison between the influenza patients treated with Lianhua Qingwen preparations combined with Oseltamivir and those treated with Oseltamivir alone. Fever clearance time was taken as the primary outcome indicator. Clinical effective rate(markedly effective and effective), time to muscle pain relief, time to sore throat relief, time to cough relief, time to nasal congestion and runny nose relief, time to negative result of viral nucleic acid test, and adverse reactions were taken as the secondary outcome indicators. The data were extracted based on the outcome indicators and then combined. The Cochrane collaboration's tool for assessing risk of bias was used to evaluate the quality of a single RCT, and the grading of recommendations assessment, development and evaluations(GRADE) system to assess the quality of a single outcome indicator. RevMan 5.3 was employed to analyze data and test heterogeneity. Finally, 16 RCTs involving 1 629 patients were included for analysis. The Meta-analysis showed that Lianhua Qingwen preparations combined with Oseltamivir was superior to Oseltamivir alone in the treatment of influenza in terms of clinical effective rate(RR=1.16, 95%CI [1.12, 1.20], P<0.000 01), fever clearance time(SMD=-2.02, 95%CI [-2.62,-1.41], P<0.000 01), time to muscle pain relief(SMD=-2.50, 95%CI [-3.84,-1.16], P=0.000 2), time to sore throat relief(SMD=-1.40, 95%CI [-1.93,-0.85], P<0.000 01), time to cough relief(SMD=-1.81, 95%CI [-2.44,-1.19], P<0.000 01), time to nasal congestion and runny nose(SMD=-2.31, 95%CI [-3.61,-1.01], P=0.000 5), and time to negative result of viral nucleic acid test(SMD=-0.68, 95%CI [-1.19,-0.16], P=0.01). However, due to the low quality of the trials, the above conclusions need to be proved by more high-quality clinical studies. In addition, we still need to attach importance to the adverse reactions of the integrated application of Chinese and western medicines.