Review

Authors: Ron Eccles

The common cold and influenza (flu) are the most common syndromes of infection in human beings. These diseases are diagnosed on symptomatology, and treatments are mainly symptomatic, yet our understanding of the mechanisms that generate the familiar symptoms is poor compared with the amount of knowledge available on the molecular biology of the viruses involved. New knowledge of the effects of cytokines in human beings now helps to explain some of the symptoms of colds and flu that were previously in the realm of folklore rather than medicine-eg, fever, anorexia, malaise, chilliness, headache, and muscle aches and pains. The mechanisms of symptoms of sore throat, rhinorrhoea, sneezing, nasal congestion, cough, watery eyes, and sinus pain are discussed, since these mechanisms are not dealt with in any detail in standard medical textbooks.

Topics: Anorexia; Chills; Common Cold; Cough; Fever; Headache; Humans; Influenza, Human; Pharyngitis; Sneezing

PubMed: 16253889
DOI: 10.1016/S1473-3099(05)70270-X

Meta-Analysis

Authors: Tetsuro Aita, Hiroaki Nakagawa, Sei Takahashi...

BACKGROUND

Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients.

METHODS

We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively.

RESULTS

We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain.

CONCLUSIONS

Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

Topics: Humans; Bacteremia; Adult; Chills; Sensitivity and Specificity

PubMed: 38863066
DOI: 10.1186/s12916-024-03467-z

Authors: Channing J Paller, Lin Wang, Wei Fu...

PURPOSE

Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration.

MATERIALS AND METHODS

This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL.

RESULTS

Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4.

CONCLUSIONS

Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted.

SIGNIFICANCE

Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME's effect on survival and chemotherapy tolerability.

Topics: Humans; Quality of Life; Chills; Neoplasms; Administration, Intravenous; Fatigue; Mistletoe; Nausea

PubMed: 36860652
DOI: 10.1158/2767-9764.CRC-23-0002

Authors: Ethan G Dutcher, Elissa S Epel, Ashley E Mason...

BACKGROUND

Concern about side effects is a common reason for SARS-CoV-2 vaccine hesitancy.

OBJECTIVE

To determine whether short-term side effects of SARS-CoV-2 messenger RNA (mRNA) vaccination are associated with subsequent neutralizing antibody (nAB) response.

DESIGN

Prospective cohort study.

SETTING

San Francisco Bay Area.

PARTICIPANTS

Adults who had not been vaccinated against or exposed to SARS-CoV-2, who then received 2 doses of either BNT162b2 or mRNA-1273.

MEASUREMENTS

Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose.

RESULTS

363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years [SD, 11.9]), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years [SD, 5.3]). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later.

LIMITATIONS

The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown.

CONCLUSION

Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake.

PRIMARY FUNDING SOURCE

National Institute on Aging.

Topics: Humans; Female; Middle Aged; Male; Prospective Studies; Antibodies, Neutralizing; COVID-19; BNT162 Vaccine; SARS-CoV-2; COVID-19 Vaccines; 2019-nCoV Vaccine mRNA-1273; Adult; Antibodies, Viral; Chills; Headache; Fatigue; Aged

PubMed: 38857503
DOI: 10.7326/M23-2956

Meta-Analysis

Authors: Ramy Abou Ghayda, Jinhee Lee, Jun Young Lee...

(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries as the duration of the pandemic is prolonged. We aimed to perform a novel systematic review and meta-analysis focusing on findings about correlations between clinical characteristics and laboratory features of patients with COVID-19. (2) Methods: We analyzed cases of COVID-19 in different countries by searching PubMed, Embase, Web of Science databases and Google Scholar, from the early stage of the outbreak to late March. Clinical characteristics, laboratory findings, and treatment strategies were retrospectively reviewed for the analysis. (3) Results: Thirty-seven ( = 5196 participants) COVID-19-related studies were eligible for this systematic review and meta-analysis. Fever, cough and fatigue/myalgia were the most common symptoms of COVID-19, followed by some gastrointestinal symptoms which are also reported frequently. Laboratory markers of inflammation and infection including C-reactive protein (CRP) (65% (95% confidence interval (CI) 56-81%)) were elevated, while lymphocyte counts were decreased (63% (95% CI 47-78%)). Meta-analysis of treatment approaches indicated that three modalities of treatment were predominantly used in the majority of patients with a similar prevalence, including antiviral agents (79%), antibiotics (78%), and oxygen therapy (77%). Age was negatively correlated with number of lymphocytes, but positively correlated with dyspnea, number of white blood cells, neutrophils, and D-dimer. Chills had been proved to be positively correlated with chest tightness, lung abnormalities on computed tomography (CT) scans, neutrophil/lymphocyte/platelets count, D-dimer and CRP, cough was positively correlated with sputum production, and pulmonary abnormalities were positively correlated with CRP. White blood cell (WBC) count was also positively correlated with platelet counts, dyspnea, and neutrophil counts with the respective correlations of 0.668, 0.728, and 0.696. (4) Conclusions: This paper is the first systematic review and meta-analysis to reveal the relationship between various variables of clinical characteristics, symptoms and laboratory results with the largest number of papers and patients until now. In elderly patients, laboratory and clinical characteristics indicate a more severe disease course. Moreover, treatments such as antiviral agents, antibiotics, and oxygen therapy which are used in over three quarters of patients are also analyzed. The results will provide "evidence-based hope" on how to manage this unanticipated and overwhelming pandemic.

Topics: Age Factors; Betacoronavirus; C-Reactive Protein; COVID-19; Chills; Coronavirus Infections; Cough; Dyspnea; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Leukocyte Count; Lymphocyte Count; Pandemics; Platelet Count; Pneumonia, Viral; SARS-CoV-2

PubMed: 32668763
DOI: 10.3390/ijerph17145026

Authors: Sajida Shah, Zainab Malik, Khurram Khaliq Bhinder...

We present a case report of a potentially lethal post-COVID complication. A 65-year-old male presented with shortness of breath and fever with chills. He had recently recovered from COVID pneumonia. Contrast enhanced CT scan chest gave the suspicion of pulmonary pseudoaneurysm. CT aortogram revealed a well-defined rounded mass in the right lung mainly occupying the lower lobe of the right lung. Angiography through the right common femoral vein was performed and it confirmed a huge pseudoaneurysm arising from the posteromedial branch of the right descending interlobar artery. As the artery was not found suitable for endovascular embolization, the patient was referred to a thoracic surgeon.

Topics: Aged; Humans; Male; Aneurysm, False; COVID-19; Pulmonary Artery; Tomography, X-Ray Computed; Dyspnea; Fever; Chills; Computed Tomography Angiography

PubMed: 37422832
DOI: 10.55519/JAMC-02-10521

Authors: Felix Schoeller, Abhinandan Jain, Adam Haar Horowitz...

We introduce ChillsDB the first validated database of audiovisual stimuli eliciting aesthetic chills (goosebumps, psychogenic shivers) in a US population. To discover chills stimuli "in the wild", we devised a bottom-up, ecologically-valid method consisting in searching for mentions of the emotion' somatic markers in user comments throughout social media platforms (YouTube and Reddit). We successfully captured 204 chills-eliciting videos of three categories: music, film, and speech. We then tested the top 50 videos in the database on 600+ participants and validated a gold standard of 10 stimuli with a 0.9 probability of generating chills. All ChillsDB tools and data are fully available on GitHub for researchers to be able to contribute and perform further analysis.

Topics: Humans; Chills; Emotions; Esthetics; Motion Pictures; Music

PubMed: 37210402
DOI: 10.1038/s41597-023-02064-8

Review

Authors: Jesús Guillamón Guillamón, Federico Dicenta, Raquel Sánchez-Pérez...

Endodormancy in temperate fruit trees like is a protector state that allows the trees to survive in the adverse conditions of autumn and winter. During this process, plants accumulate chill hours. Flower buds require a certain number of chill hours to release from endodormancy, known as chilling requirements. This step is crucial for proper flowering and fruit set, since incomplete fulfillment of the chilling requirements produces asynchronous flowering, resulting in low quality flowers, and fruits. In recent decades, global warming has endangered this chill accumulation. Because of this fact, many agrochemicals have been used to promote endodormancy release. One of the first and most efficient agrochemicals used for this purpose was hydrogen cyanamide. The application of this agrochemical has been found to advance endodormancy release and synchronize flowering time, compressing the flowering period and increasing production in many species, including apple, grapevine, kiwi, and peach. However, some studies have pointed to the toxicity of this agrochemical. Therefore, other non-toxic agrochemicals have been used in recent years. Among them, Erger + Activ Erger and Syncron + NitroActive have been the most popular alternatives. These two treatments have been shown to efficiently advance endodormancy release in most of the species in which they have been applied. In addition, other less popular agrochemicals have also been applied, but their efficiency is still unclear. In recent years, several studies have focused on the biochemical and genetic variation produced by these treatments, and significant variations have been observed in reactive oxygen species, abscisic acid (ABA), and gibberellin (GA) levels and in the genes responsible for their biosynthesis. Given the importance of this topic, future studies should focus on the discovery and development of new environmentally friendly agrochemicals for improving the modulation of endodormancy release and look more deeply into the effects of these treatments in plants.

PubMed: 35111185
DOI: 10.3389/fpls.2021.812621

Comparative Study Meta-Analysis

Authors: Oluwaseun Egunsola, Fiona Clement, John Taplin...

IMPORTANCE

Low-dose intradermal influenza vaccines could be a suitable alternative to full intramuscular dose during vaccine shortages.

OBJECTIVE

To compare the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses with full intramuscular doses to inform policy design in the event of vaccine shortages.

DATA SOURCES

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5, 2020.

STUDY SELECTION

All comparative studies across all ages assessing the immunogenicity or safety of intradermal and intramuscular influenza vaccinations were included.

DATA EXTRACTION AND SYNTHESIS

Data were extracted by a single reviewer and verified by a second reviewer. Discrepancies between reviewers were resolved through consensus. Random-effects meta-analysis was conducted.

MAIN OUTCOMES AND MEASURES

Primary outcomes included geometric mean titer, seroconversion, seroprotection, and adverse events.

RESULTS

A total of 30 relevant studies were included; 29 studies were randomized clinical trials with 13 759 total participants, and 1 study was a cohort study of 164 021 participants. There was no statistically significant difference in seroconversion rates between the 3-µg, 6-µg, 7.5-µg, and 9-µg intradermal vaccine doses and the 15-µg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but rates were significantly higher with the 15-µg intradermal dose compared with the 15-µg intramuscular dose for the H1N1 strain (rate ratio [RR], 1.10; 95% CI, 1.01-1.20) and B strain (RR, 1.40; 95% CI, 1.13-1.73). Seroprotection rates for the 9-µg and 15-µg intradermal doses did not vary significantly compared with the 15-µg intramuscular dose for all the 3 strains, except for the 15-µg intradermal dose for the H1N1 strain, for which rates were significantly higher (RR, 1.05; 95% CI, 1.01-1.09). Local adverse events were significantly higher with intradermal doses than with the 15-µg intramuscular dose, particularly erythema (3-µg dose: RR, 9.62; 95% CI, 1.07-86.56; 6-µg dose: RR, 23.79; 95% CI, 14.42-39.23; 9-µg dose: RR, 4.56; 95% CI, 3.05-6.82; 15-µg dose: RR, 3.68; 95% CI, 3.19-4.25) and swelling (3-µg dose: RR, 20.16; 95% CI, 4.68-86.82; 9-µg dose: RR, 5.23; 95% CI, 3.58-7.62; 15-µg dose: RR, 3.47 ; 95% CI, 2.21-5.45). Fever and chills were significantly more common with the 9-µg intradermal dose than the 15-µg intramuscular dose (fever: RR, 1.36; 95% CI, 1.03-1.80; chills: RR, 1.24; 95% CI, 1.03-1.50) while all other systemic adverse events were not statistically significant for all other doses.

CONCLUSIONS AND RELEVANCE

These findings suggest that reduced-dose intradermal influenza vaccination could be a reasonable alternative to standard dose intramuscular vaccination.

Topics: Antibodies, Viral; Chills; Dose-Response Relationship, Immunologic; Fever; Hemagglutination Inhibition Tests; Humans; Immunogenicity, Vaccine; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza Vaccines; Influenza, Human; Injection Site Reaction; Injections, Intradermal; Injections, Intramuscular; Seroconversion

PubMed: 33560425
DOI: 10.1001/jamanetworkopen.2020.35693

Meta-Analysis Review

Authors: Juan Pablo Botero Aguirre, Alejandra Maria Restrepo Hamid

BACKGROUND

The incidence of invasive fungal infections has increased globally as a result of several factors. Conventional amphotericin B (sodium deoxycholate) has been used as standard therapy for the treatment of invasive fungal infections; however, it is associated with adverse drug reactions, including acute kidney injury (AKI). New formulations of amphotericin B have aimed to improve the safety profile of the conventional formulation.

OBJECTIVES

This review aimed to assess the effects of amphotericin B deoxycholate versus liposomal amphotericin B on kidney function.

SEARCH METHODS

We searched Cochrane Kidney and Transplant's Specialised Register to 10 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

SELECTION CRITERIA

We included randomised controlled trials (RCTs) that compared amphotericin B sodium deoxycholate with liposomal amphotericin B.

DATA COLLECTION AND ANALYSIS

Two authors independently assessed studies for eligibility and conducted risk of bias evaluation.

MAIN RESULTS

We included 12 studies (2298 participants) in this review. Of these, 10 were meta-analysed (2172 participants). Liposomal amphotericin B was found to be significantly safer than conventional amphotericin B in terms of serum creatinine increase (RR 0.49, 95% CI 0.40 to 0.59). There was significant decrease in all infusion-related reactions in the liposomal group compared with the conventional group: fever (4 studies, 1092 participants): RR 0.39, 95% CI 0.28 to 0.55; I(2) = 32%); chills and/or rigours (5 studies, 1081 participants): RR 0.27, 95% CI 0.15 to 0.48; I(2) = 75%); fever and/or rigours (2 studies, 720 participants): RR 0.68, 95% CI 0.52 to 0.90; I(2) = 58%); nausea (6 studies, 1187 participants): RR 0.50, 95% CI 0.35 to 0.72; I(2) = 0%); and vomiting (3 studies, 1019 participants): RR 0.51, 95% CI 0.27 to 0.95; I(2) = 61%). Overall, risk of bias in included studies was low or unclear for most domains. However, blinding of participants and personnel, blinding of outcome assessment and other bias (funding) tended to have a high risk of bias. The sensitivity analysis performed did not change the significance of difference in favour of the liposomal formulation. Assessment for publication bias found that review results were robust.

AUTHORS' CONCLUSIONS

Current evidence suggests that liposomal amphotericin B is less nephrotoxic than conventional amphotericin B (when the effect on kidney function is measured as an increase in serum creatinine level equal to or greater than two-fold from the baseline level). We also found that there were fewer infusion-related reactions associated with the liposomal formulation.

Topics: Adult; Amphotericin B; Antifungal Agents; Child; Chills; Creatinine; Deoxycholic Acid; Drug Combinations; Female; Fever; Humans; Kidney; Male; Nausea; Randomized Controlled Trials as Topic; Vomiting

PubMed: 26595825
DOI: 10.1002/14651858.CD010481.pub2