BACKGROUND: Hospitalized patients recovering from coronavirus disease 2019 (COVID-19) may experience disability and suffer from significant physical and mental impairment requiring physical rehabilitation following their discharge. However, to date, no attempt has been made to collate and synthesize literature in this area. OBJECTIVE: This systematic review examines the outcomes of different physical rehabilitation interventions tested in COVID-19 patients who were discharged from hospital. SEARCH STRATEGY: A systematic search of MEDLINE/PubMed, CINAHL, Scopus and medRxiv was conducted to identify articles published up to March 2022. INCLUSION CRITERIA: This systematic review included studies of outpatient rehabilitation programs for people recovering from COVID-19 who received physical activity, exercise, or breathing training to enhance or restore functional capacity, pulmonary function, quality of life, and mental health or function. DATA EXTRACTION AND ANALYSIS: Selection of included articles, data extraction, and methodological quality assessments were conducted by two review authors respectively, and consensus was reached through discussion and consultation with a third reviewer. Finally, we review the outcomes of studies based on four categories including: (1) functional capacity, (2) pulmonary function, (3) quality of life, and (4) mental health status. RESULTS: A total of 7534 titles and abstracts were screened; 10 cohort studies, 4 randomized controlled trials and 13 other prospective studies involving 1583 patients were included in our review. Early physical rehabilitation interventions applied in COVID-19 patients who were discharged from the hospital improved multiple parameters related to functional capacity, pulmonary function, quality of life and mental health status. CONCLUSION Physical rehabilitation interventions may be safe, feasible and effective in COVID-19 patients discharged from the hospital, and can improve a variety of clinically relevant outcomes. Further studies are warranted to determine the underlying mechanisms. Please cite this article as: Rahmati M, Molanouri Shamsi M, Woo W, Koyanagi A, Won Lee SW, Keon Yon DK, Shin JI, Smith L. Effects of physical rehabilitation interventions in COVID-19 patients following discharge from hospital: A systematic review. J Integr Med. 2022; 21(2): 149-158.
Humans ; Patient Discharge ; Quality of Life ; COVID-19 ; Prospective Studies ; Hospitals ; Randomized Controlled Trials as Topic

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Humans ; Adolescent ; Pandemics ; Substance-Related Disorders/epidemiology* ; Smoking ; Ethanol ; Republic of Korea/epidemiology* ; Alcohol Drinking/epidemiology*

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.
Amphetamine* ; Animals ; Controlled Substances ; Humans ; Mice ; Parents ; Rats ; Receptors, Dopamine ; Reward ; Rodentia

A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) α-piperidinopropiophenone (PIPP) and (2) α-piperidinopentiothiophenone (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.
Animals ; Dopamine Plasma Membrane Transport Proteins ; Gene Expression ; Mice ; Nitrogen ; Rats ; Reward

Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on Cl− influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular Cl− influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.
Animals ; Anticonvulsants ; Brain Diseases ; Epilepsy ; gamma-Aminobutyric Acid* ; In Vitro Techniques ; Mice ; Pentylenetetrazole ; Rehmannia* ; Seizures* ; Water*

PURPOSE: An in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was designed to require only a limited number of cells and shorten test turnaround time with a high success rate. This study investigated the correlation between in vitro doxorubicin sensitivity of tumor cells and early systemic recurrence, defined as recurrence within 2 years after surgery. METHODS: From January 2004 to March 2007, the ATP-CRA for doxorubicin was tested in 128 patients among breast cancer patients treated at Gangnam Severance Hospital, Seoul, Korea. The American Joint Committee on Cancer stages for all patients were II and III. All patients received doxorubicin-based chemotherapy. Selected patients were divided into a chemosensitive group and a non-chemosensitive group, according to a 40% cell death rate as a cut-off value. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with breast cancer. RESULTS: The mean age of the patients investigated was 44.6-years-old, the mean follow-up period was 39.9 months, and recurrence free survival was 38.6 months. Thirteen recurrences were observed during follow-up. Among 13 patients with a recurrence, eight had a recurrence within 2 years (early recurrence). All of the early recurring patients belonged to the non-sensitive group. Doxorubicin sensitivity results measured by ATP-CRA were related with early recurrence free survival in patients with breast cancer (p=0.030). The mean cell death rate derived from the ATP-CRA for the early recurrence group tended to be lower than that of the non-early recurrence group, but the difference was not statistically significant (p=0.05). CONCLUSION: Doxorubicin sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence against doxorubicin-based adjuvant chemotherapy in patients with breast cancer.
Mortality ; Breast Neoplasms

PURPOSE: The purpose of this study was to identify biopsychosocial predictors of the quality of life in breast cancer patients. Disease factors (disease stage, type of surgery, type of treatment, family history), personal factors (age, education level, income), and psychosocial factors (psychological symptoms, optimism, self-esteem, husband's support, cancer coping) were included in biopsychosocial predictors. METHODS: A total of 128 breast cancer patients were recruited. Subjects were assessed by the Optimism Scale, the Selfesteem Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23), the Symptom Checklist-90-Revision (SCL-90-R), and the Korean Cancer Coping Questionnaire (KCCQ). RESULTS: Disease factors and personal factors were not different between the high and low quality of life group. But the psychosocial factors were significantly different. Somatization, anxiety, depression, interpersonal sensitivity, hostility, and phobic anxiety showed significantly lower scores in the high quality of life group than the low group. Optimism, self-esteem and husband's support showed significantly higher score in the high quality of life group than the low group. In a stepwise multiple regression analysis, not disease factors and personal factors but the psychosocial factors significantly predicted the quality of life in breast cancer patients. Especially, somatization and depression significantly predicted the quality of life. CONCLUSION: Among psychosocial factors, somatization and depression were the most significant predictors of the quality of life in breast cancer patients. These results supported psychosocial intervention should be needed to breast cancer patients, in order to improve the quality of life.
Anxiety ; Breast ; Breast Neoplasms ; Depression ; Hostility ; Humans ; Quality of Life ; Somatoform Disorders ; Surveys and Questionnaires

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine