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Background: Despite their unique contributions to heart failure (HF) care, home healthcare workers (HHWs) have unmet educational needs and many lack HF caregiving self-efficacy. To address this, we used a community-partnered approach to develop and pilot a HF training course for HHWs. Methods: We partnered with the Training and Employment Fund, a benefit fund of the largest healthcare union in the United States, to develop a 2-hour virtual HF training course that met HHWs’ job-specific needs. English and Spanish-speaking HHWs interested in HF training, with access to Zoom, were eligible. We used a mixed methods design with pre/postsurveys and semi-structured interviews to evaluate the course: (a) feasibility, (b) acceptability, and (c) effectiveness (change in knowledge [Dutch Heart Failure Knowledge Scale range 0−15] and caregiving self-efficacy [HF Caregiver Self-efficacy Scale range 0−100]). Results: Of the 210 HHWs approached, 100 were eligible and agreed, and 70 enrolled. Of them, 53 (employed by 15 different home care agencies) participated. Posttraining data showed significant improvements (pretraining mean [SD] versus posttraining mean [SD]; P value) in HF knowledge (11.21 [1.90] versus 12.21 [1.85]; P =0.0000) and HF caregiving self-efficacy (75.21 [16.57] versus 82.29 [16.49]; P =0.0017); the greatest gains occurred among those with the lowest pre-training scores. Participants found the course engaging, technically feasible, and highly relevant to their scope of care. Conclusions: We developed and piloted the first HF training course for HHWs, which was feasible, acceptable, and improved their HF knowledge and caregiving self-efficacy. Our findings warrant scalability to the workforce at large with a train-the-trainer model.

Importance Home health care workers care for community-dwelling adults and play an important role in supporting patients with confirmed and suspected coronavirus disease 2019 (COVID-19) who remain at home. These workers are mostly middle-aged women and racial/ethnic minorities who typically earn low wages. Despite being integral to patient care, these workers are often neglected by the medical community and society at large; thus, developing a health care system capable of addressing the COVID-19 crisis and future pandemics requires a better understanding of the experiences of home health care workers. Objective To understand the experiences of home health care workers caring for patients in New York City during the COVID-19 pandemic. Design, setting, and participants From March to April 2020, a qualitative study with 1-to-1 semistructured interviews of 33 home health care workers in New York City was conducted in partnership with the 1199SEIU Home Care Industry Education Fund, a benefit fund of the 1199 Service Employees International Union United Healthcare Workers East, the largest health care union in the US. Purposeful sampling was used to identify and recruit home health care workers. Main outcomes and measures Audio-recorded interviews were professionally transcribed and analyzed using grounded theory. Major themes and subthemes were identified. Results In total, 33 home health care workers employed by 24 unique home care agencies across the 5 boroughs of New York City participated. Participants had a mean (SD) age of 47.6 (14.0) years, 32 (97%) were women, 21 (64%) were Black participants, and 6 (18%) were Hispanic participants. Five major themes emerged: home health care workers (1) were on the front lines of the COVID-19 pandemic but felt invisible; (2) reported a heightened risk for virus transmission; (3) received varying amounts of information, supplies, and training from their home care agencies; (4) relied on nonagency alternatives for support, including information and supplies; and (5) were forced to make difficult trade-offs in their work and personal lives. Conclusions and relevance In this qualitative analysis, home health care workers reported providing frontline essential care, often at personal risk, during the COVID-19 pandemic. They experienced challenges that exacerbated the inequities they face as a marginalized workforce. Interventions and policies to better support these frontline health care professionals are urgently needed.

The peripheral administration of adenosine agonists can produce pain inhibitory effects due to adenosine A 1 receptor activation, and pain facilitatory effects due to adenosine A 2 and A 3 receptor activation. Pain facilitatory effects for A 2 -like receptors result from interactions with endogenous mediators like 5-hydroxytryptamine. Both pain facilitation and edema resulting from local administration of A 3 agonists results from release of histamine and 5-hydroxytryptamine from mast cells. Local administration of adenosine kinase, but not adenosine deaminase inhibitors, produces a local antinociception, but no pronociception occurs at higher doses due to systemic (probably spinal) pain-suppressing mechanisms being recruited. In the spinal cord, adenosine A 1 receptors produce antinociception. Inhibition of adenosine kinase, but not adenosine deaminase, also produces antinociception, and exhibits a greater separation from motor effects. Adenosine A 1 receptor agonists, as well as inhibitors of adenosine kinase, exhibit the potential for development as analgesic agents, both as local formulations, as well as systemically active agents. In both instances, a sufficient separation from adverse effects will be required.

Two non-transformed intestinal epithelial cell lines (RIE-1 and IEC-6) and three intestinal carcinoma cell lines (HT-29, T84 and MCA-38) were used to detect the toxic effects due to okadaic acid in the presence of mussel tissue homogenates. Cytotoxicity was assessed by measurement of the metabolic conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide to its corresponding formazan dye. All of the cell lines were sensitive to okadaic acid, with HT-29, RIE-1 and IEC-6 showing the greatest response. Dilutions of whole mussel tissue homogenates caused some loss of viability in most of the cell lines but had no significant effect on the viability of RIE-1 cells. In no case did the mussel homogenate compromise the dose-response curve to okadaic acid when data were normalized to the appropriate control value. These intestinal epithelial cell lines may prove useful in the bioassay of okadaic acid and related toxins.

Spinal administration of an adenosine kinase inhibitor, alone or in combination with an adenosine deaminase inhibitor, produces antinociception in inflammatory pain tests. In the present study, we examined the antinociceptive and anti-inflammatory effects produced by the peripheral (intraplantar) administration of 5'-amino-5'-deoxyadenosine (an adenosine kinase inhibitor), 2'-deoxycoformycin (an adenosine deaminase inhibitor), and combinations of both agents in the carrageenan-induced thermal hyperalgesia and paw oedema model in the rat. When injected in the ipsilateral paw immediately prior to carrageenan injection, both agents produced antinociception only at the highest dose (1 micromol), whereas a reduction in paw swelling was evident at a lower dose (300 nmol). Significant augmentation in both the antinociceptive and anti-inflammatory effects was seen when 5'-amino-5'-deoxyadenosine and 2'-deoxycoformycin were co-administered in equimolar doses at all dose levels. Both effects were mediated via activation of adenosine receptors, as indicated by blockade by an adenosine receptor antagonist. When administered into the contralateral paw, 1 micromol 5'-amino-5'-deoxyadenosine+1 micromol 2'-deoxycoformycin produced prominent antinociception, indicating a systemic drug activity. There was only a modest reduction in paw oedema in the carrageenan-injected (ipsilateral) paw, suggesting that much of this activity was locally mediated. Reversal of systemic effects on thermal thresholds by an intrathecal adenosine receptor antagonist implicates a spinal site of action in this instance. An ipsilateral administration of 1 micromol 5'-amino-5'-deoxyadenosine, but not 1 micromol 2'-deoxycoformycin, reduced carrageenan-induced c-Fos expression in the spinal dorsal horn, and this was further reduced by the peripheral co-injection of the two agents. These results provide evidence for a predominantly spinal antinociceptive effect and a predominantly peripheral anti-inflammatory effect produced by inhibitors of adenosine kinase and adenosine deaminase.

The present study examined the spinal antinociceptive effects of adenosine analogs and inhibitors of adenosine kinase and adenosine deaminase in the carrageenan-induced thermal hyperalgesia model in the rat. The possible enhancement of the antinociceptive effects of adenosine kinase inhibitors by an adenosine deaminase inhibitor also was investigated. Unilateral hindpaw inflammation was induced by an intraplantar injection of lambda carrageenan (2 mg/100 μ l), which consistently produced significant paw swelling and thermal hyperalgesia. Drugs were administered intrathecally, either by acute percutaneous lumbar puncture (individual agents and combinations) or via an intrathecal catheter surgically implanted 7–10 days prior to drug testing (antagonist experiments). N 6 -cyclohexyladenosine (CHA; adenosine A 1 receptor agonist; 0.01–1 nmol), 2-[ p -(2-carboxyethyl)phenylethylamino]-5′- N -ethylcarboxamidoadenosine (CGS21680; adenosine A 2A receptor agonist; 0.1–10 nmol), 5′-amino-5′-deoxyadenosine (NH 2 dAdo; adenosine kinase inhibitor; 10–300 nmol), and 5-iodotubercidin (ITU; adenosine kinase inhibitor; 0.1–100 nmol) produced, to varying extents, dose-dependent antinociception. No analgesia was seen following injection of 2′-deoxycoformycin (dCF; an adenosine deaminase inhibitor; 100–300 nmol). Reversal of drug effects by caffeine (non-selective adenosine A 1 /A 2 receptor antagonist; 515 nmol) confirmed the involvement of the adenosine receptor, while antagonism by 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A 1 receptor antagonist; 242 nmol), but not 3,7-dimethyl-1-propargylxanthine (DMPX; adenosine A 2A receptor antagonist; 242 nmol), evidenced an adenosine A 1 receptor mediated spinal antinociception by NH 2 dAdo. dCF (100 nmol), which was inactive by itself, enhanced the effects of 10 nmol and 30 nmol NH 2 dAdo. Enhancement of the antinociceptive effect of ITU by dCF was less pronounced. None of the antinociceptive drug regimens had any effect on paw swelling. These results demonstrate that both directly and indirectly acting adenosine agents, when administered spinally, produce antinociception through activation of spinal adenosine A 1 receptors in an inflammatory model of thermal hyperalgesia. The spinal antinociceptive effects of selected adenosine kinase inhibitors can be significantly augmented when administered simultaneously with an adenosine deaminase inhibitor.

This study examined the ability of an adenosine kinase inhibitor (5′-amino-5′-deoxyadenosine; NH2dAD), an adenosine deaminase inhibitor (2′-deoxycoformycin), and combinations of these agents to produce a peripheral modulation of the pain signal in the low concentration formalin model. Drugs were administered in combination with 0.5% formalin, or into the contralateral hindpaw to test for systemic effects, and episodes of flinching behaviors determined. Coadministration of NH2dAD 0.1–100 nmol with formalin produced antinociception as revealed by an inhibition of flinching behaviors. This action was peripherally mediated as it was not seen following contralateral administration of the NH2dAD, and was due to accumulation of adenosine and activation of cell surface adenosine receptors as it was blocked by the adenosine receptor antagonist caffeine. Antinociception was intensity-dependent, as it was not seen when higher concentrations of formalin (0.75%, 1.5%) were used. The coadministration of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine revealed the presence of an inhibitory tone of adenosine when the intrinsic antinociceptive effect of NH2dAD was obscured by the solvent or the stimulus intensity. 2′-Deoxycoformycin 0.1–100 nmol did not produce any intrinsic effect, but 100 nmol coadministered with low concentrations of NH2dAD, which lacked an intrinsic effect, augmented antinociception by NH2dAD. Again, this was a peripheral rather than a systemic response. The combined action of the adenosine kinase and deaminase inhibitors was completely reversed by coadministration of caffeine. Antinociception with NH2dAD is observed at higher concentrations of formalin in second trial experiments. This study demonstrates a peripheral antinociceptive action mediated by endogenous adenosine which accumulates following the peripheral inhibition of adenosine kinase; this action is due to activation of an adenosine A1 receptor.

Spinal administration of adenosine analogs and an adenosine kinase inhibitor produces antinociception in thermal threshold tests. In the present study, we determined the effects of N 6 -cyclohexyladenosine (adenosine A 1 receptor selective), 2-[ p -(2-carboxyethyl)phenylethylamino]-5′- N -ethyl-carboxamidoadenosine (CGS-21680) (adenosine A 2A receptor selective), and 5′- N -ethylcarboxamidoadenosine (NECA) (non-selective), on formalin induced nociceptive responses (flinching/lifting and licking/biting) using two concentrations of formalin (2% and 5%). We also examined the antinociceptive effects of 5′-amino-5′-deoxyadenosine, an adenosine kinase inhibitor, and deoxycoformycin, an adenosine deaminase inhibitor, under these conditions. Adenosine A 1 receptor agonists, but not the A 2A selective agent, produced significant antinociception, as did 5′-amino-5′-deoxyadenosine, but not deoxycoformycin. The extent of antinociception produced was greater with the lower stimulus intensity. The effects of NECA and 5′-amino-5′-deoxyadenosine were inhibited by caffeine, indicating the involvement of cell surface adenosine receptors in their actions. We conclude (a) that the adenosine A 1 , but not the A 2A , receptor is involved in spinally mediated antinociception, (b) that adenosine kinase is more important than adenosine deaminase in regulating endogenous adenosine levels in the spinal cord, and (c) that stimulus intensity is an important determinant of the efficacy of purines in the spinal cord.