An Overview of the Impact of the Covid-19 Pandemic on the Provision of Palliative Care.

The Sars-Cov-2 pandemic had an immeasurable impact on the provision of palliative care in Ireland, and continues to do so. Patients and families were affected by stringent infectious disease measures. Healthcare professionals were also impacted, with recent research demonstrating the psychological impact that the pandemic had on some of those working in palliative care during the pandemic. The services provided by palliative care services also shifted. Many patients opted to stay at home to receive end-of-life care or symptom management from their GP and community palliative homecare teams where possible. Palliative care services in the acute hospital setting were increasingly utilised to support teams to provide end-of-life care in a developing and challenging clinical environment. Communication technology was used to for multidisciplinary team meetings, to communicate with families and by community home care teams for some patient assessments. Our article outlines some of the major ways in which palliative care was impacted by the Sars-Cov-2 pandemic.

Immune Checkpoint Inhibitors and Palliative Care at the End of Life: An Irish Multicentre Retrospective Study.

Background and Objectives: Immune checkpoint inhibitors (ICIs) have less toxicity than standard chemotherapy and are now standard of care for many patients with advanced cancer. A manageable side effect profile and potential for durable responses may lead to aggressive care of the palliative patient. We sought to evaluate palliative care input and ICI use at the end of life at two Irish cancer centres. Methods: We identified deceased patients who received at least one dose of an ICI between first of January 2013 to 31st of December 2018. A retrospective electronic chart review was performed. Results: The electronic records of 102 patients were analysed. Fifty eight percent were male and the median age of diagnosis of advanced disease was 60 years (range 17-78). Median time from last dose of ICI to death was 57 days (range 8-574) and 20% of patients died within 30 days of last dose of ICI. Most patients, 92%, were referred to palliative care. The median time from palliative care referral to death was 64 days (range 1- 1010). In the last 30 days of life, 39% of patients attended the emergency department (ED) and 46% had at least one hospital admission. Late palliative care referrals, ≤3 months before death, were associated with hospitalisations in the last month of life (64% vs. 36%, P = .02). Timing of palliative care referral did not affect ICI prescribing at the end of life (P = 0.38). ICI use in the last 30 days of life was not associated with increased ED presentations or hospitalisations at the end of life. Patients who received ICI in the last month had a higher likelihood of in-hospital death (43% vs. 16%, P = 0.02). Conclusions: ICI within 30 days of death was associated with dying in hospital but did not lead to more hospitalisations and emergency department presentations. Early palliative care did not affect ICI use but reduced hospitalisations at the end of life.

Pathogenesis and recovery of tetraplegia after electrical injury.

The site of neurological damage causing paralysis after electrical trauma remains to be clarified. A patient is described who developed a flaccid tetraplegia after a high voltage electrical injury. The findings on initial examination and neurophysiological investigation showed a very severe generalised sensory-motor polyneuropathy. His subsequent follow up over 60 months showed a remarkable degree of reinnervation and the unmasking of a myelopathy. The degree of reinnervation noted suggests an axonopathy that left the other elements of the peripheral nerves relatively spared. These findings provide the most convincing evidence to date that a generalised polyneuropathy can follow electrical injury and that it results from non-thermal mechanisms such as electroporation.

Sequential changes in in vivo muscle and liver protein synthesis and plasma and tissue glutamine levels in sepsis in the rat.

We have investigated sequential changes in skeletal muscle and hepatic protein synthesis following sepsis, and their relationship to changes in circulating and tissue glutamine concentrations. Male Wistar rats underwent caecal ligation and puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h later. A group of non-operated animals were killed at the time of surgery. Protein synthesis was determined using a flooding dose of L-[4-(3)H] phenylalanine, and glutamine concentrations were measured by an enzymic fluorimetric assay. Protein synthesis in gastrocnemius muscle fell in all groups. Gastrocnemius total protein content was reduced after CLP and at 72 and 96 h after sham operation. After CLP, protein synthesis was lower at 24 h, and total protein content was lower at 72 and 96 h, than in sham-operated animals. CLP was associated with increased liver protein synthesis at all time points, whereas there was no change after sham operation. Liver protein content did not change after CLP, but was lower at 72 and 96 h after sham operation than in non-operated animals. Plasma glutamine concentrations were reduced at 24 h after sham operation, and at 72 and 96 h after CLP. Muscle glutamine concentrations were reduced in all groups, with the decrease being greater following CLP than after sham operation. In the liver, glutamine concentrations were unchanged after CLP, but increased after sham operation. In rats with sepsis, decreases in muscle protein synthesis and content are associated with markedly reduced muscle glutamine concentrations. Plasma glutamine concentrations are initially maintained, but fall later. In liver, protein synthesis is increased, while glutamine concentrations are preserved. These results support a peripheral-to-splanchnic glutamine flux in sepsis.

Targeted topical steroid therapy in sudden sensorineural hearing loss.

OBJECTIVE: To treat patients with sudden sensorineural hearing loss (SSNL) who failed oral prednisone therapy by using a round window membrane (RWM) microcatheter. This topical delivery strategy sought to improve effectiveness of steroid treatment to the inner ear by targeting drug delivery to the RWM. STUDY DESIGN: Nonrandomized prospective design. SETTING: Tertiary care facility. PATIENTS: Six patients with severe unilateral SSHL, five of whom were refractory to a course of oral steroid therapy treated within 6 weeks of SSHL and three additional patients treated more than 6 weeks after SSHL. INTERVENTION: Therapeutic use of RWM catheter. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs) and word identification scores (WIS). RESULTS: Five of the six patients treated within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline hearing, one recovered hearing that could benefit by hearing amplification, and one regained moderate improvement in PTA but not WIS. CONCLUSION: Targeted topical steroid administration avoids the significant systemic side effects of oral steroids and may offer more effective dosing than simple transtympanic injection of medicine. Although these findings are preliminary, it is possible that after further study, targeted drug delivery may be a useful technique to consider in patients with severe to profound hearing loss that have failed all other management options.

Human chorionic gonadotrophin inhibition of pregnant human myometrial contractility.

OBJECTIVE: To evaluate the effect of human chorionic gonadotrophin (hCG) on pregnant human myometrial contractility in vitro and to determine whether the hCG-elicited effect was oestrogen dependant. METHODS: Isometric tension recording was performed under physiological conditions in isolated myometrial strips from biopsies obtained at elective caesarean section. The effect of cumulative additions of hCG (0.001, 0.01, 0.1, 1.0 and 10 iu/mL) on myometrial contractility was evaluated. Secondarily, the contractile activity of pregnant myometrium following hCG exposure was investigated in tissue pre-treated with beta-oestradiol. RESULTS: hCG exerted a statistically significant relaxant effect on pregnant human myometrial tissue. The relaxant effect increased with increasing concentrations of hCG from 8.96% (SEM 2.06) (0.001 iu/mL hCG: P < 0.01 ) to a net cumulative total of 58.50% (SEM 3.74) (10 iu/mL hCG; P < 0.01). The relaxant effect was also time-dependant, increasing in magnitude throughout the duration of experiments. Beta-oestradiol did not significantly affect the response of myometrial tissue to hCG. CONCLUSIONS: These results clearly demonstrate that hCG exerts a significant concentration-dependant relaxant effect on human myometrial tissue obtained rate in pregnancy. These findings outline an inhibitory physiological role of hCG on human myometrial contractility and raise the possibility of its potential use as a tocolytic.

Effect of parathyroid hormone-related peptide on human and rat myometrial contractility in vitro.

OBJECTIVES: The aims of this study were primarily to investigate the effects of parathyroid hormone-related peptide (human fragment 1-34) on human nonpregnant and pregnant (nonlabor and labor) myometrial contractility in vitro and secondarily to compare these effects with those of parathyroid hormone-related peptide on rat myometrial contractility. STUDY DESIGN: Isometric tension recording was performed under physiologic conditions in isolated myometrial strips obtained at hysterectomy and cesarean delivery and from Sprague-Dawley rats. The effect of cumulative additions of parathyroid hormone-related peptide (1, 10, and 100 nmol/L) on myometrial contractility was measured and the significance of results was assessed by 2-way analysis of variance. RESULTS: Parathyroid hormone-related peptide exerted a statistically significant net relaxant effect on myometrial contractility in human nonpregnant myometrium (34.71%; P<.01), in human pregnant myometrium obtained before (18.27%; P <.05) but not after (10.32%; P>.05) the onset of labor, and in rat tissue (31.60%; P<.01). CONCLUSIONS: Parathyroid hormone-related peptide exerts a relaxant effect on human and rat myometrial tissue. In human myometrium, sensitivity to parathyroid hormone-related peptide is reduced in pregnancy and abolished by the onset of labor.

In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels.

OBJECTIVE: Growth hormone (GH) given to reverse muscle catabolism in critical illness increased mortality, illustrating the need for better understanding of the pathophysiology of the GH axis. We describe the relationship between changes in plasma insulin-like growth factor-I (IGF-I) and growth hormone-binding protein (GHBP) levels and hepatic growth hormone-binding in rats with sepsis. DESIGN: Randomised, controlled study. SETTING: University research laboratory. SUBJECTS: One hundred and eleven male Wistar rats. INTERVENTION: Three groups of rats underwent caecal ligation and puncture (CLP) and three groups laparotomy only (LAP). Survivors were killed at 24, 72, and 96 h. All animals were starved during the study. Twelve rats were killed at the start of the experiment (baseline) and twelve (allowed food) at 96 h. MEASUREMENTS AND RESULTS: Plasma levels of IGF-I and GHBP and binding of 125I-labelled human GH in liver homogenates were measured. IGF-I fell significantly following both CLP and LAP; at 24 h, IGF-I levels were lower after CLP than LAP (950 +/- 74 vs 1,522 +/- 60 microg/l, P = < 0.001). GHBP increased at 24 h following both CLP and LAP (45.6 +/- 1.87 and 47.7 +/- 3.01 vs 38.7 +/- 1.98 ng/ml at baseline, P = < 0.05). In LAP animals GHBP fell to below baseline by 72 h, and significantly so by 96 h (33.5 +/- 1.43, P = < 0.05), whereas GHBP remained elevated 72 h following CLP, returning to baseline by 96 h. The density of GH-binding sites in liver tended to increase, following both CLP and LAP at both 24 and 96 h, but these changes failed to achieve statistical significance. CONCLUSION: Reduced IGF-I levels in sepsis in the rat are associated with elevations in GHBP and a trend to increased hepatic GH binding. This suggests that in sepsis 'GH resistance' is not associated with reduced GH receptor numbers.

A method for active surveillance of selected communicable diseases.

In 1991, an initiative was launched in the Western Pacific Region of WHO to eradicate poliomyelitis by the year 2000. Confirmation of eradication requires a certification process, in which specific criteria must be met. A hospital-based surveillance system was developed. It was sensitive enough to detect, at least one case of acute flaccid paralysis (AFP) per 100,000 children under age 15 per year, which is considered the "background rate" of AFP. This system was instituted in 1997 in most countries in the Pacific, and included measles and neonatal tetanus as well as AFP. By mid-1998, 53 hospitals in the Pacific were submitting monthly forms indicating whether or not AFP, suspect measles, or neonatal tetanus had been seen in the preceding month. Compliance was excellent, with over 80% of forms submitted to WHO in 1998, thus meeting the certification standard. In 1999 a proposal was made to expand this method, in selected countries, to encompass most conditions presenting with acute fever plus rash, thus including, for example, cases of rubella and dengue. Important aspects of such surveillance include the capacity to confirm diagnoses in the laboratory, and to take effective public health action. A coordinated laboratory network had been established previously for virological analysis of stool specimens for conditions causing AFP, but laboratory support for other conditions is currently the responsibility of individual hospitals to arrange.

Oxygenator exhaust capnography as an index of arterial carbon dioxide tension during cardiopulmonary bypass using a membrane oxygenator.

We have studied the relationship between the partial pressure of carbon dioxide in oxygenator exhaust gas (PECO2) and arterial carbon dioxide tension (PaCO2) during hypothermic cardiopulmonary bypass with non-pulsatile flow and a membrane oxygenator. A total of 172 paired measurements were made in 32 patients, 5 min after starting cardiopulmonary bypass and then at 15-min intervals. Additional measurements were made at 34 degrees C during rewarming. The degree of agreement between paired measurements (PaCO2 and PECO2) at each time was calculated. Mean difference (d) was 0.9 kPa (SD 0.99 kPa). Results were analysed further during stable hypothermia (n = 30, d = 1.88, SD = 0.69), rewarming at 34 degrees C (n = 22, d = 0, SD = 0.84), rewarming at normothermia (n = 48, d = 0.15, SD = 0.69) and with (n = 78, d = 0.62, SD = 0.99) or without (n = 91, d = 1.07, SD = 0.9) carbon dioxide being added to the oxygenator gas. The difference between the two measurements varied in relation to nasopharyngeal temperature if PaCO2 was not corrected for temperature (r2 = 0.343, P = < 0.001). However, if PaCO2 was corrected for temperature, the difference between PaCO2 and PECO2 was not related to temperature, and there was no relationship with either pump blood flow or oxygenator gas flow. We found that measurement of carbon dioxide partial pressure in exhaust gases from a membrane oxygenator during cardiopulmonary bypass was not a useful method for estimating PaCO2.

Dissociation of pituitary-adrenal and catecholamine activation after induced cardiac arrest and defibrillation.

To avoid factors which confound attempts to characterize the neuroendocrine response to cardiac arrest, we studied the pituitary-adrenocortical and catecholamine responses to induced ventricular fibrillation (VF) and direct current cardioversion in 10 patients undergoing testing of 'implanted cardioverter defibrillator' devices under sedation. Plasma concentrations of epinephrine were increased 5 min after VF (from a mean basal of 0.39 (S.E.M. 0.09) to a peak of 0.632 (0.212) nmol litre-1; P < 0.05) but were unchanged at other times. Plasma concentrations of norepinephrine did not change at any time. Plasma concentrations of cortisol increased significantly at 10 min (from a mean of 367 (SEM 62) to 539 (64) nmol litre-1; P < 0.001) and remained increased 30 min after VF (470 (74) nmol litre-1; P < 0.05) but had returned towards baseline at 60 min, whereas plasma prolactin concentrations were increased at 5 min (from a mean of 224 (SEM 54) to 320 (63) mu. litre-1; P < 0.01) and remained increased until the end of the sampling period at 60 min (288 (65) mu. litre-1; P < 0.05). Concentrations of adrenocorticotrophic hormone (ACTH) (n = 5) tended to increase but this was not statistically significant. We conclude that a short period of cardiac arrest in lightly sedated humans activated the pituitary-adrenocortical axis but did not appear to stimulate catecholamine secretion. These findings raise questions about the nature and mechanisms of the neuroendocrine response to cardiac arrest.