Changes in arterial pH do not explain the reductions in ionised calcium observed during COVID-19 infection.

BACKGROUND: Hypocalcaemia predicts coronavirus disease 2019 (COVID-19) severity and mortality. We hypothesized an association between respiratory alkalosis secondary to hypoxia and low ionised calcium (iCa) concentration in patients with COVID-19. METHODS: Arterial blood gas samples taken from January 2019 to March 2021 were retrospectively matched with infection status. Principal components regression was undertaken to determine the correlation between pH, partial pressure arterial oxygen (PaO2), partial pressure arterial carbon dioxide (PaCO2), and iCa. RESULTS: We included 4056 patients (300 COVID-19 detected, 19 influenza detected), corresponding to 5960 arterial blood samples. The COVID-19 detected group had a statistically significantly lower iCa, PaO2 and PaCO2, and more alkalotic pH than infection-free groups. The influenza group had a lower iCa and PaCO2, higher PaO2, and a more alkalotic pH than infection-free groups, but these differences were non-significant. Principal components regression revealed that pH, PaCO2, and PaO2 explain just 2.72 % of the variance in iCa. An increase in pH by 1 unit was associated with an iCa reduction of 0.141 â€‹mmol/L (p â€‹< â€‹0.0001). CONCLUSION: Reduction in iCa concentration in patients with COVID-19 is not associated with pH derangement. Influenza infection was associated with a minor reduction in iCa in our small sample, a hitherto unreported finding, although statistical significance was not demonstrated.

Trends in medication use at the onset of and during the COVID-19 pandemic in the Republic of Ireland: An interrupted time series study.

The COVID-19 pandemic had a substantial impact on healthcare delivery, particularly in general practice. This study aimed to evaluate how dispensing of medications in primary care in Ireland changed following the COVID-19 pandemic's onset compared to expected trends. This interrupted time series study used data on medications prescribed in general practice 2016-2022 to patient eligible for state health cover, approximately one third of the population. Dispensing volumes for all therapeutic subgroups (ATC2 codes) and commonly dispensed medications were summarized. Pre-pandemic data were used to forecast expected trends (with 99% prediction intervals) using the Holt-Winters method, and these were compared to observed dispensing from March 2020 onwards. Many (31/77) therapeutic subgroups had dispensing significantly different from forecast in March 2020. Drugs for obstructive airway disease had the largest difference, with dispensing 26.2% (99%CI 19.5%-33.6%) higher than forecasted. Only two subgroups were significantly lower than forecasted, other gynaecologicals (17.7% lower, 99%CI 6.3%-26.6%) and dressings (11.6%, 99%CI 9.4%-41.6%). Dispensing of amoxicillin products and oral prednisolone were lower than forecasted in the months following the pandemic's onset, particularly during winter 2020/2021. There was a spike in dispensing for many long-term medications in March 2020, while pandemic restrictions likely contributed to reductions for other medications.

Analysis of primary care prescription trends in England during the COVID-19 pandemic compared against a predictive model.

OBJECTIVES: The COVID-19 pandemic has had an unprecedented impact across primary care. Primary care services have seen an upheaval, and more and more patients are engaging in telephone consultations in order to maintain social distancing. In the present study, we seek to quantify the effect of the pandemic on primary care prescribing. DESIGN: We conducted a retrospective analysis of the English Prescribing Dataset from January 2014 to November 2020, totalling 7 542 293 921 prescriptions. Data were separated into prepandemic and pandemic sets. A Holt-Winters predictive model was used to forecast individual drug prescribing based on historic trends. Observed data were compared with the forecast quantitatively and qualitatively. SETTING: All prescriptions signed in England and dispensed during the years 2014-2020. PARTICIPANTS: All residents of England who received a prescription from primary care facilities during 2014-2020. RESULTS: Prescribing of numerous health-critical medications was above predicted in March 2020, including salbutamol (53.0% (99% CI (41.2% to 66.9%))), insulin aspart (26.9% (99% CI (18.5% to 36.6%))) and tacrolimus (18.6% (99% CI (8.3% to 31.1%))). Medications for end-of-life symptom control increased in April, including levomepromazine hydrochloride (94.7% (99% CI (54.6% to 163.0%))). Medications requiring face-to-face visits decreased, including the local anaesthetic bupivacaine hydrochloride (86.6% (99% CI (89.3% to 82.0%))). There was no observed change in medications relating to type 2 diabetes, hypertension or mental health conditions. CONCLUSIONS: Significantly increased prescribing of several medications was observed, especially among those critical for health. A dramatic spike in end-of-life prescribing highlights the adversity faced by community practitioners during 2020. Medications involving face-to-face consultations declined, as did contraceptives, travel-related vaccines and drugs used in dementia and Parkinson's disease. Drugs relating to type 2 diabetes, hypertension and mental health were unchanged.

Development of locally relevant clinical guidelines for procedure-related neonatal analgesic practice in Kenya: a systematic review and meta-analysis.

Background Increasing numbers of neonates are undergoing painful procedures in low-income and middle-income countries, with adequate analgesia seldom used. In collaboration with a multi-disciplinary team in Kenya, we aimed to establish the first evidence-based guidelines for the management of routine procedure-related neonatal pain that consider low-resource hospital settings. METHODS: We did a systematic review by searching MEDLINE, Embase, CINAHL, and CENTRAL databases for studies published from Jan 1, 1953, to March 31, 2019. We included data from randomised controlled trials using heart rate, oxygen saturation (SpO2), premature infant pain profile (PIPP) score, neonatal infant pain scale (NIPS) score, neonatal facial coding system score, and douleur aiguë du nouveau-né scale score as pain outcome measures. We excluded studies in which neonates were undergoing circumcision or were intubated, studies from which data were unextractable, or when pain was scored by non-trained individuals. We did a narrative synthesis of all studies, and meta-analysis when data were available from multiple studies comparing the same analgesics and controls and using the same outcome measures. 17 Kenyan health-care professionals formed our clinical guideline development panel, and we used the Grading of Recommendations, Assessment, Development and Evaluation framework and the panel's knowledge of the local health-care context to guide the guideline development process. This study is registered with PROSPERO, CRD42019126620. FINDINGS: Of 2782 studies assessed for eligibility, data from 149 (5%) were analysed, with 80 (3%) of these further contributing to our meta-analysis. We found a high level of certainty for the superiority of breastfeeding over placebo or no intervention (standardised mean differences [SMDs] were -1·40 [95% CI -1·96 to -0·84] in PIPP score and -2·20 [-2·91 to -1·48] in NIPS score), and the superiority of oral sugar solutions over placebo or no intervention (SMDs were -0·38 [-0·61 to -0·16] in heart rate and 0·23 [0·04 to 0·42] in SpO2). We found a moderate level of certainty for the superiority for expressed breastmilk over placebo or no intervention (SMDs were -0·46 [95% CI -0·87 to -0·05] in heart rate and 0·48 [0·20 to 0·75] in SpO2). Therefore, the panel recommended that breastfeeding should be given as first-line analgesic treatment, initiated at least 2 min pre-procedure. Given contextual factors, for neonates who are unable to breastfeed, 1-2 mL of expressed breastmilk should be given as first-line analgesic, or 1-2 mL of oral sugar (≥10% concentration) as second-line analgesic. The panel also recommended parental presence during procedures with adjunctive provision of skin-to-skin care, or non-nutritive sucking when possible. INTERPRETATION: We have generated Kenya's first neonatal analgesic guidelines for routine procedures, which have been adopted by the Kenyan Ministry of Health, and have shown a framework for clinical guideline development that is applicable to other low-income and middle-income health-care settings. FUNDING: Wellcome Trust Research Programme, and the Africa-Oxford Initiative.

GP prescribing in Northern Ireland by deprivation index: retrospective analysis.

OBJECTIVE: In the present study, we sought to explore the relationship between socioeconomic status and prescribing magnitude and cost in primary care throughout Northern Ireland. DESIGN: We performed a retrospective data analysis of general practitioner (GP) prescribing using open-source databases with data collected from May to October 2019 to determine the number of prescriptions and cost of drugs and drug classes by area, ranking these by deprivation index. We used Kendall's tau to quantify the relationship between prescribing and deprivation. SETTING: We analysed open-source data collected from 325 GP practices in Northern Ireland during the period from May to October 2019. PARTICIPANTS: We analysed a total of 2 764 303 prescriptions signed during our study period. RESULTS: Our study indicates a clear trend of increased overall spending per patient (r=-0.1232, p=0.02) and number of prescriptions per patient (r=-0.3440, p<0.001) in areas of higher deprivation. The mean cost per item was higher in less deprived areas (r=0.3809, p<0.001). Overall, £13.79 more was spent and 3.5 more items were prescribed per patient in the most compared with the least deprived decile, although more expensive items tended to be prescribed in areas with lower socioeconomic deprivation (£11.27 per item vs £9.20 per item). We found a statistically significant correlation of prescribing of key drug classes, such as bronchodilators, antidepressants and drugs used to treat diabetes, among others, with greater deprivation. Prescribing of vaccines and drugs used in the treatment of glaucoma was correlated with lower deprivation. CONCLUSION: We provide an exploration of the correlation of prescribing with deprivation by analysing all prescriptions signed within a 6-month period in Northern Ireland. Our study broadly agrees with published literature, although a few notable exceptions are highlighted. We provide evidence of discrepancies in medication cost between areas of differing deprivation and suggest possible explanations for these trends. This information will be valuable for future investigation of disease prevalence, as well as targeting of patient education and future funding.

Involvement of the open-source community in combating the worldwide COVID-19 pandemic: a review.

The ongoing COVID-19 pandemic is unprecedented in the modern age both due to its scale and its disruption to daily life throughout the world. Widespread social isolation and restrictions in the age of modern communicative technology, coupled with some early successes for makers, have united the open-source community towards a common goal in a way not previously seen. Local hospitals and care facilities are turning to makers to print essential consumable parts, such as simple visors, while in the hardest hit areas, critical pieces of medical technology are being fabricated. While important and effective innovations are appearing almost daily, there are also some worrying trends towards hobbyists attempting manufacture of complex medical devices with little understanding of the clinical or scientific rationale behind their design. The nature of the open-source community, an area of intensive innovation, fluidity, and experimentation, jars with the exacting standards of medical device regulation. Here, we review the involvement of rapid prototyping and the open-source community in the key areas of personal protective equipment (PPE), diagnostics, critical care technology, and information acquisition and sharing, highlighting where makers and hackers have clashed with medical device regulations, and areas where the system has worked well to facilitate change.

Emerging patterns of hypercoagulability associated with critical COVID-19: A review.

While the COVID-19 pandemic sweeps the world, much evidence is being gathered regarding its novel pathological mechanisms. It is the authors' clinical experience that patients in the intensive care unit suffering from COVID-19 are extremely pro-coagulable, with venous and arterial thromboembolism frequently observed, and losses of vascular access lines and filtration circuits to thrombosis now commonplace. Here, we explore the evidence for hypercoagulability in this group, presenting evidence of both a localised pulmonary hypercoagulability, and a systemic hypercoagulability resulting in thrombosis distant to the pulmonary vasculature. Furthermore, we discuss the possible risk factors exacerbated by, or selected for in COVID-19. We review the available evidence for use of plasma D-dimer as a prognostic marker, exploring the possibility that it acts as a marker of a COVID-19-associated hypercoagulability. We review the evidence for a pro-coagulant subtype of disseminated intravascular coagulation, discussing its clinical significance. Finally, we discuss the current evidence surrounding treatment of COVID-19 hypercoagulability, including prophylactic and treatment-dose heparin, thrombolytic agents, antiplatelet agents, and direct thrombin inhibitors, among others. We suggest areas in which further investigation is urgently needed to reduce the startling incidence of thrombosis in this group, a complication no doubt contributing to morbidity and mortality.