Anticholinergic medications associated with falls and frailty in people with HIV.

BACKGROUND: Anticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study. METHODS: Anticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9). RESULTS: ACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06-9.98) and for clinical factors (OR 3.58; 95% CI 1.37-9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09-4.70 and OR 2.12; 95% CI 0.89-5.0, respectively). CONCLUSIONS: ACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible.

Effects of thermal sensation and acclimatization on cognitive performance of adult female students in Saudi Arabia using multivariable-multilevel statistical modeling.

In the hot climate of Saudi Arabia, people living year-round in air-conditioned spaces are likely to develop high expectations for homogeneity and cool temperatures, becoming potentially more sensitive if thermal conditions deviate from the comfort zone they expect. This paper presents the results from a field intervention investigating the association between participants' thermal sensations with cognitive performance in a female university in Saudi Arabia. The climatic context plays a key role in choosing Saudi Arabia, whereas the total reliance on air-conditioners (AC) for cooling is believed to have significant effects on occupants' perceptions of the comfort temperature. Results reveal discrepancies in the actual thermal sensations between the Saudi and non-Saudi participants which affected their performances. "Cool" and "Slightly Cool" sensations versus neutral were associated with significant lower percentage of errors and significant higher speed for all participants independently of any association with ethnicity and acclimatization. The estimates remained significant even after adjusting for ethnicity and the number of years spent in the country and the set temperature of AC at home. Implications of the study suggest a preference for staying cool when working independently of acclimatization status.

Combined effects of ventilation rates and indoor temperatures on cognitive performance of female higher education students in a hot climate.

Impairment in mental functions attributed to the effects of indoor air quality and thermal conditions has received considerable attention in the past decade, particularly for educational buildings where students' cognitive performance is essential to foster learning. This study explores the combined effects of indoor temperatures and CO2  levels as markers for ventilation rates on cognitive performance among female students (16-23 years old) in Saudi Arabia. The longitudinal experiments involved nine conditions combining three CO2 concentration levels (achieved via changes in ventilation) and three temperature levels involving 499 participants, all exposed to the nine conditions. The study implemented a computer-based cognitive performance battery with "9Button" keyboards. Univariable and multivariable multilevel regression models explored the association of indoor temperature and CO2  levels (as markers for ventilation rates) with cognitive performance after adjusting for potential confounders. Potential benefits were found on speed and accuracy of tasks of cognitive performance when indoor temperature was set between 20 and 23ºC and at CO2  levels of 600 ppm compared to higher temperatures and poorer ventilation rates and that both ventilation and thermal environmental control are important and need to be improved for achieving optimum learning conditions. Nevertheless, the results are relevant for short-term exposures lasting no more than 2 h.

Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion.

OBJECTIVE: European guidelines do not recommend tolvaptan for treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH), principally owing to concerns about risk of overly rapid correction of hyponatraemia. This study evaluated the real-life effectiveness and safety of tolvaptan. DESIGN: Consecutive case series. PATIENTS: Inpatients treated with tolvaptan for SIADH in 2 UK hospitals over a 3-year period. MEASUREMENTS: The primary outcome measures were serum sodium (sNa) correction at 24 and 48 h after tolvaptan therapy. RESULTS: This case series included 61 patients aged 74·4 ± 15·3 years with (mean ± SD) sNa 119·9 ± 5·5 mmol/l. The mean sNa increase 24 h after tolvaptan initiation was 9 ± 3·9 mmol/l. Excessive correction of hyponatraemia was observed in 23% of patients with all these patients having baseline sNa <125 mmol/l, but no cases of osmotic demyelination syndrome were recorded. At the end of tolvaptan therapy, sNa increase was 13·5 ± 5·9 mmol/l with 96·7% of patients having sNa increase ≥5 mmol/l in 48 h. There was a negative significant correlation (P = 0·012) between baseline sNa and 24-h change; for every 1 mmol/l reduction in baseline value, sNa increased by an additional 0·23 mmol/l (95% CI 0·05-0·41). CONCLUSIONS: Tolvaptan is effective in correcting hyponatraemia. Without rigorous electrolyte monitoring, tolvaptan carries a significant risk of overly rapid sodium correction, especially in patients with starting sNa <125 mmol/l. Tolvaptan should be used with great caution under close electrolyte monitoring.

Diagnosis of vertebral artery dissection in childhood posterior circulation arterial ischaemic stroke.

AIM: Review a series of children with posterior circulation arterial ischaemic stroke (PCAIS) to identify diagnostic modality and associations in cases of vertebral artery dissection (VAD). METHOD: Retrospective analysis of 30 cases of childhood PCAIS identified from two tertiary centres over 11 years. Clinical and demographic details were recorded. Brain and cerebrovascular imaging were reviewed. Aetiology was classified using the Childhood Arterial Ischaemic Stroke Standardized Classification and Diagnostic Evaluation criteria. Outcome was evaluated using standardized paediatric stroke outcome scores. Logistic regression was used to explore variables associated with diagnosis. RESULTS: Twenty-three patients were male (77%) and 7 were female (23%). VAD was the most commonly identified aetiology, in 15 cases (50%). Aetiology was undetermined in 12 (40%), probable cardioembolism in two, and reversible cerebral vasoconstriction syndrome in one. In those with VAD, diagnosis was made on initial magnetic resonance angiography (MRA) in six (40%). Further cases of VAD were diagnosed with catheter angiography (n=6), computed tomographic angiography (n=1), or follow-up MRA (n=2). Presence of multiple infarcts was associated with a diagnosis of VAD. INTERPRETATION: Endoluminal cerebrovascular imaging increases the rate of diagnosis of VAD in childhood PCAIS and should especially be considered if there are multiple infarcts.

A case-control study of hyponatraemia as an independent risk factor for inpatient mortality.

OBJECTIVES: Hyponatraemia is strongly associated with increased inpatient mortality, but it is unknown whether hyponatraemia per se contributes to excess mortality. Our hypothesis was that if hyponatraemic patients had significantly greater mortality compared with controls despite no difference with regard to gender, age, comorbidities and type of primary pathology, this would incriminate hyponatraemia as an independent predictor of mortality. DESIGN: Single-centre, case-control study. PATIENTS: Cases (N = 139) were hospitalized patients with serum Na ≤ 128 mmol/l over 3 months. Controls were 254 age- and gender-matched patients residing in the same hospital ward with serum Na > 128 mmol/l. MEASUREMENTS: Data were collected about age, gender, comorbidities, drug history, serum creatinine, intensive care unit (ICU) admission and length of hospitalization. The main outcome measure was inpatient mortality. RESULTS: Hyponatraemic patients had an inpatient mortality rate of 17·3% and were more than three times more likely to die during their hospital stay compared with controls (OR 3·33, 95% CI 1·68-6·58, P < 0·01) despite no statistically significant difference with respect to age, gender, comorbidities, use of common drugs, serum creatinine, ICU admission rate and length of hospitalization. Comparison of cases with the normonatraemic subgroup of controls demonstrated that cases were almost 12 times more likely to die during admission than normonatraemic controls (OR 11·89, 95% CI 2·75-51·51, P < 0·01). CONCLUSIONS: This study showed that hyponatraemia is an independent predictor of mortality, and hyponatraemia per se is likely to contribute to excess mortality. Further studies are needed to examine whether correction of hyponatraemia can reduce mortality.

Smoking and caesarean deliveries: major negative predictors for breastfeeding in the mother-child cohort in Crete, Greece (Rhea study).

Although benefits of breastfeeding have been widely promoted and accepted, exclusive breastfeeding for the first 6 months of life is far from the norm in many countries. In a prospective mother-child cohort study in Crete, Greece ('Rhea' study), we assessed the frequency of breastfeeding and its socio-demographic predictors. Information on breastfeeding was available for a period of 18 months post-partum for a cohort of 1181 mothers and their 1208 infants. The frequency of exclusive and predominant breastfeeding in the first month post-partum was 17.8% and 3.4%, respectively, with almost three-quarters of women (73.6%) ceasing any breastfeeding after 4 months post-partum. Women were less likely to initiate breastfeeding if they had a caesarean delivery (CD), whereas they were more likely to initiate breastfeeding if they had a higher education or gave birth to a private clinic. Among women breastfeeding, those who had a CD, were ex-smokers or smokers during pregnancy had a statistically significant shorter duration of breastfeeding, whereas higher education and being on leave from work were associated with a longer duration of breastfeeding. Study findings suggest suboptimal levels of exclusive and any breastfeeding and difficulty maintaining longer breastfeeding duration. CD and smoking are common in Greece and are strong negative predictors for breastfeeding initiation and/or duration, necessitating targeting women at risk early in the prenatal period so as to have a meaningful increase of breastfeeding practices in future cohorts of mothers.

Predicting cardiovascular events with fluoropyrimidine chemotherapy using a standard cardiovascular risk calculator.

AIMS: Fluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine-associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context. METHODS AND RESULTS: Single-centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3 months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety-eight patients were included (45% male; median age 64 years), with median follow up 24.5 (11.5-48.3 months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)-most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11-4.93, P = 0.03). On multivariable analysis, beta-blocker use (HR 1.04, 95% CI 1.00-1.08, P = 0.04) and higher BMI (HR 2.33, 95% CI 1.04-5.19, P = 0.04) were independently associated with incident CV events. Thirty-two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P = 0.50). CONCLUSIONS: High BMI and use of beta-blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re-challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.

Exposure to different sources of second-hand smoke during pregnancy and its effect on urinary cotinine and tobacco-specific nitrosamine (NNAL) concentrations.

BACKGROUND: To date, no research exists on the role that different sources of exposure to second-hand smoke (SHS) have on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine uptake, assessed via urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations of non-smoking pregnant women, nor the differences in NNAL concentrations among pregnant women who quit smoking in comparison to those who do not. METHODS: As part of the 'Rhea' mother childbirth cohort in Crete, Greece, 1317 mother-child pairs were followed-up until delivery, while among a subsample, maternal urine was assessed for its NNAL (n=117) and cotinine concentrations (n=377). RESULTS: Pregnant women who continued to smoke during pregnancy were found to have geometric mean urinary NNAL concentrations of 0.612 pmol/ml, in comparison to the 0.100 pmol/ml of ex-smokers and 0.0795 pmol/ml of non-smokers exposed to SHS. Exposure to SHS in the home was associated with a 4.40 ng/ml increase in urinary cotinine levels, while reported exposure to SHS in cars was associated with an even higher (8.73 ng/ml) increase in cotinine concentrations and was strongly related to NNAL concentrations. Exposure to SHS in the workplace and in public places was also shown to increase cotinine and NNAL concentrations. The NNAL:cotinine ratio was found to be higher among pregnant women who were exposed to SHS but did not smoke (p<0.001). CONCLUSIONS: Using cotinine levels as an indicator of NNK, exposure due to SHS during pregnancy leads to an underestimation of exposure to NNK uptake. Moreover, each source of exposure contributed to the increase in cotinine levels, indicating the importance of avoiding SHS exposure from any source.

How has COVID-19 changed healthcare professionals' attitudes to self-care? A mixed methods research study.

BACKGROUND: The COVID-19 pandemic fundamentally changed the way services are delivered. Self-care, including good hygiene practices and avoidance of risk was emphasised as the key measure to tackle the pandemic in the early stages. OBJECTIVE: To understand how self-reported professional attitudes, perceptions and practices of self-care have changed as a result of the COVID-19 pandemic. DESIGN: Cross-sectional online survey and semi-structured qualitative interview. SETTING: Health care. PARTICIPANTS: 304 healthcare professionals (HCPs). METHODS: A wide range of HCPs, including pharmacists, nurses, doctors, social prescribers and other designations took part in a 27-item anonymous online survey. Semi-structured qualitative interviews with nine healthcare professionals explored attitudes to and practices of self-care before and during the pandemic. Views were sought on the permanence and implications of changes. Data were analysed using routine statistics and thematic analysis to identify major themes. RESULTS: A total of 304 HCPs responded to the survey fully. Nine participated in a semi-structured interview. There was agreement that the importance of self-care has increased markedly during the pandemic. The percentage of respondents who felt that self-care was 'very' important to their clients increased from 54.3% to 86.6% since the pandemic. Personal empowerment and capacity of service users to self-care increased significantly during the pandemic. Willingness of patients to engage (74%) and poor understanding of self-care (71%) were cited as the two main barriers to self-care. A close third was digital exclusion (71%), though 86% of respondents recommended online resources and 77% the use of smartphone apps. Survey respondents believed the changes to be permanent and positive. Interviewees reported a major, and positive move to self-care with the pandemic seen as an opportunity to be grasped, but professional education would have to be aligned to make the most of it. They raised concerns as to whether the shift to self-care was perceived by users as 'abandonment' rather than 'empowerment' and whether problems had been stored rather than dealt with through self-care and therefore whether the positive changes would continue after the pandemic. CONCLUSION: Reporting their views before the pandemic, barely more than half of the professionals surveyed saw self-care as fundamentally important to the individuals they served. This changed to 86% as a result of the pandemic. Patient/client engagement with and understanding of self-care were reported as major barriers, as was digital exclusion, though increased technological solutions were used by all respondents. Concerns were raised that the permanence of the changes depended upon continued encouragement and empowerment of individuals to self-care and on its inclusion in professional education as a substantive subject.

What is the suitability of clinical vignettes in benchmarking the performance of online symptom checkers? An audit study.

OBJECTIVE: Assess the suitability of clinical vignettes in benchmarking the performance of online symptom checkers (OSCs). DESIGN: Observational study using a publicly available free OSC. PARTICIPANTS: Healthily OSC, which provided consultations in English, was used to record consultation outcomes from two lay and four expert inputters using 139 standardised patient vignettes. Each vignette included three diagnostic solutions and a triage recommendation in one of three categories of triage urgency. A panel of three independent general practitioners interpreted the vignettes to arrive at an alternative set of diagnostic and triage solutions. Both sets of diagnostic and triage solutions were consolidated to arrive at a final consolidated version for benchmarking. MAIN OUTCOME MEASURES: Six inputters simulated 834 standardised patient evaluations using Healthily OSC and recorded outputs (triage solution, signposting, and whether the correct diagnostic solution appeared first or within the first three differentials). We estimated Cohen's kappa to assess how interpretations by different inputters could lead to divergent OSC output even when using the same vignette or when compared with a separate panel of physicians. RESULTS: There was moderate agreement on triage recommendation (kappa=0.48), and substantial agreement on consultation outcomes between all inputters (kappa=0.73). OSC performance improved significantly from baseline when compared against the final consolidated diagnostic and triage solution (p<0.001). CONCLUSIONS: Clinical vignettes are inherently limited in their utility to benchmark the diagnostic accuracy or triage safety of OSC. Real-world evidence studies involving real patients are recommended to benchmark the performance of OSC against a panel of physicians.

How is the COVID-19 lockdown impacting the mental health of parents of school-age children in the UK? A cross-sectional online survey.

OBJECTIVE: Investigate the impact of the COVID-19 lockdown on feelings of loneliness and social isolation in parents of school-age children. DESIGN: Cross-sectional online survey of parents of primary and secondary school-age children. SETTING: Community setting. PARTICIPANTS: 1214 parents of school-age children in the UK. METHODS: An online survey explored the impact of lockdown on the mental health of parents with school-age children, and in particular about feelings of social isolation and loneliness. Associations between the UCLA Three-Item Loneliness Scale (UCLATILS), the Direct Measure of Loneliness (DMOL) and the characteristics of the study participants were assessed using ordinal logistic regression models. MAIN OUTCOME MEASURES: Self-reported measures of social isolation and loneliness using UCLATILS and DMOL. RESULTS: Half of respondents felt they lacked companionship, 45% had feelings of being left out, 58% felt isolated and 46% felt lonely during the first 100 days of lockdown. The factors that were associated with higher levels of loneliness on UCLATILS were female gender, parenting a child with special needs, lack of a dedicated space for distance learning, disruption of sleep patterns and low levels of physical activity during the lockdown. Factors associated with a higher DMOL were female gender, single parenting, parenting a child with special needs, unemployment, low physical activity, lack of a dedicated study space and disruption of sleep patterns during the lockdown. CONCLUSIONS: The COVID-19 lockdown has increased feelings of social isolation and loneliness among parents of school-age children. The sustained adoption of two modifiable health-seeking lifestyle behaviours (increased levels of physical activity and the maintenance of good sleep hygiene practices) wmay help reduce feelings of social isolation and loneliness during lockdown.

A digital solution to streamline access to smoking cessation interventions in England; findings from a primary care pilot (STOPNOW study).

Objectives: Despite the proven efficacy of several smoking cessation medications that have been shown to improve long-term abstinence rates, approximately two-thirds of smokers report not having used medication in their most recent quit attempt. A main barrier could be delayed access to pharmacological interventions. This study investigated the utility of a primary care linked online portal to streamline timely access to pharmacological support to patients who want to quit smoking by making an asynchronous request for treatment to their general practitioner. Study design: Prospective cohort study. Methods: An online portal with added functionality was developed, which allowed patients with a unique link to make an asynchronous request for treatment. Two GP practices identified a total of 4337 eligible patients who received an SMS or email invite to engage with an online portal including an electronic survey to capture information about smoking behaviours and to request treatment. Portal informatics and patient level data were analysed to measure the efficacy of the online system in reducing the time between making a formal request to treatment and access to pharmacological support. The primary outcome measure was the time between making a formal request for treatment and access to pharmacological support from a designated community pharmacy. Results: 323 patients (7.4%) initiated the survey, but only 56 patients completed the survey and made a formal request for treatment. 94% of participants did not return to use the portal to make a second or follow-up request for treatment. Only 3 participants completed the 12-week pathway. A total of 75 medication items were prescribed and collected by 56 patients. The time difference between the formal request to treatment and GP review ranged between 20 h and 1 week. The time difference between approval of prescription by the GP and access to medication was 5 days ± 2.1 days (range = 1.9-7.0 days). Conclusion: The widespread adoption and diffusion of an IT enabled and asynchronous primary care led remote consultation pathway can streamline timely access to smoking cessation support without the need for the patient to see a GP or an independent prescriber in the first instance.

Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study.

BACKGROUND: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA). METHODS: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires. RESULTS: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia. CONCLUSIONS: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

OBJECTIVES: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH). METHODS: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders. RESULTS: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores. CONCLUSIONS: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.

Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19.

CONTEXT: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19. METHODS: This retrospective longitudinal cohort study, including all adult patients who presented with COVID-19 to 2 hospitals in London over an 8-week period, evaluated the association of dysnatremia (serum sodium < 135 or > 145 mmol/L, hyponatremia, and hypernatremia, respectively) at several time points with inpatient mortality, need for advanced ventilatory support, and AKI. RESULTS: The study included 488 patients (median age, 68 years). At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% hypernatremic. Hypernatremia 2 days after admission and exposure to hypernatremia at any time point during hospitalization were associated with a 2.34-fold (95% CI, 1.08-5.05; P = .0014) and 3.05-fold (95% CI, 1.69-5.49; P < .0001) increased risk of death, respectively, compared to normonatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support (95% CI, 1.34-3.45, P = .0011). Hyponatremia was not a risk factor for in-hospital mortality, except for the subgroup of patients with hypovolemic hyponatremia. Sodium values were not associated with the risk for AKI and length of hospital stay. CONCLUSION: Abnormal sodium levels during hospitalization are risk factors for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively. Serum sodium values could be used for risk stratification in patients with COVID-19.

Plasma nucleotide reverse transcriptase inhibitor concentration and their associations with liver and renal parameters in people living with HIV.

: Associations between markers of liver and renal dysfunction and nucleotide reverse transcriptase inhibitor plasma exposure are ill-defined. As part of a large cohort study (Pharmacokinetic and Clinical Observations in People over Fifty), we analysed associations between alanine aminotransferase and estimated glomerular filtration rate results in people living with HIV on tenofovir disoproxil fumarate, emtricitabine, abacavir and lamivudine. While we found no associations between nucleotide reverse transcriptase inhibitor concentrations and alanine aminotransferase, lower estimated glomerular filtration rate values were associated with greater tenofovir, emtricitabine and lamivudine exposure, whereas abacavir showed no associations.

The predictors of pain extent in people living with HIV.

OBJECTIVE: To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage. DESIGN: Cross-sectional analysis of cohort study in the United Kingdom and Ireland. METHODS: Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal-Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors. RESULTS: Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4 cell count but longer exposure to immunosuppression. CONCLUSION: Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.

Polypharmacy and drug-drug interactions in older and younger people living with HIV: the POPPY study.

BACKGROUND: Polypharmacy (use of ≥ five medications) increases the risk of drug-drug interactions and can lead to negative health outcomes. This study aimed to review the medications of people living with HIV (PLWH) and HIV-negative controls in the POPPY study and evaluate the frequency of polypharmacy and potential drug-drug interactions (PDDIs). METHODS: PDDIs between non-antiretroviral (ARV) drugs were analysed using the Lexicomp® database, and PDDIs between non-ARV and ARV drugs using the Liverpool drug interaction database. Between-group differences were assessed using χ2, Mann-Whitney U and Kruskal-Wallis tests. RESULTS: This analysis included 698 PLWH ≥50 years, 374 PLWH <50 years and 304 HIV-negative controls ≥50 years. The prevalence of polypharmacy was 65.8% in older PLWH, 48.1% in younger PLWH and 13.2% in the HIV-negative group. When ARVs were excluded, 29.8% of older PLWH and 14.2% of younger PLWH had polypharmacy. The prevalence of ≥1 PDDI involving non-ARV drugs was 36.1%, 20.3% and 16.4%, respectively, in older PLWH, younger PLWH and HIV-negative controls. In PLWH the prevalence of ≥1 PDDI involving ARV and non-ARV drugs was 57.3% in older PLWH and 32.4% in younger PLWH. CONCLUSIONS: Polypharmacy and PDDIs involving non-ARV/ARV drugs and non-ARV/non-ARV drugs were common among older PLWH, highlighting the need for increased awareness and additional research on all types of PDDI.

Risk factors and impact of patterns of co-occurring comorbidities in people living with HIV.

AIMS: To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes. METHODS: Common patters of comorbidities in PLWH participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns' severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner visits using Poisson regression. RESULTS: A total of 1073 PLWH were analysed: 85.2% male, median (interquartile range) age 52 (47-59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases, mental health problems, metabolic disorders and chest/other infections (all P ≤ 0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (P < 0.001). The pattern of cardiovascular diseases was associated with poorer physical health (P = 0.02), higher risk of functional impairment (P = 0.02) and hospitalization (P < 0.001) and with higher number of general practitioner visits (P < 0.001). Severity of mental health (all P < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes. CONCLUSION: Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.