Screening for - and prevalence of - anxiety and depression in cardiac rehabilitation in the post-COVID era. An observational study.

BACKGROUND: Approximately 20-30% of patients with a cardiac disease suffer from anxiety and/or depression, leading to poor health outcomes. To identify this subgroup, clinical guidelines recommend screening for anxiety and depression in cardiac rehabilitation (CR). It is unknown how screening practice is delivered post-COVID. METHODS: This observational study used data from the National Audit of Cardiac Rehabilitation from April 2018-March 2022. Descriptive statistics were used to assess screening rates and prevalence, while a multivariate logistic regression model was performed to analyse determinants for screening for anxiety and depression among patients participating in cardiac rehabilitation. RESULTS: The population consisted of 245,705 patients, where 128,643 (52.4%) were screened and 117,062 (47.6%) were not. Patients attending CR during first year of COVID-19 were less likely to be screened. Patients with female gender, living alone, non-white ethnicity, living in the most deprived areas, current smoking, and physical inactivity were less likely to be screened, while patients who were revascularized, having an objective physical fitness test, and attending a certified CR center were more likely to be screened. For patients attending CR during COVID-19, the prevalence of anxiety and depression decreased significantly. For anxiety the prevalence dropped from 34.4% to 15.8%, for depression the prevalence dropped from 33.5% to 16.5%. CONCLUSION: CR service provision was negatively impacted during COVID-19, leading to much lower screening for anxiety and depression in the CR setting. Prevalence of anxiety and depression decreased during COVID-19 for this population, possibly because psychologically affected patients refrained from attending CR.

A case report of granulomatous lymphomatoid papulosis.

Lymphomatoid papulosis is a chronic CD30-positive cutaneous lymphoproliferative disorder that is characterized by recurring red-brown necrotic papules. It exhibits a wide spectrum of histopathologic findings and is often associated with cutaneous T-cell lymphomas. Six different histological subtypes have been classified by the WHO, but there is limited understanding regarding rare histopathologic variants. We describe a 51-year-old man who presented with recurring, necrotic papules for 6 years that progressed to involve the face, scalp, trunk, axilla, and scrotum. Histopathology demonstrated sarcoidal granulomas, along with a CD30-positive T cell infiltrate which demonstrated clonality by T cell receptor gamma gene rearrangement. A diagnosis of lymphomatoid papulosis associated with granulomas was established based on the clinical and histopathologic presentation. The clinical understanding of granulomatous lymphomatoid papulosis is limited in the available literature and more awareness of this histopathologic variant is required for accurate classification of this disorder.

Systematic screening for anxiety and depression in cardiac rehabilitation - are we there yet?

BACKGROUND: Anxiety and depression are prevalent in 20% of patients with acute coronary syndrome (ACS) and associated with poor outcomes. Guidelines recommend screening for these conditions in cardiac rehabilitation (CR) however, clinical practice is inconsistent. Sparse knowledge exists on determinants for screening. METHODS: This observational study used data from the National Audit of Cardiac Rehabilitation from January 2016-December 2019. A multivariate logistic regression model was performed to analyze patient- and provider level determinants for screening for anxiety and depression among patients with ACS. RESULTS: The population consisted of 138,018 patients, where 82,507 (59.8%) were screened and 55,511 (40.2%) were not. Younger age, non-white ethnicity, living in areas of social deprivation, current smoking, body mass index>30, and physical activity<150 min per week were negatively correlated with patients being screened. Compared to patients having a percutaneous coronary intervention, patients undergoing coronary artery bypass grafting or medical treatment were less likely to be screened. History of anxiety, depression, osteoporosis, chronic back problems, and asthma were positively correlated with screening, while chronic obstructive pulmonary disease, diabetes, hypertension, and stroke were negatively correlated with screening. Regarding provider level, certification of CR centers was positively associated with screening, while looking over time data showed an incremental negative trend in screening from 2016 to 2019. CONCLUSION: We found both patient and provider level determinants of screening for anxiety and depression. Clinical practice is still inconsistent especially for high-risk groups. We recommend systematic screening to enable tailored interventions which in turn may mitigate inequity in health outcomes.

Growth rates for freshwater ferromanganese concretions indicate regional climate change in eastern Canada at the Northgrippian-Meghalayan boundary.

The existence of freshwater ferromanganese concretions has been known for decades, but we are not aware of a generally accepted explanation for their formation, and there has been little research into their potential use as records of Holocene climate and paleohydrology. A conceptual model is presented to describe the environmental and geochemical processes which result in the formation and growth of freshwater ferromanganese concretions. In order to evaluate their potential as historical geochemical records, a concretion from Magaguadavic Lake, New Brunswick, Canada is the focus of a detailed geochronological and geochemical investigation. The radiocarbon data provide a coherent growth curve and a maximum age for the concretion of 8448 ± 43 years, consistent with the establishment of Magaguadavic Lake as a stable post-glacial lacustrine system. The data suggest accretion rates of 1.5 and 3.4 mm per 1000 years during the Northgrippian and Meghalayan stages of the Holocene, respectively. The abrupt change in growth rate observed at the stage boundary may be an indicator of Holocene climate change. These features are consistent with inferences from previous research that warmer climate in the Northgrippian led to eutrophication in some lakes in eastern North America. The results confirm that freshwater Fe-Mn concretions may yield important information about past climatic and environmental conditions.

Efficient Algorithm for the Topological Characterization of Worm-like and Branched Micelle Structures from Simulations.

Many surfactant-based formulations are utilized in industry as they produce desirable viscoelastic properties at low concentrations. These properties are due to the presence of worm-like micelles (WLMs), and as a result, understanding the processes that lead to WLM formation is of significant interest. Various experimental techniques have been applied with some success to this problem but can encounter issues probing key microscopic characteristics or the specific regimes of interest. The complementary use of computer simulations could provide an alternate route to accessing their structural and dynamic behavior. However, few computational methods exist for measuring key characteristics of WLMs formed in particle simulations. Further, their mathematical formulations are challenged by WLMs with sharp curvature profiles or density fluctuations along the backbone. Here, we present a new topological algorithm for identifying and characterizing WLMs in particle simulations, which has desirable mathematical properties that address shortcomings in previous techniques. We apply the algorithm to the case of sodium dodecyl sulfate micelles to demonstrate how it can be used to construct a comprehensive topological characterization of the observed structures.

Intensive care unit physician-delivered point of care renal tract ultrasound in acute kidney injury is feasible.

Acute kidney injury is common in critically ill patients, with ultrasound recommended to exclude renal tract obstruction. Intensive care unit clinicians are skilled in acquiring and interpreting ultrasound examinations. Intensive Care Medicine Trainees wish to learn renal tract ultrasound. We sought to demonstrate that intensive care unit clinicians can competently perform renal tract ultrasound on critically ill patients. Thirty patients with acute kidney injury were scanned by two intensive care unit physicians using a standard intensive care unit ultrasound machine. The archived images were reviewed by a Radiologist for adequacy and diagnostic quality. In 28 of 30 patients both kidneys were identified. Adequate archived images of both kidneys each in two planes were possible in 23 of 30 patients. The commonest reason for failure was dressings and drains from abdominal surgery. Only one patient had hydronephrosis. Our results suggest that intensive care unit clinicians can provide focussed renal tract ultrasound. The low incidence of hydronephrosis has implications for delivering the Core Ultrasound in Intensive Care competencies.

Does the mode of delivery in routine cardiac rehabilitation have an association with cardiovascular risk factor outcomes?

AIMS: Cardiac rehabilitation is one of the most cost-effective interventions for patients with cardiovascular disease. Worldwide supervised group-based cardiac rehabilitation is the dominant mode of delivery followed by facilitated self-managed (FSM), which is emerging as part of a cardiac rehabilitation menu. Modern research evidence, using trials and well-resourced interventions, suggests FSM is comparable to supervised rehabilitation in its outcomes for patients; however, this is yet to be established using routine clinical practice data. METHODS: Including 81,626 patients from routine clinical data in the National Audit of Cardiac Rehabilitation, this observational study investigated whether mode of delivery, supervised or FSM, was associated with similar cardiac rehabilitation outcomes. Hierarchical regression models included patient and service covariates such as age, gender, cardiac rehabilitation duration and programme staff type. RESULTS: The results showed 85% of the population received supervised cardiac rehabilitation. The FSM group were significantly older, female and predominantly in lower socioeconomic groups. The results showed that all patients on average benefit from cardiac rehabilitation, independently of mode of delivery, across all risk factors. Additional benefit of 13% and 11.4% increased likelihood of achieving the target state for physical activity and body mass index respectively when using FSM approaches. CONCLUSION: This is the first study to investigate traditional cardiovascular risk factors with cardiac rehabilitation mode of delivery using routine clinical data. Both modes of delivery were associated with comparable statistically significant positive outcomes. Despite having equivalent outcomes, FSM cardiac rehabilitation continues to be underutilised, with less than 20% of patients receiving this mode of delivery in the UK.

Does the mode of delivery in Cardiac Rehabilitation determine the extent of psychosocial health outcomes?

BACKGROUND: Cardiac Rehabilitation (CR) is a multicomponent tailored intervention aiming to reduce lifestyle risk factors and promote health in patients post cardiovascular disease. CR is delivered either as supervised or facilitated self-delivered yet little evidence exists evaluating the association between mode of delivery and outcomes. METHODS: This observational study used data routinely collected from the National Audit of Cardiac Rehabilitation from April 2012-March 2016. The analysis compared the populations receiving supervised and facilitated self-delivered modes for differences in baseline demographics, four psychosocial health measures pre and post CR and changes in anxiety, depression and quality of life following the intervention. The analysis also modelled the relationship between mode and outcomes, accounting for covariates such as age, gender, duration and staffing. RESULTS: The study contained 120,927 patients (age 65, 26.5 female) with 82.2% supervised and 17.8% self-delivered. The analysis showed greater proportion of females, employed and older patients in the self-delivered group. Following CR, patients in both groups demonstrated positive changes which were of comparable size. The regression model showed no significant association between mode of delivery and outcome in all four psychosocial outcomes when accounting for covariates (p-value>0.0.5). CONCLUSIONS: Patients benefited from attending both modes of CR showing improved psychosocial health outcomes with 3-76% change from baseline. Over half of CR programmes in the UK do not provide self-delivered CR yet this mode is known to reach older patients, female and employed patients. Facilitated self-delivered CR should be offered and supported as a genuine option, alongside supervised CR, by clinical teams.

Changes in Muscle Architecture, Explosive Ability, and Track and Field Throwing Performance Throughout a Competitive Season and After a Taper.

The purpose of this study was to examine the effects of an overreach and taper on measures of muscle architecture, jumping, and throwing performance in Division I collegiate throwers preparing for conference championships. Six collegiate track and field throwers (3 hammer, 2 discus, 1 javelin) trained for 12 weeks using a block-periodization model culminating with a 1-week overreach followed by a 3-week taper (ORT). Session rating of perceived exertion training load (RPETL) and strength training volume-load times bar displacement (VLd) were recorded weekly. Athletes were tested pre-ORT and post-ORT on measures of vastus lateralis architecture, unloaded and loaded squat and countermovement jump performance, underhand and overhead throwing performance, and competition throwing performance. There was a statistical reduction in weight training VLd/session (d = 1.21, p ≤ 0.05) and RPETL/session (d = 0.9, p ≤ 0.05) between the in-season and ORT training phases. Five of 6 athletes improved overhead throw and competition throwing performance after the ORT (d = 0.50, p ≤ 0.05). Vastus lateralis muscle thickness statistically increased after the in-season training phase (d = 0.28, p ≤ 0.05) but did not change after the ORT. Unloaded countermovement jump peak force and relative peak power improved significantly after the ORT (d = 0.59, p ≤ 0.05, d = 0.31, p ≤ 0.05, respectively). These findings demonstrate that an overreaching week followed by a 3-week taper is an effective means of improving explosive ability and throwing performance in collegiate track and field throwers despite the absence of detectable changes in muscle architecture.

Relationship between employment and mental health outcomes following Cardiac Rehabilitation: an observational analysis from the National Audit of Cardiac Rehabilitation.

BACKGROUND: Employment status has been shown to impact mental health state and intervention outcomes, yet still to be studied in a Cardiac Rehabilitation (CR) population. This observational study investigated the relationship between employment status and mental health outcomes following Cardiac Rehabilitation (CR). METHODS: All patients with an eligible cardiovascular incident entered into the National Audit of Cardiac Rehabilitation (NACR) 1 January 2013-31st December 2015. Logistic regression comparing the association between employment status and normal mental health categories. RESULTS: A total of 24,242 CR patients with completed post CR assessments were included and had representative age and gender distribution (mean 65years, 73.2% male). At baseline the unemployed status had a lower proportion of patients in normal healthy categories than other groups (T-test and chi-squared p=<0.05). The regression analyses revealed no significant association between retired and employed groups and outcome. There was significant association between unemployed patients and all mental health outcomes except anxiety; all p values<0.05 and odds ratios between 0.525 and 0.772 showing less likelihood of achieving the normal healthy category. CONCLUSIONS: This is the first UK study, using routinely collected data, to investigate in coronary heart disease patients the impact of employment status on outcomes. The findings were that when weighted for baseline differences, unemployed patients mostly had poorer outcomes. Teams involved in CR delivery should take particular care when interpreting mental health baseline measures when setting CR goals, especially in relation to unemployed patients, and efforts should be made in providing more patient tailored interventions.

Proton Mobility in b2 Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides.

A detailed energy-resolved study of the fragmentation reactions of protonated histidine-containing peptides and their b2 ions has been undertaken. Density functional theory calculations were utilized to predict how the fragmentation reactions occur so that we might discern why the mass spectra demonstrated particular energy dependencies. We compare our results to the current literature and to synthetic b2 ion standards. We show that the position of the His residue does affect the identity of the subsequent b2 ion (diketopiperazine versus oxazolone versus lactam) and that energy-resolved CID can distinguish these isomeric products based on their fragmentation energetics. The histidine side chain facilitates every major transformation except trans-cis isomerization of the first amide bond, a necessary prerequisite to diketopiperazine b2 ion formation. Despite this lack of catalyzation, trans-cis isomerization is predicted to be facile. Concomitantly, the subsequent amide bond cleavage reaction is rate-limiting.

Formation of a(1) ions directly from oxazolone b(2) ions: an energy-resolved and computational study.

It is well-known that oxazolone b2 ions fragment extensively by elimination of CO to form a2 ions, which often fragment further to form a1 ions. Less well-known is that some oxazolone b2 ions may fragment directly to form a1 ions. The present study uses energy-resolved collision-induced dissociation experiments to explore the occurrence of the direct b2→a1 fragmentation reaction. The experimental results show that the direct b2→a1 reaction is generally observed when Gly is the C-terminal residue of the oxazolone. When the C-terminal residue is more complex, it is able to provide increased stability of the a2 product in the b2→a2 fragmentation pathway. Our computational studies of the relative critical reaction energies for the b2→a2 reaction compared with those for the b2→a1 reaction provide support that the critical reaction energies are similar for the two pathways when the C-terminal residue of the oxazolone is Gly. By contrast, when the nitrogen of the oxazolone ring in the b2 ion does not bear a hydrogen, as in the Ala-Sar and Tyr-Sar (Sar = N-methylglycine) oxazolone b2 ions, a1 ions are not formed but rather neutral imine elimination from the N-terminus of the b2 ion becomes a dominant fragmentation reaction. The M06-2X/6-31+G(d,p) density functional theory calculations are in general agreement with the experimental data for both types of reaction. In contrast, the B3LYP/6-31+G(d,p) model systematically underestimates the barriers of these SN2-like b2→a1 reaction. The difference between the two methods of barrier calculation are highly significant (P < 0.001) for the b2→a1 reaction, but only marginally significant (P = 0.05) for the b2→a2 reaction. The computations provide further evidence of the limitations of the B3LYP functional when describing SN2-like reactions.

Effect of the sarcosine residue on sequence scrambling in peptide b(5) ions.

The effect of N-methylation on sequence scrambling in the fragmentation of b5 ions has been investigated by studying a variety of peptides containing sarcosine (N-methylglycine). The product ion mass spectra for the b5 ions derived from Sar-A-A-A-Y-A and Sar-A-A-Y-A-A show only minor signals for non-direct sequence ions the major fragmentation reactions occurring from the unrearranged structures. This is in contrast to the b5 ions where the Sar residue is replaced by Ala and sequence scrambling occurs. The b5 ion derived from Y-Sar-A-A-A-A shows a product ion mass spectrum essentially identical to the spectrum of the b5 ion derived from Sar-A-A-A-Y-A, indicating that in the former case macrocyclization has occurred but the macrocyclic form shows a strong preference to reopen to put the Sar residue in the N-terminal position. Similar results were obtained in the comparison of b5 ions derived from A-Sar-A-A-Y-A and Sar-A-A-Y-A-A. The product ion mass spectra of the MH(+) ions of Y-Sar-A-A-A-A and A-Sar-A-A-Y-A show substantial signals for non-direct sequence ions indicating that fragmentation of the MH(+) ions channels extensively through the respective b5 ions and further fragmentation of these species.

Non-direct sequence ions in the tandem mass spectrometry of protonated peptide amides--an energy-resolved study.

The fragmentation reactions of the MH(+) ions of Leu-enkephalin amide and a variety of heptapeptide amides have been studied in detail as a function of collision energy using a QqToF beam type mass spectrometer. The initial fragmentation of the protonated amides involves primarily formation of bn ions, including significant loss of NH3 from the MH(+) ions. Further fragmentation of these bn ions occurs following macrocyclization/ring opening leading in many cases to bn ions with permuted sequences and, thus, to formation of non-direct sequence ions. The importance of these non-direct sequence ions increases markedly with increasing collision energy, making peptide sequence determination difficult, if not impossible, at higher collision energies.

Fragmentation reactions of methionine-containing protonated octapeptides and fragment ions therefrom: an energy-resolved study.

The fragmentation reactions of the MH(+) ions as well as the b7, a7, and a7* ions derived therefrom have been studied in detail for the octapeptides MAAAAAAA, AAMAAAAA, AAAAMAAA, and AAAAAAMA. Ionization was by electrospray using a QqToF mass spectrometer, which allowed a study of the evolution of the fragmentation channels as a function of the collision energy. Not surprisingly, the product ion mass spectra for the b7 ions are independent of the original precursor sequence, indicating macrocyclization and reopening to the same mixture of protonated oxazolones prior to fragmentation. The results show that this sequence scrambling results in a distinct preference to place the Met residue in the C-terminal position of the protonated oxazolones. The a7 and a7* ions also produce product ion mass spectra independent of the original peptide sequence. The results for the a7 ions indicate that fragmentation occurs primarily from an amide structure analogous to that observed for a4 ions (Bythell et al. in J Am Chem Soc 132:14766-14779, 2010). Clearly, the rearrangement reaction they have proposed applies equally well to an ions as large as a7. The major fragmentation modes of the MH(+) ions at low collision energies produce b7, b6, and b5 ions. As the collision energy is increased further fragmentation of these primary products produces, in part, non-direct sequence ions, which become prominent at lower m/z values, particularly for the peptides with the Met residue near the N-terminus.

Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: a case-control study.

Locally acquired HEV infection is increasingly recognized in developed countries. Anti-HEV IgG seroprevalence has been shown to be high in haemodialysis patients in a number of previous studies, employing assays of uncertain sensitivity. The aim of this study was to investigate anti-HEV IgG seroprevalence in recipients of haemodialysis and renal transplants compared to a control group using a validated, highly sensitive assay. Eighty-eight patients with functioning renal transplants and 76 receiving chronic haemodialysis were tested for HEV RNA and anti-HEV IgG and IgM. Six hundred seventy controls were tested for anti-HEV IgG. Anti-HEV IgG was positive in 28/76 (36.8%) of haemodialysis and 16/88 (18.2%) of transplant patients. HEV RNA was not found in any patient. 126/670 (18.8%) of control subjects were anti-HEV IgG positive. After adjusting for age and sex, there was a significantly higher anti-HEV IgG seroprevalence amongst haemodialysis patients compared to controls (OR = 1.97, 95% CI = 1.16-3.31, P = 0.01) or transplant recipients (OR = 2.63, 95% CI = 1.18-6.07, P = 0.02). Patients with a functioning transplant showed no difference in anti-HEV IgG seroprevalence compared to controls. The duration of haemodialysis or receipt of blood products were not significant risk factors for HEV IgG positivity. Patients receiving haemodialysis have a higher seroprevalence of anti-HEV IgG than both age- and sex-matched controls and a cohort of renal transplant patients. None of the haemodialysis patients had evidence of chronic infection. The reason haemodialysis patients have a high seroprevalence remains uncertain and merits further study.

Using gas-phase guest-host chemistry to probe the structures of b ions of peptides.

Middle-sized b(n) (n ≥ 5) fragments of protonated peptides undergo selective complex formation with ammonia under experimental conditions typically used to probe hydrogen-deuterium exchange in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc., and small b(n) (n ≤ 4) fragments do not form stable ammonia adducts. We propose that complex formation of b(n) ions with ammonia is characteristic to macrocyclic isomers of these fragments. Experiments on a protonated cyclic peptide and N-terminal acetylated peptides fully support this hypothesis; the protonated cyclic peptide does form ammonia adducts while linear b(n) ions of acetylated peptides do not undergo complexation. Density functional theory (DFT) calculations on the proton-bound dimers of all-Ala b(4), b(5), and b(7) ions and ammonia indicate that the ionizing proton initially located on the peptide fragment transfers to ammonia upon adduct formation. The ammonium ion is then solvated by N(+)-H…O H-bonds; this stabilization is much stronger for macrocyclic b(n) isomers due to the stable cage-like structure formed and entropy effects. The present study demonstrates that gas-phase guest-host chemistry can be used to selectively probe structural features (i.e., macrocyclic or linear) of fragments of protonated peptides. Stable ammonia adducts of b(9), b(9)-A, and b(9)-2A of A(8)YA, and b(13) of A(20)YVFL are observed indicating that even these large b-type ions form macrocyclic structures.

Fragmentation reactions of b(5) and a (5) ions containing proline--the structures of a(5) ions.

A detailed study has been made of the b(5) and a(5) ions derived from the amides H-Ala-Ala-Ala-Ala-Pro-NH(2), H-Ala-Ala-Ala-Pro-Ala-NH(2), and H-Ala-Ala-Pro-Ala-Ala-NH(2). From quasi-MS(3) experiments it is shown that the product ion mass spectra of the three b(5) ions are essentially identical, indicating macrocyclization/reopening to produce a common mixture of intermediates prior to fragmentation. This is in agreement with numerous recent studies of sequence scrambling in b ions. By contrast, the product ion mass spectra for the a(5) ions show substantial differences, indicating significant differences in the mixture of structures undergoing fragmentation for these three species. The results are interpreted in terms of a mixture of classical substituted iminium ions as well as protonated C-terminal amides formed by cyclization/rearrangement as reported recently for a(4) ions (Bythell, Maître , Paizs, J . Am. Chem. Soc. 2010, 132, 14761-14779). Novel fragment ions observed upon fragmentation of the a(5) ions are protonated H-Pro-NH(2) and H-Pro-Ala-NH(2) which arise by fragmentation of the amides. The observation of these products provides strong experimental evidence for the cyclization/rearrangement reaction to form amides and shows that it also applies to a(5) ions.