Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Multi-Regionalism: Coherent and Realigned Caribbean Geopolitics for Sustainable Development and Sustainable Security Post-COVID-19

The existential risks of continued reactiveness by smaller Caribbean States in the post-COVID-19 global environment call for a coherent and realigned regional approach to geopolitics. The zero-sum strategic security predisposition of both existing and emerging great powers does not prioritize Caribbean interests that remain persistently elusive. Caribbean states need a multilateral cooperation framework that prioritizes their geopolitical interests above this predisposition for extra-regional influence and investments by great powers that pursue their often exclusive, and inequitable global geopolitical and governance interests. Acknowledging arguable progress after six Decades of Development, or Poverty Eradication Decades (PEDs) since 1961, including adoption of the 2030 Sustainable Development Agenda, this discussion reviewed the experience of small Caribbean states at the Organization of American States (OAS), a 1948 multilateral environment, still substantially reflective of Cold War and post-Cold War geopolitics. Multi-regionalism emerges as an alternative geopolitical framework for the coherent and realigned pursuit of Caribbean sustainable development and multidimensional security interests post-COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Transient Premature Ovarian Insufficiency Post-COVID-19 Infection.

Anti-ovarian antibodies (AOAs) have been linked to autoimmune premature ovarian insufficiency (POI). This report details a case in which a patient experienced transient POI after a COVID-19 infection and tested positive for AOA. After treatment with oral contraceptives and subsequent high-dose oral corticosteroids, the patient underwent fertility treatment with in vitro fertilization (IVF). A total of 23 oocytes were retrieved. Two euploid blastocysts and three untested blastocysts were successfully created. This report hypothesizes the connection between autoimmune POI, AOA, and COVID-19. Conflicting data have been reported linking COVID-19 and ovarian injury. However, it is suggested that COVID-19 transiently impacts the menstrual cycle and anti-Mullerian hormone (AMH) levels. Treatment to overcome poor ovarian response due to AOA has not been adequately determined; however, similar autoimmune conditions have been successfully treated with corticosteroids.

An integrated discrete event simulation and particle swarm optimisation model for optimising efficiency of cancer diagnosis pathways

The National Health Service (NHS) constitution sets out minimum standards for rights of access of patients to NHS services. The ‘Faster Diagnosis Standard’ (FDS) states that 75% of patients should be told whether they have a diagnosis of cancer or not within 28 days of an urgent GP referral. Timely diagnosis and treatment lead to improved outcomes for cancer patients, however, compliance with these standards has recently been challenged, particularly in the context of operational pressures and resource constraints relating to the COVID-19 pandemic. In order to minimise diagnostic delays, the National Physical Laboratory in collaboration with the Royal Free London (RFL) NHS Foundation Trust address this problem by treating it as a formal resource optimisation, aiming to minimise the number of patients who breach the FDS. We use discrete event simulation and particle swarm optimisation to identify areas for improving the efficiency of cancer diagnosis at the RFL. We highlight capacity-demand mismatches in the current cancer diagnosis pathways at the RFL, including imaging and endoscopy investigations. This is due to the volume of patients requiring these investigations to meet the 28-day FDS target. We find that increasing resources in one area alone does not fully solve the problem. By looking at the system as a whole we identify areas for improvement which will have system-wide impact even though individually they do not necessarily seem significant. The outcomes and impact of this project have the potential to make a valuable impact on shaping future hospital activity.

The Impact of COVID-19 on Mental Health Services in Scotland, UK.

There is a global emergency in relation to mental health (MH) and healthcare. In the UK each year, 1 in 4 people will experience MH problems. Healthcare services are increasingly oversubscribed, and COVID-19 has deepened the healthcare gap. We investigated the effect of COVID-19 on waiting times for MH services in Scotland. We used national registers of MH services provided by Public Health Scotland. The results show that waiting times for adults and children increased drastically during the pandemic. This was seen nationally and across most of the administrative regions of Scotland. We find, however, that child and adolescent services were comparatively less impacted by the pandemic than adult services. This is potentially due to prioritisation of paediatric patients, or due to an increasing demand on adult services triggered by the pandemic itself.

Are we looking for Monoclonal Gammopathy of Renal Significance ( MGRS )? An audit of investigations in current clinical practice

Monoclonal gammopathy of unknown significance (MGUS) is a premalignant condition defined as the presence of a monoclonal protein with no evidence of plasma cell/B-cell-related malignancy. The risk of progression from MGUS to a related malignancy is approximately 1% per year. MGUS patients are closely monitored for signs of progression allowing for rapid initiation of treatment. In 2012, the International Kidney and Monoclonal Gammopathy Research Group (IKMG) introduced the term Monoclonal Gammopathy of Renal Significance (MGRS). MGRS is the clonal proliferation of a nephrotoxic monoclonal protein without meeting the criteria for any other plasma cell/B-cell malignancy. The diagnosis of MGRS allows for the initiation of urgent treatment required to prevent further deterioration in renal function. Updated diagnostic criteria from the IKMG made renal biopsy essential for diagnosis of MGRS. Consequently, the IKMG set out an algorithm to guide clinicians on when to consider a renal biopsy. The parameters measured to evaluate the need for a renal biopsy include urine albumin creatinine ratio (ACR). This audit was conducted in the Clatterbridge Cancer Centre Liverpool (CCC-L) a leading cancer centre in the Northwest of England. Urine ACR was chosen as the parameter to audit as it is a cheap, non-invasive, quantitative investigation. The primary outcome of this audit is to assess the number of MGUS patients who had an ACR measured at diagnosis in the Myeloma clinic from January 2014 to December 2020. Data were collected retrospectively from electronic clinic letters and notes. The date of diagnosis was defined as the date of clinic letter in which diagnosis was first confirmed. Patients were considered to have had an ACR performed at diagnosis if ACR was measured between 28 days prior to and post the date of diagnosis. ACR performed during disease was defined as any ACR measured from 28 days prior to date of diagnosis and date of death/data collection. Data from 503 patients (249 females, 254 males) were analysed. The median age at diagnosis was 73. Table 1 shows data for patients who had an ACR measurement performed at diagnosis and during disease. There is a trend towards greater compliance to measuring ACR at diagnosis in successive years from 2014 to 2019 (Table 1). This trend reverses in 2020 when only 40.0% of patients had an ACR measured at diagnosis. For all patients where ACR was performed during disease;56.8% ( n = 179) had the highest ACR measurement of <3.0 mg/mmol with only 14.0% ( n = 44) having the highest ACR measurement of >30.0 mg/mmol. If ACR was performed at diagnosis it was more commonly repeated if the value was higher;the frequencies with which ACR was repeated were 85.7% ( n = 12), 65.1% ( n = 28) and 28.4% ( n = 31) when ACR value at diagnosis was >30.0 mg/mmol, 3.0-30.0 mg/mmol and <3.0 mg/mmol respectively. This audit has shown an increased recognition for the importance of ACR measurement with increased compliance year on year. A likely hypothesis for the reduced measurements in 2020 is the need for remote clinic appointments during the Coronavirus 2019 (Covid-19) pandemic. Following IKMG guidelines 14.0% ( n = 44) of patients would be advised to have a renal biopsy due to their ACR measurement of >30.0 mg/ mmol. Further evaluation of this patient cohort is required to audit compliance with other parameters suggested by the IKMG. A diagnostic pathway to be used at the earliest opportunity for MGUS patients may then be developed..

Preliminary analysis of the MM21 trial: Response adaptive salvage treatment with daratumumab-lenalidomide-dexamethasone (DRD) for newly diagnosed transplant eligible multiple myeloma patients failing front-line bortezomib-based induction therapy

BACKGROUND Bortezomib-based induction (V-IND) approaches are used in >90% of Australian newly diagnosed transplant eligible multiple myeloma (NDTE MM) patients (pts) with a maximum of 4 cycles of V-IND therapy available via the pharmaceutical benefits scheme (PBS) prior to a planned autologous stem cell transplantation (ASCT). However, NDTE MM patients failing V-IND (defined as best response < partial response [PR]) demonstrate shortened survival and continue to represent a sub-group of MM where a clear unmet medical need persists. The ALLG MM21 was designed to evaluate the efficacy of an early response adapted approach with a switch to an intensive Daratumumab-lenalidomide-dexamethasone (DRd)-based salvage-ASCT- consolidation strategy in patients failing V-IND. METHOD We present the results of a planned interim analysis of the multi-centre single arm study MM21 (ACTRN12618001490268). Eligible pts were NDTE MM who had received V-IND pre-ASCT and demonstrated either a sub-optimal response (SOR - defined as <minimal response [MR] after 2 cycles or <PR after 4 cycles of V-IND) or primary refractoriness (1REF - defined as disease progression while on or within 60 days of completing V-IND). Pre-ASCT DRd was DARA 16mg/kg IV days 1, 8, 15 and 22 for cycles 1 (C1) and 2, and on days 1 and 15 of C3 and C4;Lenalidomide 25mg OD D1-21;and, dexamethasone 40mg PO on D 1, 8, 15 and 22 of each 28-day cycle for C1 to C4. Anti-thrombotic and anti-viral prophylaxis was as per individual institutional practice. Between C3 and C4, patients underwent a G-CSF mobilised PBSC collection with a melphalan 200mg/m2 conditioned ACST after C4. Patients underwent D100 post-ASCT disease response assessment including EuroFlow minimal residual disease (MRD) testing. In the absence of disease progression, patients then received 12, 28-day cycles of consolidation comprising DARA IV 16mg/kg on D1, 15 of C1 and C2 and on D1 of C3 to C12, lenalidomide 25mg PO on D1-21 of C1 and C2 and 10mg OD on days 1-28 of C3 to C12;dexamethasone 40mg was weekly from C1 to C12. RESULTS Fifty patients were recruited from 7 Australian sites between March 2019 and July 2020. Median age was 61 years with 66% males. Disease status at study entry was SOR in 72% (<MR n = 9, <PR n = 27) and 1REF in 28%. Data cut-off date was June 30 2021. 45 patients (90%) received 4 complete cycles of salvage DRd. 11/50 (22%) patients did not undergo ASCT and 4 patients failed stem cell collection. Two pts were withdrawn due to treatment related gastrointestinal toxicity - persistent oesophagitis (n =1) and recurrent colitis (n=1). There were two deaths, due to COVID-19 pneumonia (n =1) and septic shock (n =1). Pre-ASCT response was evaluable in 43 patients, overall response rate (ORR) was 70% - complete response (CR) 6%, very good partial response (VGPR) 18%, partial response (PR) 46%, clinical benefit rate (CBR) 83% - MR 11% and stable disease (SD) 2% on Intention to Treat (ITT n = 50) analysis. 33 patients were assessed for MRD - MRD negative 6% on ITT (3/33 9%). Pre-consolidation disease assessment was evaluable in 37 pts, both ORR and CBR were 72% - stringent complete response (sCR) 4%, CR 14%, VGPR 24%, PR 30% ITT analysis. 31 pts were evaluated for MRD - MRD negative 28% ITT (14/31 45%). In 6 patients, MRD was omitted or could not be performed due to pre-analytical issues. Post-C2 consolidation assessment was evaluable in 37 pts, ORR 72% - sCR 2%, CR 24%, VGPR 26%, PR 20%, CBR 74% - SD 2% ITT analysis. To date, 22 patients have been evaluated for MRD with 4 patients awaiting results, MRD negative rate of 38% ITT (10/22 45%). MRD sample collection at this time-point was omitted in 7 patients, potentially skewing MRD negativity on ITT analysis. CONCLUSION Preliminary analysis of the MM21 trial demonstrates early response-adaptive escalation to DRd facilitated ASCT in the majority patients with robust ORR post-autologous stem cell transplant and substantial improvement in disease control, as reflected in improved rates of MRD and disease response to treatment. At both post-ASCT time-p ints there was significant drop off in MRD testing due to testing omission, potential skewing results of MRD analysis. MRD and duration of response analysis following C12 consolidation is planned and will be of interest. Current data suggests this drug combination shows potential for substantial benefit in the study population. (Figure Presented).

Cruising on choppy seas: the revitalization of Jamaica as a cruise destination post COVID-19

Purpose This article focuses on critical areas that must be adjusted and adopted in the post-Covid era. It explores strategies that are needed for the post-Covid period in cruise tourism in the Caribbean with special reference to endemic gaps in the sustainable development of cruising in Jamaica which resulted in the pre-pandemic status quo. The article aims to recommend ways of creating a road map for greater sustainability for cruise tourism in the Caribbean, the most tourism-dependent region of the world. Design/methodology/approach The main approach is via the frame of sustainable development pillars. The methodology involved interviews with tourism and cruise industry executives and content analysis of company documents of the Jamaica Tourist Board. Additional primary data were collected from a large cruise line serving the Caribbean market. This exercise was primarily to derive insights on their customer satisfaction data. Primary data were also collected on Covid testing by Baywest Medical in Montego Bay Jamaica. Findings It is clear from the data that the cruise industry in Jamaica has not maximized its potential. This is largely due to the posture of large private cruise lines, which have negotiated solely in favour of their bottom line. It was also found that Jamaica has suffered from its own slow approach to the diversification of its ports and surrounding communities. Additionally, another major finding revealed that the matter of visitors has been inadequately addressed;despite cruise line data indicating a need for safer, more seamless spaces. The major strength identified is the creation of "resilient corridors" in Jamaica, which have worked well in support of the return of stopover arrivals since 2021. In fact, reported Covid cases related to the corridor have a positivity rate of less than 1% while the national figure is 9.9% for the month of July 2021, according to the Ministry of Health and Wellness. Research limitations/implications This article highlights gaps in the current construct of Caribbean cruising and plots a path to bridging those gaps. The major limitation is that it focuses on the case of Jamaica. Future research should consider other islands in the region and seek to gather data directly from guests when the industry reopens, as opposed to the current approach of guest comments through cruise line documents. Practical implications The practical implications are that policy-makers will be able to apply the recommendations for creating a partnership of equals, greater port and product diversification, visitor safety improvement and optimizing the resilient corridors. This will have a significant economic impact arising from greater flows of guests and extended time spent on shore. Social implications The absence of cruising has had a major impact on the socioeconomics of communities in closeness, proximity to cruising, as evidenced in craft markets and ground transportation. These groupings are considered to be particularly vulnerable. Originality/value This paper is the first to excavate the specific hurdles, which must be tackled in the post-Covid era in Jamaica. It is of particular value to local policy-makers, local businesses and cruise lines serving the Caribbean region.

A comparison of persistence of SARS-CoV-2 variants on stainless steel.

The survival of newer variants of SARS-CoV-2 on a representative surface has been compared to the established UK circulating isolate to determine whether enhanced environmental stability could play a part in their increased transmissibility. Stainless steel coupons were inoculated with liquid cultures of the three variants, with coupons recovered over seven days and processed for recoverable viable virus using plaque assay. After drying, there was no significant difference in inactivation rates between variants, indicating that there is no increased environmental persistence from the new variants.

A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

[Formula presented] Introduction Daratumumab, when added to standard of care regimens in relapsed and untreated myeloma, has consistently demonstrated significant improvements in response rates, induction of MRD negative responses and progression-free survival (PFS) while proving highly tolerable with minor increases in overall regimen toxicity. In non-transplant eligible patients daratumumab has been added in randomized studies to lenalidomide and dexamethasone (Rd) and bortezomib, melphalan and prednisolone (VMP) backbones, but not to the VCD regimen. Furthermore, the randomized studies excluded a significant proportion of patients with comorbidities so the benefit of daratumumab in a frail, elderly myeloma population remains untested. Methods Inclusion criteria included untreated patients with symptomatic myeloma who were considered ineligible for high-dose chemotherapy with autologous stem cell transplantation due to either age >65years or the presence of comorbidities. Any degree of renal impairment, including dialysis dependence, was allowed as were patients with a prior history of systemic malignancy that had been disease-free for 2 years. Patients were randomized 1:1 to receive VCD or VCDD. VCD consisted of nine 5-week cycles of V 1.3 mg/m2 SC on Days 1, 8, 15 and 22;C 300mg/m2 PO on Days 1, 8, 15 and 22 and D 20 mg PO on Days 1, 8, 15 and 22. VCDD consisted of nine 5-week cycles of VCD plus daratumumab 16 mg/kg IV on Days 1, 8, 15 and 22 of cycles 1 and 2, Days 1 and 15 of cycles 3 to 6 and Day 1 of cycles 7 to 9, followed by daratumumab maintenance 16 mg/kg IV every 4 weeks until progression. The primary endpoint was PFS with secondary endpoints being response rates, MRD, overall survival, toxicity and quality of life. Results A total of 129 patients were randomized, but 7 did not commence intended therapy. The following modified ITT analysis is based on the 122 randomized patients, 58 in the VCD group and 64 in the VCDD group, who received therapy. Baseline characteristics were balanced between the two arms. Median age was 76 years (range, 62-91yrs), with 19% being ≥80 years of age. 30% were female. ECOG performance status was 0 (34%),1 (26%), 2 (16%) and unknown (25%). ISS stage was I (16%), II (36%), III (23%) and unknown (24%). The estimated median potential follow-up is 12.6 months. At the time of this report, the COVID-19 pandemic had impacted collection of site data. As a result, the following outcome data is provisional with a full data set to be available for presentation of the formal pre-planned interim analysis by the time of the ASH meeting. Overall response rate was 86% for VCD and 93% for VCDD. There was no significant difference between response rates after 4 cycles of induction for the VCD and VCDD arms: CR 3% vs 2%, VGPR 31% vs 41%, PR 51% vs 50%, MR 11% vs 7%, PD 3% vs 0%. Median PFS for the entire cohort (Fig A) was 21.8 months (95%CI 17.1-31.6 months). Median PFS for those treated with VCD was 18.9 months (95%CI 15.3-NR) and was 26.3 months (95%CI 17.1-31.6 months) for those treated with VCDD. In both arms combined, median PFS was 26.3 vs 21.9 months for those aged <75 vs ≥75 yrs, and not reached, 21.8 months and 19.9 months for those with ISS stage I, II and III, respectively. 19% of patients in the VCD group and 16% of patients in the VCDD group ceased therapy early, predominantly due to adverse events or death. SAEs during the induction period occurred in 44% and 52% of patients in the VCD and VCDD arms, respectively. There were 13 patients with SAEs due to infection in the VCD group and 20 in the VCDD group. Grade 3 or 4 peripheral neuropathy was uncommon, with only one case in the VCD arm. Conclusions The VCD schedule as detailed in this study appears efficacious, well tolerated and deliverable to an elderly myeloma population. The addition of daratumumab does not compromise chemotherapy delivery and may improve PFS. Formal interim analysis of the trial data will be presented at the meeting. [Formula presented] Disclosures: Mollee: Amgen: Membership on an entity's Board of D rectors or advisory committees;BMS/Celgene: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Caelum: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Reynolds: Novartis AG: Current equity holder in publicly-traded company. Janowski: Janssen: Membership on an entity's Board of Directors or advisory committees;BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;AstraZenica: Consultancy. Quach: Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria;GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy;Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Campbell: Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding;AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Gibbs: Janssen, BMS/Celgene, Amgen, Takeda, Pfizer, Caelum, Abbvie and Eidos: Membership on an entity's Board of Directors or advisory committees. D'Rozario: Abbvie: Membership on an entity's Board of Directors or advisory committees;BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Wallington-Beddoe: Amgen: Membership on an entity's Board of Directors or advisory committees. Weber: Amgen: Membership on an entity's Board of Directors or advisory committees. Spencer: Celgene, Janssen and Takeda: Speakers Bureau;AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy;Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding;AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria. OffLabel Disclosure: Daratumumab as initial treatment of myeloma

Place of Occurrence of COVID-19 Deaths in the UK: Modelling and Analysis (preprint)

We analysed publicly available data on place of occurrence of COVID-19 deaths from national statistical agencies in the UK between March 9 2020 and February 28 2021. We introduce a modified Weibull model that describes the deaths due to COVID-19 at a national and place of occurrence level. We observe similar trends in the UK where deaths due to COVID-19 first peak in Homes, followed by Hospitals and Care Homes 1-2 weeks later in the first and second waves. This is in line with the infectious period of the disease, indicating a possible transmission vehicle between the settings. Our results show that the first wave is characterised by fast growth and a slow reduction after the peak in deaths due to COVID-19. The second and third waves have the converse property, with slow growth and a rapid decrease from the peak. This difference may result from behavioural changes in the population (social distancing, masks, etc). Finally, we introduce a double logistic model to describe the dynamic proportion of COVID-19 deaths occurring in each setting. This analysis reveals that the proportion of COVID-19 deaths occurring in Care Homes increases from the start of the pandemic and past the peak in total number of COVID-19 deaths in the first wave. After the catastrophic impact in the first wave, the proportion of COVID-19 deaths occurring in Care Homes gradually decreased from is maximum after the first wave indicating residence were better protected in the second and third waves compared to the first.

Sleep Valuation Is Associated with Components of Sleep Health and Daytime Functioning in a College Sample: A Survey Study.

Sleep valuation, the worth individuals place on sleep, is an understudied construct in the field of sleep medicine. This study introduced a Sleep Valuation Item Bank and explored how sleep valuation is related to sleep health and daytime functioning within a sample of college students. The participants in this study were 247 (85% white, 83% female) undergraduate students who completed an online survey that included questions from a Sleep Valuation Item Bank and questions about sleep and daytime functioning. Correlation and regression analyses were conducted to determine associations between sleep valuation, aspects of sleep health and daytime functioning. Mediation analyses were conducted to determine whether the sleep health variables explained the associations between sleep valuation and daytime functioning. In correlation analyses, sleep valuation was negatively associated with sleepiness and sleep quality. It was also associated with daytime functioning, including general mental and physical health, depression, and anxiety. In the regression analyses, daytime impairments including poorer physical and mental health, anxiety, and depression were associated with higher sleep valuation. Poorer sleep health, including greater sleepiness and lower sleep quality, explained these associations and were associated with higher sleep valuation. Thus, while daytime impairments, such as anxiety and depression, are related to sleep valuation, this relationship may be due in part to the sleep disturbance that often co-occurs with these impairments.

Study into COVID-19 Crisis Using Primary Care Mental Health Consultations and Prescriptions Data.

The effect of the 2020 pandemic, and of the national measures introduced to control it, is not yet fully understood. The aim of this study was to investigate how different types of primary care data can help quantify the effect of the coronavirus disease (COVID-19) crisis on mental health. A retrospective cohort study investigated changes in weekly counts of mental health consultations and prescriptions. The data were extracted from one the UK's largest primary care databases between January 1st 2015 and October 31st 2020 (end of follow-up). The 2020 trends were compared to the 2015-19 average with 95% confidence intervals using longitudinal plots and analysis of covariance (ANCOVA). A total number of 504 practices (7,057,447 patients) contributed data. During the period of national restrictions, on average, there were 31% (3957 ± 269, p < 0.001) fewer events and 6% (4878 ± 1108, p < 0.001) more prescriptions per week as compared to the 2015-19 average. The number of events was recovering, increasing by 75 (± 29, p = 0.012) per week. Prescriptions returned to the 2015-19 levels by the end of the study (p = 0.854). The significant reduction in the number of consultations represents part of the crisis. Future service planning and quality improvements are needed to reduce the negative effect on health and healthcare.

Advancing Sustainable Development and Protected Area Management with Social Media-Based Tourism Data

Sustainable tourism involves increasingly attracting visitors while preserving the natural capital of a destination for future generations. To foster tourism while protecting sensitive environments, coastal managers, tourism operators, and other decision-makers benefit from information about where tourists go and which aspects of the natural and built environment draw them to particular locations. Yet this information is often lacking at management-relevant scales and in remote places. We tested and applied methods using social media as data on tourism in The Bahamas. We found that visitation, as measured by numbers of geolocated photographs, is well correlated with counts of visitors from entrance surveys for islands and parks. Using this relationship, we predicted nearly 4 K visitor-days to the network of Bahamian marine protected areas annually, with visitation varying more than 20-fold between the most and least visited parks. Next, to understand spatial patterns of tourism for sustainable development, we combined social media-based data with entrance surveys for Andros, the largest island in The Bahamas. We estimated that tourists spend 125 K visitor-nights and more than US$45 M in the most highly visited district, five times that of the least visited district. We also found that tourists prefer accessible, natural landscapes—such as reefs near lodges—that can be reached by air, roads, and ferries. The results of our study are being used to inform development and conservation decisions, such as where to invest in infrastructure for visitor access and accommodation, siting new marine protected areas, and management of established protected areas. Our work provides an important example of how to leverage social media as a source of data to inform strategies that encourage tourism, while conserving the environments that draw visitors to a destination in the first place.

Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19.

BACKGROUND: An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19. METHODS: Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale. RESULTS: 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing 'slight', 'moderate' and 'severe' functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing 'negligible' and 'no' functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233-0.661). Notably, the strongest association found was with the 'usual activities' domain of the 5-level EQ-5D questionnaire. CONCLUSION: We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms.

Detection of SARS-CoV-2 within the healthcare environment: a multi-centre study conducted during the first wave of the COVID-19 outbreak in England.

BACKGROUND: Understanding how severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spread within the hospital setting is essential in order to protect staff, implement effective infection control measures, and prevent nosocomial transmission. METHODS: The presence of SARS-CoV-2 in the air and on environmental surfaces around hospitalized patients, with and without respiratory symptoms, was investigated. Environmental sampling was undertaken within eight hospitals in England during the first wave of the coronavirus disease 2019 outbreak. Samples were analysed using reverse transcription polymerase chain reaction (PCR) and virus isolation assays. FINDINGS: SARS-CoV-2 RNA was detected on 30 (8.9%) of 336 environmental surfaces. Cycle threshold values ranged from 28.8 to 39.1, equating to 2.2 x 105 to 59 genomic copies/swab. Concomitant bacterial counts were low, suggesting that the cleaning performed by nursing and domestic staff across all eight hospitals was effective. SARS-CoV-2 RNA was detected in four of 55 air samples taken <1 m from four different patients. In all cases, the concentration of viral RNA was low and ranged from <10 to 460 genomic copies/m3 air. Infectious virus was not recovered from any of the PCR-positive samples analysed. CONCLUSIONS: Effective cleaning can reduce the risk of fomite (contact) transmission, but some surface types may facilitate the survival, persistence and/or dispersal of SARS-CoV-2. The presence of low or undetectable concentrations of viral RNA in the air supports current guidance on the use of specific personal protective equipment for aerosol-generating and non-aerosol-generating procedures.