Beyond the usual climate? Factors determining flowering and fruiting phenology across a genus over 117 years.

PREMISE: Although changes in plant phenology are largely attributed to changes in climate, the roles of other factors such as genetic constraints, competition, and self-compatibility are underexplored. METHODS: We compiled >900 herbarium records spanning 117 years for all eight nominal species of the winter-annual genus Leavenworthia (Brassicaceae). We used linear regression to determine the rate of phenological change across years and phenological sensitivity to climate. Using a variance partitioning analysis, we assessed the relative influence of climatic and nonclimatic factors (self-compatibility, range overlap, latitude, and year) on Leavenworthia reproductive phenology. RESULTS: Flowering advanced by ~2.0 days and fruiting by ~1.3 days per decade. For every 1°C increase in spring temperature, flowering advanced ~2.3 days and fruiting ~3.3 days. For every 100 mm decrease in spring precipitation, each advanced ~6-7 days. The best models explained 35.4% of flowering variance and 33.9% of fruiting. Spring precipitation accounted for 51.3% of explained variance in flowering date and 44.6% in fruiting. Mean spring temperature accounted for 10.6% and 19.3%, respectively. Year accounted for 16.6% of flowering variance and 5.4% of fruiting, and latitude for 2.3% and 15.1%, respectively. Nonclimatic variables combined accounted for <11% of the variance across phenophases. CONCLUSIONS: Spring precipitation and other climate-related factors were dominant predictors of phenological variance. Our results emphasize the strong effect of precipitation on phenology, especially in the moisture-limited habitats preferred by Leavenworthia. Among the many factors that determine phenology, climate is the dominant influence, indicating that the effects of climate change on phenology are expected to increase.

The effects of greater frequency of two most prevalent bothersome acute respiratory symptoms on health-related quality of life in the 2020 US general population.

PURPOSE: Upper respiratory tract infections (URTI) and related symptoms are widespread and a common reason for visiting primary care with cough and sore throat being most prevalent. Despite their impact on daily activities, no studies have explored the impact on health-related quality of life (HRQOL) in representative general populations. We aimed to understand the short-term impact of the two most prevalent URTI symptoms on HRQOL. METHODS: Online 2020 surveys including acute (≤ 4 weeks) respiratory symptoms (sore throat and cough) and SF-36® health survey (all with 4-week recall) were analysed using analysis of covariance (ANCOVA) in comparison with adult US population norms. Linear T-score transformation of SF-6D utility (ranging from 0 to 1) enabled direct comparisons with SF-36. RESULTS: In total, 7563 US adults responded (average age: 52 years; range: 18-100 years). Sore throat and cough lasting at least several days were experienced by 14% and 22% participants, respectively. Chronic respiratory conditions were reported by 22% of the sample. A clear and consistent pattern of group HRQOL means declining significantly (p < 0.001) for acute cough and sore throat symptom presence and severity. Declines were observed on SF-36 physical (PCS) and mental component (MCS) and health utility (SF-6D) scores controlling for covariates. Those reporting respiratory symptoms 'most days' declined ≥ 0.5 standard deviation (minimal important difference [MID]) worse with averages at the 19th and 34th centiles for cough on the PCS and MCS, and 21st to 26th centile for sore throat. CONCLUSION: Declines in HRQOL with acute cough and sore throat symptoms consistently exceeded MID standards and should not be ignored as self-limiting without intervention. Future studies on early self-care for symptom relief and its implications on HRQOL and health economics would be valuable to understand the benefits on healthcare burden and need for updating treatment guidelines.

Climate change is associated with increased allocation to potential outcrossing in a common mixed mating species.

PREMISE: Although the balance between cross- and self-fertilization is driven by the environment, no long-term study has documented whether anthropogenic climate change is affecting reproductive strategy allocation in species with mixed mating systems. Here, we test whether the common blue violet (Viola sororia; Violaceae) has altered relative allocation to the production of potentially outcrossing flowers as the climate has changed throughout the 20th century. METHODS: Using herbarium records spanning from 1875 to 2015 from the central United States, we quantified production of obligately selfing cleistogamous (CL) flowers and potentially outcrossing chasmogamous (CH) flowers by V. sororia, coupled these records with historic temperature and precipitation data, and tested whether changes to the proportion of CL flowers correlate with temporal climate trends. RESULTS: We find that V. sororia progressively produced lower proportions of CL flowers across the past century and in environments with lower mean annual temperature and higher total annual precipitation. We also find that both CL and CH flower phenology has advanced across this time period. CONCLUSIONS: Our results suggest that V. sororia has responded to lower temperatures and greater water availability by shifting reproductive strategy allocation away from selfing and toward potential outcrossing. This provides the first long-term study of how climate change may affect relative allocation to potential outcrossing in species with mixed mating systems. By revealing that CL flowering is associated with low water availability and high temperature, our results suggest the production of obligately selfing flowers is favored in water limited environments.

Development of an observer-reported outcome measure to capture the signs and impact of fever distress symptoms in infants and young children.

PURPOSE: This qualitative study aimed to construct an observer-reported outcome measure (ObsRO) to evaluate fever distress in young children. METHODS: A literature review was conducted to identify fever-related concepts. Clinical experts were interviewed for feedback on these concepts. Parents of young children were interviewed to identify behaviours the child exhibited during a recent fever episode. Fever sign and behaviour concepts endorsed by ≥ 20% parents were used to create items for the draft ObsRO. Parents of young children who recently had fever completed the ObsRO and gave feedback during two successive rounds of cognitive interviews. RESULTS: Twenty-five parents participated in the concept elicitation. Mean child age was 2.7 years (range: 0.6-5.8 years). Fever sign and behaviour concepts endorsed by ≥ 20% participants were high temperature (80%), skin hot to touch (32%), skin redness/flushing (32%), reduced appetite/drink (96%), needy/clingy/irritable (48-92%), less active/interactive (68-84%) and lethargic (64-88%). Eighteen items, four in the Fever Signs Module and 14 in the Fever Behaviours Module, were developed for the draft ObsRO. Chosen recall period was 24 h. Thirty participants (Round 1: n = 17; Round 2: n = 13), participated in cognitive interviews. Mean child age was 2.4 years (range 0.3-5.8). Round 1 feedback resulted in two Fever Signs items being combined. Three Fever Behaviour items were deleted, six revised and four unchanged. No changes were made following Round 2 feedback. Most participants understood all aspects of the ObsRO and found it user-friendly. CONCLUSION: The ObsRO will undergo further development in validation studies testing measurement properties of each item.

The phylogeographic history of a range disjunction in eastern North America: the role of post-glacial expansion into newly suitable habitat.

PREMISE: A disjunct distribution, where a species' geographic range is discontinuous, can occur through vicariance or long-distance dispersal. Approximately 75 North American plant species exhibit a ~650 km disjunction between the Ozark and Appalachian regions. This disjunction is attributed to biogeographic forces including: (1) Eocene-Oligocene vicariance by the formation of the Mississippi embayment; (2) Pleistocene vicariance from interglacial flooding; (3) post-Pleistocene northward colonization from separate glacial refugia; (4) Hypsithermal vicariance due to climate fluctuations; and (5) recent long-distance dispersal. We investigated which of these pathways most likely gave rise to the Appalachian-Ozark disjunction in Delphinium exaltatum. METHODS: We genotyped populations of D. exaltatum from five Ozark and seven Appalachian localities, analyzed genetic structure, tested the order and timing of divergences using DIYABC, and conducted niche reconstructions up to 21,000 years before present (YBP). RESULTS: Populations fell into five main genetic clusters, i.e., a group in the central Appalachians, and four "lowland" groups. DIYABC analyses showed the central Appalachian and lowland lineages diverging 11,300 to17,000 YBP, and the lowland groups diverging 6800 to 10,900 YBP. Niche reconstructions showed that suitable climate for the central Appalachian lineage experienced large spatial discontinuity starting 14,000 YBP, such that divergence and persistence before this period is less plausible than divergence thereafter. CONCLUSIONS: Our results did not fully support any of the original hypotheses. Rather, the oldest divergence likely occurred after 13,500 YBP through expansion into newly opened habitat in the Appalachians. The Appalachian-Ozark disjunction likely resulted from northward dispersal of the lowland lineage as climate warmed during the Holocene.

Health-related quality of life and work productivity in UK patients with HER2-positive breast cancer: a cross-sectional study evaluating the relationships between disease and treatment stage.

BACKGROUND: The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood. METHODS: This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance. RESULTS: Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p < 0.003). Proportions of employed patients were 50.6%, 50.9% and 27.5% in Groups 1, 2 and 3, respectively. For patients in part-time employment, the number of hours worked was significantly higher in Group 2 patients versus Group 3 (p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p < 0.001). Patients in Group 3 reported worse health utility scores (p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p < 0.001 for FACT-B and -G) than Groups 1 and 2. Poorer HRQoL was significantly associated with higher work impairment (p < 0.001), with the strongest relationships being observed between activity impairment and HRQoL (Pearson's r: 0.67). CONCLUSIONS: Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL.

Local adaptation, genetic divergence, and experimental selection in a foundation grass across the US Great Plains' climate gradient.

Many prior studies have uncovered evidence for local adaptation using reciprocal transplant experiments. However, these studies are rarely conducted for a long enough time to observe succession and competitive dynamics in a community context, limiting inferences for long-lived species. Furthermore, the genetic basis of local adaptation and genetic associations with climate has rarely been identified. Here, we report on a long-term (6-year) experiment conducted under natural conditions focused on Andropogon gerardii, the dominant grass of the North American Great Plains tallgrass ecosystem. We focus on this foundation grass that comprises 80% of tallgrass prairie biomass and is widely used in 20,000 km2 of restoration. Specifically, we asked the following questions: (a) Whether ecotypes are locally adapted to regional climate in realistic ecological communities. (b) Does adaptive genetic variation underpin divergent phenotypes across the climate gradient? (c) Is there evidence of local adaptation if the plants are exposed to competition among ecotypes in mixed ecotype plots? Finally, (d) are local adaptation and genetic divergence related to climate? Reciprocal gardens were planted with 3 regional ecotypes (originating from dry, mesic, wet climate sources) of Andropogon gerardii across a precipitation gradient (500-1,200 mm/year) in the US Great Plains. We demonstrate local adaptation and differentiation of ecotypes in wet and dry environments. Surprisingly, the apparent generalist mesic ecotype performed comparably under all rainfall conditions. Ecotype performance was underpinned by differences in neutral diversity and candidate genes corroborating strong differences among ecotypes. Ecotype differentiation was related to climate, primarily rainfall. Without long-term studies, wrong conclusions would have been reached based on the first two years. Further, restoring prairies with climate-matched ecotypes is critical to future ecology, conservation, and sustainability under climate change.

The weight-specific adolescent instrument for economic evaluation (WAItE): psychometric evaluation using a Rasch model approach.

PURPOSE: The Weight-specific Adolescent Instrument for Economic evaluation (WAItE) is a 7-item condition-specific tool assessing the impact of weight status on seven dimensions of quality of life. The content of the WAItE was developed with both treatment-seeking and non-treatment-seeking adolescents aged 11-18 years. The aim of this study was to assess the psychometric properties of the WAItE in adolescent and adult populations. METHODS: Treatment-seeking adolescents with obesity (females n = 155; males n = 123; mean age = 13.3; 13.1 years, respectively) completed the WAItE twice. An adult general population sample completed the WAItE via an online survey (females n = 236; males n = 231; mean age = 41.2; 44.3 years, respectively). The Partial Credit Model was applied to the data and item fit evaluated against published criteria. RESULTS: The WAItE had a unidimensional structure both for adolescents and adults. There was no item misfit observed for either participant samples and no differential item functioning (DIF) was present by age or gender for the adolescents. Some DIF was observed across age groups for the adult sample. For the adolescent sample, stable item locations were observed over time. CONCLUSIONS: The aim of the WAItE is to assess the impact of weight status on the lives of adolescents in cost-effectiveness evaluation of weight management programmes. The results of this study demonstrated that the WAItE has reliable psychometric properties. The instrument may therefore be used to aid informed decision around the identification of cost-effective weight management programmes in both adolescent and adult populations.

Transmission beam pattern and dynamics of a spinner dolphin (Stenella longirostris).

Toothed whales possess a sophisticated biosonar system by which ultrasonic clicks are projected in a highly directional transmission beam. Beam directivity is an important biosonar characteristic that reduces acoustic clutter and increases the acoustic detection range. This study measured click characteristics and the transmission beam pattern from a small odontocete, the spinner dolphin (Stenella longirostis). A formerly stranded individual was rehabilitated and trained to station underwater in front of a 16-element hydrophone array. On-axis clicks showed a mean duration of 20.1 µs, with mean peak and centroid frequencies of 58 and 64 kHz [standard deviation (s.d.) ±30 and ±12 kHz], respectively. Clicks were projected in an oval, vertically compressed beam, with mean vertical and horizontal beamwidths of 14.5° (s.d. ± 3.9) and 16.3° (s.d. ± 4.6), respectively. Directivity indices ranged from 14.9 to 27.4 dB, with a mean of 21.7 dB, although this likely represents a broader beam than what is normally produced by wild individuals. A click subset with characteristics more similar to those described for wild individuals exhibited a mean directivity index of 23.3 dB. Although one of the broadest transmission beams described for a dolphin, it is similar to other small bodied odontocetes.

Modulation rate transfer functions from four species of stranded odontocete (Stenella longirostris, Feresa attenuata, Globicephala melas, and Mesoplodon densirostris).

Odontocete marine mammals explore the environment by rapidly producing echolocation signals and receiving the corresponding echoes, which likewise return at very rapid rates. Thus, it is important that the auditory system has a high temporal resolution to effectively process and extract relevant information from click echoes. This study used auditory evoked potential methods to investigate auditory temporal resolution of individuals from four different odontocete species, including a spinner dolphin (Stenella longirostris), pygmy killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas), and Blainville's beaked whale (Mesoplodon densirostris). Each individual had previously stranded and was undergoing rehabilitation. Auditory Brainstem Responses (ABRs) were elicited via acoustic stimuli consisting of a train of broadband tone pulses presented at rates between 300 and 2000 Hz. Similar to other studied species, modulation rate transfer functions (MRTFs) of the studied individuals followed the shape of a low-pass filter, with the ability to process acoustic stimuli at presentation rates up to and exceeding 1250 Hz. Auditory integration times estimated from the bandwidths of the MRTFs ranged between 250 and 333 µs. The results support the hypothesis that high temporal resolution is conserved throughout the diverse range of odontocete species.

Approaching a state shift in Earth's biosphere.

Localized ecological systems are known to shift abruptly and irreversibly from one state to another when they are forced across critical thresholds. Here we review evidence that the global ecosystem as a whole can react in the same way and is approaching a planetary-scale critical transition as a result of human influence. The plausibility of a planetary-scale 'tipping point' highlights the need to improve biological forecasting by detecting early warning signs of critical transitions on global as well as local scales, and by detecting feedbacks that promote such transitions. It is also necessary to address root causes of how humans are forcing biological changes.

Phenotypic distribution models corroborate species distribution models: A shift in the role and prevalence of a dominant prairie grass in response to climate change.

Phenotypic distribution within species can vary widely across environmental gradients but forecasts of species' responses to environmental change often assume species respond homogenously across their ranges. We compared predictions from species and phenotype distribution models under future climate scenarios for Andropogon gerardii, a widely distributed, dominant grass found throughout the central United States. Phenotype data on aboveground biomass, height, leaf width, and chlorophyll content were obtained from 33 populations spanning a ~1000 km gradient that encompassed the majority of the species' environmental range. Species and phenotype distribution models were trained using current climate conditions and projected to future climate scenarios. We used permutation procedures to infer the most important variable for each model. The species-level response to climate was most sensitive to maximum temperature of the hottest month, but phenotypic variables were most sensitive to mean annual precipitation. The phenotype distribution models predict that A. gerardii could be largely functionally eliminated from where this species currently dominates, with biomass and height declining by up to ~60% and leaf width by ~20%. By the 2070s, the core area of highest suitability for A. gerardii is projected to shift up to ~700 km northeastward. Further, short-statured phenotypes found in the present-day short grass prairies on the western periphery of the species' range will become favored in the current core ~800 km eastward of their current location. Combined, species and phenotype models predict this currently dominant prairie grass will decline in prevalence and stature. Thus, sourcing plant material for grassland restoration and forage should consider changes in the phenotype that will be favored under future climate conditions. Phenotype distribution models account for the role of intraspecific variation in determining responses to anticipated climate change and thereby complement predictions from species distributions models in guiding climate adaptation strategies.

Expectancy and conditioned hearing levels in the bottlenose dolphin (Tursiops truncatus).

The hearing sensitivity of a bottlenose dolphin for a warning sound, when the exact time of the arrival of a loud sound could or could not be predicted, was measured. Sensitivity was measured when the time of onset of the loud sound was randomly varied (random-variation sessions) and when the time of onset of the loud sound and the pattern of stimulus levels was constant (fixed-stimulus sessions). The loud sound was kept the same in both of the series. The mean duration and mean range of the levels of the test/warning signal were also kept equal across experimental sessions. Hearing sensitivity was measured using the auditory evoked potential method with rhythmic trains of short pips as test stimuli. With randomly varied warning sounds, thresholds before the loud sound were on average 10.6 dB higher than the baseline thresholds. With fixed warning signals, thresholds were on average 4.4 dB higher than the baseline thresholds. Considering that the loud sounds were identical, the difference between the random-variation and the fixed-stimulus sessions cannot be explained by a direct (unconditioned) influence of sound exposure. Therefore, the data provide reliable evidence for the conditioning nature of the hearing-dampening effect and also demonstrate that hearing sensitivity change also depends on when the animal can expect the loud sound to occur.

A Differential Item Functioning Analysis of the EQ-5D in Cancer.

OBJECTIVES: To determine whether differential item functioning (DIF) was present in the EuroQol five-dimensional questionnaire (EQ-5D) used in cancer (non-small cell lung cancer and prostate cancer). METHODS: The Partial Credit Model was applied to the three-level version of the EQ-5D with data obtained from four randomized controlled trials in prostate cancer and non-small cell lung cancer completed at baseline before treatment (N = 2213). DIF was assessed across cancer type (two levels), sex (two levels), and age group (three levels) using Mantel-Haenszel chi-square statistics and evaluated against the Educational Testing Service classification rules. RESULTS: The presence of DIF was determined in 14 of 25 (56%) potential DIF contrasts in all the EQ-5D domains. Although mostly the DIF was categorized as either negligible (3 of 25 [12%]) or medium (7 of 25 [28%]), large DIF was observed in 4 of the 25 contrasts (16%). The mobility domain, in particular, showed consistently large DIF across cancer type, sex, and age. CONCLUSIONS: Given the use of the instrument in health status assessments across conditions and interventions, these results may have significant implications for the EQ-5D in health economic evaluations. Further research is warranted to determine whether these results hold for other cancers.

Transmission beam characteristics of a Risso's dolphin (Grampus griseus).

The echolocation system of the Risso's dolphin (Grampus griseus) remains poorly studied compared to other odontocete species. In this study, echolocation signals were recorded from a stationary Risso's dolphin with an array of 16 hydrophones and the two-dimensional beam shape was explored using frequency-dependent amplitude plots. Click source parameters were similar to those already described for this species. Centroid frequency of click signals increased with increasing sound pressure level, while the beamwidth decreased with increasing center frequency. Analysis revealed primarily single-lobed, and occasionally vertically dual-lobed, beam shapes. Overall beam directivity was found to be greater than that of the harbor porpoise, bottlenose dolphin, and a false killer whale. The relationship between frequency content, beam directivity, and head size for this Risso's dolphin deviated from the trend described for other species. These are the first reported measurements of echolocation beam shape and directivity in G. griseus.

Support for the beam focusing hypothesis in the false killer whale.

The odontocete sound production system is complex and composed of tissues, air sacs and a fatty melon. Previous studies suggested that the emitted sonar beam might be actively focused, narrowing depending on target distance. In this study, we further tested this beam focusing hypothesis in a false killer whale. Using three linear arrays of hydrophones, we recorded the same emitted click at 2, 4 and 7 m distance and calculated the beamwidth, intensity, center frequency and bandwidth as recorded on each array at every distance. If the whale did not focus her beam, acoustics predicts the intensity would decay with range as a function of spherical spreading and the angular beamwidth would remain constant. On the contrary, our results show that as the distance from the whale to the array increases, the beamwidth is narrower and the received click intensity is higher than that predicted by a spherical spreading function. Each of these measurements is consistent with the animal focusing her beam on a target at a given range. These results support the hypothesis that the false killer whale is 'focusing' its sonar beam, producing a narrower and more intense signal than that predicted by spherical spreading.

CONSUMER PREFERENCES FOR SCANNING MODALITY TO DIAGNOSE FOCAL LIVER LESIONS.

OBJECTIVES: Differences in the process of using liver imaging technologies might be important to patients. This study aimed to investigate preferences for scanning modalities used in diagnosing focal liver lesions. METHODS: A discrete choice experiment was administered to 504 adults aged 25 ≥years. Respondents made repeated choices between two hypothetical scans, described according to waiting time for scan and results, procedure type, the chance of minor side-effects, and whether further scanning procedures were likely to be required. Choice data were analyzed using mixed-logit models with respondent characteristics used to explain preference heterogeneity. RESULTS: Respondents preferred shorter waiting times, the procedure to be undertaken with a handheld scanner on a couch instead of within a body scanner, no side-effects, and no follow­up scans (p≤.01). The average respondent was willing to wait an additional 2 weeks for the scan if it resulted in avoiding side-effects, 1.5 weeks to avoid further procedures or to be told the results immediately, and 1 week to have the scan performed on a couch with a handheld scanner. However, substantial heterogeneity was observed in the strength of preference for desirable imaging characteristics. CONCLUSIONS: An average individual belonging to a general population sub­group most likely to require imaging to characterize focal liver lesions in the United Kingdom would prefer contrast­enhanced ultrasound over magnetic resonance imaging or computed tomography. Insights into the patient perspective around differential characteristics of imaging modalities have the potential to be used to guide recommendations around the use of these technologie

Reporting of health-related quality of life (HRQOL) data in oncology trials: a comparison of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy-General (FACT-G).

PURPOSE: The inclusion of patient-reported outcome (PRO) instruments to record patient health-related quality of life (HRQOL) data has virtually become the norm in oncology randomised controlled trials (RCTs). Despite this fact, recent concerns have focused on the quality of reporting of HRQOL. The primary aim of this study was to evaluate the quality of reporting of HRQOL data from two common instruments in oncology RCTs. DESIGN: A meta-review was undertaken of systematic reviews reporting HRQOL data collected using PRO instruments in oncology randomised controlled trials (RCTs). English language articles published between 2000 and 2012 were included and evaluated against a methodology checklist. RESULTS: Four hundred and thirty-five potential articles were identified. Six systematic reviews were included in the analysis. A total of 70,403 patients had completed PROs. The European Organization for Research and Treatment of Cancer QLQ-C30 and Functional Assessment of Cancer Therapy-General questionnaire accounted for 55 % of RCTs. Eighty per cent of RCTs had used psychometrically validated instruments; 70 % reported culturally valid instruments and almost all reported the assessment timing (96 %). Thirty per cent of RCTS reported clinical significance and missing data. In terms of methodological design, only 25 % of RCTs could be categorised as probably robust. CONCLUSION: The majority of oncology RCTs has shortcomings in terms of reporting HRQOL data when assessed against regulatory and methodology guidelines. These limitations will need to be addressed if HRQOL data are to be used to successfully support clinical decision-making, treatment options and labelling claims in oncology.

Long COVID Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation.

Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC.