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"Funnell, Mark"
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The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies
2025
The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.
Estimating the risk of long COVID is challenging because many of its symptoms are associated with other conditions. Here, the authors conduct a systematic review and meta-analysis of studies that estimate long COVID risk while accounting for background symptoms using comparator control populations.
Journal Article
Does Hypohydration Really Impair Endurance Performance? Methodological Considerations for Interpreting Hydration Research
2019
The impact of alterations in hydration status on human physiology and performance responses during exercise is one of the oldest research topics in sport and exercise nutrition. This body of work has mainly focussed on the impact of reduced body water stores (i.e. hypohydration) on these outcomes, on the whole demonstrating that hypohydration impairs endurance performance, likely via detrimental effects on a number of physiological functions. However, an important consideration, that has received little attention, is the methods that have traditionally been used to investigate how hypohydration affects exercise outcomes, as those used may confound the results of many studies. There are two main methodological limitations in much of the published literature that perhaps make the results of studies investigating performance outcomes difficult to interpret. First, subjects involved in studies are generally not blinded to the intervention taking place (i.e. they know what their hydration status is), which may introduce expectancy effects. Second, most of the methods used to induce hypohydration are both uncomfortable and unfamiliar to the subjects, meaning that alterations in performance may be caused by this discomfort, rather than hypohydration per se. This review discusses these methodological considerations and provides an overview of the small body of recent work that has attempted to correct some of these methodological issues. On balance, these recent blinded hydration studies suggest hypohydration equivalent to 2–3% body mass decreases endurance cycling performance in the heat, at least when no/little fluid is ingested.
Journal Article
Quality of life and multiple long-term conditions in Southeast Asia: a systematic review and meta-analysis
by
Ardavani, Ashkon
,
Cassambai, Shabana
,
Jeffers, Shavez
in
692/308/409
,
692/700/784
,
Asia, Southeastern - epidemiology
2026
This review systematically synthesised the evidence on quality of life measures and outcomes for people living with multiple long-term conditions in the Southeast Asia region. Results were analysed using a combination of methods, meta-analysis for studies where the same quality of life score was reported across three or more cohorts, and descriptive narrative synthesis. In total, 34 studies comprising 11,876 participants were included in the narrative synthesis and 14 of these were included in meta-analysis. The most common quality of life tools used included WHOQOL-BREF (
n
= 8) and EQ-5D-5L (
n
= 3) with pooled mean values of 70.47 (95% CI: 62.71 to 78.24) and 0.76 (95% CI: 0.67 to 0.84) respectively, indicating reduced but good quality of life. As healthcare systems adapt to the evolving challenges associated with multiple long-term conditions, understanding the tools and measures used to assess quality of life in different contexts becomes imperative to account for disease combinations and cultural nuances.
People living with multiple long-term conditions often experience reduced quality of life, but evidence from Southeast Asia is fragmented. Here the authors show that commonly used tools indicate moderately reduced yet generally good quality of life, highlighting the need for context-sensitive measurement approaches.
Journal Article
Hypohydration produced by high-intensity intermittent running increases biomarkers of renal injury in males
by
Funnell, Mark P
,
Midwood, Katharine L
,
Mears, Stephen A
in
Biomarkers
,
Body mass
,
Dehydration
2021
PurposeWhilst there is evidence to suggest that hypohydration caused by physical work in the heat increases renal injury, whether this is the case during exercise in temperate conditions remains unknown. This study investigated the effect of manipulating hydration status during high-intensity intermittent running on biomarkers of renal injury.MethodsAfter familiarisation, 14 males (age: 33 ± 7 years; V̇O2peak: 57.1 ± 8.6 ml/kg/min; mean ± SD) completed 2 trials in a randomised cross-over design, each involving 6, 15 min blocks of shuttle running (modified Loughborough Intermittent Shuttle Test protocol) in temperate conditions (22.3 ± 1.0 °C; 47.9 ± 12.9% relative humidity). During exercise, subjects consumed either a volume of water equal to 90% of sweat losses (EU) or 75 mL water (HYP). Body mass, blood and urine samples were taken pre-exercise (baseline/pre), 30 min post-exercise (post) and 24 h post-baseline (24 h).ResultsPost-exercise, body mass loss, serum osmolality and urine osmolality were greater in HYP than EU (P ≤ 0.024). Osmolality-corrected urinary kidney injury molecule-1 (uKIM-1) concentrations were increased post-exercise (P ≤ 0.048), with greater concentrations in HYP than EU (HYP: 2.76 [1.72–4.65] ng/mOsm; EU: 1.94 [1.1–2.54] ng/mOsm; P = 0.003; median [interquartile range]). Osmolality-corrected urinary neutrophil gelatinase-associated lipocalin (uNGAL) concentrations were increased post-exercise (P < 0.001), but there was no trial by time interaction effect (P = 0.073).ConclusionThese results suggest that hypohydration produced by high-intensity intermittent running increases renal injury, compared to when euhydration is maintained, and that the site of this increased renal injury is at the proximal tubules.
Journal Article
24 h severe fluid restriction increases a biomarker of renal injury in healthy males
by
Funnell, Mark P.
,
Juett, Loris A.
,
Mears, Stephen A.
in
Acute Kidney Injury - blood
,
Acute Kidney Injury - etiology
,
Acute Kidney Injury - urine
2025
Purpose
Exercise-induced hypohydration exacerbates biomarkers of renal injury, but studies isolating the effects of hypohydration without exercise have produced mixed findings. This study investigated the effects of 24-h severe fluid restriction on biomarkers of renal injury and glucose tolerance.
Methods
Fifteen males (age: 27 ± 5 y; BMI: 24.1 ± 3.8 kg/m
2
) completed two randomised trials, involving consuming either 40 mL/kg body mass water to maintain euhydration (EU) or severe fluid restriction via limiting water consumption to 100 mL (HYP). A standardised dry food diet was consumed in both trials (~ 300 g water). At baseline and 24 h post-baseline, nude body mass, and blood and urine samples (additional urine sample at 12 h) were collected. An oral glucose tolerance test was conducted after 24-h post-baseline measurements (
n
= 12).
Results
At 24 h, body mass loss (HYP: − 1.52 ± 0.34%, EU: − 0.24 ± 0.40%), plasma volume loss, serum, and urine osmolality were greater in HYP than EU (
P
≤ 0.004). Osmolality-corrected urinary kidney injury molecule-1 (uKIM-1) concentrations were greater in HYP at 12 (HYP: 1.097 ± 0.587 ng/mOsm, EU: 0.570 ± 0.408 ng/mOsm;
P
< 0.001) and 24-h (HYP: 1.932 ± 1.173 ng/mOsm, EU: 1.599 ± 1.012 ng/mOsm;
P
= 0.01). There was no trial-by-time interactions for osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (
P
= 0.781) or plasma glucose (
P
= 0.550) and insulin (
P
= 0.193) concentrations.
Conclusion
Hypohydration produced by 24-h fluid restriction increased proximal tubular injury but did not affect glucose tolerance.
Journal Article
The Impact of the Multidisciplinary Team on Medication Adherence in Type 2 Diabetes: A Narrative Review
by
Funnell, Mark P
,
Khunti, Kamlesh
,
Highton, Patrick J
in
interdisciplinary care
,
medication adherence
,
multidisciplinary team
2026
Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic disease associated with multiple long-term conditions (Multimorbidity) requiring frequent reviews and escalating pharmacotherapy. However, attainment of glycemic targets in routine clinical practice remains suboptimal, with medication non-adherence representing a major contributor to the efficacy-effectiveness gap. This narrative review summarizes the impact of multidisciplinary team (MDT) care on medication adherence in people with T2DM. We searched MEDLINE, Embase and CINAHL (9 December 2025), supplemented by Google Scholar and reference-list screening, to identify evidence on MDT models and medication adherence outcomes in adults with T2DM. We mainly included original research (n = 19) with the addition of relevant reviews (n = 2) and systematic reviews (n = 4). Overall, multifaceted interventions and collaborated care involving the MDT were associated with improved medication adherence, particularly where teams were integrated and preserved continuity rather than operating as parallel services. Medication focused MDT interventions, most commonly pharmacist led medication review and follow-up, were generally associated with improvements in adherence and, in some studies, improvements in outcomes such as quality of life and healthcare utilization. However, reliance on self-report measures and variable intervention intensity limited comparability. Behavioral adherence support, delivered by nurses or other MDT members using motivational and action planning techniques, showed modest improvements when objectively measured. Additionally, psychosocially integrated approaches addressing depression, diabetes distress and social vulnerability showed potential to improve adherence and clinical outcomes, though adherence was not consistently measured directly. Overall, MDT care appears most likely to improve adherence when interventions are structured, roles within the team are clearly defined, collaboration between professions is well integrated, behavioral and psychosocial barriers are addressed, and follow-up is of sufficient intensity and duration. Future research should standardize adherence outcomes, incorporate objective measures where feasible, control for additional consultation time, and evaluate durability and scalability of multifaceted MDT approaches beyond short-term follow-up.
Journal Article
Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis
by
Funnell, Mark P.
,
Karmacharya, Biraj
,
Bhattarai, Nikita
in
Asia
,
Asia, Southern
,
Behavior Therapy
2026
Despite the burden of tobacco use, access to cessation support in South Asia remains scarce.
This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia.
Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE.
Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (
= 6; 16.2%), nicotine replacement therapy (
= 7; 18.9%), behavioral counseling (
= 12; 32.4%), or combined/multicomponent interventions (
= 12; 32.4%). Most studies were conducted in India (
= 26; 70.3%), followed by Pakistan (
= 6; 16.2%), Nepal (
= 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (
= 0.06).
Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.
Journal Article
Fluid and electrolyte balance following consumption of skimmed milk and a plant-based soya beverage at rest in euhydrated males
2024
PurposeCow’s milk is one of the most hydrating beverages, but many individuals choose not to consume dairy in their diet due to intolerance, allergy, or dietary preference. Milk is commonly replaced with plant-based beverages, including soya which has the most comparable protein content, but little is known about their hydration potential. This study compared fluid and electrolyte balance responses between a soya beverage and skimmed cow’s milk.MethodsTen healthy males [age 27 (6) y; body mass index 24.6 (2.3) kg/m2] completed two randomised counterbalanced trials, involving consuming 1000 mL water from approximately isocaloric amounts of skimmed cow’s milk (MILK) or a sweetened soya beverage (SOYA), in four aliquots over 30 min in a euhydrated fasted state. Volume, specific gravity, and electrolyte (sodium, potassium, chloride) concentrations were determined in total-void urine samples collected pre-/post-beverage ingestion, and hourly for 180 min thereafter. Hunger, thirst, nausea and stomach fullness were rated proximal to urine samples.ResultsTotal urine mass (MILK, 986 ± 254 g; SOYA, 950 ± 248 g; P = 0.435) and urine specific gravity (P = 0.156) did not differ between trials. Potassium balance was greater in SOYA 0–180 min post-beverage (P ≤ 0.013), whilst chloride balance was greater in MILK 0–120 min post-beverage (P ≤ 0.036). Sodium balance (P = 0.258), total electrolyte balance (P = 0.258), and subjective measures (P ≥ 0.139) were not different between trials.ConclusionReplacing cow’s milk with a soya beverage did not negatively impact fluid balance in healthy young males, making it a viable option for those who choose not to consume dairy in their diet.
Journal Article
Substituting Carbohydrate at Lunch for Added Protein Increases Fat Oxidation During Subsequent Exercise in Healthy Males
by
Varley, Ian
,
Hough, John
,
Betts, James A
in
Adult
,
Appetite - physiology
,
Blood Glucose - metabolism
2025
How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear.
Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake.
Twelve healthy males completed 3 trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), or 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or they fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 hour (∼16:15) and post-exercise ad libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide 1 (GLP-1), and acylated ghrelin were measured for 5 hours post-lunch.
Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (P < .001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; P < .05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all P < .01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all P < .01). Acylated ghrelin was lower during HI-CARB and LO-CARB vs FAST (P < .01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; P < .001) and HI-CARB (-313 ± 284 kcal; P < .001).
Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake.
Journal Article
Hypohydration induced by prolonged cycling in the heat increases biomarkers of renal injury in males
2024
PurposeRecent studies have shown that hypohydration can increase renal injury. However, the contribution of hypohydration to the extent of renal injury is often confounded by exercise induced muscle damage. Therefore, the aim of the present study was to investigate the effect of manipulating hydration status during moderate-intensity cycling in the heat on biomarkers of renal injury.MethodsFollowing familiarisation, fourteen active males (age: 21 [20–22] y; BMI: 22.1 ± 1.9 kg/m2; V˙O2peak: 55 ± 9 mL/kg/min) completed two experimental trials, in a randomised cross-over design. Experimental trials consisted of up to 120 min of intermittent cycling (~ 50% Wpeak) in the heat (~ 35 °C, ~ 50% relative humidity). During exercise, subjects consumed either a water volume equal to 100% body mass losses (EU) or minimal water (HYP; 75–100 mL) to induce ~ 3% body mass loss. Blood and urine samples were collected at baseline, 30 min post-exercise and 24 h post-baseline, with an additional urine sample collected immediately post-exercise.ResultsThirty minutes post-exercise, body mass and plasma volume were lower in HYP than EU (P < 0.001), whereas serum and urine osmolality (P < 0.001), osmolality-corrected urinary kidney injury molecule-1 concentrations (HYP: 2.74 [1.87–5.44] ng/mOsm, EU: 1.15 [0.84–2.37] ng/mOsm; P = 0.024), and percentage change in osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (HYP: 61 [17–141] %, EU: 7.1 [– 4 to 24] %; P = 0.033) were greater in HYP than EU.ConclusionHypohydration produced by cycling in the heat increased renal tubular injury, compared to maintaining euhydration with water ingestion.
Journal Article