Does Prophylactic Stretching Reduce the Occurrence of Exercise-Associated Muscle Cramping? A Critically Appraised Topic.

CLINICAL SCENARIO: Exercise-associated muscle cramps (EAMC) are sudden, painful, and involuntary contractions of skeletal muscles during or after physical activity. The best treatment for EAMC is gentle static stretching until abatement. Stretching is theorized to relieve EAMC by normalizing alpha motor neuron control, specifically by increasing Golgi tendon organ activity, and physically separating contractile proteins. However, it is unclear if stretching or flexibility training prevents EAMC via the same mechanisms. Despite this, many clinicians believe prophylactic stretching prevents EAMC occurrence. CLINICAL QUESTION: Do athletes who experience EAMC during athletic activities perform less prophylactic stretching or flexibility training than athletes who do not develop EAMC during competitions? SUMMARY OF KEY FINDINGS: In 3 cohort studies and 1 case-control study, greater preevent muscle flexibility, stretching, or flexibility training (ie, duration, frequency) was not predictive of who developed EAMC during competition. In one study, athletes who developed EAMC actually stretched more often and 9 times longer (9.8 [23.8] min/wk) than noncrampers (1.1 [2.5] min/wk). CLINICAL BOTTOM LINE: There is minimal evidence that the frequency or duration of prophylactic stretching or flexibility training predicts which athletes developed EAMC during competition. To more effectively prevent EAMC, clinicians should identify athletes' unique intrinsic and extrinsic risk factors and target those risk factors with interventions. STRENGTH OF RECOMMENDATION: Minimal evidence from 3 prospective cohort studies and 1 case-control study (mostly level 3 studies) that suggests prophylactic stretching or flexibility training can predict which athletes develop EAMC during athletic competitions.

Patient-Reported Prevalence, Characteristics, and Impact of Leg Cramps in an Urban Primary Care Clinic.

This study addresses the prevalence and characteristics of leg cramps in 294 primary care patients (mean age = 46.5 years), with 51.7% reporting leg cramps. Patients who experience resting or exercise-induced leg cramps were more likely to be older and female. Cramp severity averaged 5.6 on a scale of 1-10 and disturbed sleep "sometimes" or "often" in 55% of patients. Most patients did not discuss cramps with their clinician. Our study reveals a possible shift in patients who experience leg cramps to younger age and chronicity. Resting leg cramps should be reviewed by clinicians as a symptom of declining health and advancing aging.

Muscle Cramps in Outpatients with Liver Diseases in Tokyo, Japan.

Background and Objectives: Muscle cramps are often observed in patients with liver diseases, especially advanced liver fibrosis. The exact prevalence of muscle cramps in outpatients with liver diseases in Japan is unknown. Patients and Methods: This study examined the prevalence of, and therapies for, muscle cramps in outpatients with liver diseases in Tokyo, Japan. A total of 238 outpatients with liver diseases were retrospectively examined. We investigated whether they had muscle cramps using a visual analog scale (VAS) (from 0, none, to 10, strongest), and also investigated their therapies. Results: Muscle cramps were observed in 34 outpatients with liver diseases (14.3%); their mean VAS score was 5.53. A multivariate analysis demonstrated that older age (equal to or older than 66 years) was the only significant factor as-sociated with muscle cramps. The prevalence of muscle cramps among patients with liver diseases seemed not to be higher. The problem was that only 11 (32.4%) of 34 outpatients received therapy for their muscle cramps. Conclusions: Only age is related to muscle cramps, which is rather weak, and it is possible that this common symptom may not be limited to liver disease patients.

Males, Older Age, Increased Training, Chronic Diseases, Allergies, and History of Injury Are Independent Risk Factors Associated With a History of Exercise-Associated Muscle Cramping in Distance Runners in 76 654 Race Entrants - SAFER XXIX.

OBJECTIVE: To determine independent risk factors associated with a history of exercise-associated muscle cramps (hEAMCs) in distance runner race entrants in a community-based mass participation event. DESIGN: Cross-sectional study. SETTING: 2012 to 2015, Two Oceans marathon races (21.1 and 56 km), South Africa. PARTICIPANTS: Seventy six thousand six hundred fifty-four consenting race entrants. ASSESSMENT OF RISK FACTORS: Entrants completed an online prerace medical screening questionnaire as part of the entry process. In a multiple model, sex, age, training variables, history of chronic disease, allergies, and running injuries were included as potential factors associated with hEAMC in 21.1 and 56 km entrants. MAIN OUTCOME MEASURES: Prevalence (%) and prevalence ratios (PRs, 95% confidence intervals) are reported. RESULTS: Men ( P < 0.0001) and older age (>40 years, P < 0.0001) were significantly associated with hEAMC. Therefore, the model was adjusted for sex and age group and run separately for 21.1- and 56-km entrants. Specific independent risk factors associated with hEAMC in 21.1- and 56-km entrants were: a history of chronic diseases (21.1 km: PR = 1.9; 56 km: PR = 1.6; P < 0.0001), running injury in the last 12 months (21.1 km: PR = 1.7; 56 km: PR = 1.4; P < 0.0001), history of allergies (21.1 km: PR = 1.4; 56 km: PR = 1.2; P < 0.0001), and various training variables (PR = 1.0-1.1). CONCLUSION: In 21.1- and 56-km race entrants, independent risk factors associated with hEAMC were men, older age, longer race distances, training variables, chronic diseases, history of allergies, and history of a running injury in the past 12 months.

Evaluation of the relationship between serum carnitine levels and intradialytic complications in children with kidney failure.

BACKGROUND: Carnitine plays a crucial role in the metabolism of fatty acids as well as energy production. Previous research has suggested a significant decrease in carnitine levels in patients with kidney failure and those undergoing hemodialysis. Therefore, we designed this study to assess the prevalence and characteristics of carnitine deficiency and its association with hemodialysis complications in the pediatric population. METHODS: This research was a pilot study of 29 children undergoing hemodialysis. Before hemodialysis, a 5-mL blood sample was drawn from each patient through a peripheral vein to measure serum-free carnitine levels, complete blood count with differential, blood urea nitrogen (BUN), creatinine, and electrolytes. Each patient was observed for intradialytic complications, including muscle cramps and hypotension, during 12 sessions of hemodialysis. RESULTS: We included 26 participants with a mean age of 14.23 years undergoing hemodialysis. Carnitine deficiency was revealed in 54.8% of our participants. Also, there was no significant correlation between carnitine deficiency and age, gender, and BUN levels (P = 0.698, P = 0.43, and P > 0.05, respectively). Intradialytic complications, including episodes of hypotension and muscle cramps, were more frequent in patients with carnitine deficiency (P = 0.02, P = 0.01, respectively). Other reasons for muscle cramps, such as fluid overload, nutritional status, dialysis regimen, and other important lab results (phosphorus, magnesium, etc.), were ruled out. CONCLUSION: In conclusion, we found a higher prevalence of carnitine deficiency in pediatric hemodialysis patients. Carnitine deficiency was significantly associated with increased intradialytic symptoms, including muscle spasms and hypotension. Our results could support a potential role of carnitine supplementation in pediatric patients with kidney failure for controlling intradialytic complications, but this requires further investigation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence, Clinical Characteristics, and Self-Reported Treatment of Exercise-Associated Muscle Cramping Differ Between 21.1- and 56-Km Running Race Entrants-SAFER XXII.

OBJECTIVE: To determine whether the lifetime prevalence and clinical characteristics of exercise-associated muscle cramping (EAMC) differ between runners entering a 21.1- versus 56-km road race. DESIGN: Cross-sectional study. SETTING: The 2012 to 2015 Two Oceans Marathon races (21.1 and 56 km), South Africa. PARTICIPANTS: Participants were consenting race entrants (21.1 km = 44 458; 56 km = 26 962) who completed an online prerace medical screening questionnaire. INDEPENDENT VARIABLE: A history of EAMC. MAIN OUTCOME MEASURES: The main outcome variables were lifetime prevalence (%) and clinical characteristics (muscle groups affected, timing of occurrence, severity, frequency of serious EAMC, and self-reported treatment) of a history of EAMC. Differences between 56- and 21.1-km race entrants were explored (relative risk [RR]). RESULTS: The lifetime prevalence of EAMC was 12.8%, which was higher in 56- (20.0%; 95% CI 19.5-20.6) versus 21.1-km race entrants (8.5%; 8.2-8.8) ( P = 0.0001). In all entrants, the fourth quarter was the most common onset (46.4%), calf muscles were the most commonly affected (53.1%), and most EAMCs were of mild-to-moderate severity (95%). In 56- versus 21.1-km entrants, hamstring (RR = 1.7; 1.5-1.9) and quadriceps muscle groups (RR = 1.5; 1.3-1.7) were more frequently affected ( P = 0.0001), the onset of EAMC during racing was less common in the first quarter (RR = 0.3; 0.2-0.4) ( P = 0.0001), and serious EAMC was more frequent (RR = 1.6; 1.4-1.9) ( P = 0.0001). CONCLUSIONS: In 56- versus 21.1-km runners, a history of EAMC is 2 times more frequent and muscle groups affected, onset in a race, and severity of EAMC differed. The lifetime prevalence was lower than previously reported in other events. Risk factors associated with EAMC may differ between entrants for different race distances.

Programmed vs. Thirst-Driven Drinking during Prolonged Cycling in a Warm Environment.

We compared the effect of programmed (PFI) and thirst-driven (TDFI) fluid intake on prolonged cycling performance and exercise associated muscle cramps (EAMC). Eight male endurance athletes (26 ± 6 years) completed two trials consisting of 5 h of cycling at 61% V˙O2peak followed by a 20 km time-trial (TT) in a randomized crossover sequence at 30 °C, 35% relative humidity. EAMC was assessed after the TT with maximal voluntary isometric contractions of the shortened right plantar flexors. Water intake was either programmed to limit body mass loss to 1% (PFI) or consumed based on perceived thirst (TDFI). Body mass loss reached 1.5 ± 1.0% for PFI and 2.5 ± 0.9% for TDFI (p = 0.10). Power output during the 20 km TT was higher (p < 0.05) for PFI (278 ± 41 W) than TDFI (263 ± 39 W), but the total performance time, including the breaks to urinate, was similar (p = 0.48) between conditions. The prevalence of EAMC of the plantar flexors was similar between the drinking conditions. Cyclists competing in the heat for over 5 h may benefit from PFI aiming to limit body mass loss to <2% when a high intensity effort is required in the later phase of the race and when time lost for urination is not a consideration.

Evaluation of Muscle Cramp Associated with Liver Cirrhosis with a Focus on the Liver Function and Nutritional Status.

Objective We investigated the muscle cramp status of patients with liver cirrhosis by focusing on the degree of liver damage, skeletal muscle mass, and nutritional status. Methods All enrolled patients completed a questionnaire about muscle cramps. The degree of liver damage was examined using the Child-Pugh classification and the albumin-bilirubin (ALBI) grade. The nutritional status and skeletal muscle mass were examined using the Controlling Nutritional Status (CONUT) method and the psoas muscle index (PMI). Results Among the respondents, 55.7% of the patients reported experiencing muscle cramps. An analysis of the two patient groups-those who experienced muscle cramps and those who did not-revealed significant differences in Child-Pugh classification (muscle cramp-positive vs. muscle cramp-negative: A/B/C, 54.1%/32.4%/13.5% vs. 90.0%/10.0%/0.0%; p=0.004), ALBI grade (1/2/3, 20.5%/71.8%/7.7% vs. 54.8%/38.7%/6.5%; p=0.011), modified ALBI grade (1/2a/2b/3, 20.5%/20.5%/51.3%/7.7% vs. 54.8%/22.6%/16.1%/6.5%; p=0.008), CONUT score (normal/mild/moderate/severe, 25.6%/28.2%/41.0%/5.1% vs. 22.6%/61.3%/12.9%/3.2%; p=0.024), and PMI (3.85±1.13 cm2/m2 vs. 4.94±1.86 cm2/m2; p=0.012). Conclusion Our findings suggest that muscle cramps occur more frequently in patients with liver cirrhosis due to their decreased liver function and poorer nutritional status.

The effects of diuretic use and the presence of ascites on muscle cramps in patients with cirrhosis: a nationwide study.

BACKGROUND: Administration of diuretics and the presence of ascites in patients with cirrhosis were reported to be associated with muscle cramps; however, the clinical evidence is limited. This study aimed to determine whether muscle cramps are a diuretic-induced complication and whether ascites was a factor related to muscle cramp. METHODS: A total of 1064 adult patients with cirrhosis were enrolled from 10 hospitals in Japan between June 2017 and December 2018. A questionnaire regarding cramps was completed by all patients. The ratio of extracellular water (ECW) was analyzed using the bioelectrical impedance analysis. Logistic regression analysis was performed to analyze the effects of diuretic administration and the ECW ratio on cramps. RESULTS: Patients using diuretics had a higher incidence rate, higher frequency, stronger pain, and longer duration of cramps than those who did not. In the multivariate analysis, diuretic administration and the ECW ratio values ≥ 0.4 were not significantly associated with the presence, frequency, intensity, or duration of cramps. However, in the case of patients limited to Child-Pugh B or C, diuretic use was significantly correlated with the cramp frequency. CONCLUSIONS: These results demonstrated that muscle cramps were not a complication of diuretic use in patients with cirrhosis; however, in those limited to Child-Pugh B or C, diuretic use was a factor that affected the frequency of cramps. Moreover, no association was found between the presence of ascites and cramps.

Predictors of Intradialytic Symptoms: An Analysis of Data From the Hemodialysis Study.

BACKGROUND: Most patients receiving maintenance hemodialysis (HD) experience adverse symptoms, which are associated with decreased quality of life. Despite decades of experience, our understanding of causes of HD symptoms remains limited. We aimed to identify modifiable patient- and HD-related predictors of intradialytic symptoms. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: We leveraged patient-level (n=1,838) and HD session-level (n=64,797) data from the Hemodialysis Trial. EXPOSURE: Pre-HD serum urea nitrogen (SUN) level, pre-HD systolic blood pressure (SBP), intradialytic SBP decline, and ultrafiltration rate (UFR). OUTCOMES: Intra-HD symptoms, including cramps, nausea, chest pain, headache, and lightheadedness. ANALYTICAL APPROACH: Random-effects logistic regression models. RESULTS: Overall, symptoms occurred in 10.7% of HD sessions. Higher pre-HD SUN level (per 10 mg/dL) was associated with higher adjusted odds of muscle cramping and lightheadedness (adjusted ORs [aORs] of 1.20 [95% CI, 1.17-1.22] and 1.13 [95% CI, 1.08-1.18], respectively). SBP decline (from the predialysis value to the dialysis session nadir, per each 10-mm Hg decrease) was associated with greater risk for muscle cramping, headache, chest pain, vomiting, and lightheadedness (the largest aORs were for the 2 latter symptoms: 1.24 [95% CI, 1.20-1.28] and 1.37 [95% CI, 1.33-1.42], respectively). Higher UFR (per 1 mL/kg/h) was associated with greater odds of cramping (aOR, 1.03; 95% CI, 1.02-1.03). Conversely, higher pre-HD SBP (per 10 mm Hg) was associated with reduced risk for vomiting (aOR, 0.88; 95% CI, 0.85-0.92) and lightheadedness (aOR, 0.82; 95% CI, 0.80-0.85). LIMITATIONS: Measured osmolality, dialysate prescription data, and time stamps for symptom occurrence were not available. Clinical trial data may not be broadly generalizable. CONCLUSIONS: Higher pre-HD SUN level, UFR, pre-HD SBP, and SBP decline are independently associated with different patterns of adverse intradialytic symptoms. Recognition that different symptoms may have variable causes may allow tailoring of personalized treatments in future interventional studies.

A novel muscle cramp scale (MCS) in amyotrophic lateral sclerosis (ALS).

Objective: To develop a novel muscle cramp scale (MCS) to assess frequency, severity and clinically meaningful information related to cramps among patients with amyotrophic lateral sclerosis (ALS). Methods: This new scale comprises four 5-point subdomains: (1) triggering factors, (2) frequency, (3) location, (4) severity, and (5) the degree to which cramps affect overall daily living. Thirty patients with ALS, who experienced at least 5 cramps per week, participated in a randomized test-retest study. An additional 26 patients participated in a second study assessing cramp changes over 4 weeks using the MCS and a detailed cramp diary. Results: To establish internal reliability of the scale, a Cronbach's coefficient value of 0.75 or higher was considered acceptable. Test/retest evaluations comparing in-person and telephone administration were assessed using paired t-tests and Cohen's kappa statistics. Non-significant differences were identified, and the results revealed moderate to high agreement for each item (range 0.60 to 0.95, p < 0.0001). Scale construct validity against the cramp diary was acceptable. There were essentially no significant mean differences in muscle cramps over 4 weeks measured using the MCS and diary, respectively. Conclusions: The MCS is a valid, simple, and quick measure for the assessment of muscle cramps in patients with ALS. It can be reliably administered either in person or by telephone and provides richer information than the routinely utilized cramp diary.

Low dialysate sodium levels for chronic haemodialysis.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death in dialysis patients, and strongly associated with fluid overload and hypertension. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing CV morbidity and mortality. OBJECTIVES: This review evaluated harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened studies for inclusion and extracted data. Statistical analyses were performed using random effects models, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using GRADE. MAIN RESULTS: We included 12 studies randomising 310 patients, with data available for 266 patients after dropout. All but one study evaluated a fixed concentration of low dialysate [Na+], and one profiled dialysate [Na+]. Three studies were parallel group, and the remaining nine cross-over. Of the latter, only two used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 3 (3, 8.5) weeks. Two were of a single HD session, and two of a single week's HD. Half of the studies were conducted prior to 2000, and five reported use of obsolete HD practices. Risks of bias in the included studies were often high or unclear, lowering confidence in the results.Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "efficacy" endpoints: reduced interdialytic weight gain (10 studies: MD -0.35 kg, 95% CI -0.18 to -0.51; high certainty evidence); probably reduced predialysis mean arterial blood pressure (BP) (4 studies: MD -3.58 mmHg, 95% CI -5.46 to -1.69; moderate certainty evidence); probably reduced postdialysis mean arterial BP (MAP) (4 studies: MD -3.26 mmHg, 95% CI -1.70 to -4.82; moderate certainty evidence); probably reduced predialysis serum [Na+] (7 studies: MD -1.69 mM, 95% CI -2.36 to -1.02; moderate certainty evidence); may have reduced antihypertensive medication (2 studies: SMD -0.67 SD, 95% CI -1.07 to -0.28; low certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "safety" endpoints: probably increased intradialytic hypotension events (9 studies: RR 1.56, 95% 1.17 to 2.07; moderate certainty evidence); probably increased intradialytic cramps (6 studies: RR 1.77, 95% 1.15 to 2.73; moderate certainty evidence).Compared to neutral or high dialysate [Na+], low dialysate [Na+] may make little or no difference to: intradialytic BP (2 studies: MD for systolic BP -3.99 mmHg, 95% CI -17.96 to 9.99; diastolic BP 1.33 mmHg, 95% CI -6.29 to 8.95; low certainty evidence); interdialytic BP (2 studies:, MD for systolic BP 0.17 mmHg, 95% CI -5.42 to 5.08; diastolic BP -2.00 mmHg, 95% CI -4.84 to 0.84; low certainty evidence); dietary salt intake (2 studies: MD -0.21g/d, 95% CI -0.48 to 0.06; low certainty evidence).Due to very low quality of evidence, it is uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular mass or volumes, thirst or fatigue. Studies did not examine cardiovascular or all-cause mortality, cardiovascular events, or hospitalisation. AUTHORS' CONCLUSIONS: It is likely that low dialysate [Na+] reduces intradialytic weight gain and BP, which are effects directionally associated with improved outcomes. However, the intervention probably also increases intradialytic hypotension and reduces serum [Na+], effects that are associated with increased mortality risk. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.

Overlooked muscle cramps in patients with chronic liver disease: in relation to the prevalence of muscle cramps.

INTRODUCTION: Muscle cramps are common comorbidities in chronic liver disease (CLD). Although the prevalence of these has been reported in patients with liver cirrhosis (LC), that of CLD is unknown. In this study, we aimed to clarify the prevalence and characteristics of muscle cramps in individual CLD. PATIENTS AND METHODS: A total of 432 patients with CLD who visited our hospital were enrolled. The existence of muscle cramps, frequency, time zone, duration, and the degree of pain were investigated using a medical interview questionnaire. RESULTS: The median age of the patients was 65 years and 48.6% of the patients were women. The prevalence of muscle cramps was 25.9%. Age, female sex, lower BMI, existence of comorbid diseases, and liver fibrosis were associated significantly with muscle cramps. In LC, muscle cramps were significantly frequent, and the severity and duration of these were significantly stronger and longer compared with chronic hepatitis. Female sex [odds ratio (OR): 2.26; P=0.014], diabetes (OR: 29.4; P<0.001), chronic kidney disease (OR: 8.33; P=0.004), and lower BMI (OR: 0.853; P<0.001) were independent factors associated with muscle cramps in CLD. Muscle mass indices were significantly lower among nonalcoholic fatty liver disease patients with muscle cramps, female patients, elderly patients, and patients with advanced fibrosis. CONCLUSION: The prevalence of muscle cramps was relatively high in CLD. Female sex, comorbid diabetes, and chronic kidney disease are associated with muscle cramps in CLD. Furthermore, reduced muscle mass is related to muscle cramps in nonalcoholic fatty liver disease.

Randomised clinical trial: oral taurine supplementation versus placebo reduces muscle cramps in patients with chronic liver disease.

BACKGROUND: Painful muscle cramps occur in the majority of patients with cirrhosis impacting significantly on quality of life and sleep patterns. They are frequently unrecognised or overlooked. Current management is based on anecdotal evidence or case study reports. AIM: To investigate the effect of oral taurine supplementation on frequency, duration, and intensity of muscle cramps in patients with chronic liver disease. METHODS: Patients with chronic liver disease who experienced three or more muscle cramps/week were enrolled in a double-blinded, randomised control, crossover, taurine dose-variable study. Each participant received either taurine supplementation or placebo for 4 weeks then crossed to the alternative arm. Primary outcome data for frequency, duration, and intensity of muscle cramps was recorded by participants. Participants recorded frequency, duration, and location of muscle cramps. Biochemical parameters, including serum taurine and methionine levels, were measured at each time point. Linear mixed models were used to analyse outcomes. RESULTS: Forty-nine patients were enrolled in the study and 30 patients completed the protocol. Participants who were unable to complete the protocol were not included in the final analysis due to the absence of outcome data. The mean age of participants was 54.7 years and 70% were males. Oral taurine supplementation increased serum taurine levels (P < 0.001). There were no adverse side effects associated with taurine supplementation. Participants receiving 2 g taurine/d experienced a reduction in cramp frequency (seven cramps fewer/fortnight, P = 0.03), duration (89 minutes less/fortnight P = 0.03), and severity (1.4 units less on a Likert scale P < 0.004) compared to placebo. CONCLUSIONS: Oral supplementation with 2 g taurine/d results in a clinically significant reduction in the frequency, duration, and intensity of muscle cramps in patients with chronic liver disease. Taurine should be considered as a safe and effective intervention in the management of muscle cramps in individuals with chronic liver disease. This study was registered with the Australian New Zealand Clinical Trials Register: ACTRN12612000289819.

Metformin's impact on statin-associated muscle symptoms: An analysis of ACCORD study data and research materials from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center.

Statins are widely prescribed, yet statin muscle pain limits their use, leading to increased cardiovascular risk. No validated therapy for statin muscle pain exists. The goal of the study was to assess whether metformin was associated with reduced muscle pain. A secondary analysis of data from the ACCORD trial was performed. An ACCORD sub-study assessed patients for muscle cramps and leg/calve pain while walking, typical non-severe statin muscle pain symptoms. We compared muscle pain between patients using a statin (n = 445) or both a statin and metformin (n = 869) at baseline. Overall patient characteristics were balanced between groups. Unadjusted analysis showed fewer reports of muscle cramps (35%) and leg/calve pain while walking (40%) with statins and metformin compared to statin only (muscle cramps, 42%; leg/calve pain while walking, 47%). Multivariable regression demonstrated a 22% odds reduction for muscle cramps (P = 0.049) and a 29% odds reduction for leg/calve pain while walking (P = 0.01). Metformin appears to reduce the risk of non-severe statin muscle pain and additional research is needed to confirm the findings and assess metformin's impact on statin adherence and related cardiovascular outcomes.

Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study.

BACKGROUND AND OBJECTIVES: Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to (1) identify patient-prioritized symptoms for the development of symptom relief therapies and (2) elicit preferences for treatments among individuals receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a mixed methods study that included focus groups in Carrboro, North Carolina; Tucson, Arizona; and Seattle, Washington and a nationally distributed online survey. Focus group transcripts were analyzed for patterns, and the highest priority symptoms were determined on the basis of frequency and report severity. We used focus group findings to inform survey items. Focus group and survey results were crossvalidated and synthesized for final symptom prioritization. RESULTS: There were 32 participants across three focus groups and 87 survey respondents from 27 states in the United States. The physical symptoms of insomnia, fatigue, muscle cramping, and nausea/vomiting and the mood symptoms of anxiety and depressed mood were reported by participants in all focus groups. Among survey respondents, fatigue (94%), cramping (79%), and body aches (76%) were the most common physical symptoms, and feeling depressed (66%), worried (64%), and frustrated (63%) were the most common mood symptoms. The top-prioritized symptoms were consistent across focus group and survey participants and included the physical symptoms insomnia, fatigue, and cramping and the mood symptoms anxiety, depression, and frustration. Participants indicated that symptom frequency, duration, unpredictability, and social and financial effects factored most heavily into symptom prioritization. CONCLUSIONS: Patients prioritized the physical symptoms of insomnia, fatigue, and cramping and the mood symptoms of anxiety, depression, and frustration as the top symptoms for which to find new therapies.

Relationship of muscle cramps to quality of life and sleep disturbance in patients with chronic liver diseases: A nationwide study.

BACKGROUND & AIMS: Although muscle cramps frequently occur in patients with cirrhosis, the importance of muscle cramps remains unclear. The aims of this study were to investigate the relationship of muscle cramps with quality of life (QOL) and sleep disturbance. In addition, this multi-institutional collaborative study in Japan investigated factors associated with muscle cramps in patients with cirrhosis. METHODS: A total of 1788 patients with chronic liver diseases including both non-cirrhosis and cirrhosis completed a questionnaire survey investigating: (i) frequency of muscle cramps, (ii) relationship of muscle cramps to poor QOL and sleep disturbance, (iii) characteristics of patients who require therapeutic intervention and (iv) characteristics of patients prone to experiencing muscle cramps. RESULTS: This study revealed that 51.8% of patients with cirrhosis have experienced muscle cramps. People who experienced muscle cramps were more likely to have reduced QOL and sleep disturbance if muscle cramps had (i) high frequency (occurring daily to a few times per week, P < .01); (ii) long duration (between a few minutes and a few hours, P < .01) and (iii) intense severity (visual analogue scale ≥4, P < .01). Age, female sex, positive results for hepatitis C virus, low serum albumin concentration, and cirrhosis were independent factors related to the severity of muscle cramps. CONCLUSION: Muscle cramps occurred with great frequency and were associated with various factors such as age, sex, hepatitis C virus and liver function. Many patients experience poor QOL (26.3%) due to muscle cramps, and therapeutic interventions are therefore needed.

Cramps frequency and severity are correlated with small and large nerve fiber measures in type 1 diabetes.

OBJECTIVES: To explore the correlations between different muscle cramp characteristics including cramp frequency and severity and clinical and large and small nerve fiber measures in patients with diabetes type 1 (DM 1) and 2 (DM 2). METHODS: Prospective cross sectional study of healthy controls and patients with DM 1 and DM 2 recruited between April 2009 and November 2012. Participants underwent clinical evaluation and large and small nerve fiber studies, and the frequency and correlations of muscle cramps were explored. RESULTS: 37 controls, 51 patients with DM 1, and 69 patients with DM 2 were studied. Muscle cramps were the most frequent symptom captured by the Toronto Clinical Neuropathy Score (TCNS) in all groups, up to 78% in patients with DM 2. In patients with DM 1, but not DM 2, muscle cramp frequency and severity were correlated with clinical (TCNS) and both large (electrophysiology and vibration perception thresholds) and small nerve fiber measures. CONCLUSIONS: Muscle cramps are frequent in diabetes and are correlated with clinical and both small and large nerve fiber measures in DM 1, suggesting that their origin and propagation might extend beyond the motor nerve. SIGNIFICANCE: Muscle cramps correlate with nerve fiber measures in DM 1.

Underlying Chronic Disease, Medication Use, History of Running Injuries and Being a More Experienced Runner Are Independent Factors Associated With Exercise-Associated Muscle Cramping: A Cross-Sectional Study in 15778 Distance Runners.

BACKGROUND: Exercise-associated muscle cramping (EAMC) is a significant medical complication in distance runners, yet factors associated with EAMC are poorly documented. OBJECTIVE: To document risk factors associated with EAMC in runners. DESIGN: Cross-sectional study. SETTING: Two ocean races (21.1 km, and 56 km). PARTICIPANTS: Fifteen thousand seven hundred seventy-eight race entrants. METHODS: Participants completed a prerace medical history screening tool including: training, cardiovascular disease (CVD), risk factors for, and symptoms of CVD, history of diseases affecting major organ systems, cancer, allergies, medication use, and running injury. Runners were grouped as having a history of EAMC (hEAMC group = 2997) and a control group (Control = 12 781). RESULTS: Independent factors associated with a higher prevalence ratio (PR) of hEAMC were any risk factor for CVD (PR = 1.16; P = 0.0002), symptoms of CVD (PR = 2.38; P < 0.0001), respiratory disease (PR = 1.33; P < 0.0001), gastrointestinal disease (PR = 1.86; P < 0.0001), nervous system or psychiatric disease (PR = 1.51; P < 0.0001), kidney or bladder disease, (PR = 1.60; P < 0.0001), haematological or immune disease (PR = 1.54; P = 0.0048), cancer (PR = 1.34; P = 0.0031), allergies (PR = 1.37; P < 0.0001), regular medication use (PR = 1.80; P < 0.0001), statin use (PR = 1.26; P = 0.0127), medication use during racing (PR = 1.88; P < 0.0001), running injury (PR = 1.66; P < 0.0001), muscle injury (PR = 1.82; P < 0.0001), tendon injury (PR = 1.62; P < 0.0001), and runners in the experienced category (PR = 1.22; P < 0.0001). CONCLUSION: Novel risk factors associated with EAMC in distance runners were underlying chronic disease, medication use, a history of running injuries, and experienced runners. These factors must be identified as possible associations, and therefore be considered in the diagnosis and treatment of EAMC.

Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicentre European study.

BACKGROUND AND PURPOSE: The frequency of pain and cramps is uncertain in anti-myelin associated glycoprotein antibody (anti-MAG) neuropathy. Whether these symptoms may affect function/quality of life is unknown. METHODS: A cross-sectional study of the prevalence, correlates and impact of pain, pain subtypes and cramps, their severity, frequency and anatomical distribution was performed for 55 clinically stable patients with anti-MAG neuropathy. RESULTS: Pain of any type was reported by 80% of subjects. The most common subtype was paraesthesiae and dysaesthesiae (70%). Cramps were reported by >60% of patients, with lower limb cramps in all and upper limb cramps in about 20%. Cramps affected daily activities in >30% of these subjects, sleep in 60%, ability to exercise in >30%. Total pain score correlated with several Short Form 36 health-related quality of life (SF-36 HR-QoL) measures (P < 0.05), with Inflammatory Rasch-built Overall Disability Scale (I-RODS) (P = 0.006) and 10-m timed walk (P = 0.019). An independent association was ascertained with I-RODS (P = 0.002). Different pain subtypes showed multiple associations with SF-36 HR-QoL measures and/or functional scales. Upper limb cramps had multiple SF-36 HR-QoL functional correlates, with an independent association with the Overall Neuropathy Limitation Score (ONLS) (P = 0.004). Cramp severity correlated with ONLS (P = 0.04) and I-RODS (P = 0.028) and inversely with level of physiotherapy input (P = 0.009). Cramp frequency was associated with tremor score (P = 0.004) and multiple SF-36 HR-QoL subsections. CONCLUSIONS: Neuropathic pain and cramps may affect function and quality of life in anti-MAG neuropathy. Optimizing treatments of these symptoms, including by adequate levels of physiotherapy, may be beneficial in affected patients and requires further research.