Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes.

AIMS: Data on the impact of hypoglycaemia on patients' daily lives and diabetes self-management, particularly in developing countries, are lacking. The aim of this study was to assess fear of, and responses to, hypoglycaemia experienced by patients globally. MATERIALS AND METHODS: This non-interventional, multicentre, 4-week prospective study using self-assessment questionnaires and patient diaries consisted of 27,585 patients, ≥18years, with type 1 diabetes (n=8022) or type 2 diabetes (n=19,563) treated with insulin for >12months, at 2004 sites in 24 countries worldwide. RESULTS: Increased blood glucose monitoring (69.7%) and seeking medical assistance (62.0%) were the most common responses in the 4weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes, respectively. Approximately 44% of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode. Following hypoglycaemia, 3.9% (type 1 diabetes) and 6.2% (type 2 diabetes) of patients took leave from work or study. Regional differences in fear of, and responses to, hypoglycaemia were evident - in particular, a lower level of hypoglycaemic fear and utilisation of healthcare resources in Northern Europe and Canada. CONCLUSIONS: Hypoglycaemia has a major impact on patients and their behaviour. These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies.

Journal Clubs in Sports Medicine Fellowship Programs: Results From a National Survey and Recommendations for Quality Improvement.

BACKGROUND: Journal club is a pervasive component of graduate medical education, yet there is no gold standard as to format and logistics. METHODS: Survey of primary care sports medicine fellowship directors in the United States. RESULTS: Sixty-nine program directors completed the online questionnaire (40% response rate). There were some common aspects to journal club exhibited by a majority of programs, including the general format, required attendance by fellows and expected or required attendance by faculty, the expectation that participants had at least read the article before the meeting, and that meetings occurred during the workday in the work setting without provision of food. There was considerable variation on other aspects, including the objectives of journal club, who had primary responsibility for organizing the session, the criteria for selection of articles, who was invited to attend, and the perceived problems with journal club. CONCLUSIONS: This is the first survey investigating the current state of journal club in primary care sports medicine fellowship programs. Several opportunities for educational enhancements exist within journal clubs in primary care sports medicine, including the use of structured tools to guide discussion, providing mechanisms to evaluate the journal club experience as a whole, inviting multidisciplinary team members (eg, statisticians) to discussions, and ensuring that objectives are explicitly stated to participants.

Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action.

BACKGROUND: Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once-daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity. METHODS: Time to steady state was analyzed in 195 subjects across five Phase I randomized single-center double-blind studies: three in subjects with type 1 diabetes (T1DM), including one in elderly subjects, and two in subjects with type 2 diabetes (T2DM), including one with African American and Hispanic/Latino subpopulations. Subjects received once-daily IDeg (100 U/mL, s.c.) at doses of 0.4-0.8 U/kg for 6-12 days. Time to clinical steady state was measured from first dose until the serum IDeg trough concentration exceeded 90% of the final plateau level. The IDeg concentrations were log-transformed and analyzed using a mixed-effects model with time from first dose and dose level (where applicable) as fixed effects, and subject as a random effect. RESULTS: Steady state serum IDeg concentrations were reached after 2-3 days in all subjects. In trials with multiple dose levels, time to steady state was independent of dose level in T1DM (P = 0.51) and T2DM (P = 0.75). CONCLUSIONS: Serum IDeg concentrations reached steady state within 2-3 days of once-daily subcutaneous administration in all subjects with T1DM or T2DM, including elderly and African American and Hispanic/Latino subjects. At steady state, serum IDeg concentrations were unchanged from day to day.

Acute injuries in track and field athletes: a 3-year observational study at the Penn Relays Carnival with epidemiology and medical coverage implications.

BACKGROUND: Few studies have examined acute injuries in track and field in both elite and subelite athletes. PURPOSE: To observe the absolute number and relative rates of injury in track and field athletes across a wide range of competition levels and ages during 3 years of the Penn Relays Carnival to assist with future medical coverage planning and injury prevention strategies. STUDY DESIGN: Descriptive epidemiology study. METHODS: Over a 3-year period, all injuries treated by the medical staff were recorded on a standardized injury report form. Absolute number of injuries and relative injury rates (number of injuries per 1000 competing athletes) were determined and odds ratios (ORs) of injury rates were calculated between sexes, competition levels, and events. Injuries were also broken down into major or minor medical or orthopaedic injuries. RESULTS: Throughout the study period, 48,473 competing athletes participated in the Penn Relays Carnival, and 436 injuries were sustained. For medical coverage purposes, the relative rate of injury subtypes was greatest for minor orthopaedic injuries (5.71 injuries per 1000 participants), followed by minor medical injuries (3.42 injuries per 1000 participants), major medical injuries (0.69 injuries per 1000 participants), and major orthopaedic injuries (0.18 injuries per 1000 participants). College/elite athletes displayed the lowest relative injury rate (7.99 injuries per 1000 participants), which was significantly less than that of high school (9.87 injuries per 1000 participants) and masters athletes (16.33 injuries per 1000 participants). Male athletes displayed a greater likelihood of having a minor orthopaedic injury compared with female athletes (OR, 1.36 [95% CI, 1.06-1.75]; χ2 = 5.73; P = .017) but were less likely to sustain a major medical injury (OR, 0.33 [95% CI, 0.15-0.75]; χ2 = 7.75; P = .005). Of the 3 most heavily participated in events, the 4 × 400-m relay displayed the greatest relative injury rate (13.6 injuries per 1000 participants) compared with the 4 × 100-m and 4 × 200-m relays. CONCLUSION: Medical coverage teams for future large-scale track and field events need to plan for at least 2 major orthopaedic and 7 major medical injuries per 10,000 participants. Male track and field athletes, particularly masters male athletes, are at greater risk of injury compared with other sexes and competition levels.

Upper gastrointestinal issues in athletes.

Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70%. Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. As a result of those factors, gastroesophageal reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or exercise-related transient abdominal pain (ETAP) may develop. GERD may be treated with changes in eating habits, lifestyle modifications, and training modifications. Nausea and vomiting may respond to simple training modifications, including no solid food 3 hours prior to an athletic event. Mechanical trauma, decreased splanchnic blood flow during exercise, and non-steroidal anti-inflammatory drugs (NSAID) contribute to gastritis, GI bleeding, and ulcer formation in athletes. Acid suppression with proton-pump inhibitors may be useful in athletes with persistence of any of the above symptoms. ETAP is a common, poorly-understood, self-limited acute abdominal pain which is difficult to treat. ETAP incidence increases in athletes beginning a new exercise program or increasing the intensity of their current exercise program. ETAP may respond to changes in breathing patterns or may resolve simply with continued training. Evaluation of the athlete with upper GI symptoms requires a thorough history, a detailed training log, a focused physical examination aimed at ruling out potentially serious causes of symptoms, and follow-up laboratory testing based on concerning physical examination findings.

Short-term effects of INGAP and Reg family peptides on the appearance of small ß-cells clusters in non-diabetic mice.

The Reg3 peptides INGAP-PP and human Reg3α/ß (HIP) have been hypothesized to stimulate ß-cell neogenesis in the pancreas. Administration of INGAP-PP has been shown to cause an increase in ß-cell mass in multiple animal models, reverse streptozotocin (STZ) induced diabetes in mice and reduces HbA1c levels in type 2 diabetic humans. In this study, we have examined the ability of the INGAP-PP and HIP peptides to induce ß-cell formation in vivo in normal mice through short-term administration of the peptides. We assessed the peptides ability to induce an increase in extra-islet insulin-positive cell clusters by looking at ß-cell number by point counting morphometry on pancreata that had been randomized using the smooth fractionator principle in non-diabetic NMRI mice after short-term injections of the peptides (5 d). Five day continuous BrdU labeling was used to determine if the new ß-cells were derived from replicating ß-cells. Real time quantitative RT-PCR and immuno-histochemistry was used to analyze changes in pancreatic transcription factor expression. A 1.5- to 2-fold increase in the volume of small extra-islet insulin-positive clusters post 5 d treatment with INGAP-PP and HIP as compared with mice treated with a non-peptide control or scrambled peptide (p<0.05) (n = 7) was found. Five day continuous BrdU infusion during the 5 d period showed little or no incorporation in islets or small insulin clusters. Five days of treatment with INGAP-PP or HIP, showed a tendency toward increased levels of pancreatic progenitor markers such as Ngn3, Nkx6.1, Sox9 and Ins. These are the first studies to compare and indicate that the human Reg3 α/ß (HIP) peptide has similar bioactivity in vivo as INGAP by causing formation of small ß-cell clusters in extra-islet pancreatic tissue after only 5 d of treatment. Upregulation of pancreatic transcription factors may be part of the mechanism of action.

Eminence-based medicine versus evidence-based medicine: level V evidence in sports medicine.

Through extensive survey analysis, we investigated expert opinion in sports medicine. The study had 3 purposes: to provide clinical guidance for cases in which the correct action is not necessarily apparent, to examine expert opinion itself, and to delineate areas of future study. A total of 500 members of the American Medical Society for Sports Medicine and the American Orthopaedic Society for Sports Medicine evaluated a set of 25 statements on unresolved issues in sports medicine. The following 10 statements were deemed false: "It's okay for 12-year-old pitchers to throw curve balls; it's the pitch count that matters"; "Resistance training ('weight lifting') should be avoided until physeal closure"; "Jogging during pregnancy is to be avoided"; "At an athletic event, if sideline coverage is offered by an emergency medical technician and athletic trainer, there is little additional benefit from having a physician present"; "Contact sport athletes who sustain a second concussion should be excluded from contact sports permanently"; "The utility of pre-season medical screening is derived from the history; as such, student-athletes should complete a questionnaire, with physical examination reserved for only those with a positive relevant history"; "Femoroacetabular impingement is a myth-the designation of anatomic variation as disease"; "An AC (acromioclavicular) separation in a contact athlete should not be treated surgically if the athlete won't give up the sport; it will fail"; "Ankle taping induces weakness and atrophy of the dynamic stabilizers of the ankle"; "Only autografts should be used in ACL (anterior cruciate ligament) surgery, as allografts have an unnecessary high failure rate in clinical practice." One statement was accepted as true: "Surgery to treat anterior (patello-femoral) knee pain in a patient with normal patellar mechanics and stability is contraindicated." In short, expert opinion may be a helpful adjunct to clinical practice. Expert opinion cannot replace individual judgment and certainly does not trump the primary medical literature. Yet when better evidence is lacking, expert opinion is valuable for even the staunchest practitioner of evidence-based medicine.

Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity.

BACKGROUND: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown. CONCLUSIONS/SIGNIFICANCE: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.

Acupuncture in primary care.

Acupuncture, an ancient traditional Chinese medical therapy, is used widely around the world. When practiced by a certified provider, it is safe and patients often find it calming and relaxing. Animal and human studies have found a physiologic basis for acupuncture needling in that it affects the complex central and peripheral neurohormonal network. Although it is unclear whether acupuncture is beneficial over sham/placebo acupuncture, acupuncture care yields clinically relevant short- and long-term benefits for low back pain, knee osteoarthritis, chronic neck pain, and headache. The integration of acupuncture into a primary care setting also appears to be cost-effective. The practice of acupuncture in primary care requires rigorous training, financial discipline, and good communication skills. When done correctly, acupuncture is beneficial for both patients and providers.

Exertional leg pain: teasing out arterial entrapments.

Vascular causes of exertional lower extremity pain are relatively rare, but may be the answer in athletes refractory to treatment for the more common overuse syndromes of the lower extremities. It is important to differentiate these vascular causes from chronic exertional compartment syndrome (CECS), medial tibial stress syndrome (MTSS), and stress fractures in order to develop appropriate treatment plans, avoid complications, and return athletes to play expeditiously. Important vascular etiologies to be considered are popliteal artery entrapment syndrome (PAES), endofibrotic disease, popliteal artery aneurysm, cystic adventitial disease, and peripheral arterial dissections. The diagnostic workup involves angiography or noninvasive vascular studies such as Doppler ultrasound or magnetic resonance angiography in both the neutral and provocative positions. Treatment of these vascular abnormalities typically involves surgical correction of the vascular anomaly.