Shockwave Treatment vs Surgery for Proximal Fifth Metatarsal Stress Fractures in Soccer Players: A Pilot Study.

BACKGROUND: To compare the clinical, radiologic, and functional outcomes between shockwave and operative treatments for proximal fifth metatarsal stress fractures in soccer players in a pilot study. METHODS: Between 2017 and 2019, 18 soccer players with fifth metatarsal stress fractures attended at Mutualidad de Futbolistas Españoles-Delegación Catalana were included. Patients were randomly assigned into 2 groups receiving either surgery with an intramedullary screw (group 1) or high-energy focused extracorporeal shockwave treatment (group 2 performed once a week for 3 weeks using 2000 impulses at an energy flux density of 0.21 mJ/mm2 and 4 Hz frequency). Clinical (pain), radiologic (bone healing), and functional (Tegner Activity Scale and American Orthopaedic Foot & Ankle Society [AOFAS] ankle-hindfoot scales) outcomes before and after receiving the treatment were compared between both groups. In addition, ability and time to return to play was also compared between groups. RESULTS: No patients were lost to follow-up. There were no statistically significant differences at last follow-up between surgery and extracorporeal shockwave treatment for bone healing, pain relief, AOFAS ankle-hindfoot score, Tegner score, and time return to play. No complications were reported in either of the 2 groups. CONCLUSION: In this pilot study, extracorporeal shockwave treatment and operative treatment were found to be equally effective at reducing pain, achieving bone healing, and allowing the soccer players to return to play after proximal fifth metatarsal stress fractures. This study suggests that ESWT may be a good option for the management of proximal fifth metatarsal stress fractures in soccer players. If this approach proves successful in larger trials, the shockwave approach might help avoid known complications of the surgical treatment like wound problems, nerve injury, and hardware intolerance. Further investigations with larger sample size should be conducted in order to confirm the present conclusions. LEVEL OF EVIDENCE: Level II, therapeutic, pilot randomized controlled trial.

Comorbidity clusters associated with newly treated type 2 diabetes mellitus: a Bayesian nonparametric analysis.

Type 2 diabetes mellitus (T2DM) is associated with the development of chronic comorbidities, which can lead to high drug utilization and adverse events. We aimed to identify common comorbidity clusters and explore the progression over time in newly treated T2DM patients. The IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records, was used to identify all patients with a first-ever prescription for a non-insulin antidiabetic drug (NIAD) between January 2006 and December 2019. We selected 58 chronic comorbidities of interest and used Bayesian nonparametric models to identify disease clusters and model their progression over time. Among the 175,383 eligible T2DM patients, we identified the 20 most frequent comorbidity clusters, which were comprised of 14 latent features (LFs). Each LF was associated with a primary disease (e.g., 98% of patients in cluster 2, characterized by LF2, had congestive heart failure [CHF]). The presence of certain LFs increased the probability of having another LF active. For example, LF2 (CHF) frequently appeared with LFs related to chronic kidney disease (CKD). Over time, the clusters associated with cardiovascular diseases, such as CHF, progressed rapidly. Moreover, the onset of certain diseases led to further complications. Our models identified established T2DM complications and previously unknown connections, thus, highlighting the potential for Bayesian nonparametric models to characterize complex comorbidity patterns.

Opioid sales and opioid-related poisonings in Switzerland: A descriptive population-based time-series analysis.

Background: To examine time trends and characteristics of calls related to opioid poisonings reported to the National Poison Centre and opioid sales in Switzerland. Methods: We used population-level data from the Swiss National Poisons Information Centre on reported opioid-related poisonings and data provided by the Swiss Pharmacists' Association (pharmaSuisse) based on IQVIA data to identify sold opioid packages. The rate of opioid-related poisoning calls and dispensed opioid packages per 100,000 Swiss inhabitants between 2000 and 2019 were plotted by year and annual trends were assessed. All analyses were stratified by individual opioid and potency (strong vs weak). Findings: There was a significant 177% increase in the rate of calls for opioid-related poisonings (1·4 to 3·9 per 100,000 inhabitants, p<0·001) and a 91·3% increase in opioid sales (from 14,364·0 to 27,477·6 per 100,000 inhabitants, p<0.001). The increase associated with strong opioids was higher when compared to weak opioids, in both poison centre calls and sales. In 2019, tramadol was the most frequently reported opioid in the poison centre data (35·7%, n=133) and sales (37·5%, n=8,863,377), followed by oxycodone calls (24·4%, n=91) and sales 23·4%, n= 552,751). Poisoning calls and sales related to oxycodone increased substantially between 2009 and 2016, as did the rate of poison centre calls requiring medical care. Interpretation: Calls to the Swiss National poison centre and sales for opioid have increased substantially in Switzerland in the last two-decades. Increases were primarily driven by oxycodone and tramadol; however, sales have attenuated since 2016. Our findings mirror other European countries and stress the importance of surveillance and monitoring. Funding: The research did not receive external funding. Translation of the abstract in German, French and Italian are available in the Supplementary section.

Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients.

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.

A Fermented Milk Product Containing B. lactis CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions.

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota.

Community Pharmacist-Administered COVID-19 Vaccinations: A Pilot Customer Survey on Satisfaction and Motivation to Get Vaccinated.

In response to the coronavirus disease 2019 (COVID-19) pandemic, Swiss health authorities approved and ordered two mRNA vaccines in 2021. The canton of Zurich was the second in Switzerland to allow community pharmacists to administer the COVID-19 mRNA Vaccine Moderna to the adult population. We aimed to pilot a customer satisfaction questionnaire regarding COVID-19 vaccinations in Zurich pharmacies. Questions focused on satisfaction with different aspects of the service, motivation for getting the vaccination, and reasons for being vaccinated in a pharmacy. Zurich pharmacies administered 68,169 COVID-19 doses until June 2021, and 421 questionnaires were filled. Respondents' mean age was 43.5 (±13.2) years, with 42.3% reporting being women and 46.1% being men. Of the 372 complete questionnaires, 98.7% of the respondents would have recommended the service to others. High levels of satisfaction were reported concerning pre-vaccination discussion (98.9%), pharmacies' information level on COVID-19 vaccines (98.9%), general comfort with receiving the vaccination in a pharmacy (99.5%), injection technique (99.2%), and premises used (98.1%). Most respondents (57.3%) would have had the option of another vaccination provider, but the pharmacies were chosen for their opening hours, ease of access, and perceived trust. The availability of pharmacist-administered services may be an important contributor to a successful vaccination programme in Switzerland.

A Network Analysis of Drug Combinations Associated with Acute Generalized Exanthematous Pustulosis (AGEP).

Acute generalized exanthematous pustulosis (AGEP) is a rare skin adverse drug reaction. The pathophysiology and causative drugs associated with AGEP are poorly understood, with the majority of studies in AGEP focusing on a single-drug-outcome association. We therefore aimed to explore and characterize frequently reported drug combinations associated with AGEP using the WHO pharmacovigilance database VigiBase. In this explorative cross-sectional study of a pharmacovigilance database using a data-driven approach, we assessed individual case safety reports (ICSR) with two or more drugs reported to VigiBase. A total of 2649 ICSRs reported two or more drugs. Cardiovascular drugs, including antithrombotics and beta-blockers, were frequently reported in combination with other drugs, particularly antibiotics. The drug pair of amoxicillin and furosemide was reported in 57 ICSRs (2.2%), with an O/E ratio of 1.3, and the combination of bisoprolol and furosemide was recorded 44 times (1.7%), with an O/E ratio of 5.5. The network analysis identified 10 different communities of varying sizes. The largest cluster primarily consisted of cardiovascular drugs. This data-driven and exploratory study provides the largest real-world assessment of drugs associated with AGEP to date. The results identify a high frequency of cardiovascular drugs, particularly used in combination with antibiotics.

National Poison Center Calls Before vs After Availability of High-Dose Acetaminophen (Paracetamol) Tablets in Switzerland.

Importance: Acetaminophen (paracetamol) is among the most widely used pain medications worldwide; while safe within the therapeutic range, intake exceeding 4000 mg/d can lead to hepatotoxicity. Prior evidence suggests that limiting the availability of large quantities of acetaminophen is associated with decreased acetaminophen-related poisonings and mortality; in Switzerland, 500-mg tablets are available over-the-counter (OTC) and, as of October 2003, 1000-mg tablets are available with prescription. Objective: To evaluate the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings. Design, Setting, and Participants: This cross-sectional study used a quasi-experimental interrupted time series analysis to evaluate 15 790 acetaminophen poison records from January 1, 2000, to December 31, 2018. All calls for acetaminophen-related poisonings identified from the National Swiss Poisons Centre and all sales for oral acetaminophen tablets (prescription and OTC) dispensed between January 2000 and December 2018 were included. Exposure: October 3, 2003 (Q4 2003), was defined as the intervention date, corresponding to the date of market entry for 1000-mg acetaminophen tablets in Switzerland. Main Outcomes and Measures: The primary outcome was the number of quarterly acetaminophen-related poison calls to the National Poison Centre. Additional outcomes included quarterly sales for acetaminophen and change in poisoning circumstances, stratified by preintervention and postintervention periods and by formulation (ie, 500-mg and 1000-mg tablets). Results: Between 2000 and 2018, 15 790 acetaminophen-related poisoning calls were identified, of which 10 628 (67.3%) were regarding women, and the mean (SD) age of patients was 25.2 (18.2) years. The interrupted time series analysis identified a significant increase in the slope for the number of reported poisonings following the intervention point, particularly for accidental circumstances (z score, -3.62; P < .001). In the preintervention period, 120 of 961 poisonings (15.3%) involved a dose greater than 10 000 mg, while for the postintervention period, 1140 of 5696 (30.6%) had a dose larger than 10 000 mg (P < .001). There was a rapid uptake in 1000-mg acetaminophen sales, while sales of the 500-mg tablet decreased slightly. Since 2012, a mean (SD) of 20.7 million (1.4 million) 1000-mg tablets were dispensed quarterly compared with 2.7 million (0.5 million) 500-mg tablets. Conclusions and Relevance: This study found a significant increase in acetaminophen dispensing and acetaminophen-related poisonings in Switzerland following the approval of 1000-mg tablets in 2003. The availability of 1000-mg acetaminophen should be re-evaluated to minimize the potential for accidental poisonings.

Early Postoperative Endoscopic Recurrence in Crohn's Disease Is Characterised by Distinct Microbiota Recolonisation.

BACKGROUND AND AIMS: Intestinal microbiota dysbiosis is implicated in Crohn's disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota. METHODS: Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms. RESULTS: The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] <0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR. CONCLUSIONS: Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.

Effects of autologous adipose-derived regenerative stem cells administered at the time of anterior cruciate ligament reconstruction on knee function and graft healing.

PURPOSE: To compare the healing and clinical outcomes of anterior cruciate ligament (ACL) reconstruction between patients with or without intraoperative administration of adipose-derived regenerative stem cells (ADRC). METHODS: Between 2013 and 2014, the outcomes of 20 soccer players undergoing ACL reconstruction using bone-patellar tendon-bone autograft infiltrated with ADRC at the end of the procedure were compared to a historical, matched cohort of 19 soccer players undergoing the same procedure without ADRC. Outcomes were obtained at baseline, and 6 and 12 months postop for IKDC (International Knee Documentation Committee), Lysholm, and Lequesne, and at 2, 4, 6, and 12 months postop for VAS (visual analogue scale) for pain and graft maturation to evaluate the ligamentization process (magnetic resonance imaging (MRI)-based). RESULTS: Both groups significantly improved the IKDC (p < 0.001 in both groups), Lysholm (p < 0.001 in both groups), Lequesne index (p < 0.001 in both groups), VAS for pain (p = 0.002 for the ADRC and p < 0.001 for the control group), and MRI scores (p < 0.001 in both groups) in the 12 months postop compared to baseline scores. However, there were no significant differences in the improvement of the outcomes between groups across time (p > 0.05). All patients returned to sports after surgery, but 8 (40%) patients in the ADRC and 13 (68.4%) patients in the control group had lower Tegner activity score at 12 months postop. CONCLUSIONS: Patients receiving ADRC at the time of ACL reconstruction significantly improved knee function and healing/maturation of the graft at 12 months. However, this improvement was not statistically significant compared to a control group undergoing ACL reconstruction alone.