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Change in Patient Enrollment After Site Principal Investigator Turnover in Surgical Clinical Trials

JAMA Netw Open. 2024 Jun 3;7(6):e2415340. doi: 10.1001/jamanetworkopen.2024.15340.

NO ABSTRACT

PMID:38842812 | DOI:10.1001/jamanetworkopen.2024.15340

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Physical Activity, Cardiovascular Status, Mortality, and Prediabetes in Hispanic and Non-Hispanic Adults

JAMA Netw Open. 2024 Jun 3;7(6):e2415094. doi: 10.1001/jamanetworkopen.2024.15094.

ABSTRACT

IMPORTANCE: Data are limited on the association of physical activity (PA) with incident cardiovascular disease (CVD) and mortality in prediabetes, especially in racial and ethnic minority groups, including Hispanic and Latino populations.

OBJECTIVE: To determine the association of PA with incident CVD and mortality by prediabetes status among Hispanic or Latino and non-Hispanic adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data from 2 cohorts of adults with prediabetes or normoglycemia who were free of CVD at baseline visit: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from baseline examination through 2017, with median (IQR) follow-up of 7.8 (7.2-8.5) years, and the Framingham Heart Study (FHS) with non-Hispanic participants from index examination through 2019, with median (IQR) follow-up of 9.6 (8.1-10.7) years. Analyses were conducted between September 1, 2022, and January 10, 2024.

EXPOSURE: The primary exposure was baseline accelerometry-measured moderate to vigorous PA, insufficient vs sufficient to meet 2018 Physical Activity Guidelines for Americans (PAG) in both cohorts; additional accelerometer-measured exposures in HCHS/SOL were steps per day, sedentary behavior, and counts per min.

MAIN OUTCOMES AND MEASURES: The outcome was a composite of incident CVD or all-cause mortality, whichever came first.

RESULTS: This cohort study included 13 223 participants: from HCHS/SOL, there were 9456 adults (all self-identified Hispanic or Latino ethnicity; survey-adjusted mean [SD] age, 38.3 [13.9] years, unweighted counts 5673 (60.0%) female; 4882 [51.6%] with normoglycemia; 4574 [48.4%] with prediabetes), and from FHS there were 3767 adults (3623 [96.2%] non-Hispanic and 140 [3.7%] Hispanic or Latino ethnicity, with 4 [0.1%] participants missing ethnicity; mean [SD] age, 54.2 [13.6] years; 2128 (56.5%) female; 2739 [72.7%] with normoglycemia; 1028 [27.3%] with prediabetes). Not meeting PAG was associated with higher risk of the composite outcome among participants with normoglycemia (vs PAG met; hazard ratio [HR], 1.85 [95% CI, 1.12-3.06]), but not among participants with prediabetes (HR, 1.07 [95% CI, 0.72-1.58]). For HCHS/SOL, no statistically significant association was found between the composite outcome and other PA metrics, although estimated HRs tended to be higher for lower activity in the normoglycemia group but not for the prediabetes group (eg, for steps less than vs at least 7000 per day, the HR was 1.58 [95% CI, 0.85-2.93] for normoglycemia vs 1.08 [95% CI 0.67-1.74] for prediabetes). While there was also no association in HCHS/SOL between the composite outcome and sedentary behavior, results were similar in the prediabetes group (HR per 30 minutes per day of sedentary behavior, 1.05 [95% CI 0.99-1.12]) and in the normoglycemia group (HR, 1.07 [95% CI 0.98-1.16]).

CONCLUSIONS AND RELEVANCE: In this cohort study of US Hispanic or Latino and non-Hispanic adults, lower moderate to vigorous PA levels were associated with CVD or mortality among participants with normoglycemia but not participants with prediabetes. Adults with prediabetes may benefit from reducing sedentary behavior and improving multiple lifestyle factors beyond improving moderate to vigorous PA alone.

PMID:38842811 | DOI:10.1001/jamanetworkopen.2024.15094

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Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type

JAMA Netw Open. 2024 Jun 3;7(6):e2415102. doi: 10.1001/jamanetworkopen.2024.15102.

ABSTRACT

IMPORTANCE: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial.

OBJECTIVE: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023.

EXPOSURES: Bypass surgery and conservative management.

MAIN OUTCOMES AND MEASURES: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects.

RESULTS: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

PMID:38842810 | DOI:10.1001/jamanetworkopen.2024.15102

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Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom-Dominant Psychosis

JAMA Netw Open. 2024 Jun 3;7(6):e2415110. doi: 10.1001/jamanetworkopen.2024.15110.

ABSTRACT

IMPORTANCE: Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge.

OBJECTIVE: To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis.

DESIGN, SETTING, AND PARTICIPANTS: This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023.

EXPOSURE: Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD.

MAIN OUTCOMES AND MEASURES: Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery.

RESULTS: This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002).

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

PMID:38842809 | DOI:10.1001/jamanetworkopen.2024.15110

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COVID-19 Vaccination Coverage and Factors Associated With Vaccine Uptake Among People With HIV

JAMA Netw Open. 2024 Jun 3;7(6):e2415220. doi: 10.1001/jamanetworkopen.2024.15220.

ABSTRACT

IMPORTANCE: People with HIV (PWH) may be at increased risk for severe outcomes with COVID-19 illness compared with people without HIV. Little is known about COVID-19 vaccination coverage and factors associated with primary series completion among PWH.

OBJECTIVES: To evaluate COVID-19 vaccination coverage among PWH and examine sociodemographic, clinical, and community-level factors associated with completion of the primary series and an additional primary dose.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health record data to assess COVID-19 vaccination information from December 14, 2020, through April 30, 2022, from 8 health care organizations of the Vaccine Safety Datalink project in the US. Participants were adults diagnosed with HIV on or before December 14, 2020, enrolled in a participating site.

MAIN OUTCOMES AND MEASURES: The percentage of PWH with at least 1 dose of COVID-19 vaccine and PWH who completed the COVID-19 vaccine primary series by December 31, 2021, and an additional primary dose by April 30, 2022. Rate ratios (RR) and 95% CIs were estimated using Poisson regression models for factors associated with completing the COVID-19 vaccine primary series and receiving an additional primary dose.

RESULTS: Among 22 058 adult PWH (mean [SD] age, 52.1 [13.3] years; 88.8% male), 90.5% completed the primary series by December 31, 2021. Among 18 374 eligible PWH who completed the primary series by August 12, 2021, 15 982 (87.0%) received an additional primary dose, and 4318 (23.5%) received a booster dose by April 30, 2022. Receipt of influenza vaccines in the last 2 years was associated with completion of the primary series (RR, 1.17; 95% CI, 1.15-1.20) and an additional primary dose (RR, 1.61; 95% CI, 1.54-1.69). PWH with uncontrolled viremia (HIV viral load ≥200 copies/mL) (eg, RR, 0.90 [95% CI, 0.85-0.95] for viral load 200-10 000 copies/mL vs undetected or <200 copies/mL for completing the primary series) and Medicaid insurance (eg, RR, 0.89 [95% CI, 0.87-0.90] for completing the primary series) were less likely to be fully vaccinated. By contrast, greater outpatient utilization (eg, RR, 1.07 [95% CI, 1.05-1.09] for ≥7 vs 0 visits for primary series completion) and residence in counties with higher COVID-19 vaccine coverage (eg, RR, 1.06 [95% CI, 1.03-1.08] for fourth vs first quartiles for primary series completion) were associated with primary series and additional dose completion (RRs ranging from 1.01 to 1.21).

CONCLUSIONS AND RELEVANCE: Findings from this cohort study suggest that, while COVID-19 vaccination coverage was high among PWH, outreach efforts should focus on those who did not complete vaccine series and those who have uncontrolled viremia.

PMID:38842808 | DOI:10.1001/jamanetworkopen.2024.15220

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Physician Specialty Differences in Unprofessional Behaviors Observed and Reported by Coworkers

JAMA Netw Open. 2024 Jun 3;7(6):e2415331. doi: 10.1001/jamanetworkopen.2024.15331.

ABSTRACT

IMPORTANCE: Because unprofessional behaviors are associated with patient complications, malpractice claims, and well-being concerns, monitoring concerns requiring investigation and individuals identified in multiple reports may provide important opportunities for health care leaders to support all team members.

OBJECTIVE: To examine the distribution of physicians by specialty who demonstrate unprofessional behaviors measured through safety reports submitted by coworkers.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among physicians who practiced at the 193 hospitals in the Coworker Concern Observation Reporting System (CORS), administered by the Vanderbilt Center for Patient and Professional Advocacy. Data were collected from January 2018 to December 2022.

EXPOSURE: Submitted reports concerning communication, professional responsibility, medical care, and professional integrity.

MAIN OUTCOMES AND MEASURES: Physicians’ total number and categories of CORS reports. The proportion of physicians in each specialty (nonsurgeon nonproceduralists, emergency medicine physicians, nonsurgeon proceduralists, and surgeons) who received at least 1 report and who qualified for intervention were calculated; logistic regression was used to calculate the odds of any CORS report.

RESULTS: The cohort included 35 120 physicians: 18 288 (52.1%) nonsurgeon nonproceduralists, 1876 (5.3%) emergency medicine physicians, 6743 (19.2%) nonsurgeon proceduralists, and 8213 (23.4%) surgeons. There were 3179 physicians (9.1%) with at least 1 CORS report. Nonsurgeon nonproceduralists had the lowest percentage of physicians with at least 1 report (1032 [5.6%]), followed by emergency medicine (204 [10.9%]), nonsurgeon proceduralists (809 [12.0%]), and surgeons (1134 [13.8%]). Nonsurgeon nonproceduralists were less likely to be named in a CORS report than other specialties (5.6% vs 12.8% for other specialties combined; difference in percentages, -7.1 percentage points; 95% CI, -7.7 to -6.5 percentage points; P < .001). Pediatric-focused nonsurgeon nonproceduralists (2897 physicians) were significantly less likely to be associated with a CORS report than nonpediatric nonsurgeon nonproceduralists (15 391 physicians) (105 [3.6%] vs 927 [6.0%]; difference in percentages, -2.4 percentage points, 95% CI, -3.2 to -1.6 percentage points; P < .001). Pediatric-focused emergency medicine physicians, nonsurgeon proceduralists, and surgeons had no significant differences in reporting compared with nonpediatric-focused physicians.

CONCLUSIONS AND RELEVANCE: In this cohort study, less than 10% of physicians ever received a coworker report with a concern about unprofessional behavior. Monitoring reports of unprofessional behaviors provides important opportunities for health care organizations to identify and intervene as needed to support team members.

PMID:38842804 | DOI:10.1001/jamanetworkopen.2024.15331

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Home Blood Pressure Telemonitoring and Nurse Case Management in Black and Hispanic Patients With Stroke: A Randomized Clinical Trial

JAMA. 2024 Jun 6. doi: 10.1001/jama.2024.6609. Online ahead of print.

ABSTRACT

IMPORTANCE: Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown.

OBJECTIVE: To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension.

DESIGN, SETTING, AND PARTICIPANTS: Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. Black and Hispanic study participants were enrolled between April 18, 2014, and December 19, 2017, with a final follow-up visit on December 31, 2019.

INTERVENTIONS: Participants were randomly assigned to receive either HBPTM alone (12 home BP measurements/week for 12 months, with results transmitted to a clinician; n = 226) or NCM plus HBPTM (20 counseling calls over 12 months; n = 224).

MAIN OUTCOMES AND MEASURES: Primary outcomes were change in SBP at 12 months and rate of recurrent stroke at 24 months. Final statistical analyses were completed March 14, 2024.

RESULTS: Among 450 participants who were enrolled and randomized (mean [SD] age, 61.7 [11.0] years; 51% were Black [n = 231]; 44% were women [n = 200]; 31% had ≥3 comorbid conditions [n = 137]; 72% had household income <$25 000/y [n = 234/324]), 358 (80%) completed the trial. Those in the NCM plus HBPTM group had a significantly greater SBP reduction than those in the HBPTM alone group at 12 months (-15.1 mm Hg [95% CI, -17.2 to -13.0] vs -5.8 mm Hg [95% CI, -7.9 to -3.7], respectively; P < .001). The between-group difference in SBP reduction at 12 months, adjusted for primary care physician clustering, was -8.1 mm Hg (95% CI, -11.2 to -5.0; P < .001) at 12 months. The rate of recurrent stroke was similar between both groups at 24 months (4.0% in the NCM plus HBPTM group vs 4.0% in the HBPTM alone group, P > .99).

CONCLUSIONS AND RELEVANCE: Among predominantly low-income Black and Hispanic stroke survivors with uncontrolled hypertension, addition of NCM to HBPTM led to greater SBP reduction than HBPTM alone. Additional studies are needed to understand the long-term clinical outcomes, cost-effectiveness, and generalizability of NCM-enhanced telehealth programs among low-income Black and Hispanic stroke survivors with significant comorbidity.

TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02011685.

PMID:38842799 | DOI:10.1001/jama.2024.6609

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Analysis of Prevalence, Socioeconomic and Disease Trends of Non-Melanoma Skin Cancer in New Zealand from 2008 to 2022

J Epidemiol Glob Health. 2024 Jun 6. doi: 10.1007/s44197-024-00250-4. Online ahead of print.

ABSTRACT

BACKGROUND: Skin cancer shows geographic and ethnic variation. New Zealand-with a predominantly fair-skinned populations, high UV indices and outdoor lifestyles-has high rates of skin cancer. However, population prevalence data is lacking. This study aimed to determine the demographics and socioeconomic disease trends of non-melanoma skin cancer prevalence in New Zealand from a large targeted-screening study.

METHODS: A targeted screening programme was conducted among 32,839 individuals, Fitzpatrick Skin Types I to IV in Auckland, New Zealand during the 2008-2022 period. This data was analyzed retrospectively. Linear regression models were used to assess statistical trends of skin cancer prevalence over time, along with associated factors that included demographics, disease trends and overall prevalence.

RESULTS: A total of 32,839 individuals were screened and 11,625 skin cancers were detected. 16,784 individuals were females who had 4,378 skin cancers. 16,055 individuals were males who had 5,777 skin cancers. 54 males and 65 females had multiple skin cancers. The article presents detailed descriptions of tumour types and subtypes detected, age groups, demographic and socioeconomic information. regarding the non-melanoma skin cancers detected.

CONCLUSION: Overall men have more non-melanoma skin cancer (NMSC) than females; however females develop more BCC on the lips. BCC is three times more common in the 31-50 age group, whereas SCC are significantly more prevalent after age 80. Prevalence of BCC has not changed over the 15-year timeframe of the study but SCC has increased. Older ages and higher incomes are associated with higher rates of NMSC in New Zealand.

PMID:38842790 | DOI:10.1007/s44197-024-00250-4

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Safety and efficacy of unilateral focused ultrasound pallidotomy on motor complications in Parkinson’s disease (PD): a systematic review and meta-analysis

Neurol Sci. 2024 Jun 6. doi: 10.1007/s10072-024-07617-2. Online ahead of print.

ABSTRACT

To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in Parkinson’s disease (PD) patients. A comprehensive search strategy was implemented through August 15, 2023, and updated on February 13, 2024, across six databases, identifying studies relevant to unilateral focused ultrasound pallidotomy and PD. Eligibility criteria included observational studies, clinical trials, and case series reporting on the impact of the intervention on motor complications in PD patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment utilized appropriate tools for different study designs. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. Five studies were included in our study, involving 112 PD patients undergoing FUS pallidotomy. UPDRS-II analysis revealed a significant improvement from baseline (mean difference (MD): -3.205, 95% CI: -4.501, -1.909, P < 0.001). UPDRS-III overall change was significant (MD: -10.177, 95% CI: [-12.748, -7.606], P < 0.001). UPDRS-IV showed a significant change from baseline (MD: -5.069, 95% CI: [-5.915, -4.224], P < 0.001). UDysRS demonstrated a significant overall improvement (MD: -18.895, 95% CI: [-26.973, -10.818], P < 0.001). The effect of FUS pallidotomy on motor complications in PD patients was effective, with a significant decrease in the UPDRS and UDysRS, reflecting improvement. The incidence of adverse events (headaches, pin-site pain, difficulty walking, and sonication-related head pain) of the FUS pallidotomy was not statistically significant, indicating its safety.

PMID:38842771 | DOI:10.1007/s10072-024-07617-2

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A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains

Clin Drug Investig. 2024 Jun 6. doi: 10.1007/s40261-024-01370-2. Online ahead of print.

ABSTRACT

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders.

OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains.

METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0.

RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± – 1.5 and – 2.6 ± – 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC.

CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains.

CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

PMID:38842764 | DOI:10.1007/s40261-024-01370-2