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.
BACKGROUND: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE).
METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure\'s onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments.
RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as \"Responder with Relapse\", 11 as \"Resistant\", 6 as \"Pyridoxine First Approach\", and 2 as \"Responders\". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up.
CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects. To overcome DOX limitations, two novel pyridoxine-derived doxorubicin derivatives were synthesized (DOX-1 and DOX-2). In the present study, their antitumor activity and mechanism of action were investigated. Of these two compounds, DOX-2, in which the pyridoxine fragment is attached to the doxorubicin molecule via a C3 linker, revealed higher selectivity against specific cancer cell types compared to doxorubicin and a promising safety profile for conditionally normal cells. However, the compound with a C1 linker (DOX-1) was not characterized by selectivity of antitumor action. It was revealed that DOX-2 obstructs cell cycle progression, induces apoptosis via the mitochondrial pathway without the development of necrosis, and showcases antioxidant capabilities, underlining its cell-regulatory roles. In contrast to doxorubicin\'s DNA-centric mechanism, DOX-2 does not interact with nuclear DNA. Given these findings, DOX-2 presents a new promising direction in cancer therapeutics, which is deserving of further in vivo exploration.

BACKGROUND: This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that can affect pediatrics with Wilson\'s Disease (WD).
METHODS: A prospective cohort study was conducted at an outpatient clinic in Turkey among pediatric patients (2 to 18 years) with WD between November 2022 and April 2023. The Medication Adherence Report Scale (MARS-5) as a subjective and Medication Possession Ratio (MPR) as an objective assessment were scored. Physical, genetic and biochemical parameters, the Pediatric Quality of Life Inventory (PedsQL) for both parents and patients, Childhood Depression Inventory, State Trait Anxiety Inventory were also administered.
RESULTS: A total of 30 pediatric outpatients who were prescribed D-penicillamine (n = 27) or trientine (n = 3) as chelators and zinc (n = 29) and pyridoxine (n = 19) as supplements were included. Proteinuria (n = 3), skin rash (n = 2), and gastrointestinal upset (n = 2) were observed. When the correlation between MARS-5 and duration of follow-up was examined, a significant negative correlation was found (p = 0.014). According to MPRs, non-adherence rates (missed doses ≥ 20%) were 29.6%, 17.2% and 5.3% for D-penicillamine, zinc and pyridoxine, respectively. PedsQL scores were higher than those of parents, with a positive correlation between them (p < 0.001). Also, there was a significant positive correlation between PedsQL and State Anxiety Inventory (p < 0.001). Comparing the change in urinary copper levels between different levels of treatment knowledge, significant differences were observed between high- and low levels (p = 0.043).
CONCLUSIONS: Overall, nonadherence rates were 23.3% based on MARS-5 and 5.3-29.6% based on MPR. It is essential to consider factors such as the duration of follow-up, biochemical parameters, treatment knowledge, quality of life and anxiety as potential influencers of medication adherence.

UNASSIGNED: Pyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE.
UNASSIGNED: A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life.
UNASSIGNED: Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy.
UNASSIGNED: A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.

Pyridoxal-5-phosphate (PLP) is the bioactive derivative of vitamin B6, functioning as a coenzyme in over 150 metabolic pathways. Insufficient PLP levels could be associated with the onset and progression of diabetes. This study aimed to assess the effects of pyridoxine adjuvant treatment on blood glucose levels in patients with type 2 diabetes mellitus (T2DM). This interventional, randomized, open-label study was conducted in the Mesan Governorate, with participants from the Mesan Center for Diabetes and Endocrinology as the study population. This study included patients newly diagnosed with T2DM. Patients were randomized into three groups: Group 1, the control group, treated with non-pharmacological therapy (lifestyle modification) (n=20); Group 2, treated with Metformin 500 mg/day in addition to non-pharmacological therapy (lifestyle modification) (n=20). Group 3 was treated with Metformin 500 mg/day plus vitamin B6 300 mg/day in addition to non-pharmacological therapy (lifestyle modification) (n=68). The findings revealed a considerably favorable impact of pyridoxine adjuvant treatment with Metformin on blood glucose levels and other study variables. Compared to the patients in the control group G1, the reductions in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were statistically significant in groups G2 and G3 after a 4-week treatment period. Similar results were observed for fasting serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels, with a significant decrease in groups G2 and G3 (p<0.05). Furthermore, the reductions in indoleamine 2,3-dioxygenase levels were also significantly higher in groups G2 and G3 at the end of the 4-week treatment period (-14.48% vs -21.16%) (p<0.05). Adding pyridoxine adjuvant therapy to Metformin treatment could effectively improve the blood glucose levels of patients with T2DM.

Several risk factors, including nutritional/lifestyle ones, play a role in gastric cancer etiology. Further interactions with mental health have also been emphasized. We hypothesized that individuals with mental disorders would exhibit compromised nutrient intake, increasing their risk of gastric cancer. The state of mental health was evaluated in 82 patients with gastric cancer and 95 healthy controls using the 21-item Depression-Anxiety-Stress Scale. The participants\' dietary intakes were evaluated by a 168-item food frequency questionnaire. Based on fully adjusted logistic regressions, there was a significant association between depression (OR = 1.938, CI 95%: 1.009-3.723) and stress (OR = 2.630, CI 95%: 1.014-6.819) with increased odds of gastric cancer. According to fully adjusted multinomial regressions, vitamins A and B6, beta-carotene, and black tea decreased the odds of depression, based on comparing the control group with cases of depression, while sugar and salt increased its odds. The highest significant association was found for salt intake and anxiety in cases with present anxiety (OR = 4.899, 95% CI: 2.218-10.819), and the highest significant protective effect was found for vitamin B6 and depression in cases with present depression (OR = 0.132, 95% CI: 0.055-0.320). However, considering causal relationships and clarifying the underlying mechanisms is imperative and requires further investigation. Advising healthy dietary patterns, e.g., a Mediterranean diet rich in vitamins, minerals, and phytochemicals such as vitamin A, B6, beta-carotene, and fiber, is expected to reduce the odds of gastric cancer, possibly related to lower levels of anxiety and depression.

Background: The B vitamins can potentially help prevent migraine. This study was designed to examine the effects of supplementation with thiamine (B1), pyridoxine (B6), cobalamin (B12), folic acid (B9), and a combination of these vitamins on women with episodic migraine (EM). Methods: This study was a double-blind, placebo-controlled, randomized, clinical trial conducted on 120 women with EM. The participants were divided into the 6 groups of B1 (n = 20), B6 (n = 20), B12 (n = 20), B9 (n = 20), vitamin B complex (n = 20), and placebo (n = 20). Subjects received 1 capsule daily for 12 weeks. As part of the baseline and post-intervention phases, paper-based headache diaries were used to record the number of abortive drugs consumed and the frequency of headache attacks, and the Migraine Disability Assessment Questionnaire (MIDAS) was used to assess migraine disability. Results: A 16-week study on women with EM revealed that the mean changes in the frequency of headache attacks decreased significantly in all vitamin groups in comparison with the placebo group (P < 0.001). In contrast to the placebo, there was also a significant improvement in the migraine disability score in each vitamin group (P < 0.001). The 12-week supplementation with vitamins B9, B1, B6, B12, and B complex also brought on a significant decrease in the use of abortive drugs compared to the placebo group (P = 0.032). Conclusion: The results of this study showed that B1, B6, B12, and B9, and a combination of these vitamins could be effective as an adjuvant in treatment and prophylaxis of EM. Further large trials with long-term follow-ups will be required to confirm our results.

BACKGROUND: Some mothers may seek lactation inhibition on personal, social, or medical grounds. The common drug used for lactation inhibition is cabergoline. Several adverse effects and contraindications are known for this drug. Its use is contraindicated for patients with hypertensive disorders and fibrotic, cardiac, or hepatic diseases. In addition, pyridoxine (vitamin B6) has been used for this indication, with no significant adverse effect, following studies that demonstrated its efficacy.
OBJECTIVE: This study aimed to compare the efficiency of cabergoline vs pyridoxine for lactation inhibition.
METHODS: A randomized controlled trial was conducted. Postpartum patients who requested lactation inhibition were randomly allocated to receive either cabergoline (1 mg once on postpartum day 1 or divided to 0.25 mg twice a day for 2 days thereafter, according to the departmental protocol, which is in line with the manufacturer recommendations) or pyridoxine (200 mg 3 times a day for 7 days). The patients enrolled were free of diseases in which contraindications to cabergoline are present. All patients completed a questionnaire for assessing breast engorgement, breast pain, and milk leakage on a scale of 0 (no symptom) to 5 (severe symptom) on days 0, 2, 7, and 14. The primary outcome was lactation inhibition success, defined as a score of 0 for both engorgement and pain on day 7. The secondary outcomes included the assessment of milk leakage, adverse effects, fever, mastitis, and treatment discontinuation or alteration.
RESULTS: Of note, 45 and 43 patients received cabergoline or pyridoxine, respectively, and were included in the analysis following the intention-to-treat principle. Cabergoline was superior to pyridoxine in inhibiting lactation at day 7 (78% vs 35%, respectively; P<.0001). Mild symptoms, defined as a score of 0 to 2 for breast engorgement and pain, at day 7 were 40 (89%) in the cabergoline group and 29 (67%) in the pyridoxine group (P=.01). The incidence of milk leakage was lower in the cabergoline group after 7 and 14 days than in the pyridoxine group (9% vs 42% [P=.0003] and 11% vs 31% [P=.02], respectively). Cabergoline had more adverse effects than pyridoxine (31% vs 9%, respectively; P=.01), but all adverse effects were mild. The rates of mastitis and fever that were related to engorgement were similar in the cabergoline and pyridoxine groups (4 [9%] vs 2 [5%], respectively; P=.67). Furthermore, 9 patients (21%) in the pyridoxine group switched to or added cabergoline because of treatment failure. Accordingly, on day 7, the pyridoxine success rate was reduced from 35% (15 women) to 28% (12 women) and from 67% (29 women) to 53% (23 women) for a score of 0 and 0 to 2 for both engorgement and pain, respectively.
CONCLUSIONS: Cabergoline was superior to pyridoxine in inhibiting lactation. Cabergoline had more adverse effects, but no major adverse effect was documented in either treatment group. As pyridoxine inhibited lactation successfully in previous studies and in 67% of patients in this study, its use should be considered in women with contraindications for cabergoline.

Background Pre-menstrual syndrome (PMS) is a condition associated with altered hormone levels during the menstrual phase of females and is characterised by physical, emotional, and behavioural symptoms that have a negative impact on the quality of life of females. The symptoms of PMS may vary between individuals, but the major complication is pain, especially during menstrual days. The current treatment strategy involves the use of hormonal therapies and analgesics for symptomatic relief, but these therapies have a risk of potential side effects. The use of herbal and nutraceutical supplements in PMS conditions is increasing due to their long-term safety and proven efficacy. The current real-world study aimed to evaluate the efficacy and tolerability of Ezedayz® tablets containing Vitex agnus-castus extract (EVX40™), vitamin B6, and magnesium in PMS subjects. Methodology A real-world, open-label study was conducted involving 64 participants with varied severity of PMS symptoms. Participants were categorised into Group A (N=23) receiving standard therapies, Group B (N=20) receiving Ezedayz® tablets, or Group C (N=21) receiving standard and Ezedayz® therapy. Standard therapies were provided as per physician supervision, and Ezedayz® tablets were given for 90 days. All subjects were evaluated on core symptoms of PMS like menstrual backache, menstrual cramps, joint or muscle pain, and headache using the numerical rating scale (NRS), and quality-of-life (QoL) was evaluated using a QoL questionnaire. A spontaneous reporting methodology was used to evaluate the tolerability of the therapies provided. Statistical analysis was performed as per the statistical plan. A p-value of <0.05 was considered statistically significant. Results Out of 64 participants, five were lost to follow-up, and the data of 59 participants were included in the final analysis. All groups showed improvement in all evaluated parameters, but Group B and Group C showed greater improvement at the end of the study in all evaluated parameters. The quality-of-life assessment revealed greater improvement in Group B and Group C participants compared to Group C in all evaluated QoL parameters. No serious side effects were observed in any subjects. Conclusion The results of the current study conclude that the nutraceutical composition of Vitex agnus-castus extract, vitamin B6, and magnesium is effective in reducing the severity of PMS symptoms and improving the quality of life of PMS subjects. The nutraceutical therapy provided greater relief from PMS symptoms compared to standard therapy alone, and this effect was augmented when the nutraceutical therapy was provided in combination with standard therapies. Similarly, the improvement in quality-of-life parameters was greater in subjects treated with nutraceuticals alone or in combination therapy. Despite the limitations of the study, the results of the current study are promising, and the nutraceutical composition (Ezedayz®) can be effectively used in clinical settings to control symptoms and improve the quality of life of PMS patients.