Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

UNASSIGNED: Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). However, the exploration of its optimal target dose is ongoing. This study aimed to summarize the best evidence to inform this clinical issue.
UNASSIGNED: We searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).
UNASSIGNED: Six hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction (p < 0.001, p < 0.001, p < 0.001) and at least 75% reduction (p < 0.001, p = 0.007, p < 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators (p < 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure (p = 0.006) but not on at least 50% reduction. Weight loss (p = 0.002), decreased appetite (p = 0.04), and all-cause withdrawal (p = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.
UNASSIGNED: The higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454.

UNASSIGNED: This study aimed to investigate the relationship between the dose and efficacy of acupuncture in treating limb dysfunction during acute stroke.
UNASSIGNED: Studies were searched from seven databases, including PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), VIP information database (VIP), and China Biology Medicine Database (CBM). All databases were searched until August 1, 2023 from inception. The risk of bias was assessed using Cochrane Collaboration\'s risk of bias tool (RoB2). Meta-analyses were performed using RevMan V.5.4 and Stata 12.0 statistical software. We used Fugl-Meyer Assessment (FMA) to measure recovery of limb dysfunction, NIH Stroke Scale (NIHSS) to measure neurological deficits, and Barthel index, Modified Barthel Index (MBI), and Activities of Daily Living (ADL) to measure activities of daily living. The primary outcome measure is FMA. After examining and integrating the raw data, we performed a meta-analysis using a 3-step process. First, we investigated the dose-related effects of acupuncture at varying doses and determined the optimal dosage for maximum therapeutic benefits. Second, we determined the difference between post-intervention and baseline scores on the outcomes of interest to determine minimal clinically important differences (MCID) to provide evidence for clinical treatment. Third, by combining the results of step 1 and step 2, we made the recommendations employing the Grades of Recommendations, Assessment, Development and Evaluations (GRADE) tool.
UNASSIGNED: Twenty-six studies containing 1947 participants were included, among which 61.5% of RCTs had a low risk of bias. Through the three-step analysis, the effect in improving limb dysfunction of acute stroke varied across different acupuncture dosages. Regarding the frequency of acupuncture, the results demonstrated a significant improvement in the low (every other day) and moderate-frequency (once a day) groups (low frequency: MD: 9.02, 95%CI: 5.40-12.64, p < 0.00001; moderate frequency: MD: 10.11, 95%CI: 5.05-15.18, p < 0.00001, heterogeneity (p = 0.87), I2 = 0%). For the acupuncture retention time, the results showed no significant difference between the short and medium retention groups (short retention time: MD: 0.05, 95% CI: -0.21-0.31, p = 0.71; medium retention time: MD: -1.16, 95% CI: -2.80-0.48, p = 0.17, heterogeneity (p < 0.00001), I2 = 99%). For the course of acupuncture, the results showed a significant improvement in the short course treatment (less than 2 weeks) group (MD: 14.87, 95% CI: 12.18-17.56, p < 0.00001, heterogeneity (p = 0.45), I2 = 0%).
UNASSIGNED: Our study demonstrated the effectiveness of different acupuncture dose in improving limb dysfunction. The pooled data suggested that the optimal intervention dose for acupuncture interval time was low (every other day) and moderate frequency (once a day), the optimal intervention dose for needle course time was short course treatment (less than 2 weeks). But we did not find the optimal intervention dose for needle retention time. Future studies of higher quality are needed to confirm this.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, CRD42023447202.

OBJECTIVE: Low doses of lithium, as might be used for mood or dementia prevention, do not carry the same renal, toxicity, and tolerability problems of doses used for prophylaxis or treatment of mania. However, thyroid effects of low doses have not been investigated. Our goal in this study was to assess the changes in thyroid-stimulating hormone (TSH) associated with a broad range of lithium levels, including those well below the therapeutic range for bipolar disorders.
METHODS: This study was conducted in a small healthcare system with 19 associated primary care clinics served by a Collaborative Care program of psychiatric consultation. In this retrospective review of electronic records, we searched for patients who had received a lithium prescription and both pre- and post-lithium thyroid-stimulating hormone (TSH) levels.
RESULTS: Patients with low lithium levels (<0.5 mEq/L, N = 197) had a mean thyroid-stimulating hormone (TSH) increase of 0.52 mIU/L. Patients with maintenance lithium levels (0.5-0.8 mEq/L; N = 123) had a mean TSH increase of 1.01 mIU/L; and patients with antimanic lithium levels (>0.8 mEq/L; N = 79) had a mean TSH increase of 2.16 mIU/L. The probability of TSH exceeding the upper limit of normal in our laboratory (>4.2 mIU/L) was positively associated with pre-lithium TSH.
CONCLUSIONS: These results suggest that the risk of lithium-induced hypothyroidism is dose-related, and relatively small with very low doses, but thyroid monitoring, including a pre-lithium TSH, is still warranted.

Progress has been achieved by using acupuncture widely for poor endometrial receptivity (PER). However, different acupuncture dosages may lead to controversy over efficacy.
To evaluate the evidence-based conclusions of dose-related acupuncture on infertile women with PER.
References were retrieved from nine databases from inception to 26 February 2022. This meta-analysis included randomized controlled trials (RCTs) that investigated the dose-related efficacy of acupuncture for PER with outcomes of endometrium receptivity (ER) parameters by transvaginal sonography (TVS) and the subsequent pregnancy outcomes in three acupuncture-dose groups: the high-dosage group (three menstrual cycles), the moderate-dosage group (one menstrual cycle), and the low-dosage group (two or four days). Since there remained sufficient heterogeneity among the three subsets, we prespecified seven subgroup variables (four clinical and three methodological) to investigate the heterogeneities.
A total of 14 RCTs (1,564 women) of moderate or low overall quality were included. The results were different when the dosage of acupuncture was restricted. For the moderate or high-dosage group, CPR and part of ER parameters were improved in the acupuncture group (i.e., CPR: OR = 2.00, 95% CI [1.24, 3.22], p = 0.004, I 2 = 0% in one menstrual cycle; OR = 2.49, 95%CI [1.67, 3.72], p < 0.05, I 2 = 0% in three menstrual cycles). However, for the low-dosage group, no statistical difference was observed in CPR (OR = 0.07, 95% CI [-0.10, 0.23], p = 0.44, I 2 = 82%) and a part of the ER parameters. In subgroup analysis, four subgroup variables (the routine treatment, risk of performance bias, duration of acupuncture treatment, and the age of participants) could explain some of the heterogeneities across all trials.
The finding indicated that the trend of relatively more acupuncture dosage showed better effects for poor endometrial receptivity among PER women. It remains a potential heterogeneity in our studies. Further high-quality trials with a homogeneity trial design need to be conducted.

The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM).
We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted.
A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 < 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes.
This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.

BACKGROUND: Contrast-induced nephropathy (CIN) is a frequent cause of hospital-acquired acute kidney injury. Previous animal models developed to explore the pathogenesis of CIN were based primarily on surgery or indomethacin treatment. Thus, we sought to explore a novel CIN rat model comparable to the human CIN.
RESULTS: Both serum creatinine and tubular injury score were used to assess the successful establishment of the present model. In our study, dehydration duration and the iohexol dosage were found to be the two most important factors to develop a rat CIN model. And, dehydration for 3 days plus furosemide (10 mL/kg) injection before iohexol (15 mL/kg) administration was demonstrated the optimal strategy. Renal injury induced by 15 mL/kg iohexol was almost twice more severe than 10 mL/kg. Moreover, significant renal function decrease, morphological damage and mitochondrial dysfunction occurred as early as 6 h after iohexol injection, not 24 h as previous studies reported. Unexpectedly, we firstly discovered that dehydration after iohexol administration did not increase the extent of renal damage, indicating that hydration after contrast media exposure may be ineffective.
CONCLUSIONS: A novel CIN rat model based on dehydration and iohexol exposure was established and validated to assist in understanding and preventing CIN.

Violence and drug use are significant public health challenges that are strongly linked. It is known that alcohol plays a major role in the causation of unnatural deaths and that stimulants like cocaine and amphetamine are often implicated in aggressive acts or violence. However, a clear causal relationship between these substances and aggression, and more specifically a blood concentration threshold at which intoxicated aggression emerges is lacking. In case of a crime and subsequent law enforcement, knowledge about dose-response relationships could be of pivotal importance when evaluating the role of alcohol and drugs in aggressive offences.
The present review aimed to determine whether there is a causal relation between intoxication with these psychoactive substances and aggression, and to define blood concentration thresholds above which these substances elicit aggression.
Empirical articles published between 2013 and 2017 and review papers containing the predefined search strings were identified through searches in the PubMed and Embase databases and additional reference list searches. The complete search query yielded 1578 publications. Initially all articles were manually screened by title and abstract. Articles with irrelevant titles, given the selected search terms and review aims were discarded. Remaining articles were carefully studied and those that did not comply with the main objectives of this review were discarded. At the end of this process, 167 titles were found eligible for review.
While placebo-controlled experimental studies clearly showed a causal link between alcohol and aggression, it is evident that such a link has not yet been established for cocaine and amphetamines. In case of alcohol, it is clear that there are various individual and contextual factors that may contribute to the occurrence of an aggressive act during intoxication. A clear threshold blood alcohol concentration has not been defined yet for alcohol, but a statistically significant increase of aggression has been demonstrated at a dose of 0.75 g/kg and higher. Future studies into intoxicated aggression should include multiple doses of alcohol and stimulants and take into account individual and contextual factors.

BACKGROUND: Venlafaxine is a serotonin norepinephrine reuptake inhibitor that is used for mood, anxiety, and pain disorders. We report a case of dose-related paresthesias in association with venlafaxine use in a patient with major depressive disorder.
METHODS: A young male patient with major depression started treatment with venlafaxine XR at 37.5 mg/d, and the dose was titrated to 75 mg/d with no significant adverse effects. Upon increasing the dose to 150 mg/d, the patient reported tingling, numbness, and itching in his upper extremities. The dose was reduced to 75 mg/d, at which time, the symptoms disappeared. Since the patient still had target symptoms of depression, the patient was willing to try increasing the dose back to 150 mg/d. Upon rechallenge, the tingling, numbness, and itching reappeared. The dose of venlafaxine was decreased back to 75 mg/d. Per the Naranjo scale, the probability score for the above adverse drug reaction is 5 (probable). We discuss the published evidence of paresthesias associated with antidepressants and clinical implications for recognizing paresthesias during venlafaxine treatment that may be useful for clinicians.
CONCLUSIONS: Clinicians need to be aware of the possible emergence of paresthesias with venlafaxine treatment, especially at doses of ≥ 150 mg/day. Patients who receive venlafaxine for pain disorders should be closely monitored for worsening of pain symptoms and may require adjustment of their doses.