Clinical toxicity associated with tiazofurin

Summary Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23–36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity ( grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 uM) and prolonged exposure to plasma levels exceeding 50 uM may result in a higher incidence of serious non-hematologic toxicity.     

注射用阿奇霉素治疗细菌性感染临床观察

目的 :评价国产注射用阿奇霉素治疗细菌性感染的临床疗效和安全性。方法 :采用随机对照方法 ,将 43例下呼吸道感染和 33例泌尿道感染分验证组和对照组。 43例验证组给予注射用阿奇霉素 0 .2 5 g静脉滴注 ,每天 1次 ;33例对照组给予注射用头孢呋辛 1.5g静脉滴注 ,每天 2次 ,两组疗程均为 5天。结果 :验证组有效率为 83.7% ,细菌清除率为 72 .5 % ,药物敏感率为 80 .8% ;对照组有效率为 81.8% ,细菌清除率为 77.4% ,药物敏感率为 82 .2 % ,两组差异均无显著性 (P >0 .0 5 )。两组不良反应轻微。结论 :注射用阿奇霉素是一种有效、安全的治疗细菌性感染的抗生素     

穴位体表电刺激对术后PCEA的强化效应

目的　观察穴位体表电刺激对术后患者硬膜外自控镇痛（PCEA）效果、镇痛药用量、血清皮质醇浓度和不良反应的影响。方法　 选择经腹全宫切除术患者40例（ASAⅠ～Ⅱ级）,随机分成二组,每组20例。A组：于术后第4,8小时 Han's各刺激30 min,术后行PCEA。B组：单纯行术后PCEA（对照组）。术后随访镇痛效果、镇静评分、布氏舒适评分（BCS）,分段记录24 h镇痛药用量及总按压次数/实进次数（D1/D2）比值,血清皮质醇含量,肛门恢复排气时间和不良反应情况。结果　两组镇痛效果满意,A组BCS评分高于B组（P＜0.05）。A组镇痛药用量为（31.7±1.9）ml,与对照组（34.2±2.1）ml相比差异有显著性（P＜0.01）。血清皮质醇浓度两组均较术前下降,但A组术后8 h的下降幅度大于对照组。A组恢复肛门排气时间快于B组,而且恶心、呕吐与对照组相比有所减少。结论　术后患者硬膜外腔自控镇痛（PCEA）复合应用穴位体表电刺激,可增强镇痛效果,减少用药量,降低不良反应,是安全有效的复合镇痛方法。     

Mother and clinician experiences of a trial of a video feedback parent–infant intervention for mothers experiencing difficulties consistent with ‘personality disorder’: A qualitative interview study

Objectives

We explored mothers' and clinicians' experiences of a video feedback intervention adapted for perinatal ‘personality disorder’ (VIPP-PMH) and the acceptability of a randomised controlled trial (RCT) examining its effectiveness.

Design

In-depth qualitative interviews with participants from a two-phase feasibility study of the VIPP-PMH intervention. Participants were mothers experiencing enduring difficulties in managing emotions and relationships, consistent with a ‘personality disorder’, and their 6- to 36-month-old children.

Methods

Forty-four qualitative interviews were conducted, including all nine mothers receiving VIPP-PMH during the pilot phase, 25 of the 34 mothers participating in the RCT (14 allocated to the VIPP-PMH arm and 9 from the control arm), 11 of the 12 clinicians delivering VIPP-PMH and one researcher. Interview data were thematically analysed.

Results

Mothers described feeling motivated to take part in the research and understood the need for randomisation. Research visits were largely experienced positively, with some suggestions for improvement in questionnaire timing and accessibility. Almost all mothers initially felt anxious about being filmed, but reported positive experiences of the intervention, particularly valuing its non-judgemental, positive and child-focussed nature, their supportive relationship with the therapist and the insights they gained on their child.

Conclusions

The findings indicate the likely feasibility and acceptability of undertaking a future definitive RCT of the VIPP-PMH intervention in this population. In designing a future trial, a positive and non-judgemental therapeutic relationship will be important to allay mothers' anxieties about being filmed, and careful consideration should be given to the timing and accessibility of questionnaires used.     

Controlled Release of Theophylline Monohydrate from Amylodextrin Tablets: In Vitro Observations

Amylodextrin is a linear dextrin and can be produced by enzymatic hydrolysis of the -1,6 glycosidic bonds of amylopectin. Tablets compacted from pure amylodextrin showed good binding properties and did not disintegrate in aqueous media. Extended and decreasing drug release rates were found for tablets of 300 mg with a diameter of 9 mm containing 70% amylodextrin and 30% theophylline monohydrate, when compacted at 5 kN. Almost-constant drug release rates were obtained for these tablets when compacted at 10 or 15 kN. Nearly constant drug release rates were also shown for amylodextrin tablets with a drug load up to 75% compacted at 10 kN. Both release rate and release profile could be adjusted by selecting tablet thickness and incorporation of either lactose as a highly soluble excipient or talc as a hydrophobic excipient.     

Comparison between nafarelin acetate andd-Trp6-LHRH for temporary pituitary suppression in in vitro fertilization (IVF) patients: A prospective crossover study

Purpose Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 g/daily in their first cycle and received d-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their first cycle and received nafarelin in the second.Results Estradiol suppression was achieved by both d-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P=0.0005) and the length of administration of hMG required for ovarian stimulation (P=0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P=0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.Conclusion Our results demonstrate that nafarelin acetate is comparable to d-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with fewer ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.     

Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide

Purpose. The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO₂ (PCA-process) and to study the influence of various process parameters on their morphological characteristics. Methods. The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO₂ was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO₂ in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO₂ phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. Results. Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO₂. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. Conclusions. The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.     

Creative versus repetitive dance therapies to reduce the impact of fibromyalgia and pain: A systematic review and meta-analysis

Background and purposePhysical exercise is one of the most effective interventions to reduce fibromyalgia symptoms. Previous studies have reported benefits of dance-based intervention on the fibromyalgia impact, health-related quality of life and pain, regardless the interventions were based on creative- or repetitive dance. This study aimed to compare the effectiveness of creative and repetitive dance interventions.MethodsPRISMA guidelines were followed in this systematic review. The Cochrane Library, PubMed, Trip, Google Scholar, Web of Science (WOS), Embase and Scopus databases were selected to identify potential articles. Studies were included if they met the following inclusion criteria: to be a clinical trial or a randomized controlled trial, include people with fibromyalgia, have a comparison group and evaluate the impact of the disease, pain or quality of life. Fifteen articles fulfilled the inclusion criteria. The methodological quality of the studies was assessed using the Cochrane Collaboration's tool.ResultsDance-based interventions significantly reduced fibromyalgia impact (standardized mean difference = −0.69), pain (standardized mean difference = −0.70 and increased quality of life (standardized mean difference = 0.43) of people with fibromyalgia. The effectiveness of dance interventions is increased when a creative component is added, since it can lead to higher improvements in pain, impact of the disease and improving quality of life.ConclusionDance-based interventions are significantly effective in reducing the impact of fibromyalgia, pain as well as increasing health-related quality of life. Subgroup analyses suggest that creative dance-based interventions could be more effective than repetitive dance-based interventions to reduce pain and fibromyalgia impact. However, results must be taken with caution due to the large heterogeneity and the small number of articles.     

Feasibility,acceptability and effects of dance therapy in stroke patients: A systematic review

IntroductionStroke is the leading cause of non-traumatic disability in adults, with balance and gait disturbances representing the main limitations of body functions. Dance therapy (DT) has shown positive effects in older adults and in patients with neurological pathologies. This systematic review aims to examine the feasibility, acceptability and effects of DT in stroke rehabilitation, specifically on functional gains of gait and balance.MethodsA systematic search was carried out for articles published in the MEDLINE, PEDro, Web of Science, Scopus and CINHAL in February 2021 and updated in April 2021. Results: Eight studies were included (2 clinical cases, 5 case series and 1 randomized controlled trial), 7 of them in patients with chronic stroke and only 1 in subacute stroke phase. The most widely used dance modality was tango and ballet, with sessions ranging from 30 to 110 min. DT seems to show positive effects on post-stroke body functions and activities such as gait and balance. Reported dropout rates are inconsistent, no adverse effects were reported, and participant satisfaction was high.ConclusionGiven the heterogeneity and uneven quality of the included studies, strong conclusions cannot be put forward on the effectiveness of DT in post-stroke body function and activities. Nevertheless, DT seems to be safe and acceptable therapy for patients, and no adverse effects have been reported. More studies with a high level of evidence and feasibility are needed to determine the patient profile, the characteristics of the intervention, the participation rate and the role of the rehabilitation professional most likely to generate optimal benefit.     

The most immature infants: Is evidence-based practice possible?

IntroductionAt extremely low gestational ages, preterm infants are markedly physiologically immature, thus their responses to common clinical interventions may differ from more mature preterm babies. This study was performed to describe the evidence base which is available to make care decisions for such infants.MethodsA literature search of recent large neonatal randomized controlled trials (RCTs) was performed to determine the representation of infants <25 weeks of gestation, and whether it is clear if the overall results applied to the most immature infants.ResultsAmong 30 multi-centre RCTs in neonatology from the last 5 years, many excluded the most immature infants, and those that included them rarely presented the impacts of the intervention on the most at-risk group. Over 25,000 infants of under 32 weeks gestational age (GA) were included in these trials. Eight trials presented results of the primary outcome for infants of <26 weeks GA (n = 2,152) and a further four trials for infants <25 weeks, n = 711.ConclusionThe evidence base for treatment decisions for the highest risk infants in the NICU is severely limited. RCTs in extremely preterm infants should not exclude the highest risk group, and lower limits of gestational age (or body weight) should be avoided, any infant receiving intensive care should be eligible regardless of how immature. The results among the most immature infants should be presented separately, or be easily available, in order to build a database of effective treatments among infants of 22,23, and 24 weeks GA.