A guide to interpreting estimated median age of survival in cystic fibrosis patient registry reports

Survival statistics, estimated using data collected by national cystic fibrosis (CF) patient registries, are used to inform the CF community and monitor survival of CF populations. Annual registry reports typically give the median age of survival, though different registries use different estimation approaches and terminology, which has created confusion for the community. In this article we explain how median age of survival is estimated, what its interpretation is, and what assumptions and limitations are involved. Information on survival from birth is less useful for individuals who have already reached a certain age and we propose use of conditional survivor curves to address this. We provide recommendations for CF registries with the aim of facilitating clear and consistent reporting of survival statistics. Our recommendations are illustrated using data from the UK Cystic Fibrosis Registry.     

Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data

Background

Cystic fibrosis (CF) is the most common inherited disease in Caucasians, affecting around 10,000 individuals in the UK today. Prognosis has improved considerably over recent decades with ongoing improvements in treatment and care. Providing up-to-date survival predictions is important for patients, clinicians and health services planning.

Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis

Dornase alfa has been shown to reduce markers of inflammation and neutrophil-associated metalloproteinases in cystic fibrosis (CF), suggesting a potential benefit from use of this therapy early in the disease. However, observational studies indicate that dornase alfa is often reserved for "sicker" patients. A 2-year, early intervention study of dornase alfa in CF patients with early lung disease demonstrated significant improvements in lung function and risk of exacerbation compared to placebo. A more recent analysis, using the database of the large observational Epidemiologic Study of Cystic Fibrosis (ESCF), found that initiation of dornase alfa has the potential to alter the course of CF by decreasing the rate of lung function decline in children and adults. These encouraging results, possibly linked to indirect effects on inflammation, suggest a greater role for dornase alfa therapy in the early treatment of CF, where it may help preserve lung function and potentially extend survival.     

PPH术与开放式外剥内扎术治疗混合痔远期疗效的对照研究（附130例报告）

目的探讨PPH治疗混合痔的临床远期疗效及并发症等。方法将130例混合痔患者随机分为A、B两组,各65例,A组采用PPH治疗,B组采用开放式外剥内扎术治疗。在术后48～60个月时进行随访,观察指标包括术后远期有效率、远期并发症发生率、术后再发率、远期患者满意度等。结果共完成130例临床随访观察（A组65例,B组65例）。A组在远期并发症发生率、远期患者满意度均显著优于B组（P〈0.05、P〈0.01）;其他观察指标两组间无显著差异。结论 PPH术在远期并发症发生率、远期患者满意度等方面优于开放式外剥内扎术,远期有效率、术后再发率与开放式外剥内扎术相似。     

Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes

Background

Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared.

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1 s [ppFEV₁] < 40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV₁: 34 [31–36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV₁ from baseline at 2-hours (median [IQR] relative change: ? 19 [? 21 to ? 11]%, p < 0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV₁ < 40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease.     

Using multiple imputation and propensity scores to test the effect of car seats and seat belt usage on injury severity from trauma registry data

Background

Missing data and the retrospective, nonrandomized nature of trauma registries can decrease the quality of registry-based research. Therefore, we used multiple imputation and propensity scores to test the effect of car seats and seat belt usage on injury severity in children involved in motor vehicle crashes.

Methods

All children admitted after injury from motor vehicle crashes who had complete data on seat belt or car seat usage from 2003 to 2006 were included in the study. The sample was divided into children younger than 4 years (n = 130) or 5 years or older (n = 575) and analyzed for seat belt usage, car seat usage, injury severity score, revised trauma score, and Glasgow Coma Scale score. Data were analyzed before and after matching on propensity scores after multiple imputation.

Results

There were no outcome differences between car seat users and non-car seat users. However, there were significant improvements in injury severity score (7.0 vs. 10.1, P = .002) and revised trauma score (7.6 vs 7.3, P = .013 for seat belt users compared to nonusers) even after matching on propensity score.

Conclusion

Multiple imputation and propensity scores demonstrated the efficacy of seat belts, but not car seat in this preliminary study. This statistical method can strengthen registry-based research.     

Enhancement of the Therapeutic Effect of Albendazole on Cystic Echinococcosis using a Herbal Product

Purpose: Albendazole is the drug of choice for chemotherapy of cystic echinococcosis (CE) but 40% of patients do not respond to it satisfactorily. With regard to the previously reported scolicidal activity of Zataria multiflora, this study was done to evaluate the efficacy of the co-administration of albendazole and Z. multiflora aromatic water (AW) on hydatid cysts in a murine model. Materials and Methods: Laboratory mice were infected with 1,500 viable protoscoleces. After development of hydatid cysts, the infected mice were allocated into four treatment and one control group. The mice of groups 1, 2, 3, and 4 were treated orally with albendazole (100 mg/kg), Z. multiform AW (100 ml/l), albendazole (100 mg/kg) – Z. multiform AW and albendazole ((50 mg/kg) – Z. multiform AW respectively. Two months later, all the mice were euthanized and necropsied and the number, size and weight of hydatid cysts were compared between different groups. Results: The size of the largest cysts, as well as the total weight of cysts, were significantly lower (p < .05) in the mice treated with albendazole (50 mg/kg) – Z. multiflora AW in comparison to those treated with albendazole (100 mg/kg) alone. Conclusions: The results of this study revealed the superiority of co-administration of albendazole and Z. multiflora AW to albendazole alone in the treatment of CE in laboratory mice. Since Z. multiflora AW is a safe and useful drink, it may be used successfully to enhance the therapeutic effect of albendazole in the patients infected with hydatid disease.     

Achieving the 'bifecta' using salvage cryotherapy for locally recurrent prostate cancer: analysis of the Cryo On-Line Data (COLD) registry data

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The cancer‐specific outcomes of salvage cryotherapy for locally recurrent prostate cancer have been well established within contemporary scientific literature. However, very little is known about the outcomes of salvage cryotherapy encompassing health‐related quality of life considerations such as continence after treatment. We think the present study is quite novel, as it proposes a new therapeutic endpoint to evaluate the efficacy and outcomes of salvage therapies for locally recurrent prostate cancer, which we have termed the ‘bifecta’. In addition, we report that in a large multicentre data registry, such as the COLD Registry, the therapeutic ‘bifecta’ can be achieved in most patients.

OBJECTIVES

• ? To evaluate the contemporary outcomes of salvage cryotherapy for locally recurrent prostate cancer using the Cryo On‐Line Data (COLD) Registry.
• ? We also evaluate the outcomes of salvage cryotherapy in achieving the therapeutic ‘bifecta’ consisting of: (i) achieving a post‐cryotherapy nadir serum PSA level of <0.6 ng/mL and (ii) no urinary incontinence.

PATIENTS AND METHODS

• ? A prospectively, centrally collected secure online database has been developed of patients undergoing salvage cryoablation for locally recurrent prostate cancer. Of the patients undergoing salvage cryotherapy (in the absence of neoadjuvant hormonal ablative therapy) included within the COLD Registry, complete medical records pertaining to continence status and serial PSA measurements after treatment were available in 183 patients.

RESULTS

• ? The therapeutic ‘bifecta’ was achieved in 133 of these patients (72.7%).
• ? Of the patients achieving the ‘bifecta’, the mean (sd ) age at presentation was 71.5 (6.6) years.
• ? Most patients (91%) had a baseline pre‐salvage total serum PSA level of <10 ng/mL and a pre‐treatment biopsy Gleason score of <8 (85%).
• ? The mean duration of follow‐up of patients achieving the ‘bifecta’ was 36.5 months.

CONCLUSIONS

• ? The therapeutic ‘bifecta’, a new surrogate benchmark for salvage therapies, can be achieved in most patients undergoing salvage cryotherapy.
• ? Therefore, salvage cryotherapy is a reasonable treatment choice for locally recurrent prostate cancer in appropriately selected patients.

     

肾移植术后PRA与移植肾功能长期预后关系的研究

目的  研究肾移植术后患者群体反应性抗体(PRA)对移植肾功能长期预后的影响。方法 研究对象为首都医科大学附属北京友谊医院1994年1月至2004年12月进行肾移植手术且在术后2周左右行PRA检测并获得随访患者224例。根据肾移植术后2周左右的PRA检测结果分为阴性组(195例)和阳性组(29例)。阴性组患者于2007年再次检测PRA, 两组患者于近期(2013年10月至2014年4月)检测血清肌酐(Scr), 了解肾功能情况。比较PRA阳性患者(含PRA复查阳性者)和PRA阴性患者的移植肾功能长期正常率。结果 阳性组患者29例, 2014年4月复查18例患者肾功能丧失(17例)或下降(1例), 11例患者肾功能正常。阴性组患者195例, 于2007年复查PRA阴性者153例, 2014年4月复查肾功能正常患者148例, 肾功能下降或丧失者5例;于2007年复查PRA阳性者42例, 移植肾功能均不同程度下降或丧失。2004年前PRA阳性和2007年复查PRA阳性患者共71例, 2014年4月复查肾功能正常患者11例, 移植肾功能长期正常率为15.5%。PRA阴性患者153例, 2014年4月复查肾功能正常患者148例, 移植肾功能长期正常率为96.7%。PRA阳性患者和PRA阴性患者的移植肾长期存活率比较, 差异有统计学意义(P<0.005)。结论 肾移植术后产生PRA对移植肾长期预后有明显影响。      

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary Exacerbations

Background

Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx.

The use of a vertical infraclavicular brachial plexus block in a patient with myasthenia gravis: effects on lung function

A patient who was suffering an exacerbation of myasthenia gravis dislocated her elbow. She underwent closed reduction of the dislocation under vertical infraclavicular brachial plexus blockade. The technique was successful but was associated with a 29% decrease in forced vital capacity, from 1.7 l to 1.2 l. The patient did not show any symptoms of ventilatory failure. Her recovery was uncomplicated.     

Comparison of the effects of open and endovascular aortic aneurysm repair on long-term renal function using chronic kidney disease staging based on glomerular filtration rate

OBJECTIVE: It has been suggested that endovascular aneurysm repair (EVAR) in concert with serial contrast-enhanced computed tomography (CT) surveillance adversely impacts renal function. Our primary objectives were to assess serial renal function in patients undergoing EVAR and open repair (OR) and to evaluate the relative effects of method of repair on renal function. METHODS: A thorough retrospective chart review was performed on 223 consecutive patients (103 EVAR, 120 OR) who underwent abdominal aortic aneurysm (AAA) repair. Demographics, pertinent risk factors, CT scan number, morbidity, and mortality were recorded in a database. Baseline, 30- and 90-day, and most recent glomerular filtration rate (GFR) were calculated. Mean GFR changes and renal function decline (using Chronic Kidney Disease [CKD] staging and Kaplan-Meier plot) were determined. EVAR and OR patients were compared. CKD prevalence (>or=stage 3, National Kidney Foundation) was determined before repair and in longitudinal follow-up. Observed-expected (OE) ratios for CKD were calculated for EVAR and OR patients by comparing observed CKD prevalence with the expected, age-adjusted prevalence. RESULTS: The only baseline difference between EVAR and OR cohorts was female gender (4% vs 12%, P = .029). Thirty-day GFR was significantly reduced in OR patients (P = .047), but it recovered and there were no differences in mean GFR at a mean follow-up of 23.2 months. However, 18% to 39% of patients in the EVAR and OR groups developed significant renal function decline over time depending on its definition. OE ratios for CKD prevalence were greater in AAA patients at baseline (OE 1.28-3.23, depending upon age group). During follow-up, the prevalence and severity of CKD increased regardless of method of repair (OE 1.8-9.0). Deterioration of renal function was independently associated with age >70 years in all patients (RR 2.92) and performance of EVAR compared with OR (RR 3.5) during long-term follow-up. CONCLUSIONS: Compared with EVAR, OR was associated with a significant but transient fall in GFR at 30 days. Renal function decline after AAA repair was common, regardless of method, especially in patients >70 years of age. However, the renal function decline was significantly greater by Kaplan-Meier analysis in EVAR than OR patients during long-term follow-up. More aggressive strategies to monitor and preserve renal function after AAA repair are warranted.     

Effectiveness of the caverno-dorsal vein shunt (Barry shunt) on prolonged ischaemic priapism and its effect on the post-operative long-term erectile function

Ischaemic priapism is the most common form of priapism and requires urgent treatment. In this study, we evaluated the effectiveness of the caverno-dorsal vein shunt on resolution of ischaemic priapism and on the post-operative long-term erectile function in patients presenting with priapism. The study included 10 patients admitted to our hospital for priapism between 2010 and 2018. The median age of the patients was 31 (24–66) years. The median priapism time was 13.5 (7–38) hours. The blood gas measurements were taken from the corpus cavernosum, and the drainage of the corpus cavernosum was performed as an emergency intervention. Then, the corpus cavernosum was irrigated with 0.01% adrenaline 5 times in 20-min intervals. The caverno-dorsal vein shunt procedure was performed in cases without regression of priapism. Two months after, the operation shunt was closed. Detumescence occurred in all patients. Eight of 10 patients maintained their erectile function. In 2 patients, severe erectile dysfunction occurred at post-operative 2 months following a priapism attack and penile prosthesis implantation was performed in these 2 patients. Our study showed that caverno-dorsal vein shunt procedure is effective in providing detumescence and maintaining potency in cases with ischaemic priapism. In our opinion, caverno-dorsal vein shunt can be considered as the first treatment of choice for refractory low-flow priapism.     

The use of an in vivo model to study the effects of hyperhomocysteinaemia on vascular function

BACKGROUND/AIMS: To use an in vivo rat model of hyperhomocysteinaemia (HHCy) to study its impact on vascular function. METHODS: Twenty rats were fed either a control or HHCy-inducing diet for 10 wk. The response of aortic rings to contraction with phenylephrine, and relaxation to acetylcholine (endothelium-dependant relaxation) or sodium nitroprusside (endothelium-independent relaxation) was analyzed. The results were compared using an analysis of variance (ANOVA). RESULTS: There was a significant elevation of HCy in the treated group (20.5 versus 1.6 micromol/L, P = 0.004). There was no significant difference between the two groups in blood pressure measurements (ANOVA, P = 0.152). In a dose-dependant manner, phenylephrine elicited significantly greater contraction in aorta taken from HHCy rats than that taken from controls (ANOVA, P < 0.001), acetylcholine elicited significantly less percentage relaxation in aorta taken from HHCy rats than from controls (ANOVA, P = 0.003) and though sodium nitroprusside stimulated less percentage relaxation in aorta taken from HHCy rats than controls, this did not reach significance (ANOVA, P = 0.051). CONCLUSIONS: In diet induced hyperhomocysteinaemic rats, there is enhanced vascular contraction in response to phenylephrine and impaired endothelium-dependant relaxation in response to acetylcholine.     

Delayed graft function: risk factors and the relative effects of early function and acute rejection on long-term survival in cadaveric renal transplantation

Delayed graft function (DGF) and acute rejection have both been associated with reduced renal allograft survival. In some studies, they have been shown to have an interactive effect. We studied the risk factors for DGF and the relative impact of DGF and rejection on both short- and long-term survival in recipients of cadaveric renal transplants. Data from the Oxford Transplant Centre Database were assessed on 710 cadaver allografts over a 10-yr period, during which time all recipients received cyclosporin-based immunosuppressive protocols. The interaction between DGF and acute rejection was examined using logistic and Cox multivariate regression. Long cold ischaemia time (CIT), sensitisation and older donor age were found to be independent predictors of DGF. The occurrence of DGF resulted in a reduced 5-yr survival (56 vs. 75%). However, the effect of DGF was confined to the first year post-transplant, as there was no significant difference in survival, as measured by half-life (t1/2) of grafts functioning at 1 yr, with DGF alone and a group with good early function (t1/2 = 21.3 vs. 20.0 yr). There was no increase in acute rejection in grafts with DGF. However, the combination of DGF and acute rejection resulted in the worst short-term graft survival (68% at 1 yr, compared to 92.3% in those grafts with no DGF or acute rejection) and this continued over the long term (t1/2 = 10.5 yr). These data suggest that early function is critical to the success of renal transplantation. The effects of DGF are limited to the first year post-transplant. Long-term graft survival may be improved by efforts to limit CITs, particularly for grafts from older donors and sensitised recipients.     

Early effects of the ex vivo evaluation system on graft function after swine lung transplantation

Objectives:Ex vivo lung evaluation (ex vivo) has been developed as a useful method by which to assess lungs from donation-after-cardiac death (DCD) donors prior to transplant. However, the safety of the ex vivo circulation itself with respect to grafts has not been fully investigated. The aim of this study is to evaluate the effects of the ex vivo circuit using a swine lung transplant model. Methods: Lungs with or without 2-h warm ischemia were used. To assess post-transplant graft function, the left lung was transplanted after 2-h ex vivo or cold preservation; blood gas analysis of the left pulmonary vein (partial pressure of oxygen, PO₂) was performed during the 6-h post-transplant follow-up period. Data were compared between the ex vivo (+) and ex vivo (−) groups. Results: Partial pressure of oxygen/ inspired oxygen fraction (PO₂/FiO₂) in the ex vivo (−) group was significantly greater than that in the ex vivo (+) group until 3 h after transplant. The PO₂/FiO₂ levels in both groups then increased and became similar at 6 h after transplant, regardless of whether ischemic or non-ischemic lungs (p < 0.001 and p = 0.004, respectively) were used. Conclusions: Negative effects of the ex vivo system were limited and seen only in the immediate post-transplant period. Therefore, in DCD swine lung transplantation, the ex vivo system appears to be safe.     

Cost-effectiveness analysis of newer anticholinergic drugs for urinary incontinence vs oxybutynin and no treatment using data on persistence from the Swedish prescribed drug registry

Study Type – Therapy (cost effectiveness) Level of Evidence 2a What's known on the subject? and What does the study add? Anticholinergic drugs are a common treatment alternative in urinary incontinence, which results in large costs for caregivers. So far, most cost‐effectiveness analyses of anticholinergic drugs have focused on small putative differences between the newer anticholinergics. This study takes a novel approach by treating the clinical effects of the newer alternatives as similar and evaluating them as a group in relation to no treatment and oxybutynin (immediate release). It also uses registry data to account for persistence.

OBJECTIVE

• ? To analyse the cost‐effectiveness of newer anticholinergic drugs in relation to oxybutynin immediate release (IR) and no treatment for patients with urgency urinary incontinence.

PATIENTS AND METHODS

• ? A decision analytic model was constructed.
• ? Results were collected from randomized trials and combined with registry data on persistence of medicine use and estimated number of severe adverse events.
• ? The setting corresponds to Swedish clinical practice.
• ? The costs and effects of the treatment options were analysed over a period of 1 year. Costs included drug costs, treatment costs and costs for pad use. Patients' utilities were based on treatment effect and the lack or presence of adverse events.

RESULTS

• ? No treatment was the least costly treatment but also resulted in the fewest number of quality adjusted life years (QALYs).
• ? Treatment with newer anticholinergic drug medications is the most costly option but also the most efficient treatment. Sensitivity analyses showed that the results were robust.
• ? Treatment with newer anticholinergics resulted in a cost per QALY gained of €21 045 compared with no treatment and no effect and €65 435 compared with no treatment and placebo effect. Compared with oxybutynin IR, the cost per QALY gained was €37 119. These calculations are based on relatively low pad costs, resulting in higher costs per QALY for the original drugs.

CONCLUSIONS

• ? The newer anticholinergic medications are likely to be cost effective in relation to oxybutynin IR.
• ? The cost‐effectiveness of the newer anticholinergics compared with no treatment depends on assumptions of the effect of no treatment, the severity of the treated condition and the treated individual's risk of adverse events.
• ? Treatment is less likely to be cost effective for elderly persons or for persons otherwise at higher risk for adverse events.