Adaptive design method based on sum of p-values

Bauer and Kohne proposed an adaptive design using Fisher's combination of independent p-values based on subsamples from different stages (Biometrics 1994; 50(4):1029-1041). Their method provides great flexibility in the selection of statistical methods for hypothesis testing of subsamples. However, the choices for the stopping boundaries are not flexible enough to meet practical needs (Biometrics 2001; 57(3): 886-891). In this paper, an adaptive design method is proposed using linear combination of the independent p-values. The method provides great flexibility in the selection of stopping boundaries and no numerical integration is required for the two-stage designs. The stopping boundaries and p-values can be calculated manually. The operating characteristics of the adaptive designs are studied using computer simulations with and without sample size adjustment. Examples are presented for superiority and non-inferiority trials with different endpoints (normal, binary, and survival) under different adaptations. The statistical efficiency of the proposed method is compared with other methods based on conditional power.     

A novel puborectalis muscle artificial anal sphincter system with the module of sensory perception

This article presents a novel puborectalis muscle artificial anal sphincter system (PM-AASS) with the module of sensory perception for treating severe faecal incontinence (FI). Due to the implantable feature of PM-AASS, this system applied low-power design and the total energy consumption could drop to 48.8 Ah/d. To reduce the injury of intestine and the pressure exerted on intestine, the actuator, including the structure of tings and the robot mechanism, of PM-AASS was presented and the middle ring was optimised. To realise the sensory perception, the intestinal flexible pressure sensors, comprising the radial sensors and the axial sensors, were designed. The sensors calibration showed the R-square of each fitting line were above 0.998, which presented a high goodness of fit and indicated we could figure out the pressure value with the analogue voltage captured by MCU. Through the in-vitro experiment, the results that the radial sensors were more relevant to the occlusion threshold while the axial sensors had more effect on the alarm threshold could be concluded. The practicability of the PM-AASS was verified by the results of the in-vivo experiment, which showed that the PM-AASS had the effect of improvement to the anorectal internal pressure.     

Ultraflexible,large-area,physiological temperature sensors for multipoint measurements

We report a fabrication method for flexible and printable thermal sensors based on composites of semicrystalline acrylate polymers and graphite with a high sensitivity of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit large resistance changes near body temperature under physiological conditions with high repeatability (1,800 times). Device performance is largely unaffected by bending to radii below 700 µm, which allows for conformal application to the surface of living tissue. The sensing temperature can be tuned between 25 °C and 50 °C, which covers all relevant physiological temperatures. Furthermore, we demonstrate flexible active-matrix thermal sensors which can resolve spatial temperature gradients over a large area. With this flexible ultrasensitive temperature sensor we succeeded in the in vivo measurement of cyclic temperatures changes of 0.1 °C in a rat lung during breathing, without interference from constant tissue motion. This result conclusively shows that the lung of a warm-blooded animal maintains surprising temperature stability despite the large difference between core temperature and inhaled air temperature.Temperature control plays a very important role in homeostasis, and body temperature varies both spatially and temporally in an effort to transfer heat between the living body and the environment via skin and respiratory organs. Accurate measurement of localized temperature changes in soft tissue regardless of large-scale motion is important in understanding thermal phenomena of homeostasis and realizing future sophisticated health diagnostics (1–3). Therefore, flexible temperature sensors which softly interface with tissue have been investigated frequently for applications in the medical field. However, these applications require the combination of sensitivity, fast response time, stability in physiological environments, and multipoint measurement. Before this work, to our knowledge, no experiment has simultaneously demonstrated orders-of-magnitude changes in electrical properties (sensitivity) repeatedly at varying physiological temperatures and conditions (stability) in a robust, easy-to-fabricate, flexible temperature sensor (processability).When sensors and electronics are directly attached to the surface of an animal body, the use of soft and flexible electronic devices is expected to reduce mechanical stress induced on the body. From this viewpoint, the field of flexible electronics has attracted much attention recently. The ability to gather information such as pressure and temperature from curvilinear and dynamic surfaces without impairing the movement or usability of the users is unmatched by conventional silicon electronics. There have been reports of the potential application of flexible electrodes on ultrathin substrates (4), flexible sensors that measure biological signals, electrocardiograms, temperature, pressure (5, 6), organic amplifier systems (7), high-sensitivity pressure sensors (8), and ultrathin and imperceptible devices (9, 10).To measure spatial and temporal temperature gradients of the body, multiple temperature sensors have to be attached on the freely curved surface of the body. One practical solution is to apply multiple discrete temperature sensors to the skin such as thermocouples (11), thermistors (12), or resistive temperature detectors (4, 6, 13) with individual wirings for data readout. Indeed, there are many excellent temperature sensors that exhibit fast response, mechanical flexibility, physiological stability, and/or high sensitivity (4, 6, 13). For example, the thermal sensors using metals as resistors exhibit the change of resistivity less than 1% for the thermal change of 5 °C (6, 13), which can be perfectly resolved by a high-precision electronic circuit. To realize scalable designs for multipoint measurements and/or to ensure sufficient accuracy of temperature measurement on dynamically moving objects due to strain-induced performance changes of sensors, however, it is important to significantly increase change of resistivity, ideally up to several orders-of-magnitude change. Although line-of-sight–based techniques including infrared thermographs and thermotropic liquid crystals (14) are capable of spatial temperature mapping, they require separation between the sensor and target object and, therefore, are unsuitable for implanted devices.Alternatively, positive temperature coefficient (PTC) polymers (15) have been used to fabricate mechanically flexible temperature sensors that exhibit orders-of-magnitude changes in resistivity over just a few degrees (16). Extraordinarily large resistivity changes can eliminate the need for per-pixel amplification circuitry, as the output signal of the sensor can be directly multiplexed and fed to external recording equipment, ultimately reducing device complexity and manufacturing costs. The PTC effect in conductive-filled polymers results from an increase in the specific volume as the temperature increases, typically during progression through the melting point of crystalline regions (17, 18). For this reason, resistivity is changed drastically by change in temperature for only a few degrees. However, very few polymer PTC materials with sensitivity near physiological temperatures have been demonstrated, and have yet to be fabricated in highly flexible geometries. Besides flexibility and multipoint measurement requirements, each sensor has to exhibit high sensitivity (<0.1 °C) near body temperatures, fast response time (less than 100 ms), and cyclic repeatability. This work demonstrates a highly tuned polymer composite that changes six orders of magnitude over less than 5 °C near body temperature with high cyclic stability. To the best of the authors’ knowledge, no other temperature sensors, either rigid or flexible, organic or inorganic, simultaneously exhibit these qualities—less than 0.1 °C sensitivity, cyclic stability near 37 °C, easily processable, with low-complexity readout circuitry. These properties will enable a wide range of medical and nonmedical devices. Competing inorganic devices require complex postamplification of low signals, which complicates readout and the device architecture. Specifically, the need for per-pixel amplification limits the proliferation of simple medical sensors that lend themselves to continued miniaturization, low power utilization, and wireless addressability. Competing organic devices suffer in terms of repeatability, commonly exhibiting less than 100 stable thermal cycles (16, 19, 20). This work presents an important step toward the realization of implantable and wearable devices that are sensitive, cyclically stable, and processable.     

Comparison of percutaneous nephrolithotomy and retrograde flexible nephrolithotripsy for the management of 2-4 cm stones: a matched-pair analysis

Study Type – Therapy (case control) Level of Evidence 3b What's known on the subject? and What does the study add? Recently European Association of Urology 2011 guidelines on urolithiasis recommended retrograde intrarenal surgery as the second‐line therapy for the treatment of kidney stones <10 mm in diameter. This study shows that retrograde intrarenal surgery may be an alternative therapy to percutaneous nephrolithotomy, with acceptable efficacy and low morbidity for 2–4 cm stones.

OBJECTIVE

• ? Currently, the indications for retrograde intrarenal surgery (RIRS) have been extended due to recent improvements in endoscopic technology. In this study, we compare the outcomes of percutaneous nephrolithotomy (PCNL) and RIRS in the treatment of 2–4 cm kidney stones.

MATERIALS AND METHODS

• ? Between September 2008 and January 2011, 34 patients who had renal stones ranging from 2 to 4 cm in diameter were treated with RIRS. The outcomes of these patients were compared with patients who underwent PCNL using matched‐pair analysis (1:1 scenario).
• ? The matching parameters were the size, number and location of the stones as well as age, gender, body mass index, solitary kidney, degree of hydronephrosis, presence of previous shock wave lithotripsy and open surgery.
• ? Data were analysed using Fisher's exact test, Student's t test and the Mann–Whitney U test.

RESULTS

• ? Stone‐free rates after one session were 73.5% and 91.2% for RIRS and PCNL respectively (P= 0.05). Stone‐free rate in the RIRS group improved to 88.2% after the second procedure.
• ? Mean operation duration was 58.2 (±) 13.4 min in the RIRS group but 38.7 (±) 11.6 min in the PCNL group (P < 0.0001). Blood transfusions were required in two patients in the PCNL group.
• ? Overall complication rates in the PCNL group were higher, but the differences were not statistically significant. Hospitalization time was significantly shorter in the RIRS group (30.0 + 37.4 vs 61.4 + 34.0 h, respectively; P < 0.001).

CONCLUSION

• ? Satisfactory outcomes can be achieved with multi‐session RIRS in the treatment of 2–4 cm renal stones. RIRS can be used as an alternative treatment to PCNL in selected cases with larger renal stones.

     

Is whole colonic imaging necessary for symptoms of change in bowel habit and/or rectal bleeding?

Aim Following the introduction of a 2-week-wait (2ww) cancer pathway, many units are triaging patients with change in bowel habit (CIBH) and/or rectal bleeding (RB) straight to colonoscopy. Evidence suggests that right-sided colonic cancer does not present with these symptoms, hence imaging the left colon only is satisfactory. If this were substantiated, patients could be offered a flexible sigmoidoscopy (FS) alone. This study aimed to review presenting symptoms of patients diagnosed with a right-sided colonic malignancy and assess whether their tumours would be missed based on this practice. Method This is a retrospective analysis of patients who underwent curative resection for a proximal colonic malignancy over a 4-year period. Two-week-wait referral proforma and case notes were analysed for mode of presentation. Results Of 206 elective right hemicolectomies performed, 20/206 (9.7%) patients presented in the absence of either iron deficiency anaemia or palpable abdominal mass. Twelve patients had polyposis identified in the left colon and eight patients had no left-sided colonic pathology. One patient had a strong family history of colon cancer (two first-degree relatives) in the group absent of left-sided pathology. Conclusion Twelve patients who had left-sided polyposis and one patient with a strong family history would have undergone whole colonic imaging based on current colorectal cancer management guidelines. The remaining seven patients with right-sided cancer would have been missed if FS were the only investigation used. Patients presenting on the 2ww with symptoms of a CIBH and/or RB can be adequately investigated with a FS with a 3% chance of missing a proximal cancer.     

Endobronchial findings of hydatid cyst disease: a report of five pediatric cases

Hydatid disease is still an important public health problem throughout the world. Diagnosis of the disease is generally based on clinical and radiological findings. Evaluation of pulmonary disorders by flexible bronchoscopy (FOB) is a rapidly developing facility, but diagnostic and therapeutic FOB for pulmonary hydatid cysts is still controversial. This study examines the findings of endobronchial hydatid cyst disease in five pediatric patients from Turkey, and clinical experience about this subject is reviewed. All our patients presented with unusual symptoms of the disease, and for all of them, diagnosis had been delayed using current diagnostic methods. As a result of our experience, it can be reported that the endobronchial appearance of the hydatid cyst membrane is whitish-yellow, and it is difficult to differentiate it radiologically from some other common causes of endobronchial lesions in childhood, such as endobronchial tuberculosis, foreign body aspirations, mucous plaques, and granulation scars. The findings of these cases show that, hydatid cyst should also be kept in mind in differential diagnosis of endobronchial lesions. In the diagnosis of pulmonary hydatid cyst in children without typical clinical and radiological findings of the disease, FOB examination is a valuable diagnostic procedure.     

经皮肾镜联合输尿管软镜碎石取石术的手术配合

目的总结经皮肾镜联合输尿管软镜碎石取石术治疗肾鹿角状结石患者的手术配合经验。方法分析30例肾鹿角状结石患者实施经皮肾镜联合输尿管软镜碎石取石的术中配合要点。结果患者均手术顺利,一期清石率平均86.0%,二期总清石率平均为95.0%。术中发生大出血1例,未发生肾穿孔、腹膜穿孔、液气胸及周围脏器损伤。结论充分做好术前准备,熟悉手术步骤,与手术医生默契的配合,可提高手术效率,缩短手术时间,增加手术安全性。     

Unusual cause of chronic cough in a four-year-old cured by uvulectomy

A 4-year-old boy had a history of persistent barking cough unresponsive to medical treatment since infancy. He described a feeling of something in his throat. When investigated by flexible fiberoptic bronchoscopy, the only abnormality was the uvula resting in contact with the epiglottis. The cough was no longer present after uvulectomy.     

Clinical utility of cricopharyngeal distensibility measurements during endoscopic myotomy for Zenker’s diverticulum

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