结节性甲状腺肿并存甲状腺癌262例回顾性分析

【摘要】 目的 总结结节性甲状腺肿并存甲状腺癌的临床特点及其诊断和治疗要点。方法 回顾性分析中国医科大学附属第一医院1998年1月至2007年12月手术治疗并经病理证实的262例结节性甲状腺肿并存甲状腺癌病人的临床资料。结果 该组262例,占同期手术治疗甲状腺癌病人的33.9%。发病年龄以40～59岁多见,男:女为1∶5.2。临床表现以结节性甲状腺肿的临床表现为主。除近期行补充根治手术25例术前已明确诊断外,术前超声检查怀疑恶性病变者占70.0%,其中砂砾钙化39.2%。术中冰冻切片快速病理检查诊断准确率为93.2%,16例假阴性,无假阳性病例。肿块直径<2.0 cm 者占62.9%,其中微小癌40.1%,临床I期病例74%。病理类型以乳头状癌为主（93.1%）。手术方式包括患侧腺叶加峡部切除或加对侧腺叶次全切除术和全甲状腺切除术,对怀疑有颈部淋巴结转移者行颈淋巴结清扫术122例,46例有淋巴结转移。结论 结节性甲状腺肿并存甲状腺癌的癌灶较小且淋巴结转移发生率低,乳头状癌占绝对优势;术前超声和术中冰冻切片快速病理检查是提高并存甲状腺癌检出率的关键;对结节性甲状腺肿病人定期随访有利于提高并存甲状腺癌的早期诊断率。     

结节性甲状腺肿合并甲状腺癌38例诊治分析

目的 探讨结节性甲状腺肿合并甲状腺癌的诊治方法.方法 回顾性分析我院2000年1月至2006年12月手术治疗的635例结节性甲状腺肿病例中38例并存甲状腺癌患者的临床资料.结果 同期手术治疗结节性甲状腺肿患者635例,合并甲状腺癌38例(5.98%),病理检查结果:微小癌变17例,双叶癌7例,乳头状癌23例,滤泡状癌7例,髓样癌4例,未分化癌3例,甲状腺肉瘤样伴鳞癌分化1例,所有患者均行术中快速冷冻病理检查,并根据病理检查结果采取不同的手术方式.结论 结节性甲状腺肿术前检查怀疑甲状腺癌者应行细针穿刺及术中快速冰冻切片病理检查有利于确诊,可有效避免再次手术;甲状腺全切 131I放射治疗残余灶和/或转移灶 足量L-型甲状腺素钠抑制治疗有利于降低复发和死亡.     

结节性甲状腺肿合并分化型甲状腺癌诊断与治疗

目的：探讨结节性甲状腺肿合并分化型甲状腺癌的临床特点及诊治原则。 方法：回顾性分析2003年10月—2011年10月收治的47例结节性甲状腺肿合并分化型甲状腺癌的临床资料。 结果：患者均表现为颈部包块或颈部增粗,术前B超显示结节伴细沙粒样钙化者19例（40.43%）。47例患者均行手术治疗,术后经病理学检查确诊为分化型甲状腺癌（其中乳头状癌36例,占76.60%;滤泡样癌11例,占23.40%）,手术方式包括：患侧腺叶+峡部全切术+VI区淋巴结清扫;两侧腺叶+峡部全切术+VI区淋巴结清扫;颈部淋巴结肿大、转移者加行改良颈清扫术。术后均给予左旋甲状腺素片治疗。47例患者术后随访6~36个月,平均为（15.6±8.9）个月,3例分别于术后16~33个月复发,再次手术,效果良好。全组无死亡病例。 结论：结节性甲状腺肿合并甲状腺癌术前诊断困难,术前超声检查可提供可考依据,术中快速冷冻切片病理学检查是提高甲状腺癌检出率的关键;个体化、精细规范的手术治疗对结节性甲状腺肿合并分化型甲状腺癌有良好的治疗效果。     

结节性甲状腺肿并存甲状腺癌的治疗

目的:探讨结节性甲状腺肿并存甲状腺癌时的临床特征、治疗和预后。方法:回顾性分析1991年1月～2000年12月经手术治疗的结节性甲状腺肿合并有甲状腺癌的临床资料。结果:同期中,共手术治疗结节性甲状腺肿3955例中,内25例合并甲状腺癌(0.63%)。男6例,女19例,年龄12～65(36.8±13.1)岁。12例为微小的甲状腺乳头状癌,12例为乳头状甲状腺癌,1例为滤泡状甲状腺癌。有颈淋巴结转移者4例,3例位于颈侧,1例位于气管前。术前和术中诊断出甲状腺癌者占32%,术后病理检查时发现的为68%。术后随访10个月～10年,2例因颈淋巴结肿大而再次手术治疗,1例为甲状腺癌淋巴结转移,1例为淋巴结反应性增生。结论:结节性甲状腺肿合并甲状腺癌者预后较好。一方面,不应简单地认为结节性甲状腺肿是良性病变,而忽略同时存在恶性结节的可能性;另一方面,也不应过分强调甲状腺癌存在于结节性甲状腺肿中的可能性而随意放宽手术指征,或扩大手术范围。     

结节性甲状腺肿合并甲状腺癌25例

目的：探讨结节性甲状腺肿中甲状腺癌的临床特征和预后。方法：回顾性分析手术治疗结节性甲状腺肿合并甲状腺癌２５例临床资料。结果：２５例结节性甲状腺肿合并甲状腺癌,男６例,女１９例,年龄１２～６５（３６．８±１３．１）岁,占同期手术治疗３９５５例结节性甲状腺肿的０．６３％。术前、术中诊断甲状腺癌的占３２％,６８％为术后病理检查发现。甲状腺微小癌占４８％。结论：结节性甲状腺肿合并甲状腺癌预后较好。不能简单地认为结节性甲状腺肿是良性病变而忽略对其的处理,也不应过分强调甲状腺癌在治疗结节性甲状腺肿中的地位随意放宽手术指征,或扩大手术。     

结节性甲状腺肿并存甲状腺癌118例的诊断与治疗

目的探讨结节性甲状腺肿并存甲状腺癌的临床特点和诊治原则,旨在提高对该病诊断和治疗的认识。 方法回顾性分析118例结节性甲状腺肿与甲状腺癌并存的临床资料。 结果本组病史平均(12.6±3.5)年;年龄平均(34.4±5.8)岁;术前彩超诊断率为34.4%。伴发甲亢率为3.4%;乳头状癌为其主要病理类型。随访5年未发现明确复发病例。 结论病史长及年龄偏大的结节性甲状腺肿患者易合并甲状腺癌存在;结节性甲状腺肿的手术适应证应适当放宽;本病术前诊断率低,应重视术中对可疑结节的探查;应常规行术中冰冻病理检查。确诊后应行甲状腺全切除术及患侧颈淋巴结清扫。     

结节性甲状腺肿合并甲状腺癌176例

目的:分析结节性甲状腺肿合并甲状腺癌的发病率、发病原因及其诊断、治疗及预后。方法:回顾性分析176例结节性甲状腺肿合并甲状腺癌的临床资料,分析其临床特征,病理结果和随访等临床资料。结果:结节性甲状腺肿合并甲状腺癌术前诊断率为50.5%。病理示:乳头状癌136例,滤泡状癌8例,癌髓样4例,微小癌25例,肉瘤样变1例,病变诊断为恶性但分类困难2例。结论:结节性甲状腺肿合并甲状腺癌的发生率高,近一半能术前确诊,手术治疗效果好。     

结节性甲状腺肿合并甲状腺微小癌72例临床分析

目的总结结节性甲状腺肿合并甲状腺微小癌的临床特点及其诊断和治疗要点。方法回顾分析1993-01—2010-01手术治疗并病理证实的72例结节性申状腺肿合并甲状腺微小癌患者的临床资料。结果该组72例,占同期手术治疗结节性甲状腺肿患者的6.2%。术前彩超检查可疑恶性者占20.8%。术中快速冰冻检查诊断准确率为98.6%。病理类型以乳头状癌为主(93.1%)。手术方式主要是患侧腺叶+峡部切除+对侧腺叶次全/部分切除。结论结节性甲状腺肿合并甲状腺微小癌以乳头状癌为主,淋巴结转移发生率低。术中快速冰冻检查是诊断结节性甲状腺肿合并甲状腺微小癌的关键。对结节性甲状腺肿合并甲状腺微小癌不做预防性淋巴结清扫是安全的。     

桥本甲状腺炎183例外科治疗分析

目的 总结桥本甲状腺炎（HD）及其并存病的外科诊治经验。 方法 回顾分析1999年1月至2007年10月浙江大学医学院附属第二医院经手术后病理证实183例HD病人的临床资料。 结果 183例均经手术治疗。其中单纯HD 104例,HD合并甲状腺癌49例（26.7%,其中局部癌变5例,微小乳头状癌32例,直径>1.0cm的甲状腺乳头状癌12例）,HD合并结节性甲状腺肿15例（8.2%）,HD合并腺瘤样结节8例（4.4%）,HD合并Graves病7例（3.8%）。手术方式据病变部位及性质和术中冰冻切片而定。以术后病理诊断为标准,术前诊断HD的正确率为78.7%,诊断甲状腺癌为53.1%;术中FS诊断HD的正确率为95.6%,诊断甲状腺癌为95.9%。1例微小乳头状癌行双侧甲状腺次全切除术后2年局部复发,1例HD行双侧甲状腺次全切术后4年结节复发,余无复发和转移现象。 结论 综合应用临床查体,自身抗体检测及影像学检查等资料有助于提高HD的术前诊断正确率;HD合并其他甲状腺疾病的发生率高,应警惕并存甲状腺癌,特别是微小癌的可能性。     

结节性甲状腺肿合并甲状腺癌的诊断与治疗

目的探讨结节性甲状腺肿合并甲状腺癌的临床特点和诊治原则。方法回顾性分析2005年1月—2007年12月期间收治的40例结节性甲状腺肿合并甲状腺癌患者的临床病例资料。结果结节性甲状腺肿合并甲状腺癌中结节钙化的发生率(42.5%)明显高于单纯结节性甲状腺肿(16.7%)(P0.05);甲状腺单个结节癌变发生率(20.8%)显著高于一侧多个结节者(4.66%)(P0.01)。仅4例术前诊断为结节性甲状腺肿合并甲状腺癌。40例患者均行手术治疗,术中常规快速冷冻病理检查,并根据病理检查结果采取不同的手术方式,包括一侧全切4例,一侧全切一侧次全切除27例,双侧次全切1例,双侧全切8例。40例患者中行一侧颈部淋巴结清扫术11例。术后未发生明显声嘶,3例术后出现抽搐或手足麻木。孤立性结节的癌变率显著高于多发性结节(P0.05)。结论对单侧孤立结节或有钙化的甲状腺结节,应高度警惕结节恶变可能,需积极手术治疗;对结节性甲状腺肿术中必须行快速冷冻切片病理检查,以明确诊断。结节性甲状腺肿合并甲状腺癌需按甲状腺癌的处理原则进行。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.