A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect.

Non-adherence to immunosuppressant medications is an important risk factor for graft dysfunction. To evaluate the effectiveness of adherence-enhancing interventions, we reviewed adherence intervention studies in solid organ transplant recipients (all ages). Using the following databases: PsycINFO, PubMed, Scopus, and ScienceDirect, we identified 41 eligible studies. Only three non-randomized trials showed a possible positive effect on objective indicators of transplant outcomes (such as rejection, liver enzyme levels, kidney function). None of the 21 RCTs showed an improvement in transplant outcomes. Three studies showed a higher rate of adverse events in the intervention group as compared with controls, although this may be related to ascertainment bias. Improvement in adherence as measured indirectly (eg, with electronic monitoring devices) was not aligned with effects on transplant outcomes. We conclude that adherence interventions, to date, have largely been ineffective in improving transplant outcomes. To improve this track record, intervention efforts may wish to concentrate on non-adherent patients (rather than use convenience sampling, which excludes many of the patients who need the intervention), use direct measures of adherence to guide the interventions, and employ strategies that are intensive and yet engaging enough to ensure that non-adherent patients are able to participate.

The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study.

Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1-17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.

PTSD in solid organ transplant recipients: Current understanding and future implications.

PTSS are quite prevalent in transplant recipients, although full-scale PTSD may not be that common. Those symptoms have been linked to poor transplant outcomes, perhaps owing to non-adherence to medications and other recommendations, brought about by the avoidance dimension of the PTSD/PTSS construct (patients may avoid taking their medications because they serve as reminder of the emotionally traumatic event--the transplant). It is possible to treat PTSD via specific psychotherapeutic techniques, and the treatment has been shown to be safe and likely effective in other populations. Therefore, practitioners who treat transplant recipients should be familiar with the presentation and treatment of those symptoms. This manuscript provides a systematic literature review of the PTSD/PTSS presentation in the pediatric transplant setting, a synthesis of available research findings, and suggestions for current care and future research.

Improving adherence to medications in pediatric liver transplant recipients.

We describe results from a clinical program, which aimed at improving adherence to medications in children who had a liver transplant. We followed the medical outcomes of 23 children and adolescents who participated in a clinical adherence-improvement protocol during the years 2001-2002. The protocol included identification of non-adherent patients by examining tacrolimus blood levels and intervention by increasing the frequency of clinic visits for non-adherent patients. In the two-yr preintervention (1999-2000), there was no improvement in any of the outcomes. After the intervention, the number of patients with high alanine aminotransferase levels (100 and above) decreased significantly, from eight before the intervention to four afterwards. Other outcomes, including the number of rejection episodes (three before, none after) and the degree of adherence to tacrolimus, also improved, but the improvement did not reach statistical significance. Although non-adherent patients were called to clinic more often under the protocol, the intervention did not lead to increased outpatient costs. This adherence--improvement intervention appears to be promising in improving outcomes in pediatric liver transplant recipients. Larger, controlled studies are needed to establish the efficacy of this or other approaches.

The feasibility of in vivo resection of the left lobe of the liver and its use for transplantation.

The anatomical possibility of resecting the left lobe of the liver (segments II and III) in living subjects and using it for transplantation was evaluated. A group of 60 cadaveric livers were dissected at autopsy. The vascular and biliary elements of the left lobe were isolated and the lobe was resected and evaluated for possible grafting. The left lobe was 12-28% (mean 19.4%) of the liver mass. An extrahepatic segment of the left hepatic vein was isolated in 95% of specimens. Arterial blood supply to the left lobe consisted of a single artery (92%) or two arteries (8%). A single portal vein segment to the left lobe (type I) was found in 35% livers. Portal vein branches originated from a common orifice (type II, 35%) or separately (type III, 30%) from the left portal vein, and in these instances, preparation of a portal segment necessitated partial section of the left portal vein wall. Biliary drainage was extrahepatic in 56 livers and consisted of a single duct (type I, 78%), or two ducts (type II, 15%). The resected left lobe was evaluated as satisfactory (single hepatic vein and artery, types I or II portal vein, type I bile duct) in 48% of cases, while a less-satisfactory lobe (type III portal vein or type II bile duct) was obtained in 33%. It was found anatomically difficult or impossible to resect the left lobe for possible transplantation in 11 (19%) liver specimens.

Pulmonary functional abnormalities after upper dorsal sympathectomy. A comparison between the supraclavicular and transaxillary approaches.

Results of pulmonary function studies were compared in two groups of 12 patients each, in whom upper dorsal sympethectomy was performed by the supraclavicular or by the transaxillary approach. Patients were evaluated clinically, radiologically and functionally before operation and again three weeks, three months and six months after denervation. Findings suggest that an increase in small airway resistance concomitant with some degree of pneumoconstriction occurred after upper dorsal sympathectomy by both routes. Musclar transection and possible phrenic nerve retraction damage due to the operative procedure could not be the cause of the above abnormalities because the inspiratory and expiratory forces, inspiratory peak flow and diaphragmatic movement were not significantly reduced after operation by both approaches. However, in a few cases, extrapleural hematomas, segmental atelectasis and relaxation of the daiphrgm could have contributed to the loss of the lung volume. This was evident only in the early period and was obvious in the transaxillary approach group.

Early endoscopic sphincterotomy in the management of acute gallstone pancreatitis in elderly patients.

Eighteen elderly patients with acute attacks of gallstone pancreatitis underwent early endoscopic sphincterotomy of the papilla of Vater. Eleven patients were considered to be at high risk for surgery due to chronic cardiorespiratory or renal problems. The outcome of these patients was compared with that of 20 consecutive elderly patients with gallstone pancreatitis treated at the same time by means other than endoscopic sphincterotomy. Endoscopic sphincterotomy resulted in an immediate clinical improvement in all patients, except in one patient who developed transient cholangitis; there was no mortality. In contrast, there was one death (5%) and 20% morbidity in the controls. Mean hospitalization period was shorter in patients undergoing sphincterotomy (6 compared with 9.5 days), although the patients managed by sphincterotomy were initially more seriously ill than controls. Only two of the 11 high-risk patients underwent elective cholecystectomy; all others were well during a mean follow-up of 22 months. It is concluded that early endoscopic sphincterotomy is highly effective and safe in acute attacks of gallstone pancreatitis in elderly high-risk patients.

Endoscopic sphincterotomy in patients with gallbladder in situ: the influence of periampullary duodenal diverticula.

Forty-four elderly patients (mean age, 77.2 years; range, 65 to 95) with acute bile duct obstruction, with gallbladder in situ, underwent endoscopic sphincterotomy without subsequent cholecystectomy during the same hospitalization. Thirty patients had periampullary duodenal diverticula, and 14 had no diverticula. Because periampullary diverticula were associated with biliary and pancreatic complications, possibly as a result of stasis in the diverticula, the clinical course in patients with and without diverticula was compared. Endoscopic sphincterotomy was well tolerated and resulted in a rapid clinical improvement in all patients. There were four complications related to the procedure (pancreatitis, two, and cholangitis, two), all were treated conservatively, and there were no deaths. The clinical outcome was similar in both groups of patients. During a mean follow-up of 25 months (range, 6 to 58), only two patients (one of each group) underwent elective cholecystectomy 2 and 3 months after initial presentation. It is concluded that endoscopic sphincterotomy is a safe and effective alternative to surgery as an initial treatment in elderly patients with choledocholithiasis and gallbladder in situ. Periampullary duodenal diverticulum does not interfere with the favorable results of endoscopic sphincterotomy in patients with gallbladder in situ.

Endorectal advancement flap repair of rectovaginal and other complicated anorectal fistulas.

BACKGROUND: Surgical correction of rectovaginal and complicated anal-perineal fistulas has been associated with high rates of complications and failure of repair. METHODS: This paper reports on 107 patients treated during the past 10 years by endorectal advancement flap repair. Ninety-two percent of the patients were women with mean age of 38 years (range, 20 to 71 years). Seventy-one had low rectovaginal, 28 had anterior anal-perineal, and 8 had posterior anal-perineal fistulas. The causes were obstetric injury, 48; cryptoglandular abscess-fistula, 31; Crohn's disease, 24; and trauma or after operation, 4. The technique completely preserves the sphincter muscle, covers the internal opening of the fistula tract with healthy rectal wall, and provides counter drainage to aid healing. RESULTS: No deaths occurred in the series. Persistent or recurrent fistula occurred in 17 patients (16%). Nine patients whose initial operation failed underwent a secondary successful operation. Continence status was unchanged in 80%, improved in 18%, and was unknown in two patients who still had intestinal flow diversion. Recurrence of the fistula did not result in destruction of the sphincter mechanism in those patients who underwent simultaneous reconstructive operation. CONCLUSIONS: The endorectal advancement flap repair successfully treated 93% of the complicated anorectal fistulas, avoiding fecal diversion and improving, not injuring, sphincter function.

Radiation therapy as definitive treatment for selected invasive rectal cancer.

BACKGROUND: Eighty-four patients with invasive rectal adenocarcinoma were definitively treated with radiation during a period of 9 years in an attempt to achieve "local control" (eradication of rectal cancer and its associated morbidity) without radical resective surgery. METHODS: Initially, endocavitary radiation alone was used in 13 patients with "ideal" carcinomas and in six patients with aggressive cancers. To improve local control, 4500 cGy external radiation before the 6000 cGy endocavitary radiation was used to treat 28 ideal lesions, 15 "nonideal" but potentially curable cancers, 14 aggressive cancers, and 8 patients with incurable metastatic disease. RESULTS: Endocavitary radiation alone resulted in local control for 8 of 13 patients with ideal carcinomas (62%); eventually 11 of 13 (85%) had control after three successful salvage abdominoperineal resections. Local control was accomplished in none of six patients with aggressive cancers. Use of external radiation before endocavitary radiation achieved local control in 93% of patients with ideal lesions, eventually 100% after two salvage abdominoperineal resections. Of the 15 nonideal but potentially curable lesions, 100% had eradication of local disease with the combined modalities. Of the 14 with aggressive cancers and 8 with metastatic disease, 19 suffered failure of local control (86%). Eight of these had local salvage by surgical resection; the others died with local failure within 6 months. CONCLUSIONS: External radiation, combined with endocavitary radiation, is excellent, definitive treatment for selected, favorable, invasive rectal cancers; however, there is little place for nonresective management of aggressive rectal cancer, even for palliation, unless life expectancy is less than 6 months.

Esophageal perforation after fiberoptic endoscopic injection sclerotherapy for esophageal varices.

Esophageal perforation is a rare major complication of fiberoptic endoscopic injection sclerotherapy for bleeding esophageal varices. This complication occurred in 1% (two) of our patients. Both patients recovered with conservative treatment. Although mild symptoms continued for a long period after the procedure, esophageal stenosis did not occur.

The association of biliary and pancreatic anomalies with periampullary duodenal diverticula. Correlation with clinical presentations.

Fifty-eight symptomatic patients with periampullary duodenal diverticula (PDD) were examined for pancreatic and biliary anomalies using endoscopic retrograde cholangiopancreatography (ERCP), ultrasonography, and other imaging modalities. The pathologic findings in these patients were compared with those in a matched group of 58 patients without PDD, who were simultaneously undergoing a similar investigation for the same clinical presentations. Pathologic findings in the pancreas and/or biliary tree were detected in 70.7% of all patients with PDD, compared with 39.7% in the control group. In patients with PDD, pancreatobiliary anomalies were detected in all patients who presented with jaundice, 85% of patients with pancreatitis, and 27.8% of patients with abdominal pain, as compared with 60%, 40%, and 17%, respectively, in the control group. In 23 patients, ERCP findings demonstrated pancreatobiliary abnormalities that were not detected by other imaging modalities. Fifteen of the patients with PDD and pancreatobiliary anomalies had undergone cholecystectomy between six months and five years previously. We conclude that ERCP is essential in the investigation of all patients with PDD, especially those presenting with jaundice or pancreatitis. Biliary surgery in patients with PDD and a dilated bile duct should include a biliary drainage procedure to prevent recurrence of pancreatobiliary disease.

Jejunogastric intussusception. A new diagnostic test.

Jejunogastric intussusception is a rare complication of gastrojejunal reconstruction of unknown cause. There are two types of jejunogastric intussusception: the acute type, presenting as a surgical emergency, and the chronic intermittent type, which is difficult to diagnose and is usually of mild symptomatology but which may progress to the acute type with the incarceration of the intussusceptum. With two case reports and a literature review, an endoscopic diagnostic maneuver is proposed, hinting at disordered motility with reversed peristalsis as a possible causative factor. Corrective surgical treatment to prevent recurrence and incarceration in chronic cases is advocated. Treatment should include dismantling of the efferent loop, which is the most frequent intussusceptum.

A prospective study of posttraumatic stress symptoms and nonadherence in survivors of a myocardial infarction (MI).

We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.

[Treatment of recurrent ulcer with cimetidine].

The most effective treatment of recurrent ulcer is re-operation, which is associated with high rates of mortality or complications, and of recurrences. Antacid treatment is disappointing. There are conflicting reports of the effect of cimetidine. We present a prospective study of 10 patients with recurrent ulcer treated with cimetidine, 1.0 g/day for six weeks, with endoscopic follow up. The ulcer healed in five after six weeks of treatment and in seven after 12 weeks, but recurred 2-8 months later. We conclude that cimetidine has a shortterm effect in recurrent ulcer and is indicated only in high risk patients.

Mental health and quality-of-life concerns related to the burden of food allergy.

As food allergy increases, more research is devoted to its influence on patient and family mental health and quality of life (QoL). This article discusses the effects on parent and child QoL, as well as distress, while appraising the limitations of knowledge given the methods used. Topics include whether QoL and distress are affected compared with other illnesses, assessment of distress and QoL in parents compared with children, concerns about food allergy-related bullying, and the necessity for evidence-based interventions. Suggestions are offered for how to improve QoL and reduce distress on the way to better coping with food allergy.