Peritonsillar abscess drainage: using oropharyngeal endoscopy as a therapeutic adjunct and training tool.

BACKGROUND: Peritonsillar abscess, or quinsy, is one of the most common emergency presentations to ENT departments, and is the most common deep tissue infection of the head and neck. In the UK, junior members of the ENT team are regularly required to independently assess, diagnose and treat patients with peritonsillar aspiration or incision and drainage. ISSUE: Inexperienced practitioners can stumble at several obstacles: poor access due to trismus; poor lighting; difficulty in learning the therapeutic procedure; and difficulty in accurately documenting findings and treatment. SOLUTION: To counter these and other difficulties, the authors describe the routine use of video endoscopy as a training tool and therapeutic adjunct in the management of quinsy.

Cost-effectiveness of combining systematic identification and treatment of co-morbid major depression for people with chronic diseases: the example of cancer.

BACKGROUND: Co-morbid major depression occurs in approximately 10% of people suffering from a chronic medical condition such as cancer. Systematic integrated management that includes both identification and treatment has been advocated. However, we lack information on the cost-effectiveness of this combined approach, as published evaluations have focused solely on the systematic (collaborative care) treatment stage. We therefore aimed to use the best available evidence to estimate the cost-effectiveness of systematic integrated management (both identification and treatment) compared with usual practice, for patients attending specialist cancer clinics. METHOD: We conducted a cost-effectiveness analysis using a decision analytic model structured to reflect both the identification and treatment processes. Evidence was taken from reviews of relevant clinical trials and from observational studies, together with data from a large depression screening service. Sensitivity and scenario analyses were undertaken to determine the effects of variations in depression incidence rates, time horizons and patient characteristics. RESULTS: Systematic integrated depression management generated more costs than usual practice, but also more quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) was £11,765 per QALY. This finding was robust to tests of uncertainty and variation in key model parameters. CONCLUSIONS: Systematic integrated management of co-morbid major depression in cancer patients is likely to be cost-effective at widely accepted threshold values and may be a better way of generating QALYs for cancer patients than some existing medical and surgical treatments. It could usefully be applied to other chronic medical conditions.

Treatment of depression in adults with cancer: a systematic review of randomized controlled trials.

BACKGROUND: Depression is a leading cause of disease burden worldwide and is especially problematic in people with chronic diseases, including cancer. Although depression can be effectively treated in the general population using antidepressant medication and psychological treatments, these treatments may have different benefits and harms in cancer patients. Previous reviews have not adequately addressed this topic. We therefore aimed to determine which, if any, treatments are effective for patients with diagnoses of both cancer and depression. METHOD: We conducted a systematic review of relevant randomized controlled trials identified through searches of Medline, EMBASE, PsycINFO and The Cochrane Central Register of Controlled Trials (CENTRAL). RESULTS: Seven relatively small trials met the selection criteria. These provided some evidence that antidepressant medication, given alone or in combination with a psychological treatment, may be effective. We found no good evidence for psychological treatments given alone or for any other forms of treatment. CONCLUSIONS: There is very limited evidence from clinical trials to guide the treatment of cancer patients with a diagnosis of depression, especially for psychological treatments. High quality trials of treatments for depression in patients with cancer are urgently needed.

Screening medical patients for distress and depression: does measurement in the clinic prior to the consultation overestimate distress measured at home?

BACKGROUND: Medical patients are often screened for distress in the clinic using a questionnaire such as the Hospital Anxiety and Depression Scale (HADS) while awaiting their consultation. However, might the context of the clinic artificially inflate the distress score ? To address this question we aimed to determine whether those who scored high on the HADS in the clinic remained high scorers when reassessed later at home. METHOD: We analysed data collected by a distress and depression screening service for cancer out-patients. All patients had completed the HADS in the clinic (on computer or on paper) prior to their consultation. For a period, patients with a high score (total of > or = 15) also completed the HADS again at home (over the telephone) 1 week later. We used these data to determine what proportion remained high scorers and the mean change in their scores. We estimated the effect of ' regression to the mean' on the observed change. RESULTS: Of the 218 high scorers in the clinic, most [158 (72.5 %), 95% confidence interval (CI) 66.6­78.4] scored high at reassessment. The mean fall in the HADS total score was 1.74 (95% CI 1.09­2.39), much of which could be attributed to the estimated change over time (regression to the mean) rather than the context. CONCLUSIONS: Pre-consultation distress screening in clinic is widely used. Reassuringly, it only modestly overestimates distress measured later at home and consequently would result in a small proportion of unnecessary further assessments. We conclude it is a reasonable and convenient strategy.

Prevalence of depression in adults with cancer: a systematic review.

BACKGROUND: Depression has substantial effects on cancer patients' quality of life. Estimates of its prevalence vary widely. We aimed to systematically review published studies to obtain the best estimate of the prevalence of depression in clinically meaningful subgroups of cancer patients. DESIGN: Systematic review that addressed the limitations of previous reviews by (i) including only studies that used diagnostic interviews; (ii) including only studies that met basic quality criteria (random or consecutive sampling, ≥70% response rate, clear definition of depression caseness, sample size ≥100); (iii) grouping studies into clinically meaningful subgroups; (iv) describing the effect on prevalence estimates of different methods of diagnosing depression. RESULTS: Of 66 relevant studies, only 15 (23%) met quality criteria. The estimated prevalence of depression in the defined subgroups was as follows: 5% to 16% in outpatients, 4% to 14% in inpatients, 4% to 11% in mixed outpatient and inpatient samples and 7% to 49% in palliative care. Studies which used expert interviewers (psychiatrists or clinical psychologists) reported lower prevalence estimates. CONCLUSIONS: Of the large number of relevant studies, few met our inclusion criteria, and prevalence estimates are consequently imprecise. We propose that future studies should be designed to meet basic quality criteria and employ expert interviewers.

In situ photopolymerized hydrogels for vascular and peritoneal wound healing.

The process of wound healing in internal organs lined with mesothelial cells is different in some respects from healing in cutaneous injuries. Hertzler (1) noted that cutaneous wound re-epithelialization takes place from the wound borders, but peritoneal defects become re-mesothelialized simultaneously. Most organs in the pelvic cavity possess a mesothelial lining that can be injured as a result of trauma from surgical intervention or handling. It is generally agreed that the remesothelialization of the peritoneum can take place over 5-8 d (2). During this period, events of inflammation and mesothelial repair occur that can set the course for postsurgical adhesion formation. Postsurgical adhesion formation, or the formation of scar tissue bridges between organs in the pelvic cavity, is an undesirable result of a natural healing process. Ryan et al. (3) showed experimentally that the surface of bowel is subject to demesothelialization and loss of native fibrinolytic activity by surgical manipulation, whether it is allowed to dry or is kept moist with saline. This denuded surface could allow blood clots to form and act as precursors to adhesion formation before remesothelialization can occur. The formation of adhesions can distort the normal anatomy and natural positioning of organs, and has often been implicated in postoperative pelvic pain and bowel obstructions, in addition to other complications. Ryan recommended that to minimize adhesion formation, tissue exposure and manipulation should be minimized (3).

Efficacy and biocompatibility of a photopolymerized, synthetic, absorbable hydrogel as a dural sealant in a canine craniotomy model.

OBJECT: A canine craniotomy model was used to evaluate the dural sealing efficacy and biocompatibility of a novel, synthetic, bioresorbable hydrogel. METHODS: Bilateral craniotomies were performed in 24 dogs assigned to six survival periods. In each animal a parasagittal durotomy was created and then repaired. At the treatment sites the hydrogel sealant was applied over the dural repair and photopolymerized. The repair was tested for leaks to 20 cm H2O by using a Valsalva maneuver. At the control sites the incisions were sutured and tested for leaks only. After uneventful survival periods, the leak test was repeated in three of the four animals in each group. Bone-dura adhesion was evaluated, after which the dura and underlying brain were removed, fixed, and examined histologically. En bloc histological investigation was performed on a specimen obtained from the fourth animal in each group. Over a 56-day period, 18 treated sites were tested for leaks. A leak was detected at a site remote from that of the repair in one animal; this was excluded from analysis. Thus 17 of 17 treated sites remained free of leaks. On the control side of one animal, there was a leak from a new dural tear at the cranial end of the durotomy, which occurred when the bone flap was removed. This site was also excluded from analysis. Eleven of 17 leak-tested control sites remained free of leaks over the study period. Bone-dura adhesions occurred in 15 of 19 control sites and had a mean adhesion score of 1.37 (range 0-4), whereas adhesions occurred in 10 of 19 treated sites with a mean adhesion score of 0.84 (range 0-3). No cortical reaction was noted. CONCLUSIONS: This novel hydrogel sealant is efficacious in sealing dural repair sites measuring up to 2 mm. Healing of the underlying dura is not compromised and exposed cortical tissue is not altered histologically.

Pneumostasis of experimental air leaks with a new photopolymerized synthetic tissue sealant.

Air leak is a major contributor to increased length of stay and postoperative morbidity following pulmonary surgery. The effectiveness of a new photopolymerized synthetic hydrogel (FocalSeal, Focal, Inc., Lexington, MA) as a sealant for pulmonary air leaks was determined in 10 mongrel dogs (20-35 kg). The animals were anesthetized and underwent left-sided anterolateral thoracotomy with amputation of a 2 x 3-cm segment of the lung apex. Hemostasis was achieved and terminal bronchial openings of 1.5 to 3 mm with vigorous air leaks were identified. After successful injury, the dogs were randomly assigned to sealant (n = 5) or control (n = 5) groups. In treated animals, the sealant was applied by brushing the solution to the cut parenchymal surface and solidified while briefly interrupting ventilation (40-60 seconds) using visible illumination (450-550 nm) from a xenon light source. Controls received no sealant. A single chest tube was maintained at the injury site with a continuous negative pressure of 20 cm of water. All dogs were extubated and allowed to breathe spontaneously under sedation for 24 hours. Chest radiographs were taken postsurgery and presacrifice. All control animals (n = 5) showed persistent vigorous air leak for the duration of the 24-hour observation period. All treated air leaks resolved immediately, and four of five remained sealed throughout the observation period. One leak reappeared after 17 hours due to inadequate sealant thickness over a 3-mm terminal bronchus. Gross evaluation of the treatment group at the end of 24 hours demonstrated intact sealant well adherent to the parenchyma. No evidence of atelectasis or excessive edema was seen, and no sealant-related complications or toxic effects were noted. Radiologically, lungs were fully inflated. Histologic evaluation at 24 hours revealed no evidence of a strong cellular response to the synthetic sealant, and no fibrosis or adhesions were seen, the onset of the healing process was favorable, indicating good biocompatability. In conclusion, this material was found to be an effective means for sealing bronchial and parenchymal air leaks in this model and warrants clinical evaluation.

Efficacy of adhesion barriers. Resorbable hydrogel, oxidized regenerated cellulose and hyaluronic acid.

OBJECTIVE: To compare a novel resorbable hydrogel barrier with two previously studied barriers, oxidized regenerated cellulose and hyaluronic acid, for the prevention of postoperative adhesions. STUDY DESIGN: Two models were employed in the rat uterine horn, one of adhesion formation after devascularization and serosal injury and one of adhesion reformation after adhesiolysis RESULTS: In the devascularization model, hydrogel treatment reduced the mean extent of adhesion formation from 73% in the control group to 13% (P < .005). Hyaluronic acid pretreatment reduced the extent of adhesion formation to 44% (P < .05), while oxidized regenerated cellulose failed to reduce formation (P > .25). In the adhesiolysis model, treatment with the hydrogel reduced the mean extent of adhesion formation from 87% in the control group to 20% (P < .005). Neither the oxidized regenerated cellulose nor the hyaluronic acid treatments lowered the extent of adhesion formation from the control group (P > .25). The hydrogel barrier was observed to be resorbed over a five-day period and remained adherent to the tissue during resorption. CONCLUSION: Resorbable hydrogel barriers are highly effective in the reduction of adhesion formation and reformation in the rat. This probably due to the good biocompatibility and retention of these materials upon the site of application.

Characterization of the formation of interfacially photopolymerized thin hydrogels in contact with arterial tissue.

The aim of this study was to examine the conditions under which an interfacial photopolymerization process results in hydrogel barriers. Visible light initiated interfacial photopolymerization of a polyoxyethylene glycol (PEG)-co-poly(alpha-hydroxy acid) copolymer based on PEG 8000 macromonomer was performed on porcine aortic tissue, resulting in conformal hydrogel barriers. The process conditions were optimized in vitro for the formation of a 5-100 microns thick barrier.

Cytokine therapy for arterial restenosis: inhibition of neointimal hyperplasia by gamma-interferon.

Inhibition of neointimal hyperplasia by gamma-interferon (gIFN) treatment was evaluated. Four groups of Sprague-Dawley rats (n = 72) weighing 500 g underwent endothelial injury of the carotid artery using the previously described Fogarty catheter technique. Group I (controls, n = 8) received one phosphate-buffered saline (PBS) injection 24h before injury and every 24h thereafter for a total of eight injections. Groups II (n = 8) and III (n = 8) received daily injections of 200,000 units of gIFN according to the same schedule except that group III did not receive the preoperative dose. Animals were killed on postoperative day 14. Histologic sections were analyzed morphometrically and immunohistochemically. Both gIFN groups had a statistically significant 50% reduction of the cross-sectional area of the neointimal hyperplasia compared with that of the controls (P < 0.01). Cell replication analysis of smooth muscle cells in the media and neointima revealed no statistically significant difference between controls and gIFN-treated groups. Group IV consisted of 48 rats that were treated with either PBS or gIFN on a schedule similar to that of groups I and II. Animals were killed at frequent time intervals during the first 7 days after injury. Their arteries were analyzed histologically and immunohistochemically. The results confirm previous findings that gIFN reduces the development of neointimal hyperplasia following arterial injury. The results also indicate that smooth muscle cells restore their proliferative activity by 7 days after discontinuation of gIFN treatment. It is proposed that efficacy of gIFN can be enhanced by lengthening the period of treatment.

A new photopolymerizable blood vessel glue that seals human vessel anastomoses without augmenting thrombogenicity.

A new nonbiologic photopolymerizable glue, polyethyleneglycol 400 diacrylate, was studied with respect to its mechanical and biochemical interaction with human blood vessels. Using the human placental artery model, we tested the ability of polyethyleneglycol 400 diacrylate to prevent leakage of blood at the site of vascular anastomoses, which are made porous by the presence of tissue gaps and suture puncture sites. Fibrin glue is known to augment local vessel thrombogenicity through the presence of the coagulation enzyme thrombin. We tested the effect of externally applied polyethyleneglycol 400 diacrylate (which does not contain thrombin) on luminal thrombin activity and platelet deposition from flowing human blood. At a shear rate of 312 per second and a transmural pressure of 80 cm H2O, the leakage rate of saline from human placental artery anastomoses was 1.0 +/- 1.2 ml/min (n = 8). When the same anastomoses were then glued, 7 of 8 of the anastomoses leaked less than 0.05 ml/min (p < 0.05). Platelet deposition to human vessels was not influenced by the external application of polyethyleneglycol 400 diacrylate either on intact vessels (no polyethyleneglycol 400 diacrylate, 0.51 +/- 0.28 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.47 +/- 0.26 x 10(6) platelets/cm2; n = 7) or at anastomoses (no polyethyleneglycol 400 diacrylate, 0.69 +/- 0.36 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.53 +/- 0.33 x 10(6) platelets/cm2; n = 8), p > 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention.

The aim of this study was to optimize the properties of a lubricious bioerodible hydrogel barrier for the prevention of postoperative adhesions. Water-soluble macromers based on block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) or poly(glycolic acid) with terminal acrylate groups were used, and these macromers were gelled in vivo by exposure to long wavelength ultraviolet light. The precursor was photopolymerized from buffered saline solution while in contact with the tissues. This resulted in the conformal coating of the tissue with an adherent hydrogel film, while forming a nonadhesive barrier at the free surface, on the treated wound site. The hydrogels were evaluated in two animal models of postsurgical adhesions, first in a rat cecum abrasion model and then in a rabbit uterine horn ischemia model. In the rat cecum model, six of seven animals treated with a hydrogel, with glycolide in the precursor as the comonomer, showed no adhesions; untreated animals and animals treated with precursor, but not gelled with light, showed consistent dense adhesions. In the rabbit uterine horn ischemia model, using hydrogels with lactide in the precursor as the comonomer, and PEG of molecular weight from 6,000 to 18,500 Da, adhesions were dramatically reduced, with occurrence in none of seven animals treated with a gel containing PEG 10,000. By contrast, the seven animals in the control group demonstrated a mean of 35% involvement of the horn length in dense, fibrous adhesions. These materials, photopolymerized in vivo in direct contact with the tissues, appear to form an adherent hydrogel barrier that is highly effective in reducing postoperative adhesions in the models used.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of islet of langerhans surfaces with immunoprotective poly(ethylene glycol) coatings via interfacial photopolymerization.

Poly(ethylene glycol) (PEG) has been used previously to alter immune interactions and systemic clearance of therapeutic proteins. We present herein chemical approaches for the conceptually similar treatment of therapeutic cells and tissues whereby immune and cell adhesive interactions may be reduced or interrupted, in the context of the transplantation of xenogeneic islets of Langerhans for the treatment of insulin-dependent diabetes mellitus. Visible-light-initiated interfacial photopolymerization of multifunctional PEG-based macromers was performed directly upon the surface of rat islets of Langerhans to produce conformal barrier hydrogel coatings with thickness of order 10 microm. The islets continued to be normal in ultrastructure and function as reflected by response to a glucose challenge in vitro.

Polyimide-polyethylene glycol block copolymers: synthesis, characterization, and initial evaluation as a biomaterial.

Block copolyimides with varying amounts of polyethylene glycol (PEG) were synthesized and characterized by copolymerization of diaminodiphenyl ether (DDE), amino terminated PEG, and benzophenone tetracarboxylic acid dianhydride (BTDA). Strong materials were obtained, with enhanced flexibility as compared to the parent DDE-BTDA polyimide homopolymer. Incorporation of PEG led to an increase in water absorption by these copolymers, and hydrophilicity was increased as reflected by a decrease in air-water-polymer contact angle. These materials supported less cell adhesion in vitro than the parent polyimide homopolymer. Short term in vivo evaluation of these copolymers showed reduced fibrous encapsulation than was observed in the absence of PEG.

Prevention of postoperative adhesions in the rat by in situ photopolymerization of bioresorbable hydrogel barriers.

OBJECTIVE: To assess the efficacy of a novel resorbable hydrogel barrier for preventing postoperative adhesions in animals. METHODS: A hydrogel barrier was formed in situ by photopolymerizing a solution of a macromolecular prepolymer in buffered saline using long-wavelength ultraviolet light. Two models in the rat were evaluated. In a primary adhesion model, devascularization and serosal injury were performed on the uterine horns using bipolar electrocautery. The prepolymer solution was applied to the horns and illuminated to form the barrier. On the seventh postoperative day, the fraction of the length of the horns involved in adhesions was scored, as was the quality of the adhesions. In a readhesion model, adhesions were formed as described and were surgically lysed on the seventh day, then were treated subsequently with the barrier and scored after 7 additional days. Each group in both models consisted of seven animals per treatment condition. Four prepolymer concentrations were examined in the primary adhesion model, and the optimal one was examined in the readhesion model. RESULTS: A conformal hydrogel barrier coating was formed upon in situ photopolymerization and adhered to the treated tissues. No residual hydrogel barrier was observed 7 days after application of the optimal gel concentrations. In the primary adhesion model, the mean fraction of the horns involved in adhesions was reduced significantly, from 76% in controls to 10% (P < .0001), and treatment with a 10% solution of prepolymer was determined to be optimal (P = .025). In the readhesion model, surgical lysis of adhesions alone did not reduce adhesions significantly (from 86% to 79%; P = .3), whereas lysis with barrier treatment did (79% to 28%; P = .002). CONCLUSIONS: In situ photopolymerization allowed the formation of adherent, conformal barriers, which demonstrated high efficacy in the prevention of adhesion formation and reformation in animals. This efficacy and ease of use warrant clinical evaluation.

Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon alginate-poly(l-lysine) microcapsules for enhanced biocompatibility.

The biocompatibility of microcapsules made by the co-acervation of alginate and poly(l-lysine) (PLL) was enhanced by coating the surface of these microcapsules with a poly(ethylene glycol) (PEG)-based hydrogel. The hydrogel was formed by an interfacial photopolymerization technique using visible light from an argon ion laser. The light absorbing chromophore, eosin Y, was immobilized on the microcapsule surface. This restricted the formation of the PEG hydrogel to the surface of the microcapsule. The presence of the PEG gel on the surface was confirmed by fluorescent dextran entrapment, by direct visualization after dissolution of the underlying membrane and by electron spectroscopy for chemical analysis. The biological response of such microcapsules was evaluated by intraperitoneal implantation in mice. The PEG-coated microcapsules were found to be less inflammatory and were seen not to elicit a fibrotic response, as was the case with alginate-PLL microcapsules.