Reduction of postsurgical adhesions with Intergel adhesion prevention solution: a multicenter study of safety and efficacy after conservative gynecologic surgery.

OBJECTIVE: To assess the safety and efficacy of the Intergel adhesion prevention solution, a 0.5% ferric hyaluronate gel, in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy with a planned second-look laparoscopy. DESIGN: Randomized, third-party blinded, placebo-controlled, parallel group. SETTING: Eleven centers in the United States, and five centers in Europe. PATIENT(S): Women aged 18-46 years who wanted to retain their fertility. INTERVENTION(S): Patients received 300 mL of Intergel solution (n = 143) or lactated Ringer's solution (n = 138) as an intraperitoneal instillate at the completion of surgery. MAIN OUTCOME MEASURE(S): At second-look laparoscopy 6-12 weeks later, the presence of adhesions was evaluated at 24 abdominal sites. RESULT(S): Patients treated with Intergel solution (n = 131) had significantly less adhesions compared to controls (n = 134). Adhesion extent and severity were also significantly reduced. The American Fertility Society score for adnexal adhesions was reduced 59% in the patients in whom the Intergel solution was used. The safety profile of the patients treated with the Intergel solution was comparable to those treated with lactated Ringer's solution. CONCLUSION(S): The Intergel solution was safe and highly efficacious in reducing the number, severity, and extent of adhesions throughout the abdomen after peritoneal cavity surgery.

Bias and prevalence effects on kappa viewed in terms of sensitivity and specificity.

Paradoxical effects of bias and prevalence on the kappa coefficient are examined using the concepts of sensitivity and specificity. Results that appear paradoxical when viewed as a 2 x 2 table of frequencies do not appear paradoxical when viewed as a pair of sensitivity and specificity measures where each observer is treated as a predictor of the other observer. An adjusted kappa value can be obtained from these sensitivity/specificity measures but simulation studies indicate that it would result in substantial overestimation of reliability when bias or prevalence effects are observed. It is suggested that investigators concentrate on obtaining populations with trait prevalence near 50% rather than searching for statistical indices to rescue or excuse inefficient experiments.

Interexaminer reliability of the palpation of trigger points in the trunk and lower limb muscles.

OBJECTIVES: To determine the interexaminer reliability of palpation of three characteristics of trigger points (taut band, local twitch response, and referred pain) in patients with subacute low back pain, to determine whether training in palpation would improve reliability, and whether there was a difference between the physiatric and chiropractic physicians. DESIGN: Reliability study. SETTING: Whittier Health Campus, Los Angeles College of Chiropractic. PARTICIPANTS: Twenty-six nonsymptomatic individuals and 26 individuals with subacute low back pain. INTERVENTION: Twenty muscles per individual were first palpated by an expert and then randomly by four physician examiners. MAIN OUTCOME MEASURES: Palpation findings. RESULTS: Kappa scores for palpation of taut bands, local twitch responses, and referred pain were .215, .123, and .342, respectively, between the expert and the trained examiners, and .050, .118, and .326, respectively, between the expert and the untrained examiners. Kappa scores for agreement for palpation of taut bands, twitch responses, and referred pain were .108, -.001, and .435, respectively, among the nonexpert, trained examiners, and -.019, .022, and .320, respectively, among the nonexpert, untrained examiners. CONCLUSIONS: Among nonexpert physicians, physiatric or chiropractic, trigger point palpation is not reliable for detecting taut band and local twitch response, and only marginally reliable for referred pain after training.

Sample size calculations when outcomes will be compared with an historical control.

The usual formulae for calculating sample size are not valid when a treated cohort will be compared with an historical control population. Methods appropriate for a single group study may greatly underestimate the required sample size because they, in effect, assume a control population of infinite size. Methods appropriate for a two-group study require specification of the proportions of patients in the two groups--a requirement that can not be met when the size of the historical control group is fixed. An easily programmed iterative solution is presented and simulations indicating the validity of the method are performed.

Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study.

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo-controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.

Comparative study of the clinical effectiveness of a pyrethrin-based pediculicide with combing versus a permethrin-based pediculicide with combing.

In a randomized, evaluator-blinded clinical trial, 190 patients were treated for Pediculus humanus capitis infestations with a pyrethrin-piperonyl-butoxide pediculicide (RID; Py-PB) and a permethrin pediculicide (NIX; PM). A total of 160 patients were evaluable for nit-combing speed, 156 patients were evaluable for efficacy at day 7, and 150 patients were evaluable for efficacy at day 14. Both Py-PB and PM showed 100% efficacy at day 7. At day 14, one patient in the PM group had an apparent reinfestation. The Py-PB group had significantly lower mean combing times (P=0.04), but because the PM group had more nits, the two groups were not significantly different in combing speed expressed as seconds per nit. Multiple regression and covariance analyses suggested that the greater speed of the Py-PB comb might have been masked by this baseline difference. Three patients had mild adverse experiences (Py-PB: erythema, PM: erythema and tingling sensation). No patients were removed from the study because of adverse events. In conclusion, this controlled clinical study demonstrated that both Py-PB and PM provided 100% efficacy following a single application. Differences attributable to comb design favored the Py-PB "rake" comb, but this requires additional evaluation and confirmation.

Reduction of serum lactate by sodium dichloroacetate, and human pharmacokinetic-pharmacodynamic relationships.

Sodium dichloroacetate (DCA) or placebo, two infusions 30 min in duration and 8 h apart, was administered to healthy subjects under double-blind conditions. The objectives were to characterize accurately the tolerability of DCA, its pharmacokinetics, and the reduction of resting serum lactate concentration by DCA. A hybrid, one-compartment pharmacokinetic model fitted best, with zero-order elimination mean of 27.9 micrograms/ml/h at concentrations above about 80 to 120 micrograms/ml, and with first-order elimination (mean kelim = 0.54) at lower serum concentrations of DCA. Resting serum lactate was dose-independently, maximally reduced within 15 min of the end of all active infusions. The duration of suppression of resting serum lactate was dose-dependent, from 4.5 h (30 mg/kg) to > 8 h (100 mg/kg). Second infusions (15-50 mg/kg) again promptly and maximally reduced resting serum lactate. Hysteresis loops were asymmetrical for all doses but exhibited change in shape that was dose-dependent; no good pharmacokinetic-pharmacodynamic model could be fitted that was consistent between doses. Infusions were well tolerated, 100 mg/kg + 50 mg/kg being the highest doses. Somnolence, the only dose-related adverse event, was reported by 3 of 37 subjects at times corresponding to the highest serum DCA concentrations. This study demonstrates the tolerability of i.v. DCA, proposes a simple pharmacokinetic model for its elimination, characterizes the dose-response relationship in terms of time course of effect, shows the dissociation between elimination of DCA and offset of response and will guide further studies of DCA in patients with head injury or stroke.

Exact power calculations when the dependent variable is a single proportion and the number of events is small.

This paper presents methods for calculating the exact power to reject the null hypothesis that an observed event rate is significantly lower than a clinically relevant alternative event rate or that the confidence interval is less than a specified range when the hypothesis will be tested using exact binomial confidence intervals. SAS programs that perform the calculations are presented and the results are compared with power calculations using the normal approximation. The method can be extended to studies involving paired comparisons but, in that case, it does not appear to provide a significant advantage over normal approximation methods.

Logistic equations in the analysis of S-shaped curves.

A version of the logistic equation that provides useful descriptive parameters for the asymptote, slope and inflection point of the curve is presented and is suggested for use in empirically fitting S-shaped curves to data. A short SAS program that easily calculates the parameter values is shown.

Management of hymenoptera sting anaphylaxis: a preventive medicine survey.

The evaluation of aftercare instructions given to patients suffering from hymenoptera sting anaphylaxis was the objective of the study. Part of this evaluation included asking the physicians questions to examine the knowledge on which they based their aftercare instructions. Survey questionnaires were completed by 124 of 174 (71%) physicians who worked in an emergency department or urgent care center. Fifty-eight percent of the physicians never provided written avoidance instructions, 24% provided or prescribed anaphylaxis ID bracelets, 44% referred all of their patients to an allergist for further evaluation, and 73% reported prescribing an Epi-pen or Ana-kit to all hymenoptera sting anaphylaxis victims. Twenty-four percent of physicians did not know where to obtain anaphylaxis identification bracelets. This survey demonstrates that a substantial number of physicians practicing emergency medicine are not providing appropriate aftercare instructions to patients, and substantiates the need for educational efforts to increase the awareness of physicians concerning the implications of hymenoptera allergy and the value of proper preventive measures.

Balancing allocation of subjects in biomedical research: a minimization strategy based on ranks.

A new method for ensuring the comparability of groups of experimental subjects is proposed. All subjects are ranked on each measured pretreatment variable and differences between groups in the means and the standard deviations of these ranks are minimized by systematically exchanging subjects when those exchanges yield less imbalance between groups. This method was designed for small studies in which pretreatment data from all subjects are known before the start of the experiment. A series of computer simulations suggests that this procedure is effective in balancing groups on several variables although the amount of computer time required becomes excessive as the number of subjects is increased.

A randomized double-blind study of inosiplex (isoprinosine) therapy in patients with alopecia totalis.

Twenty-five of 34 patients with alopecia totalis of at least 1 year's duration and associated defects in cell-mediated immunity completed a randomized, double-blind, placebo-controlled crossover trial of the therapeutic effect of inosiplex, a synthetic immunomodulator. Each patient received 20 weeks of treatment with inosiplex and 20 weeks with placebo in randomized order. Eleven patients were identified clinically as responders to inosiplex in terms of hair regrowth. Scalp biopsy results correlated well with drug therapy. Enhanced immune function was found in the majority of responding patients; however, statistical analysis of the results of the entire patient population revealed limited significant differences. No patient experienced adverse side effects attributable to therapy. These results show that inosiplex is a safe and effective therapy for certain patients with alopecia totalis.

The effect of stress on colon motor and electrical activity in irritable bowel syndrome.

The present investigation was designed to study the role of stress on the physiologic mechanisms of the colon in irritable bowel syndrome (IBS). Patients with IBS were compared with normal controls during resting and stress (mental arithmetic, cold pressor, and fear stressor). The results indicated that IBS patients had significantly higher motor activity than normals in the resting state but did not differ from them in the mean dominant frequency of the basal electrical rhythm (BER) or the proportion of the time they had 2-4 cycles per minute (cpm) slow-wave activity. Stress significantly increased motor activity in both groups although they did not differ significantly from each other during stress. Stress increased the proportion of 2-4 cpm slow-wave activity in IBS patients, but decreased in the controls. The type of stressor, however, did not influence either motor or electrical activity. Although IBS patients were significantly older than the controls and scored higher on the MMPI scales of Hypochondriasis, Hysteria, and Depression, these factors did not significantly influence differences in motor or electrical activity between the groups. The results are discussed in terms of the role of learning in the colon.

Medical registers as historical controls: analysis of an open clinical trial of inosiplex in subacute sclerosing panencephalitis.

Clinical trials of treatments for rare or fatal diseases must often use historical rather than randomized concurrent controls. Randomized trials may not be possible if (1) the number of patients available is quite small, (2) ethical considerations discourage the assignment of patients to control treatments known to be ineffective or (3) some evidence suggests that the proposed new treatment is substantially more effective than the control. We suggest that, when randomization is not feasible, adequately maintained medical registers can serve as a source of control patients. Investigators must pay careful attention to prognostic factors that might bias the results. However, statistical techniques for controlling such bias exist and, if these are properly employed, registry-derived historical controls can be used to evaluate the effectiveness of treatment.

Colonic dysfunction in patients with thoracic spinal cord injury.

Severe constipation is a debilitating concomitant of complete traumatic thoracic spinal cord injury. In order to investigate the pathophysiology of this symptom, we studied colonic compliance, as well as motor and myoelectrical activity, in the fasting and postprandial states and after neostigmine stimulation in 9 patients with clinically and electrophysiologically documented complete thoracic spinal cord injury. Electrophysiologic studies, including nerve conduction velocities, cortical and spinal somatosensory-evoked responses, and bulbocavernosus reflex responses, as well as urinary bladder cystometry, documented normal peripheral somatosensory function, integrity of the distal spinal cord, conus medullaris and cauda equina, and interruption of the somatosensory and descending spinal pathways proximal to the cauda equina. These 9 patients with spinal cord injury demonstrated a decrease in colonic compliance compared with a control group (p less than 0.01). They failed to demonstrate the postprandial increase in colonic motor and myoelectrical activity observed in a control group (p less than 0.01), but did respond to neostigmine with an increase in both motor and myoelectrical activity (p less than 0.02), suggesting an intact myogenic component. In these patients, decreased colonic compliance and absent postprandial colonic motor and myoelectrical activity may be mediated by ablation of outflow from higher centers to the lower spinal cord and may be correlates of visceral neuropathy and severe constipation.

Psychological factors in the treatment of back pain by spinal manipulation.

Ninety patients with low back pain completed a short form of the Minnesota Multiphasic Personality Inventory (MMPI) and, subsequently, received spinal manipulative therapy. Most (84%) of the patients reported immediate relief following manipulation but the extent of that relief was not correlated with any psychological measure. However, several days after treatment, the percentage of patients reporting improvement was much lower (55%) and lack of improvement was associated with elevated scores on hypochondriasis (Hs), and functional low back pain (Lb). Unimproved patients also tended to report longer durations of back pain prior to treatment. Multiple regression analyses indicated that pain duration and the psychological factors were independent predictors of the response to treatment. It is suggested that, although a single manipulative treatment will often relieve the immediate cause of back pain, underlying psychosomatic factors may predispose the condition to recur.

Observations on the immunomodulator NPT 15392 in New Zealand Black mice.

NPT 15392, an experimental drug with immunomodulatory activities, was administered to New Zealand Black (NZB) mice over an extended period of time. Anti-erythrocyte antibody levels and spleen weights increased with age in NZB mice, while hematocrits (Hct) declined slightly. In addition, both antierythrocyte antibody and spleen weights were negatively correlated with Hct (-0.545 and -0.848, respectively). NPT 15392 therapy retarded the development of anti-erythrocyte antibody in young mice (11 weeks old), and reduced the levels of this autoantibody in 38 week old animals. The slight improvement in the index of anemia in the older treated mice was also accompanied by a substantially lower spleen weight. No significant effect of NPT 15392 therapy was observed on Hct levels. These results indicate that NPT 15392 has a modifying effect on the evolution of the autoimmune process in this strain of mouse.