Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

Gaussian Thermal Operations and The Limits of Algorithmic Cooling.

The study of thermal operations allows one to investigate the ultimate possibilities of quantum states and of nanoscale thermal machines. Whilst fairly general, these results typically do not apply to continuous variable systems and do not take into account that, in many practically relevant settings, system-environment interactions are effectively bilinear. Here we tackle these issues by focusing on Gaussian quantum states and channels. We provide a complete characterization of the most general Gaussian thermal operation acting on an arbitrary number of bosonic modes, which turn out to be all embeddable in a Markovian dynamics, and derive necessary and sufficient conditions for state transformations under such operations in the single-mode case, encompassing states with nonzero coherence in the energy eigenbasis (i.e., squeezed states). Our analysis leads to a no-go result for the technologically relevant task of algorithmic cooling: We show that it is impossible to reduce the entropy of a system coupled to a Gaussian environment below its own or the environmental temperature, by means of a sequence of Gaussian thermal operations interspersed by arbitrary (even non-Gaussian) unitaries. These findings establish fundamental constraints on the usefulness of Gaussian resources for quantum thermodynamic processes.

Rapid detection of Legionella spp in water samples by ScanVIT method: comparison of acid vs heat treatment.

BACKGROUND: A rapid detection of Legionella bacteria in water samples is crucial to minimize the risk of acquiring infections, especially in health care facilities. Different detection methods and different decontamination procedures have been reported to affect the recovery of Legionella spp. Our goal was to test the recovery of Legionella pneumophila and Legionella non-pneumophila species using a kit based on non-specific and species-specific probes to treat water samples after two different decontamination procedures. METHODS: The study was conducted with samples collected in the teaching hospital "Le Scotte" of Siena (Italy). Waters samples were analyzed by: i) ScanVIT method after treatment with acids; ii) ScanVIT method after heating; and iii) cultural standard method after heating. The results of the decontamination procedures and the detection methods were evaluated by comparing the number of Legionella-positive and -negative samples, and the recovery rates (CFU l-1) obtained by ScanVIT and the standard method. RESULTS: We find that ScanVIT method is highly sensitive with both decontamination treatments, yielding a higher recovery of L. pneumophila compared to the standard method. Conversely, ScanVIT associated with the acid-treatment yielded the highest recovery of L. non-pneumophila. CONCLUSIONS: The acid-treatment combined to the ScanVIT method increases the recovery of L. non-pneumophila in water samples compared to both ScanVIT associated with heat-treatment and standard culture method. Thus, this method may represent the best choice to detect L. non-pneumophila in water samples and reduce the risk of infection due to underestimation of Legionella loads.

Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies: a cohort study.

OBJECTIVE: To assess the postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies (ART) in children at 3 years of age. DESIGN: A cohort study of children conceived by ART. SETTING: Maternal-Fetal Medicine Unit, Hospital Clinic Barcelona, Spain. POPULATION SAMPLE: Eighty singleton pregnancies conceived by ART and 80 spontaneously conceived (controls) followed from fetal life up to childhood. METHODS: Cardiovascular evaluation was performed at 3 years of corrected age, including echocardiography, carotid intima-media (cIMT) by ultrasound, and blood pressure. MAIN OUTCOME MEASURES: Postnatal persistence of cardiovascular changes in children conceived by ART. RESULTS: Compared with controls, children conceived by ART showed larger atria (right atrial area: control 4.9 cm2 (0.9) versus ART 5.5 cm2 (0.9), P < 0.001), more globular ventricles (right ventricular sphericity index: control mean 1.8 (SD 0.5) versus ART 1.6 (0.2), P < 0.001), and signs of systolic (tricuspid annular plane systolic excursion: control 18 mm (2) versus ART 16 mm (3), P < 0.001) and diastolic dysfunction (isovolumic relaxation time: control 68 ms (12) versus ART 79 ms (12), P < 0.001). ART children also presented increased systolic blood pressure (control 90 mmHg (6) versus ART 94 mmHg (5), P < 0.003) and cIMT (control 0.52 µm (0.14) versus ART 0.60 µm (0.16), P < 0.001) as compared with those spontaneously conceived. CONCLUSIONS: Cardiovascular changes previously reported in ART fetuses persist postnatally at 3 years of age. These results underscore the importance of future studies for assessing the long-term cardiovascular health associated with ART. TWEETABLE ABSTRACT: Cardiovascular changes described in fetuses conceived by ART, persist in children at 3 years of age.

Use of a systematic risk analysis method (FMECA) to improve quality in a clinical laboratory procedure.

BACKGROUND: Risk management is a set of actions to recognize or identify risks, errors and their consequences and to take the steps to counter it. The aim of our study was to apply FMECA (Failure Mode, Effects and Criticality Analysis) to the Activated Protein C resistance (APCR) test in order to detect and avoid mistakes in this process. METHODS: We created a team and the process was divided in phases and sub phases. For each phase we calculated the probability of occurrence (O) of an error, the detectability score (D) and the severity (S). The product of these three indexes yields the RPN (Risk Priority Number). Phases with a higher RPN need corrective actions with a higher priority. RESULTS: The calculation of RPN showed that more than 20 activities have a score higher than 150 and need important preventive actions; 8 have a score between 100 and 150. Only 23 actions obtained an acceptable score lower than 100. CONCLUSIONS: This was one of the first experience of application of FMECA analysis to a laboratory process, and the first one which applies this technique to the identification of the factor V Leiden, and our results confirm that FMECA could be a simple, powerful and useful tool in risk management and helps to identify quickly the criticality in a laboratory process.

Mobility trends of Patients across Italian Regions: implications for planning and evaluation of hospital services.

BACKGROUND: The study of patients' mobility is useful for health planning and identifying deficiencies in care supply. The Italian Health Service, with 21 different regional realities, can be considered as a macrocosmic test bench. Our study aims: (1) to describe the trend of patients' hospital mobility across the Italian Regions; (2) to offer an immediate visual approach for decision making; (3) to identify some factors involved in patient's mobility. STUDY DESIGN: Observational cross sectional study. METHODS: We used ordinary and day hospital discharge data from 1998 to 2014. The study was carried out using: (1) the Gandy's Nomogram (GN), a graphical tool that assesses the power of attraction and the escape's containment of hospital regional networks; (2) the vector analysis; (3) the trend analysis with Cuzik's test; (4) the panel data analysis, with multiple logistic regression model. RESULTS: The mean number of annual admissions, in Italian hospitals, was 10,976,290, progressively decreasing from 2001 to 2014, and 7% of it occurred "in mobility". We have drawn the different paths of patients' mobility by Regions and observed critical situations almost in Regions of Southern Italy, compared with Regions of the Centre-North. Moreover we analyzed the factors implied in such mobility, highlighting that attraction is influenced by the hospitalization rate in private structures, by the percentage of graduates in the Regions, and by the number of hospital beds/10,000 inhabitants; while escapes are influenced by GDP per capita, by the number of hospital beds/10,000 inhabitants and by the sanitary expenses per capita of the Region. CONCLUSIONS: We have shown the potentialities of the GN, applicable at micro level but also on a large scale in the analysis of patients' hospital mobility; and this, together with panel data analysis, can lead to a more conscious and effective health planning.

History and Medicine: ex voto as a tool for health and epidemiological surveillance.

BACKGROUND: Ex voto is a donation for a divinity, a Saint or to Virgin Mary for a received mercy. From the analysis of an ex voto it's possible to obtain lots of information and therefore it can be used as a tool for health and epidemiological surveillance, to study morbidity in the past. The aim of this study was the creation of a database to rebuild epidemiological events and diseases, using ex voto as a source of health surveillance. METHODS: We chose to study votive pictures using three types of sources: photographed alive, on-line archives, books and photographic collections. Ex voto have been saved in an Hard Disk, numbered and inserted in a database, then analyzed using Stata®. RESULTS: total of 6231 ex voto were collected and catalogued in our database. Ex voto referring to diseases are the most represented (41%), but they have decreased with the time. Road accidents (21.4%) have a constant increase, especially with the appearance of cars and motorcycles. Aggressions (5.45%) decrease constantly; warlike accidents (4.44%) had a peak in the period including both world wars; non professional accidents (10.60%) and accidents at work (3.79%) increase without peaks; maritime accidents (8.88%) have not uniform ups and downs during the time. CONCLUSIONS: The database let us rebuild epidemiological events of the past, which are not deductible from other sources. Our purpose is to expand in the space-time our source data in order to perform an interesting comparison between past and present.

Functional taping applied to upper limb of children with hemiplegic cerebral palsy: a pilot study.

Functional taping with elastic bandages and adhesive tapes could limit the action of upper limb spastic muscles and sustain that of weaker muscles in children with hemiplegic cerebral palsy (CP). 16 young children with CP (3±2 years old) were enrolled in this pilot study including 5 months of taping in conjunction with conventional physical therapy, followed by 7 months of physical therapy alone (taping wash-out), and other 5 months of taping plus therapy. Large improvements in the Melbourne assessment score were found in the first period in which taping was used (+15.4%, p<0.001) and also in the second one despite 8 drop-outs (+8.4%, p=0.012), but not during the taping wash-out (- 4.6%; p=0.093). These results suggest that children with CP could benefit from the continuous correction provided by taping in order to limit the development of improper upper limb motor schemas and to favour that of proper ones.

High incidence of false-positive PET scans in patients with aggressive non-Hodgkin's lymphoma treated with rituximab-containing regimens.

BACKGROUND: Positron emission tomography (PET) is a powerful predictor of relapse and survival in non-Hodgkin's lymphomas (NHLs) based on studies carried out in the prerituximab era. Little is known about the predictive power of PET in rituximab-treated patients. PATIENTS AND METHODS: Patients with aggressive B-cell NHL with baseline and follow-up PET studies were included. Clinical characteristics, PET and computed tomography scans, biopsy results, and outcomes were reviewed. PET was defined as positive if higher than mediastinal or background activity was observed. RESULTS: In all, 51 patients (diffuse large B cell-38; mantle cell lymphoma-13) treated with rituximab-containing regimens were included. For 13 of 40 patients (32.5%), mid-therapy PET studies were positive and 9 of 48 patients (18.7%) had positive posttherapy PET. The positive predictive value (PPV), negative predictive value (NPV), sensitivity (Se), and specificity (Sp) of the mid-therapy PET for predicting relapse were 33% [95% confidence interval (CI) 19% to 49%], 68% (95% CI 51% to 81%), 33% (95% CI 6% to 76%), and 68% (95% CI 49% to 82%), respectively. For posttherapy PET, the relapse PPV, NPV, Se and Sp were 19% (95% CI 9% to 33%), 81% (95% CI 67% to 91%), 13% (95% CI 0.6% to 53%), and 80%(95% CI 64% to 90%), respectively. CONCLUSIONS: Compared with previous reports in prerituximab era, addition of rituximab resulted in reduced PPV and sensitivity of mid- and posttherapy PET in patients with aggressive B-cell NHL.

Prevalence of 'poor sleep' among patients with multiple sclerosis: an independent predictor of mental and physical status.

BACKGROUND: Patients with multiple sclerosis (MS) report sleep disturbances more frequently than the general population. Besides specific sleep disturbances, many other conditions could impair nocturnal rest in this population. In addition, information regarding the role of disrupted sleep on quality of life (QoL) in MS patients is lacking. This study was performed to bridge this gap. METHODS: A total of 120 patients with MS were enrolled into the study. Demographic, socioeconomic and clinical characteristics (clinical course and duration of MS, EDSS score, therapeutic information, presence of pain, presence of sexual and/or bladder dysfunction, localization of demyelinating plaques, and presence of anxiety and depression) were collected. The Pittsburgh Sleep Quality Index (PSQI), the Charlson Comorbidity Index (CCI) and the Italian version of the 36-item Short Form (SF-36) were used to assess quality of sleep, comorbidity and QoL, respectively. RESULTS: Nearly half (47.5%) of MS patients were classified as "poor sleepers," having significantly higher EDSS (3.1+/-1.4 vs. 2.3+/-1.4, p=0.009) and CCI scores (0.19+/-0.4 vs. 0.03+/-0.2, p=0.009) than "good sleepers." In addition, pain due to MS was more common among "poor sleepers" (33.3% vs. 17.7%, p=0.05). Scores for each domain of the SF-36, and the mental component summary (MCS) and physical component summary (PCS) scores were significantly lower in poor sleepers than in good sleepers (p<0.001 for each score). Of the different variables associated with MCS, the only independent predictors of mental status were: presence of sexual and/or bladder dysfunction and global PSQI score. The independent predictors for physical status (PCS) were age, EDSS score and global PSQI score. CONCLUSIONS: Poor sleep is common in patients with MS, representing an independent predictor of QoL. Patients with MS who are poor sleepers should receive immediate assessment and treatment, bearing in mind that, in addition to specific sleep disturbances, other clinical conditions (both related and unrelated to MS) can disrupt nocturnal sleep.

Actual controversies in twin delivery: from the analysis of the case histories to a reasoned protocol.

AIM: Twin pregnancy has to be considered a risk pregnancy. One of its most controversial aspects is delivery. There is no agreement on the following topics: gestational age at term (GA), mode of delivery, use of epidural analgesia or oxytocic acceleration, impact of chorionicity and amnionicity. The aim of this study was to develop a twin delivery management protocol. METHODS: A retrospective study over a cohort population of 481 twin deliveries that occurred in the Department of Obstetrics of the San Raffaele Hospital of Milan (Italy) from 1996 to 2007 was conducted, and the results were compared with those present in literature. RESULTS: Management of twin pregnancies that exceed the 37 week is controversial. There is an inclination towards fixing bichorionic and monochorionic pregnancy terms at 38 and 35 weeks respectively. In our case history, 73.8% of monochorionic and 15% of bichorionic pregnant women delivered after the 35 and 38 week respectively, without repercussions on the neonatal outcome. A longer gestational age appears to decrease the occurrence of lower Apgar scores and neonatal morbidity. This study, which exclusively considered twin pregnant women with both fetuses in cephalic presentation eligible for a vaginal delivery, did not find any significant differences in neonatal outcome among the types of deliveries. Moreover, the authors observed that the average maternal blood loss in cesarean section (CS) is significantly greater than that of vaginal deliveries. CONCLUSIONS: In consideration of its safety for mother and fetuses, vaginal delivery of two cephalic fetuses at 38 and 35 weeks for bichorionic and monochorionic pregnancies respectively may be considered as a valid alternative to elective cesarean section.

[Treatment of hyperandrogenism and hyperinsulinemia in PCOS patients with essential amino acids. A pilot clinical study]. / Trattamento dell'perandrogenismo e dell'perinsulinemia con aminoacidi essenziali in pazienti affette da sindrome dell'ovaio policistico. Uno studio pilota.

AIM: Women with polycystic ovary syndrome (PCOS) report frequently hyperinsulinemia. The aim of this study was to evaluate the effects of 16-weeks therapy with essential amino acids supplements on metabolic and clinical indices in PCOS. METHODS: For this study ten women with PCOS and fasting hyperinsulinemia were enrolled. The study comprised 16 weeks of therapy with oral essential amino acids (Aminopril, NAMED, Milan, Italy) administered 4 g twice per day. Body mass index, hirsutism score, serum levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, lipoprotein(a), serum adrenal and ovarian androgens, fasting glucose and insulin concentrations, T, DHEAS, gonadotropins, and sex hormone-binding globulin (SHBG), were assessed before and after treatment with essential amino acids. RESULTS: A significant decrease in fasting insulin, total T, luteneizing hormone and follicle-stimulating hormone was reported after amino acids therapy and increase in SHBG, leading to a decrease in the free T index. In addition, a significant reduction in hirsutism score was reported. No significant decrease in mean body mass index and in lipid pattern was reported. CONCLUSION: A decline of insulin after treatment with essential amino acids was observed in women with PCOS as well as total and bioavailable T, leading to significant improvement of clinical symptoms of hyperandrogenism.

Restless legs syndrome: diagnosis, epidemiology, classification and consequences.

Restless legs syndrome (RLS) is a sensorimotor disorder characterised by a complaint of an almost irresistible urge to move the legs. RLS is diagnosed clinically by means of the four essential criteria of the International Restless Legs Syndrome Study Group. In doubtful cases, neurophysiological examinations, such as polysomnography and/or a suggested immobilisation test, can be performed to confirm a clinical suspicion of RLS. Several other conditions may present sensorimotor complaints with features similar to RLS; a careful sleep history is required to avoid a misdiagnosis. Three different scales have been validated to assess the severity of RLS. In the general population, RLS prevalence ranges from 0.1% to 11.5%, with a high number of patients affected by a primary form of the sleep disturbance (70%-80%). However, several clinical conditions have been associated with RLS, such as iron deficiency, uraemia, pregnancy and polyneuropathy. Furthermore, recent studies show that RLS may be associated also to type 2 diabetes mellitus and to multiple sclerosis. RLS has a negative impact on sleep, cognitive functions, quality of life and mental status. Higher awareness of RLS among physicians is required; it remains an underdiagnosed clinical condition.

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Diagnostic studies in patients with sickle cell anemia and acute abdominal pain.

Twenty-eight patients with sickle cell disease who presented with acute abdominal pain were evaluated with clinical laboratory, ultrasound, and biliary scintigraphic studies to determine their predictive capabilities for differentiating veno-occlusive disease (sickle cell crisis) from acute biliary disease. Eleven patients were treated surgically and 17 medically. Gallstones were demonstrated in 25 (90%) of the patients studied by ultrasound, and biliary scans were abnormal in nine patients (32%). Abnormal laboratory and radiological studies (ultrasound, biliary scintigraphy) were not significantly different in the two groups and had a low positive predictive value for detection of acute biliary disease. Nevertheless, normal biliary scintigraphy had high negative predictive value in that, if normal, it gave assurance that the cystic duct was patent and unnecessary surgery could be obviated in this high-risk category of patients.

Current status of systemic intravenous radiopharmaceuticals for the treatment of painful metastatic bone disease.

PURPOSE: Intractable bone pain secondary to bone metastasis from prostate, lung, breast, and other malignancies is a major problem in the management of the oncological patient. Because a number of factors are implicated in the pathophysiology of bone pain, a multidisciplinary approach in its assessment and treatment is often required. Treatment often includes the use of analgesic drug therapy; however, radiation therapy, hormonal therapy, chemotherapy, and surgery may also be needed. METHODS AND MATERIALS: The use of systemic radionuclide therapy may often be helpful to relieve bone pain and improve the quality of life. In the setting of diffuse bone metastasis, intractable to conventional therapy, various radioisotopes have been advocated. These include phosphorous-32, iodine-131, strontium-89, yttrium-90, samarium-153, and rhenium-186, often as either the anionic phosphate or as a ligand (HEDP, EDTMP). RESULTS: When these agents are used, pain relief often occurs in approximately 2-4 weeks and lasts several weeks to months with responses seen in 60-80% of patients, depending on the extent of disease and stage the patient is treated. Retreatment has been possible in certain cases with further palliation being offered and improvement in the various quality of life parameters being noted. CONCLUSION: Myelotoxicity has been a limiting factor with certain isotopes and has led to the development of less toxic bone seeking agents. Although these each have unique physical and biokinetic properties requiring different doses and protocols for administration, they all appear to localize in osteoblastic metastatic sites in sufficient amounts to provide bone pain palliation.

From monoclonal antibodies to peptides and molecular recognition units: an overview.

Various antigen-specific monoclonal antibodies (Mabs) are now being used clinically. Applications include in vitro testing (radioimmunoassay) and in vivo imaging (radioimmunoscintigraphy) for the early detection and staging of disease. Mabs can also be used as vehicles for delivering therapy (radioimmunotherapy) or to assess effects of therapeutic interventions. This review delineates those components making up antibody structure and discusses their functional significance. The method for radiolabeling immunoconjugates without altering their immunoreactivity or biological properties is dependent on an understanding of the structural units of the antibody and the labeling technique used. With the advent of genetic engineering, it has become feasible to design antibodies to circumvent certain adverse features or enhance a certain property. A review of the various "designer" antibodies and their relative advantages in the clinical setting is presented.

Therapy of metastatic bone pain.

Bone metastasis is a common sequella of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Currently, the treatment of bone pain remains palliative at best with systemic therapy (analgesics, hormones, chemotherapy, steroids, and bisphosphonates) as well as local treatments (such as surgery, nerve blocks, and external beam radiation). However, many of these treatments are limited in their efficacy or duration and have significant side effects that seriously limit the cancer patient's quality of life. Various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studies, improved survival. Additional radiopharmaceuticals are under investigation and appear promising. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment.