Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

[A microcytic sideroblastic anemia successfully treated with B6 vitamin]. / Une anémie microcytaire sidéroblastique carentielle traitée efficacement par de la vitamine B6.

INTRODUCTION: Sideroblastic anemia is a rare cause of microcytic anemia, which is characterized by ring sideroblasts on bone marrow aspirate. This anemia can be congenital or acquired. CASE REPORT: We report the case of an alcoholic 49-year-old man who presented with a severe microcytic sideroblastic anemia related to pyridoxine (B6 vitamin) deficiency. Acid folic deficiency was associated. The blood count normalized within one month after vitamin supplementation. CONCLUSION: Pyridoxine deficiency must be sought in sideroblastic anemia in patients at risk.

Third trimester screening for alloimmunisation in Rhc-negative pregnant women: evaluation of the Dutch national screening programme.

OBJECTIVE: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester screening ('late' alloimmunisation), and subsequent haemolytic disease of the fetus and newborn (HDFN), to assess risk factors for late alloimmunisation. DESIGN: Prospective cohort and nested case-control study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort. METHODS: Prospective inclusion of Rhc-negative women with negative first trimester screening and of screen-negative controls. Assessment of incidence and numbers needed to screen (NNS) of late alloimmunisation and HDFN; logistic regression analysis to establish risk factors for late alloimmunisation. MAIN OUTCOME MEASURES: Late alloimmunisation, HDFN. RESULTS: Late alloimmunisation occurred in 99 of 62 096 (0.159%) Rhc-negative women; 90% had c/E antibodies and 10% non-Rhesus antibodies. Severe HDFN (fetal/neonatal transfusion) occurred in two of 62 096 (0.003%) of Rhc-negative women and 2% of late alloimmunisations; moderate HDFN (phototherapy) occurred in 20 children [22.5%; 95% confidence interval (CI), 13.8-31.1%]. Perinatal survival was 100%. The NNS to detect one HDFN case was 2823 (31 048 for severe, 3105 for moderate HDFN). Significant risk factors were former blood transfusion [odds ratio (OR), 10.4; 95% CI, 1.14-94.9], parity (P-1: OR, 11.8; 95% CI, 3.00-46.5; P > 1: OR, 7.77; 95% CI, 1.70-35.4) and amniocentesis/chorionic villus sampling during current pregnancy (OR, 9.20; 95% CI, 1.16-72.9). CONCLUSIONS: Additional screening of Rhc-negative women improved the detection of late alloimmunisation and HDFN, facilitating timely treatment, with a NNS of 2823. Independent risk factors for late alloimmunisation were blood transfusion, parity and chorionic villus sampling/amniocentesis in the current pregnancy. The occurrence of most factors before the current pregnancy suggests a secondary immune response explaining most late alloimmunisations. TWEETABLE ABSTRACT: Third trimester screening for alloimmunisation in Rhc-neg women improves detection and treatment of severe HDFN.

The safety of high-dose buprenorphine administered subcutaneously in cats.

The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats.

Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer.

Neoadjuvant therapy is increasingly becoming a valid treatment option for patients with locally advanced pancreatic cancer (LAPC). In borderline resectable disease, neoadjuvant therapy is employed to improve the probability of margin-clear resections. In non-metastatic, non-resectable pancreatic cancer, treatment primarily aims to induce disease control, but may achieve conversion to surgical resectability in some patients. Several treatment modalities including chemotherapy, chemoradiotherapy (CRT) or the sequential use of both have been investigated in numerous, mostly small and non-randomized studies. Nevertheless, there is a consistent finding that neoadjuvant therapy can induce resectability in up to 30%-40% of LAPC patients. Once resection has been achieved, overall survival appears to be comparable to that observed for primarily resectable patients. Thus, patient selection evolves as an important aspect of neoadjuvant therapy; retrospective analyses identified induction chemotherapy as an appropriate tool to define LAPC patients who may benefit most from subsequent treatment with CRT. The clinical importance of induction chemotherapy may further increase once highly active protocols such as the FOLFIRINOX or the gemcitabine plus nab-paclitaxel regimen are introduced into novel multimodality treatment concepts.

Short-term effects of high-dose zoledronic acid treatment on bone mineralization density distribution after orthotopic liver transplantation.

Patients with "hepatic" bone disease exhibit increased fracture incidence. The effects on bone material properties, their changes due to orthotopic liver transplantation (OLT), as well as zolendronate (ZOL) treatment have not yet been investigated. We studied bone mineralization density distribution (BMDD) in paired transiliacal biopsies (at and 6 months after OLT) from patients (control CON n = 18, treatment group ZOL n = 21, the latter treated with i.v. ZOL at doses of 4 mg/month) for how bone at the material level was affected by the "hepatic" disease in general, as well as by OLT and ZOL in particular. (1) BMDD parameters at baseline reflected disturbed bone matrix mineralization in "hepatic" bone disease combined with low turnover. Trabecular bone displayed a decrease in mean and most frequent calcium concentration (Ca(MEAN) -2.9% and Ca(PEAK) -2.8%, respectively; both P < 0.001), increased heterogeneity of mineralization (Ca(WIDTH) +12.2%, P = 0.01), and increased percentage of bone areas with low mineralization (Ca(LOW) +32.4%, P = 0.02) compared to normal; however, there were no differences compared to cortical bone. (2) Six months after OLT, ZOL-treated trabecular bone displayed reduced Ca(LOW) (-32.0%, P = 0.047), cortical bone increased Ca(MEAN) (+4.2%, P = 0.009), increased Ca(PEAK) (+3.3%, P = 0.040), and decreased Ca(LOW) (-55.7, P = 0.038) compared to CON and increased Ca(MEAN) compared to baseline (+1.9, P = 0.032) without any signs of hyper- or defective mineralization. These changes as consequence of the antiresorptive action of ZOL visible already after 6 months result in beneficial effects on bone matrix mineralization, likely contributing to the significant decrease in fracture incidence observed in these patients 2 years post transplantation.

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. STUDY DESIGN AND METHODS: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. RESULTS: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. CONCLUSION: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

Adherence to yoga and exercise interventions in a 6-month clinical trial.

BACKGROUND: To determine factors that predict adherence to a mind-body intervention in a randomized trial. DESIGN: We analyzed adherence data from a 3-arm trial involving 135 generally healthy seniors 65-85 years of age randomized to a 6-month intervention consisting of: an Iyengar yoga class with home practice, an exercise class with home practice, or a wait-list control group. Outcome measures included cognitive function, mood, fatigue, anxiety, health-related quality of life, and physical measures. Adherence to the intervention was obtained by class attendance and biweekly home practice logs. RESULTS: The drop-out rate was 13%. Among the completers of the two active interventions, average yoga class attendance was 77% and home practice occurred 64% of all days. Average exercise class attendance was 69% and home exercise occurred 54% of all days. There were no clear effects of adherence on the significant study outcomes (quality of life and physical measures). Class attendance was significantly correlated with baseline measures of depression, fatigue, and physical components of health-related quality of life. Significant differences in baseline measures were also found between study completers and drop-outs in the active interventions. Adherence was not related to age, gender, or education level. CONCLUSION: Healthy seniors have good attendance at classes with a physically active intervention. Home practice takes place over half of the time. Decreased adherence to a potentially beneficial intervention has the potential to decrease the effect of the intervention in a clinical trial because subjects who might sustain the greatest benefit will receive a lower dose of the intervention and subjects with higher adherence rates may be functioning closer to maximum ability before the intervention. Strategies to maximize adherence among subjects at greater risk for low adherence will be important for future trials, especially complementary treatments requiring greater effort than simple pill-taking.

Non-invasive physical treatments for chronic/recurrent headache.

BACKGROUND: Non-invasive physical treatments are often used to treat common types of chronic/recurrent headache. OBJECTIVES: To quantify and compare the magnitude of short- and long-term effects of non-invasive physical treatments for chronic/recurrent headaches. SEARCH STRATEGY: We searched the following databases from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of the Cochrane Pain, Palliative Care and Supportive Care review group. Selected complementary medicine reference systems were searched as well. We also performed citation tracking and hand searching of potentially relevant journals. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing non-invasive physical treatments for chronic/recurrent headaches to any type of control. DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted trial information and scored trials for methodological quality. Outcomes data were standardized into percentage point and effect size scores wherever possible. The strength of the evidence of effectiveness was assessed using pre-specified rules. MAIN RESULTS: Twenty-two studies with a total of 2628 patients (age 12 to 78 years) met the inclusion criteria. Five types of headache were studied: migraine, tension-type, cervicogenic, a mix of migraine and tension-type, and post-traumatic headache. Ten studies had methodological quality scores of 50 or more (out of a possible 100 points), but many limitations were identified. We were unable to pool data because of study heterogeneity. For the prophylactic treatment of migraine headache, there is evidence that spinal manipulation may be an effective treatment option with a short-term effect similar to that of a commonly used, effective drug (amitriptyline). Other possible treatment options with weaker evidence of effectiveness are pulsating electromagnetic fields and a combination of transcutaneous electrical nerve stimulation [TENS] and electrical neurotransmitter modulation. For the prophylactic treatment of chronic tension-type headache, amitriptyline is more effective than spinal manipulation during treatment. However, spinal manipulation is superior in the short term after cessation of both treatments. Other possible treatment options with weaker evidence of effectiveness are therapeutic touch; cranial electrotherapy; a combination of TENS and electrical neurotransmitter modulation; and a regimen of auto-massage, TENS, and stretching. For episodic tension-type headache, there is evidence that adding spinal manipulation to massage is not effective. For the prophylactic treatment of cervicogenic headache, there is evidence that both neck exercise (low-intensity endurance training) and spinal manipulation are effective in the short and long term when compared to no treatment. There is also evidence that spinal manipulation is effective in the short term when compared to massage or placebo spinal manipulation, and weaker evidence when compared to spinal mobilization. There is weaker evidence that spinal mobilization is more effective in the short term than cold packs in the treatment of post-traumatic headache. REVIEWERS' CONCLUSIONS: A few non-invasive physical treatments may be effective as prophylactic treatments for chronic/recurrent headaches. Based on trial results, these treatments appear to be associated with little risk of serious adverse effects. The clinical effectiveness and cost-effectiveness of non-invasive physical treatments require further research using scientifically rigorous methods. The heterogeneity of the studies included in this review means that the results of a few additional high-quality trials in the future could easily change the conclusions of our review.

Randomized controlled trial of yoga and exercise in multiple sclerosis.

OBJECTIVE: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). METHODS: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. RESULTS: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. CONCLUSION: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

A descriptive study of medical and chiropractic patients with chronic low back pain and sciatica: management by physicians (practice activities) and patients (self-management).

BACKGROUND: A practice-based study of ambulatory patients with low back pain noted a long-term outcome advantage for self-referred chiropractic (DC) patients over medical (MD) patients within a subgroup of patients with chronic low back pain and radiating pain below the knee. The frequency of self-care education by physicians in both provider cohorts coupled with current thinking on management of chronic low back pain led to an exploration and description of physicians' noncore practice activities and patients' self-management attitudes and behaviors. METHODS: A longitudinal, practice-based, observational study was undertaken in 14 general practice and 51 chiropractic community-based clinics. We enrolled 2945 consecutive patients with ambulatory low back pain of mechanical origin; of these, 268 comprised the subgroup of patients with chronic low back pain and radiating pain below the knee. The patients' low back status was followed for 1 year. Data on physicians' practice activities were obtained from doctor questionnaires completed at each patient visit and from chart abstraction. Patient data obtained from self-administered questionnaires at enrollment included sociodemographics, complaint characteristics, health status, and health encounter preferences. Questionnaires mailed at 2 weeks, 1 month, 3 months, 6 months, and 12 months collected data on low back complaint status and satisfaction with treatment. At 1 to 3 years follow-up, mailed questionnaires collected data on patients' self-management attitudes and behaviors. RESULTS: Physicians' core practice activities were as expected. Exercise plans and self-care education (>55%) were conspicuous in the frequency of their use in the DC cohort. MD patients appeared to rely more on family and friends for support during periods of back trouble. DC patients were characterized by greater self-efficacy motivation (P = .000). Both groups showed evidence of self-care activities during and between bouts of back pain, although MD patients were far more likely to choose bed rest (P = .007). CONCLUSIONS: The chiropractic encounter may have enhanced patients' self-efficacy motivation, leading to better coping abilities and better pain and disability outcomes. Understanding, respecting, and capitalizing on the role and influence of psychosocial factors can help all physicians become more effective healers and counselors for their patients with back pain.

Pain, disability, and satisfaction outcomes and predictors of outcomes: a practice-based study of chronic low back pain patients attending primary care and chiropractic physicians.

BACKGROUND: Few studies exist on the prognostic value of demographic, clinical, or psychosocial factors on long-term outcomes for patients with chronic low back pain. OBJECTIVE: This study reports on long-term pain and disability outcomes for patients with chronic low back pain, evaluates predictors of long-term outcomes, and assesses the influence of doctor type on clinical outcome. METHODS: Sixty chiropractic (DC) and 111 general practice (MD) physicians participated in data collection for a prospective, longitudinal, practice-based, observational study of ambulatory low back pain of mechanical origin. The primary outcomes, measured at 6 months and 12 months, were pain (by using the Visual Analog Scale), and functional disability (by using the Revised Oswestry Disability Questionnaire). Satisfaction was a secondary outcome. RESULTS: Overall, long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians. Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee. However, an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts (adjusted differences = 8.0 to 15.2; P <.002). A greater proportion of chiropractic patients were satisfied with all aspects of their care (P =.0000). The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes. Income, smoking, comorbidity, and chronic depression were also identified as predictors of outcomes in this study. CONCLUSION: Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes. Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction. Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians' practice activities that better serve these patients' needs.

Efficacy of spinal manipulation for chronic headache: a systematic review.

BACKGROUND: Chronic headache is a prevalent condition with substantial socioeconomic impact. Complementary or alternative therapies are increasingly being used by patients to treat headache pain, and spinal manipulative therapy (SMT) is among the most common of these. OBJECTIVE: To assess the efficacy/effectiveness of SMT for chronic headache through a systematic review of randomized clinical trials. STUDY SELECTION: Randomized clinical trials on chronic headache (tension, migraine and cervicogenic) were included in the review if they compared SMT with other interventions or placebo. The trials had to have at least 1 patient-rated outcome measure such as pain severity, frequency, duration, improvement, use of analgesics, disability, or quality of life. Studies were identified through a comprehensive search of MEDLINE (1966-1998) and EMBASE (1974-1998). Additionally, all available data from the Cumulative Index of Nursing and Allied Health Literature, the Chiropractic Research Archives Collection, and the Manual, Alternative, and Natural Therapies Information System were used, as well as material gathered through the citation tracking, and hand searching of non-indexed chiropractic, osteopathic, and manual medicine journals. DATA EXTRACTION: Information about outcome measures, interventions and effect sizes was used to evaluate treatment efficacy. Levels of evidence were determined by a classification system incorporating study validity and statistical significance of study results. Two authors independently extracted data and performed methodological scoring of selected trials. DATA SYNTHESIS: Nine trials involving 683 patients with chronic headache were included. The methodological quality (validity) scores ranged from 21 to 87 (100-point scale). The trials were too heterogeneous in terms of patient clinical characteristic, control groups, and outcome measures to warrant statistical pooling. Based on predefined criteria, there is moderate evidence that SMT has short-term efficacy similar to amitriptyline in the prophylactic treatment of chronic tension-type headache and migraine. SMT does not appear to improve outcomes when added to soft-tissue massage for episodic tension-type headache. There is moderate evidence that SMT is more efficacious than massage for cervicogenic headache. Sensitivity analyses showed that the results and the overall study conclusions remained the same even when substantial changes in the prespecified assumptions/rules regarding the evidence determination were applied. CONCLUSIONS: SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has an effect comparable to commonly used first-line prophylactic prescription medications for tension-type headache and migraine headache. This conclusion rests upon a few trials of adequate methodological quality. Before any firm conclusions can be drawn, further testing should be done in rigorously designed, executed, and analyzed trials with follow-up periods of sufficient length.

Assessing the value of hospital-in-the-home: lessons from Australia.

OBJECTIVES: To identify factors that influence the cost-effectiveness of hospital-in-the-home (HITH) and to discuss the impact of funding arrangements in creating incentives or disincentives for the establishment of HITH services. METHODS: A review of HITH services in Australia was undertaken. Based on the review, factors affecting the relative costs of HITH and conventional care were identified, in particular, the effect of funding and organisational arrangements on the incentives for managers and providers to choose between HITH and conventional care. RESULTS: The review of HITH services identified a wide range of models of HITH in Australia. Factors identified as important to the success of HITH included demographic and location issues, referral mechanisms, the choice of staffing and the management of the programme. However, it was clear that the structure of the programme often related to funding arrangements. Issues such as 'incentive funding', establishment costs and opportunity for cost-shifting were identified as being relevant to incentives for the efficient provision of HITH. CONCLUSIONS: Evaluations are essential to inform decisions about whether HITH is likely to be a viable and cost-effective alternative to inpatient care. However, the relative costs of HITH and conventional care will depend on local factors. From the point of view of the decision-maker, these will be affected by funding and organisational arrangements. Funders must be aware that complex financial incentives may mask the true costs of HITH services relative to hospital services. They need to ensure that the incentives created by funding arrangements are transparent.

Practice-based research: the Oregon experience.

BACKGROUND: Practice-based research links community-based physicians and their patients with investigators at academic institutions. In 1992, Western States Chiropractic College developed an infrastructure, the Center for Outcomes Studies, to support practice-based research. The Low Back Pain Study, undertaken in collaboration with Oregon Health Sciences University, 111 medical physicians, and 60 chiropractors, relied on the Center for Outcomes Studies infrastructure for support in project implementation and maintenance. RESULTS: Challenges, many of them critical, were a regular occurrence: dealing with unforeseen obstacles, establishing and maintaining physician buy-in, establishing and maintaining staff buy-in, implementing the protocol as directed and with minimal intrusiveness, maintaining enthusiasm for the project over time, and knowing where (and where not) to allocate the Study's time, energy, and money. Strategies were developed to overcome or minimize the impact of problems on a case-by-case basis. CONCLUSIONS: Successful practice-based research requires an awareness of study design issues and an appreciation of clinical practice logistics and priorities. Every effort must be made to include doctors and office staff in the implementation of the study in a manner that minimizes the study's intrusiveness and its economic impact on office organization, routine, and personnel. Investigators must understand and accept that there will be areas of the research environment over which they have no direct control. The challenges will be many, but they will be diminished by the rewards.

Patient characteristics and physicians' practice activities for patients with chronic low back pain: a practice-based study of primary care and chiropractic physicians.

BACKGROUND: Chronic low back pain sufferers are among those who account for the greatest usage of health care resources. Primary care medical (MD) physicians and chiropractic (DC) physicians treat most of these patients. OBJECTIVES: To study patient characteristics and physician practice activities for patients with chronic low back pain treated by DC physicians and MD physicians. METHODS: A longitudinal, practice-based observational study was undertaken in 14 general practice and 51 DC community-based clinics. A total of 2945 consecutive patients with ambulatory low back pain of mechanical origin were enrolled; 835 patients were in the chronic subgroup. Patients were followed for 12 months. Data were obtained on all of the following: patient demographics, health status, and psychosocial characteristics; history, duration, and severity of low back pain and disability; physicians' practice activities; and low back complaint status at 1 year. RESULTS: Patients treated by MD physicians were younger and had lower incomes; their care was more often paid for by a third party; their baseline pain and disability were slightly greater. In addition, patients treated by MD physicians had one fourth as many visits as patients treated by DC physicians. Utilization of imaging procedures by enrolling physicians was equivalent for the two provider groups. Medications were prescribed for 80% of the patients enrolled by MD physicians; spinal manipulation was administered to 84% of patients enrolled by DC physicians. Physical modalities, self-care education, exercise, and postural advice characterized low back pain management in both provider groups. Patients' care-seeking was not exclusive to one provider type. Most patients experienced recurrences (patients treated by MD physicians, 59.3%; patients treated by DC physicians, 76.4%); 34.1% of patients treated by MD physicians and 12.7% of patients treated by DC physicians reported 12 months of continuous pain. Only 6.7% of patients treated by MD physicians and 10.9% of patients treated by DC physicians reported 1 resolved episode during the year. CONCLUSIONS: Differences in sociodemographics, present pain intensity, and functional disability may distinguish patients with chronic low back pain seeking care from primary care medical physicians from those seeking care from DC physicians. Although the primary treatment modality differs, the practice activities of MD physicians and DC physicians have much in common. Long-term evaluation suggests that chronic back pain is persistent and difficult to treat for both provider types.

Patient characteristics, practice activities, and one-month outcomes for chronic, recurrent low-back pain treated by chiropractors and family medicine physicians: a practice-based feasibility study.

BACKGROUND: Chronic low-back pain is a significant public health problem for which few therapies are supported by predictable outcomes. In this report, practice activities and 1-month outcomes data are presented for 93 chiropractic patients and 45 medical patients with chronic, recurrent low-back pain. DESIGN: A prospective, observational, community-based feasibility study involving chiropractors and family medicine physicians. SETTING: Forty private chiropractic clinics, the outpatient clinic of the Department of Family Medicine at Oregon Health Sciences University, and 5 other Portland area family medicine clinics. OUTCOMES MEASURES: The main outcome measures were pain severity, functional disability, sensory and affective pain quality at 1 month, and patient satisfaction assessed at 7 to 10 days and at 1 month. RESULTS: Although differences were noted in age, sex, education, and employment, the patients were closely matched at baseline with respect to frequency, severity, and type of low-back pain and the psychosocial dimensions of general health. The treatment of choice for chiropractors was spinal manipulation and physical therapy modalities; for medical physicians antiinflammatory agents were most frequently used. Chiropractic patients averaged 4 visits, and medical patients averaged 1 visit. On average, chiropractic patients showed improvement across all outcomes: 31% change in pain severity, 29% in functional disability, 36% in sensory pain quality, and 57% in affective pain quality. Medical patients showed minimal improvement in pain severity (6%) and functional disability (1%) and showed deterioration in the sensory (29%) and affective (26%) dimensions of pain quality. Satisfaction scores were higher for chiropractic patients. Outcomes for medical patients were heavily dependent on psychosocial status at baseline. CONCLUSION: Patients with chronic low-back pain treated by chiropractors show greater improvement and satisfaction at 1 month than patients treated by family physicians. Nonclinical factors may play an important role in patient progress. Findings from the Health Resources and Services Administration-funded project will include a report on the influence of practice activities, including more frequent visits by chiropractic patients, on the clinical course of low-back pain and patient outcomes. (J Manipulative Physiol Ther 2000;23:239-45).

Expression analysis of human HL60 cells exposed to 60 Hz square- or sine-wave magnetic fields.

A total of 960 complementary DNA (cDNA) clones from an HL60 cell cDNA library were screened to discover genes that were differentially expressed in HL60 cells exposed to 60 Hz square-wave magnetic fields (MFs) compared to sham-exposed cells. Square-wave fields are rich in odd harmonic frequency content. We used a two-gel cDNA library screening method (BIGEL) to identify treatment-induced alterations in gene expression. Four cDNA clones were tentatively identified as differentially expressed after exposure to square-wave MFs at 2 mT for 24 h. BIGEL-identified genes (GenBank accession number) corresponding to these clones were: TI227H (D50525), EST Homo sapiens partial cDNA (Z17814), human ribosomal protein S13 (L01124), and AICAR transformylase mRNAs (D82348). The differences in mRNA levels were not confirmed in test compared to experimental cells by Northern analysis. In other experiments, we used concurrent exposure to 60 Hz sine- or square-wave MFs (0 or 2 mT, duration of 3 or 24 h, no postexposure delay). In addition to the four BIGEL genes, we also investigated MYC, HSP70, RAN and SOD1. In the case of MYC and HSP70, square-wave MFs appeared to exhibit more marked alterations when compared to sinusoidal waveforms, but the overall results indicated no effect of possible differential magnetic-field-induced expression of all eight genes. In contrast, alterations of mRNA levels were observed for seven genes after exposure to X irradiation, hyperthermia and TPA. These results are contrary to previously proposed similarities between the action of these agents and MF effects on gene transcription.

Lipase-catalysed production of biodiesel fuel from some Nigerian lauric oils.

Fatty acids esters were produced from two Nigerian lauric oils, palm kernel oil and coconut oil, by transesterification of the oils with different alcohols using PS30 lipase as a catalyst. In the conversion of palm kernel oil to alkyl esters (biodiesel), ethanol gave the highest conversion of 72%, t-butanol 62%, 1-butanol 42%, n-propanol 42% and iso-propanol 24%, while only 15% methyl ester was observed with methanol. With coconut oil, 1-butanol and iso-butanol achieved 40% conversion, 1-propanol 16% and ethanol 35%, while only traces of methyl esters were observed using methanol. Studies on some fuel properties of palm kernel oil and its biodiesel showed that palm kernel oil had a viscosity of 32.40 mm2/s, a cloud point of 28 degrees C and a pour point of 22 degrees C, while its biodiesel fuel had a viscosity of 9.33 mm2/s, a cloud point of 12 degrees C and a pour point of 8 degrees C. Coconut oil had a viscosity of 28.58 mm(2)/s, a cloud point of 27 degrees C and a pour point of 20 degrees C, while its biodiesel fuel had a viscosity of 7.34 mm2/s, a cloud point of 5 degrees C and a pour point of -8 degrees C. Some of the fuel properties compared favourably with international biodiesel specifications.