Low-level laser therapy for carpal tunnel syndrome: systematic review and network meta-analysis.

BACKGROUND: Splinting is recommended by various organisations as a non-surgical first-line treatment for carpal tunnel syndrome (CTS), despite the limited evidence supporting its effectiveness. Previous studies on the effectiveness of low-level laser therapy (LLLT) have reported mixed results, and this systematic review aimed to resolve this controversy. OBJECTIVE: To perform a network meta-analysis (NMA) for evaluating the effectiveness of LLLT compared with other conservative treatments for CTS. METHODS: Eighteen electronic databases were searched for potential randomised controlled trials (RCTs). RCTs evaluating LLLT or other non-surgical treatments as an add-on to splinting were included. Included RCTs measured at least one of the following three outcomes with validated instruments: pain, symptom severity and functional status. RESULTS: Six RCTs (418 patients) were included. NMA suggested that LLLT plus splinting has the highest probability (75%) of pain reduction, compared with sham laser plus splinting (61%), ultrasound plus splinting (57%) and splinting alone (8%). However, while LLLT plus splinting is significantly more effective than sham laser plus splinting for pain reduction, the magnitude is not clinically significant (Visual Analogue Scale mean difference -0.53cm, 95% confidence interval -1.01 to -0.05cm; P=0.03, I2=25%). The effect of LLLT plus splinting on symptom severity and functional status was not superior to splinting alone. CONCLUSION: The use of LLLT in addition to splinting for the management of CTS is not recommended, as LLLT offers limited additional benefits over splining alone in terms of pain reduction, reduction of symptom severity or improved functional status. PROSPERO for systematic reviews and meta-analyses registration number CRD42017082650.

The use of health related quality of life data to produce information sheets for patients with head and neck cancer.

INTRODUCTION: Health related quality of life information gives patients and carers an indication of how they will be affected following treatment. Such knowledge can promote realistic expectations and help patients come to terms with their outcome. The aim of this paper is to describe the background development of patient information sheets produced at our unit. METHODS: The data were compiled using a common head and neck cancer specific quality of life questionnaire (University of Washington Quality of Life [UW-QOL]). There are 12 domains comprising activity, appearance, anxiety, chewing, mood, pain, recreation, saliva, shoulder, speech, swallowing and taste. The data were collected over 19 years at our unit and focus on follow-up records at around 2 years as this gives a good indication of health related quality of life in survivorship. UW-QOL questionnaires were available from 1,511 patients treated following primary diagnosis of head and neck cancer, and there were 24 subgroups based on cancer site, stage and treatment. There were 2 other subgroups: 132 having transoral laser resection and 176 having laryngectomy. RESULTS: The patient and carer research forum helped to design the information sheets, which display overall quality of life, percentages with 'good' outcome and 'significant problem' by domain, and the most important domains. Three examples are included in this paper: early stage oral cancer treated by surgery alone, early laryngeal cancer treated by surgery alone, and late stage oropharyngeal cancer treated by surgery and postoperative radiotherapy. All 26 subgroup information sheets are available in booklet form and on the internet. CONCLUSIONS: How the surgical community best utilises this type of resource needs further research.

Lineage factors and differentiation states in lung cancer progression.

Lung cancer encompasses a heterogeneous group of malignancies. Here we discuss how the remarkable diversity of major lung cancer subtypes is manifested in their transforming cell of origin, oncogenic dependencies, phenotypic plasticity, metastatic competence and response to therapy. More specifically, we review the increasing evidence that links this biological heterogeneity to the deregulation of cell lineage-specific pathways and the transcription factors that ultimately control them. As determinants of pulmonary epithelial differentiation, these poorly characterized transcriptional networks may underlie the etiology and biological progression of distinct lung cancers, while providing insight into innovative therapeutic strategies.

'What will I be like' after my diagnosis of head and neck cancer?

Consequences of treating head and neck cancer are reflected in health-related quality of life (HRQOL) patient-reported outcomes. HRQOL is an important outcome alongside survival and recurrence. However, relatively little HRQOL information is in a format that patients and oncology teams can easily interpret as a guide to likely outcomes following curative treatment. The study aim was to collate University of Washington Quality of Life (UW-QOL) questionnaires collected 1995-2012 at the Regional Head and Neck Surgical Unit with a view of summarizing key clinical-demographic influences on HRQOL outcomes at 2 years following diagnosis. Patients completing UW-QOL questionnaires at 9-60 months had their record closest to 2 years selected for cross-sectional analyses, while all questionnaires were analyzed to assess temporal trends. 65 % (1,134) of survivors to 9 months had a UW-QOL record in the cross-sectional analysis (median 23 months). Overall 1,349 completed 5,573 UW-QOL questionnaires. Various associations were seen, notably late overall clinical staging and treatment adversely associated with UW-QOL physical functioning domains. Logistic regression was used to better understand the predictive factors of UW-QOL outcome and determined the final formatting of tables for results. These tables provide important reference data about UW-QOL outcome at 2 years relevant to patients at the outset of their cancer journey. The increasing amount of HRQOL data allows for quite detailed subgroup analysis, which can help give patients and the clinical team a better understanding of likely long-term HRQOL outcomes. How this is best utilized in clinical care needs further evaluation.

Dynamic MR imaging patterns of cerebral fat embolism: a systematic review with illustrative cases.

Different MR imaging patterns of cerebral fat embolism have been reported in the literature without a systematic review. Our goal was to describe the patterns, explore the relationship between disease course and the imaging patterns, and discuss the underlying mechanism. We reveal 5 distinctive MR imaging patterns: 1) scattered embolic ischemia occurring dominantly at the acute stage; 2) confluent symmetric cytotoxic edema located at the cerebral white matter, which mainly occurs at the subacute stage; 3) vasogenic edematous lesions also occurring at the subacute stage; 4) petechial hemorrhage, which persists from the acute to the chronic stage; and 5) chronic sequelae, occurring at late stage, including cerebral atrophy, demyelinating change, and sequelae of infarction or necrosis. Underlying mechanisms of these imaging patterns are further discussed. Recognition of the 5 evolving MR imaging patterns of cerebral fat embolism may result in adjustment of the appropriate management and improve the outcome.

Holographic video at 40 frames per second for 4-million object points.

We propose a fast method for generating digital Fresnel holograms based on an interpolated wavefront-recording plane (IWRP) approach. Our method can be divided into two stages. First, a small, virtual IWRP is derived in a computational-free manner. Second, the IWRP is expanded into a Fresnel hologram with a pair of fast Fourier transform processes, which are realized with the graphic processing unit (GPU). We demonstrate state-of-the-art experimental results, capable of generating a 2048 x 2048 Fresnel hologram of around 4 × 10(6) object points at a rate of over 40 frames per second.

Computer generation of binary Fresnel holography.

Binarization of Fresnel holograms by direct thresholding based on the polarity of the fringe pattern is studied. It is found that if the hologram is binarized (i.e., for black and white hologram pixels) in this manner, only the edges of the object are preserved in the reconstructed image. To alleviate the errors caused by binarization, the use of error diffusion has been routinely employed. However, the reconstructed image using such standard technique is heavily contaminated with random noise. In this paper, we propose a novel noniterative method for generating Fresnel holograms that are suitable for binarization. Our method is capable of preserving good visual quality on the reconstructed images.

Percutaneous endoscopic gastrostomy--indications and outcome of our experience at the Singapore General Hospital.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is widely used for patients with dysphagia from neurological causes and head and neck malignancy. We examined the indications, complication rates and long term outcome of PEG inserted in our department. METHODS: We performed a study of PEG inserted in our department between January 1995 to March 2000. Consecutive patients with PEG inserted during this period were identified from our database that contained demographic data, primary and secondary underlying medical conditions, and immediate complications after the procedure. Casenotes were reviewed and caregivers (relatives or staff at nursing homes) were contacted for information on long term outcome at the time of this study between April 2000. Data was collected in standard form designed for this study. RESULTS: 181 cases of PEG insertion were performed during the study period. 174 patients were successfully followed up and reviewed. The median age was 70.5 (range 24 to 93) years old and there were 111 males. Indications for PEG insertion were: cerebrovascular diseases (60.4%), Parkinson's disease and other neuromuscular disorders (10.9%), nasopharyngeal carcinoma and other upper gastrointestinal malignancies (24.7%), and head injury (4%). Superficial wound infection (22.4%) and granuloma formation (31%) were common minor complications. Major complications were infrequent: peritonitis (2.3%) and gastrointestinal bleeding (0.6%). The mortality rates were 11.5% and 28.2% at one and six months respectively. Only one death from peritonitis was directly attributed to the procedure, most deaths were due to underlying co-morbidities with pneumonia being the most common cause. The proportion of the first PEG tubes removed or replaced were 12.2% and 35.5% at one and six months respectively. Thirty tubes were replaced due to blockage at median interval of 9.6 months. 9.7% of PEG tubes functioned longer than 24 months. CONCLUSIONS: Our results confirm the safety of PEG tubes in elderly patients with multiple co-morbidities. Major complications of the procedure were infrequent but produced grave consequences in these elderly patients with multiple co-morbidities. As such, patients considered for PEG feeding should have reasonable prognosis and the procedure is inappropriate for patients with rapidly progressive and incurable diseases.

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

Patients with long-standing diabetes commonly suffer from gastric neuromuscular dysfunction (gastropathy) causing symptoms ranging from postprandial bloating to recurrent vomiting. Autonomic neuropathy is generally believed to be responsible for diabetic gastropathy and the underlying impairments in gastric emptying (gastroparesis) and receptive relaxation, but the specific mechanisms have not been elucidated. Recently, it has been recognized that interstitial cells of Cajal generate electrical pacemaker activity and mediate motor neurotransmission in the stomach. Loss or defects in interstitial cells could contribute to the development of diabetic gastroparesis. Gastric motility was characterized in spontaneously diabetic NOD/LtJ mice by measuring gastric emptying and by monitoring spontaneous and induced electrical activity in circular smooth muscle cells. Interstitial cells of Cajal were studied by Kit immunofluorescence and transmission electron microscopy. Diabetic mice developed delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent. Our observations suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy.

Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers.

This report summarizes the results of two double-blind, single-center, randomized studies that used a two-period crossover design. The objective of these two studies was to compare the safety, tolerability, pharmacokinetics, and pain score at the subcutaneous (sc) injection site of a phosphate-buffered recombinant human erythropoietin (EPREX, epoetin alfa, r-HuEPO) formulated with a new stabilizer (glycine and Polysorbate 80) with the commercially available EPREX formulations, which uses human serum albumin (HSA) as the stabilizer. Twenty-four healthy male volunteers were enrolled in each of the two studies. In the first study, subjects received a single 150 IU/kg sc dose of r-HuEPO using the 2000 IU/mL (2K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In the second study, subjects received a single 750 IU/kg sc dose of r-HuEPO using the 40 000 IU/mL (40K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In each study, r-HuEPO was administered over two separate dosing periods, each separated with a 28-day washout period. There were no significant differences in AUC and C(max) for either strength of r-HuEPO formulated with or without the new stabilizer, indicating that the absorption and disposition characteristics of the two formulations were similar after sc administration. Both r-HuEPO strengths with and without the new stabilizer were safe and well tolerated; the safety and tolerability profiles of both formulations for each r-HuEPO concentration were comparable. There were no statistically significant differences in pain score for either strength of r-HuEPO with and without the new stabilizer. It was concluded that the two phosphate-buffered r-HuEPO concentrations formulated with and without the new stabilizer are pharmacokinetically equivalent.

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects.

OBJECTIVES: To understand the pharmacokinetic and pharmacodynamic properties of recombinant human erythropoietin (epoetin alfa) and to continue to optimize dosing regimens by determining whether administration of single high doses of epoetin alfa is as effective as repeated administration. METHODS: Epoetin alfa was administered as single subcutaneous doses of 300, 450, 600, 900, 1200, 1350, 1800, and 2400 IU/kg and in multiple subcutaneous dose regimens: 150 IU/kg 3 times a week for 4 weeks and 600 IU/kg once per week for 4 weeks in 2 open-label, randomized placebo-controlled studies in healthy volunteers. RESULTS: The absorption rate of epoetin alfa after subcutaneous administration was independent of dose, whereas clearance was dose-dependent in that it decreased with increasing dose. There was a linear relationship between response measured as percentage of reticulocytes area under the curve (AUC) and erythropoietin AUC for single doses up to 1800 IU/kg. Beyond the 1800 IU/kg dose, there was a saturation of response. The mean percentage of reticulocytes after single-dose regimens began to increase by days 3 to 4, reached their maximum at days 8 to 11, and returned to baseline values by day 22. In contrast, the mean percentage of reticulocytes after both multiple-dose regimens were maintained above baseline values through day 22 as both regimens stimulated modest but sustained increases in percentage of reticulocytes (1% to 2%). The mean percentage of reticulocytes AUC for 600 IU/kg epoetin alfa given once a week for 4 weeks was apparently greater than the mean percentage of reticulocytes AUC for 150 IU/kg 3 times a week for 4 weeks. Although daily oral iron supplementation was given, mean serum ferritin levels declined by approximately 75% through day 22 in subjects treated with multiple doses of epoetin alfa. CONCLUSIONS: These findings show that the pharmacologic response to epoetin alfa is a function of dose and dosing regimen. Repeated administration of epoetin alfa was more effective in stimulating a reticulocyte response than single-dose administration of the same total amount of epoetin alfa.

Conjunctivitis caused by Thelazia callipaeda infestation in a woman.

Thelazia is a nematode (Spirurida) that can parasitize the mammalian conjunctival sac. This is the first reported case of ocular. Thelazia callipaeda infestation in Taiwan. A 41-year-old woman experienced swelling, itching sensation and occasional blurred vision of the right eye 2 weeks after a small group of flies swarmed her eye while she was hiking. Her symptoms were first misdiagnosed as allergic conjunctivitis at a local medical clinic. During her first visit to our outpatient department, five white thread-like living worms were discovered on the superior and inferior fornices. The worms were cream-colored, slender and approximately 1 cm in length. Follicular and papillary conjunctivitis was noted in her right eye. After removing the worms, the symptoms resolved and no other worms were found in the following 2 months. This case is a remainder to physicians that parasitic infestation should be included in the differential diagnoses of ocular itching, conjunctivities, and blurred vision after insect contact.

Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses.

The pharmacokinetics of once-daily oral levofloxacin (study A) or intravenous levofloxacin (study B) in 40 healthy male volunteers were investigated in two separate randomized, double-blind, parallel-design, placebo-controlled studies. Levofloxacin at 500 mg or placebo was administered orally or intravenously as a single dose on day 1; daily oral or intravenous dosing resumed on days 4 to 10. In a third study (study C), the comparability of the bioavailabilities of two oral and one intravenous levofloxacin formulations were investigated with 24 healthy male subjects in an open-label, randomized, three-way crossover study. Levofloxacin at 500 mg as a single tablet or an intravenous infusion was administered on day 1; following a 1-week washout period, subjects received the second regimen (i.e., the other oral formulation or the intravenous infusion); the third and final regimen was administered following a 1-week washout period. The concentrations of drug in plasma and urine were measured by validated high-pressure liquid chromatography methods. Pharmacokinetic parameters were estimated by noncompartmental methods. In both study A (oral levofloxacin) and study B (intravenous levofloxacin), steady state was attained within 48 h after the start of the multiple dosing on day 4. Levofloxacin pharmacokinetics were linear and predictable for the single and multiple 500-mg, once-daily oral and intravenous dosing regimens, and the values of the pharmacokinetic parameters for the oral and intravenous administrations were similar. Study C indicated that levofloxacin was rapidly and completely absorbed from the oral tablets, with mean times to the maximum concentration of drug in serum of approximately 1.5 h and mean absolute bioavailability of > or =99%. These results support the interchangeability of the oral and intravenous routes of levofloxacin administration.

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy.

PURPOSE: This study was designed to evaluate the absolute bioavailability (F value) of 2-chlorodeoxyadenosine (cladribine; 2-CdA) after multiple oral administrations, and the intersubject variability after oral and 2-hour intravenous (IV) administration schedules in patients with malignancy. PATIENTS AND METHODS: Patients with advanced malignancies were eligible. There were two treatment cycles; during cycle 1, patients received 2-CdA solution at 0.28 mg/kg/d orally under fasting conditions for 5 consecutive days concomitantly with omeprazole, and 4 weeks later during cycle 2 patients received 2-CdA as a 2-hour IV infusion of 0.14 mg/kg/d for 5 consecutive days. Serial blood samples for 2-CdA plasma levels were obtained after drug administrations on days 1 and 5 during each treatment cycle. RESULTS: Ten patients completed cycles 1 and 2. The F value of oral 2-CdA measured on days 1 and 5 was 37.2% and 36.7%, respectively. For both oral and IV multiple administrations, there was no significant accumulation in maximum concentration (Cmax), and the intersubject variabilities (coefficient of variation [CV], approximately 40%) in Cmax and area under the concentration-time curve from 0 to 24 hours [AUC(0-24)] values were comparable for both routes on days 1 and 5. A three-compartment open model was applied to the plasma concentration data after oral and IV administrations and resulted in good agreement between observed and simulated concentration-time profiles. Neutropenia was the principal adverse event observed when 2-CdA was administered orally and IV. CONCLUSION: The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

Diagnostic imaging of Salmonella-related mycotic aneurysm of aorta by CT.

The purpose of this study was to review the computed tomography (CT) appearance of mycotic aneurysm of the aorta caused by Salmonella infection. Eight patients were suggested to have mycotic aneurysm of the aorta by clinical presentation of fever, abdominal or back pain, leukocytosis, and pulsatile abdominal mass in addition to positive blood or tissue culture of salmonella. All underwent plain radiography, abdominal sonography, and CT for confirmation. Five patients died during hospitalization despite medical or surgical treatment. CT features of mycotic aneurysm of aorta included (a) hazy aortic wall with rupture; (b) gas-forming inflammation around the aneurysm; (c) retroperitoneal paraaortic fluid collection and vertebral erosion; and (d) thrombus formation within a false lumen after aneurysmal rupture. Because of its availability and noninvasiveness, CT is the major diagnostic modality to use for Salmonella-related mycotic aneurysm.

Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.

PURPOSE: The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. METHODS: Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. RESULTS AND CONCLUSIONS: The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (approximately 20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).

Acute intracranial subdural haematoma resulting from lumbar myelography.

We report a case of acute intracranial subdural haematoma after lumbar myelography with Iopamidol. The haematoma was successfully treated by emergency craniotomy. The bleeding came from cortical bridging veins as confirmed by surgery. This rare complication should be suspected in patients who complain of prolonged headache or develop a neurological deficit after myelography.

Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'-monophosphate increases hypothalamic levels of neuropeptide Y.

This investigation examined in vivo the relationship between the nucleotide cAMP and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL), which are known to potentiate feeding behavior. In brain-cannulated rats, third ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the paraventricular nucleus (mPVN), while having no impact in other hypothalamic areas. These site-specific changes in NPY occurred in the absence of any alteration in circulating levels of insulin, corticosterone, aldosterone or glucose, or of changes in hypothalamic levels of GAL. These findings implicate cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing neurons, projecting from the ARC to the mPVN, that are believed to be involved in energy homeostasis.

A Single-Dose Bioavailability Study of Pamidronate Disodium after Oral Administration as Encapsulated Enteric-Coated Pellets, Enteric-Coated Tablets, and a Solution to Patients with Postmenopausal Osteoporosis.

This was a pilot, single-center, single-dose, open-label, randomized three-way crossover study comparing the relative bioavailability of pamidronate disodium after oral doses of the drug administered as four capsules, each containing 75 mg enteric-coated pellets, two 150-mg enteric-coated tablets and 300 mg in solution (reference standard) in patients with postmenopausal osteoporosis. Results from seven patients are reported; five subjects completed all three phases of the study---one received solution and pellets, and another one received pellets and tablets. The onset of urinary excretion (an indicator of relative onset of oral absorption) of pamidronate disodium occurred in the first 2 h in all (except one) patients for solution and pellets, whereas the onset of urinary excretion for the tablets was prolonged and more variable. The extent of absorption was estimated in terms of percent of administered dose excreted in urine up to 72 h after dosing. The extend of absorption was highest after the pellets (mean plus minus S.D., 0.37 plus minus 0.27%), followed by the solution (0.20 plus minus 0.16%). The extent of absorption after the tablets (0.09 plus minus 0.10%) was the lowest and most variable. The poorer and more variable bioavailability of the tablets may be explained by the longer and more variable residence time of the tablets in the stomach.

Pharmacokinetics of Pamidronate Disodium in Cancer Patients after a Single Intravenous Infusion of 30-, 60- or 90-mg Dose over 4 or 24 Hours.

The objective of this study was to determine the pharmacokinetics of pamidronate disodium in plasma and urine after a single intravenous infusion of the drug to cancer patients at risk for developing bone metastases. Thirty-six patients were randomized into six treatment groups to receive 30-, 60- or 90-mg doses of the drug by 4- or 24-h intravenous infusions. Plasma and urine samples were collected at intervals for up to 144 h after drug administration and were assayed for pamidronate disodium using validated reversed-phase HPLC methods. The percentage of the administered dose excreted in urine following a 4- or 24-h infusion of 30-, 60- or 90-mg pamidronate disodium ranged from 30% to 60% except for one individual who excreted 96% by this route of elimination. There was a linear relationship between amount of drug excreted in urine and dose. Curve fitting of ARE (amount of drug to be excreted in urine) data indicated that the disposition kinetics of the drug was consistent with a biexponential process with overall mean plus minus S.D. half-life values of 2.1 plus minus 1.8 and 26.9 plus minus 8.7 h for the alpha and beta phases, respectively. The results of this study showed that the drug exhibited dose proportionality in its pharmacokinetic behavior over the 30--90-mg range regardless of whether it was infused over a 4- or 24-h interval.