Showing papers on "Symptomatic relief published in 2015"

Neuropathic Pain: Principles of Diagnosis and Treatment

Abstract: Neuropathic pain is caused by disease or injury of the nervous system and includes various chronic conditions that, together, affect up to 8% of the population. A substantial body of neuropathic pain research points to several important contributory mechanisms including aberrant ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and pathological activation of microglia. Clinical evaluation of neuropathic pain requires a thorough history and physical examination to identify characteristic signs and symptoms. In many cases, other laboratory investigations and clinical neurophysiological testing may help identify the underlying etiology and guide treatment selection. Available treatments essentially provide only symptomatic relief and may include nonpharmacological, pharmacological, and interventional therapies. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). Individualized multidisciplinary patient care is facilitated by careful consideration of pain-related disability (eg, depression and occupational dysfunction) as well as patient education; repeat follow-up and strategic referral to appropriate medical/surgical subspecialties; and physical and psychological therapies. In the near future, continued preclinical and clinical research and development are expected to lead to further advancements in the diagnosis and treatment of neuropathic pain.

Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial

Abstract: Background:Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention.Purpose:To evaluate the benefit provided by platelet-rich plasma (PRP) injections to treat knee joint degeneration in comparison with hyaluronic acid (HA), the most common injective treatment currently adopted for this condition.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 443 patients were screened, and 192 of them were enrolled in the study according to the following inclusion criteria: (1) unilateral symptomatic knee with history of chronic pain (at least 4 months) or swelling and (2) imaging findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly int...

Traditional and Contemporary Mindfulness: Finding the Middle Path in the Tangle of Concerns

Abstract: Contemporary mindfulness has grown through innumerable secular and clinical programs. This rapid growth has raised two main concerns from the Buddhist community: the accuracy of the teachings and the impact of not explicitly including ethics as part of the teachings. Specific concerns include a potential weakening of the concept of right mindfulness and, as a corollary, misunderstanding the intent mindfulness as being a technique for symptomatic relief. With respect to the absence of explicit ethics in the teachings, concerns are expressed that this omission risks misappropriating mindfulness practices so that they do more harm than good. This article explores the main criticisms expressed by Traditional Mindfulness community and assesses the validity of these criticisms. The dialogue between traditional and contemporary mindfulness practitioners is an opportunity to examine the conceptual integrity of mindfulness-based interventions (MBIs) with respect to what comprises right mindfulness, assess whether MBIs include the factors that can extend them beyond symptomatic relief, and reflect on the issues related to teaching ethics as part of an MBI program. Because ethics is viewed in Traditional Mindfulness as a foundation for a meditative practice, it is explored in detail for its potential contribution to MBIs.

Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses.

Abstract: Purpose The aims of this study were (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) injection in the treatment of knee joint cartilage degenerative pathology, (2) to provide a framework for analysis and interpretation of the best available evidence to provide recommendations for use (or lack thereof) of PRP in the setting of knee osteoarthritis (OA), and (3) to identify literature gaps where continued investigation would be suggested. Methods Literature searches were performed for meta-analyses examining use of PRP versus corticosteroids, hyaluronic acid, oral nonsteroidal anti-inflammatory drugs, or placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine meta-analyses that provided the highest level of evidence. Results Three meta-analyses met the eligibility criteria and ranged in quality from Level II to Level IV evidence. All studies compared outcomes of treatment with intra-articular platelet-rich plasma (IA-PRP) versus control (intra-articular hyaluronic acid or intra-articular placebo). Use of PRP led to significant improvements in patient outcomes at 6 months after injection, and these improvements were seen starting at 2 months and were maintained for up to 12 months. It is unclear if the use of multiple PRP injections, the double-spinning technique, or activating agents leads to better outcomes. Patients with less radiographic evidence of arthritis benefit more from PRP treatment. The use of multiple PRP injections may increase the risk of self-limited local adverse reactions. After application of the Jadad algorithm, 3 concordant high-quality meta-analyses were selected and all showed that IA-PRP provided clinically relevant improvements in pain and function compared with the control treatment. Conclusions IA-PRP is a viable treatment for knee OA and has the potential to lead to symptomatic relief for up to 12 months. There appears to be an increased risk of local adverse reactions after multiple PRP injections. IA-PRP offers better symptomatic relief to patients with early knee degenerative changes, and its use should be considered in patients with knee OA. Level of Evidence Level IV, systematic review of Level II through IV studies.

Targeting Hsp90/Hsp70-Based Protein Quality Control for Treatment of Adult Onset Neurodegenerative Diseases

Abstract: Currently available therapies for adult onset neurodegenerative diseases provide symptomatic relief but do not modify disease progression. Here we explore a new neuroprotective approach based on drugs targeting chaperone-directed protein quality control. Critical target proteins that unfold and aggregate in these diseases, such as the polyglutamine androgen receptor in spinal and bulbar muscular atrophy, huntingtin in Huntington's disease, α-synuclein in Parkinson's disease, and tau in Alzheimer's disease, are client proteins of heat shock protein 90 (Hsp90), and their turnover is regulated by the protein quality control function of the Hsp90/Hsp70-based chaperone machinery. Hsp90 and Hsp70 have opposing effects on client protein stability in protein quality control; Hsp90 stabilizes the clients and inhibits their ubiquitination, whereas Hsp70 promotes ubiquitination dependent on CHIP (C terminus of Hsc70-interacting protein) and proteasomal degradation. We discuss how drugs that modulate proteostasis by inhibiting Hsp90 function or promoting Hsp70 function enhance the degradation of the critical aggregating proteins and ameliorate toxic symptoms in cell and animal disease models.

Targets, models and challenges in osteoarthritis research

Abstract: Osteoarthritis is a chronic degenerative disorder of the joint and represents one of the most common diseases worldwide. Its prevalence and severity are increasing owing to aging of the population, but treatment options remain largely limited to painkillers and anti-inflammatory drugs, which only provide symptomatic relief. In the late stages of the disease, surgical interventions are often necessary to partially restore joint function. Although the focus of osteoarthritis research has been originally on the articular cartilage, novel findings are now pointing to osteoarthritis as a disease of the whole joint, in which failure of different joint components can occur. In this Review, we summarize recent progress in the field, including data from novel ‘omics’ technologies and from a number of preclinical and clinical trials. We describe different in vitro and in vivo systems that can be used to study molecules, pathways and cells that are involved in osteoarthritis. We illustrate that a comprehensive and multisystem approach is necessary to understand the complexity and heterogeneity of the disease and to better guide the development of novel therapeutic strategies for osteoarthritis.

Therapeutic strategies for neuroendocrine liver metastases.

Abstract: Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.

Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain

Abstract: Objective To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs. Methods Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient9s Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs. Results Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy. Conclusions Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes. Trial registration number NCT00809354

Targeting megakaryocytic-induced fibrosis in myeloproliferative neoplasms by AURKA inhibition

Abstract: Primary myelofibrosis (PMF) is characterized by bone marrow fibrosis, myeloproliferation, extramedullary hematopoiesis, splenomegaly and leukemic progression. Moreover, the bone marrow and spleens of individuals with PMF contain large numbers of atypical megakaryocytes that are postulated to contribute to fibrosis through the release of cytokines, including transforming growth factor (TGF)-β. Although the Janus kinase inhibitor ruxolitinib provides symptomatic relief, it does not reduce the mutant allele burden or substantially reverse fibrosis. Here we show through pharmacologic and genetic studies that aurora kinase A (AURKA) represents a new therapeutic target in PMF. Treatment with MLN8237, a selective AURKA inhibitor, promoted polyploidization and differentiation of megakaryocytes with PMF-associated mutations and had potent antifibrotic and antitumor activity in vivo in mouse models of PMF. Moreover, heterozygous deletion of Aurka was sufficient to ameliorate fibrosis and other PMF features in vivo. Our data suggest that megakaryocytes drive fibrosis in PMF and that targeting them with AURKA inhibitors has the potential to provide therapeutic benefit.

Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation.

Abstract: PURPOSE. To evaluate the clinical and ultrasonographic changes in the morphology and vascularity of the common extensor tendon after injecting platelet-rich plasma (PRP) or corticosteroid (CS) for recalcitrant lateral epicondylitis (LE). METHODS. 30 patients aged 18 to 60 years with recalcitrant (>6 months) LE not responsive to oral medication or non-invasive treatment were randomised to receive PRP (n=15) or CS (n=15) injection. Patients were assessed using the visual analogue scale (VAS) for pain, Disabilities of the Arm, Shoulder and Hand Scale (DASH) score, Oxford Elbow Score, modified Mayo Clinic performance index for the elbow (modified Mayo score), and hand grip strength. Ultrasonography was performed by a musculoskeletal ultrasonologist to evaluate for tear at the common extensor origin, oedema at the common extensor origin, cortical erosion, probe-induced tenderness, and thickness of the tendon. RESULTS. The VAS for pain, DASH score, Oxford Elbow Score, modified Mayo score, and hand grip strength all improved significantly from pre-injection to the 6-month follow-up in the PRP and CS groups. However, in the CS group, the scores generally peaked at 3 months and then deteriorated slightly at 6 months indicating recurrence of symptoms, which involved 46.7% of the CS patients. At 6 months, the number of patients positive for various ulrasonographic findings generally decreased. However, in the CS group, the number of patients with reduced thickness of the common extensor tendon increased from 2 to 12, and the number of patients with cortical erosion at the lateral epicondyle increased from 9 to 11. CONCLUSION. PRP appeared to enable biological healing of the lesion, whereas CS appeared to provide short-term, symptomatic relief but resulted in tendon degeneration.

Does Timing of Previous Intra-Articular Steroid Injection Affect the Post-Operative Rate of Infection in Total Knee Arthroplasty?

Abstract: Intra-articular steroid injections are widely used for symptomatic relief of knee osteoarthritis. This study used a national database to determine if there is an association between preoperative intra-articular knee injection at various time intervals prior to ipsilateral TKA and infection. The incidence of infection within 3 months (2.6%, OR 2.0 [1.6-2.5], P < 0.0001) and 6 months (3.41%, OR 1.5 [1.2-1.8], P < 0.0001) after TKA within 3 months of knee injection was significantly higher than our control cohort. There was no significant difference in patients who underwent TKA more than 3 months after injection. Ipsilateral knee injection within three months prior to TKA is associated with a significant increase in infection.

Hypersensitivity Pneumonitis: A Comprehensive Review.

Abstract: Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex pulmonary syndrome mediated by the immune system and caused by inhalation of a wide variety of antigens to which the individual has been previously sensitized. The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP. Due to the lack of a diagnostic gold standard, the diagnosis of HP is not straightforward and relies on the integration of a number of factors, including history of exposure, precipitating antibodies to the offending antigen, clinical features, bronchoalveolar lavage, and radiological and pathologic features. However, in the appropriate setting, a high index of suspicion is critically important and may obviate the need for more invasive tests. Clinical presentation and natural history vary widely. Acute forms generally resolve without sequelae, while chronic forms, which are caused by persistent low-grade exposures, are associated with poor prognosis. Corticosteroids may be useful in acute episodes for symptomatic relief or in chronic and progressive disease, but their long-term efficacy has never been validated in prospective clinical trials. Ideally, patients with HP should be referred to centers with expertise, as the overlap with other forms of interstitial lung disease may be substantial. Making the correct diagnosis has critical therapeutic and prognostic implications.

Serotonin: A New Hope in Alzheimer's Disease?

Abstract: Alzheimer’s disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enhance serotonin concentration in the synaptic cleft have been debated as possible therapeutic strategies to slow the progression of AD. In this Viewpoint, we discuss exciting new insights regarding the modulation of serotonin signaling for AD prevention and therapy.

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Abstract: Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential.

Dry mouth and older people.

Abstract: Dry mouth is more common among older people than in any other age group. Appropriate definition and accurate measurement of dry mouth is critical for better understanding, monitoring and treatment of the condition. Xerostomia is the symptom(s) of dry mouth; it can be measured using methods ranging from single questions to multi-item summated rating scales. Low salivary flow (known as salivary gland hypofunction, or SGH) must be determined by measuring that flow. The relationship between SGH and xerostomia is not straightforward, but both conditions are common among older people, and they affect sufferers' day-to-day lives in important ways. The major risk factor for dry mouth is the taking of particular medications, and older people take more of those than any other age group, not only for symptomatic relief of various age-associated chronic diseases, but also in order to reduce the likelihood of complications which may arise from those conditions. The greater the number taken, the greater the associated anticholinergic burden, and the more likely it is that the individual will suffer from dry mouth. Since treating dry mouth is such a challenge for clinicians, there is a need for dentists, doctors and pharmacists to work together to prevent it occurring.

Presentation and management of pulmonary artery sarcoma.

Abstract: Pulmonary artery sarcoma (PAS) is a rare but aggressive malignancy that leads to heart failure and death without treatment. Here we reviewed the presentation and management of patients treated at a national centre for pulmonary endarterectomy (PEA) and its associated hospital in Cambridge, UK. Details of PAS patients treated at Papworth and Addenbrooke’s Hospitals between 2000 and 2014 were reviewed. Twenty patients were diagnosed with PAS (11 males, 9 females), with a median age of presentation of 57 years (range 27–77). Presenting symptoms include dyspnoea (20), chest pain/tightness (7), oedema (5), constitutional symptoms (5), cough (3) and haemoptysis (3). Twelve patients were in group III/IV of the NYHA functional classification of symptoms. Initial CT scans were suggestive of thromboembolism in seven patients. Histological findings were of intimal sarcoma (13) and high grade sarcoma NOS (6). Median overall survival (OS) was 17 months. Fourteen patients underwent PEA to relieve vascular obstruction, while six had inoperable and/or metastatic disease. There were three peri-operative deaths. Although there was no difference in median OS between patients who had PEA and those who did not (20 vs 17 months, P = 0.2488), surgery provided significant symptomatic improvement and some with long-term survival. Five patients received post-surgical chemotherapy (anthracycline +/− ifosfamide), and after completion four also had radiotherapy. Patients who received post-operative chemo- and radio-therapy showed a trend towards better survival compared to those who had surgery alone (24 vs 8 months, P = 0.3417). For palliative chemotherapy, partial responses were observed with the VID regimen and pegylated liposomal doxorubicin. Stable disease was achieved in a patient with intimal sarcoma with rhabdomyosarcomatous differentiation on third-line cisplatin and topotecan. The longest surviving patient (102 months) has had PEA, adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later, which were treated with radiofrequency ablation. PAS often presents with symptoms mimicking pulmonary hypertension, heart failure or thromboembolic disease. PEA provides good symptomatic relief and in some cases, offers a chance of long-term survival. Although outcome appears to be better when PEA is combined with post-operative chemo- and radio-therapy, further studies are warranted.

Effect of pursed lips expiration on the pulmonary pressure-flow relationship in obstructive lung disease.

Abstract: The effect of pursed lips expiration in patients with chronic obstructive pulmonary disease has been investigated from the standpoint of its effect on alveolar ventilation (1) and vital capacity (2). The rapid symptomatic relief obtained by pursed lips breathing occurs before the effect of any ventilatory change could become manifest and while exchanging tidal volumes much smaller than vital capacity. This led the writers to study the short term effects of this maneuver. The purpose of the study was to define the pressure, flow, and volume relationships in chronic obstructive pulmonary disease with and without the adclition of an external expiratory obstruction designed to simulate pursed lips expiration during tidal respiration.

High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells

Abstract: Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development.

Prophylactic melatonin significantly reduces Alzheimer’s neuropathology and associated cognitive deficits independent of antioxidant pathways in AβPP swe /PS1 mice

Abstract: Alzheimer’s disease (AD) underlies dementia for millions of people worldwide, and its occurrence is set to double in the next 20 years. Currently, approved drugs for treating AD only marginally ameliorate cognitive deficits, and provide limited symptomatic relief, while newer substances under therapeutic development are potentially years away from benefiting patients. Melatonin (MEL) for insomnia has been proven safe with >15 years of over-the-counter access in the US. MEL exerts multiple complementary mechanisms of action against AD in animal models; thus it may be an excellent disease-modifying therapeutic. While presumed to provide neuroprotection via activation of known G-protein-coupled melatonin receptors (MTNRs), some data indicate MEL acts intracellularly to protect mitochondria and neurons by scavenging reactive oxygen species and reducing free radical formation. We examined whether genetic deletion of MTNRs abolishes MEL’s neuroprotective actions in the AβPPswe/PSEN1dE9 mouse model of AD (2xAD). Beginning at 4 months of age, both AD and control mice either with or without both MTNRs were administered either MEL or vehicle in drinking water for 12 months. Behavioral and cognitive assessments of 15-month-old AD mice revealed receptor-dependent effects of MEL on spatial learning and memory (Barnes maze, Morris Water Maze), but receptor-independent neuroprotective actions of MEL on non-spatial cognitive performance (Novel Object Recognition Test). Similarly, amyloid plaque loads in hippocampus and frontal cortex, as well as plasma Aβ1–42 levels, were significantly reduced by MEL in a receptor-independent manner, in contrast to MEL’s efficacy in reducing cortical antioxidant gene expression (Catalase, SOD1, Glutathione Peroxidase-1, Nrf2) only when receptors were present. Increased cytochrome c oxidase activity was seen in 16mo AD mice as compared to non-AD control mice. This increase was completely prevented by MEL treatment of 2xAD/MTNR+ mice, but only partially prevented in 2xAD/MTNR- mice, consistent with mixed receptor-dependent and independent effects of MEL on this measure of mitochondrial function. These findings demonstrate that prophylactic MEL significantly reduces AD neuropathology and associated cognitive deficits in a manner that is independent of antioxidant pathways. Future identification of direct molecular targets for MEL action in the brain should open new vistas for development of better AD therapeutics.

The Meniscus-Deficient Knee: Biomechanics, Evaluation, and Treatment Options

Abstract: Meniscal tears are the most common knee injury, and partial meniscectomies are the most common orthopaedic surgical procedure. The injured meniscus has an impaired ability to distribute load and resist tibial translation. Partial or complete loss of the meniscus promotes early development of chondromalacia and osteoarthritis. The primary goal of treatment for meniscus-deficient knees is to provide symptomatic relief, ideally to delay advanced joint space narrowing, and ultimately, joint replacement. Surgical treatments, including meniscal allograft transplantation (MAT), high tibial osteotomy (HTO), and distal femoral osteotomy (DFO), are options that attempt to decrease the loads on the articular cartilage of the meniscus-deficient compartment by replacing meniscal tissue or altering joint alignment. Clinical and biomechanical studies have reported promising outcomes for MAT, HTO, and DFO in the postmeniscectomized knee. These procedures can be performed alone or in conjunction with ligament reconstruction or chondral procedures (reparative, restorative, or reconstructive) to optimize stability and longevity of the knee. Complications can include fracture, nonunion, patella baja, compartment syndrome, infection, and deep venous thrombosis. MAT, HTO, and DFO are effective options for young patients suffering from pain and functional limitations secondary to meniscal deficiency.

Adherence, tolerance and effectiveness of two different pelvic support belts as a treatment for pregnancy-related symphyseal pain - a pilot randomized trial

Abstract: Pregnancy-related pubic symphysis pain is relatively common and can significantly interfere with daily activities. Physiotherapist-prescribed pelvic support belts are a treatment option, but little evidence exists to support their use. This pilot compared two pelvic belts to determine effectiveness (symptomatic relief), tolerance (comfort) and adherence (frequency, duration of use). Unblinded, 2-arm, single-center, randomized (1:1) parallel-group trial. Twenty pregnant women recruited from the community (Dunedin, New Zealand), with physiotherapist-diagnosed symphyseal pain, were randomly allocated to wear either a flexible or rigid belt for three weeks. One author, not involved in data collection, randomized the allocation to trial group. The unblinded primary outcome was the Patient Specific Functional Scale (PSFS). Secondary outcomes were pain intensity during the preceding 24 hours and preceding week (visual analogue scale [VAS]), and disability (Modified Oswestry Disability Questionnaire [MODQ]). Duration of use (hours) was recorded daily by text messaging. Participants were assessed at baseline, by weekly phone interviews and at intervention completion (three weeks). To assess comfort, women wore the alternate belt in the fourth week. Twenty pregnant women (mean ± SD age, 29.4 ± 6.5 years; mean gestation at baseline, 30.8 ± 5.2 weeks) were randomized to treatment groups (flexible = 10, rigid =10) and all were included in analysis. When adjusted for baseline, PSFS scores were not significantly different between groups at follow up (mean difference −0.1; 95% CI: −2.5 to 2.3; p =0.94). Pain in the preceding 24 hours reached statistical significance in favor of the flexible belt (VAS, p = 0.049). Combining both groups’ data, function and pain were significantly improved at three weeks (mean difference −2.3; 95% CI: 1.2 to 3.5; p< 0.001). Belts were worn for an average of 4.9 ± 2.9 hours per day; women preferred the flexible belt. No adverse events were reported. These preliminary results suggest the flexible pelvic support belt may be more effective in reducing pain and is potentially better tolerated than a rigid belt. Based on these data, a larger trial is both feasible and clinically useful. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12614000898651 , 25th August, 2014.

Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy

Abstract: Objective To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. Methods In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. Results There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. Interpretation VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin.

The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial

Abstract: Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California) The placebo was formulated from maltodextrin Study participants were instructed to take the product once daily for 4 weeks Data collected included subjective symptom scores related to lactose intolerance Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0033), abdominal cramping (p = 0012), vomiting (p = 00002), and overall symptom score (p = 0037) No adverse events were reported The present study has found that this unique DDS-1 strain of Lactobacillus acidophilus, manufactured by Nebraska Cultures, is safe to consume and improves abdominal symptom scores compared to placebo with respect to diarrhea, cramping, and vomiting during an acute lactose challenge