Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Editorial: Optimizing opioid prescriptions in the emergency department.

Optimizing opioid prescriptions in the emergency department is essential to address the opioid pandemic while ensuring patient wellbeing. This requires a comprehensive approach that includes exploring alternatives to opioids for pain management, identifying individuals at risk for opioid addiction, implementing evidence-based guidelines, and involving doctors in the management of opioid addiction.

Systemic Inflammation Status Relates to Anti-inflammatory Drug Benefit and Survival in Rectal Cancer.

BACKGROUND: Systemic inflammation status has been recognized as a sensitive marker associated with survival in cancers and anti-inflammatory treatment outcomes in inflammation-derived diseases. This study aimed to investigate the role of systemic inflammation status as a predictive marker for survival and anti-inflammatory treatment benefit in rectal cancer patients. METHODS: A total of 475 patients with stage I-III rectal cancer receiving curative resection were prospectively enrolled. The platelet-neutrophils to lymphocytes ratio (PNLR) that integrates neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios was applied to enable a comprehensive evaluation of systemic inflammation status and investigate its association with survival and nonsteroidal anti-inflammatory drugs (NSAIDs) benefit. Patients were grouped according to baseline PNLR and perioperative use of NSAIDs. RESULTS: The high-PNLR group had worse 5-y disease-free survival (DFS) compared with the low-PNLR group (61.2% versus 70.9%, P = 0.014). Multivariate analyses confirmed that PNLR was an independent predictor for DFS (hazard ratio [HR] 1.42, 95% CI: 1.03-1.97, P = 0.031). A nomogram including PNLR and other independent prognostic factors was developed and validated to predict DFS. In the high-PNLR subset, NSAIDs group had a 21.3% lower risk of recurrence than non-NSAIDs group (P = 0.009), and multivariate analysis confirmed the independently significant association of perioperative NSAIDs use with better DFS (hazard ratio 0.36, 95% CI 0.16-0.78, P = 0.010). However, this association was not significant in the low-PLR subset. CONCLUSIONS: Baseline PNLR could be used to predict DFS and NSAIDs benefit in rectal cancer patients. This study highlights the potential survival benefit from the anti-inflammatory treatment in the patients with elevated systemic inflammation status in cancer patients.

Diclofenac Diminished the Unfolded Protein Response (UPR) Induced by Tunicamycin in Human Endothelial Cells.

Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells. RT PCR analysis showed that diclofenac significantly inhibited activation of ER stress-responsive genes, i.e., CHOP/DITT3, GRP78/HSPA5 and DNAJB9. Additionally, the drug diminished the significant upregulation and release of the GRP78 protein, as evaluated using the ELISA assay, which was likely to be involved in the mechanism of the UPR activation resulting in apoptosis induction in endothelial cells. These results suggest the value of diclofenac as a factor capable of restoring the ER homeostasis in endothelial cells by diminishing the UPR.

Response of Two Crop Plants, Zea mays L. and Solanum lycopersicum L., to Diclofenac and Naproxen.

Among numerous contaminants, the ubiquitous occurrence of nonsteroidal anti-inflammatory drugs (NSAIDs) in the environment and their plausible harmful impact on nontarget organisms have made them one of the most important areas of concern in recent years. Crop plants can also potentially be exposed to NSAIDs, since the concentration of these pharmaceuticals is constantly rising in the surface water and soil. Our goal was to evaluate the stress response of two crop plants, maize and tomato, to treatment with selected NSAIDs, naproxen and diclofenac. The focus of the research was on the growth response, photosynthetic efficiency, selected oxidative stress factors (such as the H2O2 level and the rate of lipid peroxidation) as well as the total phenolic content, which represents the non-enzymatic protectants against oxidative stress. The results indicate that susceptibility to the NSAIDs that were tested is dependent on the plant species. A higher sensitivity of tomato manifested in growth inhibition, a decrease in the content of the photosynthetic pigments and a reduction in the maximum quantum efficiency of PSII and the activity of PSII, which was estimated using the Fv/Fm and Fv/F0 ratios. Based on the growth results, it was also possible to reveal that diclofenac had a more toxic effect on tomato. In contrast to tomato, in maize, neither the content of the photosynthetic pigments nor growth appeared to be affected by DFC and NPX. However, both drugs significantly decreased in maize Fv and Fm, which are particularly sensitive to stress. A higher H2O2 concentration accompanied, in most cases, increasing lipid peroxidation, indicating that oxidative stress occurred in response to the selected NSAIDs in the plant species that were studied. The higher phenolic content of the plants after NSAIDs treatment may, in turn, indicate the activation of defense mechanisms in response to the oxidative stress that is triggered by these drugs.

NSAIDs in CKD: Are They Safe?

The management of pain in patients with chronic kidney disease (CKD) is challenging for many reasons. These patients have increased susceptibility to adverse drug effects due to altered drug metabolism and excretion, and there are limited safety data for use in this population despite a high pain burden. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been regarded as dangerous for use in patients with CKD because of their risk for nephrotoxicity and thus alternative classes of analgesics, including opioids, have become more commonly used for pain control in this population. Given the well-established risks that opioids and other analgesics pose, further characterization of the risk posed by NSAIDs in patients with CKD is warranted. NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension. The risk for these nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate. In this review, we offer recommendations for the cautious use of NSAIDs in the CKD population after careful consideration of these risk factors on an individualized basis.

The association between nonsteroidal anti-inflammatory drugs and skin cancer: Different responses in American and European populations.

OBJECTIVE: To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations. METHODS: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations. RESULTS: Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses. CONCLUSIONS: The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.

Direct detection of diclofenac radical produced by ultraviolet irradiation using electron spin resonance method.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as an antipyretic analgesic owing to its strong anti-inflammatory action in clinical treatment. However, diclofenac can cause injury, with gastrointestinal mucosal lesions and skin photosensitivity as the main side effects. In general, photosensitive drugs contain photosensitive chemical sites, and form free radicals under ultraviolet irradiation, leading to phototoxic reactions. Therefore, this study focuses on free radical production in photosensitive reactions of diclofenac. The free radical production mechanism of diclofenac under ultraviolet irradiation, which might result in photo-toxicity, was clarified using a direct electron spin resonance method. When diclofenac was irradiated with ultraviolet light (254 nm), diclofenac radicals were generated depending on the ultraviolet irradiation time and stably present for 30 min at room temperature. Diclofenac radicals were produced by the ultraviolet irradiation system depending on the dose of diclofenac until 2 mM. Therefore, diclofenac radicals might directly or indirectly react with various biomolecules to cause phototoxicity, other side effects, and new diclofenac pharmacology owing to its stability of diclofenac radicals.

Indomethacin elicits proteasomal dysfunctions develops apoptosis through mitochondrial abnormalities.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that are mainly used to treat pain, inflammation, and fever via cyclooxygenase-2 (COX-2) inhibition. There are abundant findings that uncover the hidden critical chemotherapeutics potential of NSAIDs in cancer treatment. However, still the precise mechanism by which NSAIDs could be used as an effective anti-tumor agent in the prevention of carcinogenesis is not well understood. Here, we show that indomethacin, a well-known NSAID, induces proteasomal dysfunction that results in accumulation of unwanted proteins, mitochondrial abnormalities, and successively stimulate apoptosis in cells. We observed the interaction of indomethacin with proteasome and noticed the massive accumulation of intracellular ubiquitin-positive proteins, which might be due to the suppression of proteasome activities. Furthermore, we also found that exposure of indomethacin causes the accumulation of critical proteasomal substrates that consequently generate severe mitochondrial abnormalities and prompt up key apoptotic events in cells. Our results demonstrate how indomethacin affects normal proteasomal functions and induces mitochondrial apoptosis in cells. These findings also improve our current understanding of how NSAIDs can exhibit crucial anti-proliferative effects in cells. In near future, our findings may suggest a new possible strategy for the development of specific proteasome inhibitors in conjunction with other chemo-preventive anticancer agents.

Risk of acute myocardial infarction with real-world NSAIDs depends on dose and timing of exposure.

PURPOSE: Real-life use of nonsteroidal anti-inflammatory drugs (NSAIDs) is dynamic. This study aimed to characterize the temporal association between time-varying NSAID exposure and acute myocardial infarction (MI). METHODS: Nested case-control analyses were conducted on a Quebec administrative health cohort. NSAID dose, confounders, and outcome status were determined for each day of follow-up. To better account for dose and timing of past exposures, flexible weighted cumulative exposure models were also fitted. RESULTS: The cohort consisted of 233 816 older adults including 21 256 acute MI cases. Dose-related increased risks of MI were found with current use of all NSAIDs. In models not accounting for duration of use, ORs (95%CI) for the most common current daily dose vs. no current exposure were: celecoxib 200 mg: 1.16 (1.10, 1.22), diclofenac 150 mg: 1.59 (1.38, 1.84), ibuprofen 1200 mg: 1.42 (1.17, 1.74), naproxen 750 mg: 1.38 (1.21, 1.58), and rofecoxib 25 mg: 1.54 (1.43, 1.66). Weighted cumulative exposure models confirmed that all NSAIDs-including naproxen-are associated with an increased risk of MI and suggested that doses taken up to 3 weeks ago for rofecoxib, ibuprofen, and naproxen and up to 75 days ago for diclofenac and celecoxib may contribute to the current MI risk. However, the celecoxib risk seems to require continuous use for more than 30 days, whereas for other NSAIDs, a heightened MI risk occurs within 7 days. CONCLUSIONS: Weighted cumulative exposure analysis uncovered NSAID-specific differences in the immediate MI risk and how this risk seems to accumulate. KEY POINTS Accurate assessment of drug safety requires an etiologically correct model encompassing all relevant aspects of exposure. Weighted cumulative exposure models suggest that the relative importance of past doses on the risk of MI differs among NSAIDs. All common NSAIDs are associated with an increased MI risk. Celecoxib MI risk seems to depend on continuously using the drug for more than 30 days, whereas for ibuprofen, rofecoxib, diclofenac, and naproxen, a heightened MI risk occurs within 7 days of use.

Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study.

PURPOSE: The SALT study found similar per-user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a threefold higher risk in nonoverdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP. METHODS: Case-population study in the 1/97 sample of the French population claims database. Acute liver injury was identified from hospital discharge summaries, from 2009 to 2013. Exposure for cases was dispensing of NSAID or NOP resulting in exposure within 30 days before admission. Population exposure was the number of patients using the drugs over the study timeframe and total number of DDD dispensed. RESULTS: Of 63 cases of ALI, 13 had been exposed to NSAIDs and 24 to NOP. Events per million DDD (95% CI) ranged from 0.46 (0.09-1.34) (ketoprofen) to 1.43 (0.04-7.97) (diclofenac combinations), 0.43 (0.23-0.73) all NSAIDs combined, 0.58 (0.37-0.86) for NOP. There was no association with average duration of treatment. Per patient risk ranged from 19.5 (5.31-49.9) (ibuprofen) per million users to 37.2 (19.8-63.6) all NSAIDs combined, 58.0 (37.2-86.3) for NOP. There was a linear relationship between average treatment duration and per-user risk (R2  = 0.51, P < .05 for NSAIDs, R2  = 0.97, P < .01 for NOP). CONCLUSIONS: Risk of hospital admission for ALI with NSAIDs and NOP was similar and indicative of a dose and duration-related effect (pharmacological) effect. Acute liver injury rates were not predictive of ALFT risk.

Enhanced recovery after surgery in children: Promising, evidence-based multidisciplinary care.

Enhanced recovery after surgery (ERAS) is a multimodal approach to the care of the surgical patient focused on reducing the stress response and associated physiologic changes that accompany surgery. Over the past 20 years, ERAS programs have been found to result in reduced LOS and complications in adult patients. Despite abundant adult literature describing implementation and outcomes of enhanced recovery programs, pediatric data in this area is sparse. This educational review describes the history and elements of ERAS protocols, reviews the available evidence in adult and pediatric populations, compares and contrasts ERAS with the PSH, and offers strategies for implementation and ideas for future directions of ERAS in children.

Acute Respiratory Infection and Use of Nonsteroidal Anti-Inflammatory Drugs on Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study.

Background: Previous studies have suggested that acute respiratory infection (ARI) and nonsteroidal anti-inflammatory drugs (NSAIDs) use could trigger acute myocardial infarction (AMI). In some countries, physicians prescribe NSAIDs for patients with ARI for symptom relief. However, there is no research evaluating whether NSAIDs use during ARI episodes may increase the risk of AMI. Methods: We identified 9793 patients with an incident hospitalization of AMI (index date) between 2007 and 2011. Using case-crossover design, we compared the following exposure status between the case (1-7-day before index date) and matched control period (366-372-day before index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional logistic regression models were used to estimate odds ratios adjusted for potential confounders. Results: Nonsteroidal anti-inflammatory drugs use during ARI was associated with a 3.4-fold increased risk of AMI (adjusted odds ratio [aOR] = 3.41; 95% confidence interval [CI] = 2.80-4.16), ARI without NSAIDs use was associated with a 2.7-fold increased risk (aOR = 2.65; 95% CI = 2.29-3.06), and NSAIDs use only was associated with a 1.5-fold increased risk (aOR = 1.47; 95% CI = 1.33-1.62). Moreover, parenteral NSAIDs were associated with much higher risk in ARI patients (aOR = 7.22; 95% CI = 4.07-12.81). Conclusions: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs, was associated with a further increased risk of AMI.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol do not affect 6-month mood-stabilizing treatment outcome among 482 patients with bipolar disorder.

BACKGROUND: Many mood disorder patients need analgesics due to increased pain sensitivity. Recent studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit antidepressant treatment, which requires replication before clinical recommendations. METHODS: The Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study randomized participants to 6 months lithium or quetiapine treatment. Use of NSAIDs and paracetamol was assessed throughout the study period and psychopathology measured with the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) and Bipolar Inventory of Symptoms Scale (BISS). The effects of NSAIDs and paracetamol on treatment outcome were examined using mixed effects linear regression adjusted for age, gender, body mass index, smoking status, exercise, and somatic diseases. RESULTS: Among 482 participants, 177 (36.7%) used NSAIDs and/or paracetamol during the study. NSAID and paracetamol users did not differ from nonusers with respect to treatment outcome with lithium or quetiapine at any time point during 6 months treatment on the overall CGI-BP (ß = 0.001 (95% CI = -0.01 to -0.01), P = .87), the BISS (ß = 0.01 (95% CI = -0.17 to 0.15), P = .91), nor the CGI-BP subscales for depression or mania. Users of NSAIDs only (n = 76), paracetamol only (n = 62), and users of both NSAIDs and paracetamol (n = 39) showed no statistical difference compared to nonusers (all P > .3). CONCLUSIONS: This is the first trial to show that use of NSAIDs and paracetamol, alone or in combination, does not affect lithium- or quetiapine-based bipolar disorder mood-stabilizing treatment outcomes. Prior studies have suggested that NSAIDs may inhibit antidepressant treatment, whereas our results support findings indicating no detrimental effects of NSAIDs or paracetamol on affective disorder treatment.

Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis.

OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen-Antioxidant Mutual Prodrugs.

Dexibuprofen-antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a-c were obtained by reacting its -COOH group with chloroacetyl derivatives 3a-c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a-c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a-c interacts with the residues present in active binding sites of target protein. The stability of drug-target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk.

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management.

Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis.

Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy.

Effect of pulsed radiofrequency to the suprascapular nerve (SSN) in treating frozen shoulder pain: A randomised controlled trial.

BACKGROUND: Treatment for frozen shoulder (FS) focuses on pain control and restoring movement and strength through physical therapy. We aimed to evaluate the efficacy of pulsed radiofrequency (PRF) lesioning of the suprascapular nerve for the treatment of FS pain. METHODS: Forty patients with FS were enrolled and randomly assigned into the intervention group (n = 20) that received PRF and a control group (n = 20) which received medical treatment (NSAIDs). Patients were followed-up for a total of three months. The primary outcome was the pain intensity, measured by the Numeric Pain Rating Scale (NRS). The secondary outcomes included shoulder range of motion (ROM) evaluation measured by simple shoulder test (SST); Likert-type-based patient satisfaction scale; and any adverse events (AEs) throughout the treatment period. All results were measured at baseline, at the end of one week, four weeks and 12 weeks after treatment. RESULTS: At 12 weeks post-procedure, the intervention group significantly improved their pain (NRS dropped to 2.80 ± 0.5) and there was significant improvement in range of motion (SST from 6.55% ± 2.0% to 76.50% ± 6.5) compared to control group. CONCLUSIONS: PRF lesioning of the SSN is a fast and effective modality in treating frozen shoulder pain and improving ROM for three months.