Duloxetine; the clinical picture described is of diabetic neuropathy. Of the drugs proposed, the first choice would be a dual antidepressant such as duloxetine.

A woman diagnosed with type 1 diabetes mellitus for 24 years. She comes to the office with 3 months of clinical evolution of tingling in both feet, with distribution in sock, with paresthetic pain and sensation of hot feet predominantly at night, which significantly interferes with sleep. Which of the following drugs would you use in the first line for the treatment of her pathology?

Treatment-induced diabetes neuropathy: description of singular clinical signs to reach a prompt diagnosis.

A 23-year-old woman diagnosed with type 1 diabetes mellitus in 2011 came to our outpatient office because of an inability to walk correctly. She was under a basal bolus insulin regimen. In the summer of 2016, she experienced a rapid improvement in her glycaemic control. A few weeks later, she started to complain of a severe burning pain in the soles of her feet (pain score 10/10). Neither macrovascular nor microvascular complications were detected. The patient was forced to walk barefoot due to an intense pain using shoes or socks and used to soak her feet in water for several hours daily. She also developed severe intolerance to environmental heat, both indoors and outdoors. A diagnosis of treatment-induced diabetic neuropathy was made. The patient was admitted to a general ward to start pain therapy. After a 6-month course of different neuropathic pain drugs, the patient was able to walk autonomously again.

When the Treatment Becomes the Problem.

A 47-year-old white male with a 5-year history of type 2 diabetes mellitus presented to clinic with uncontrolled hyperglycemia, weight loss, and body aches that impeded his ability to work and sleep. He had initially controlled his diabetes successfully with weight loss and exercise. However, in the previous 6 months he had noticed unintentional weight loss. He was evaluated at another clinic where he was prescribed sitagliptin/metformin (Janumet) for his uncontrolled hyperglycemia. After 6 weeks his blood glucose had not significantly improved, and an endocrinologist prescribed insulin glargine (Lantus) and insulin aspart (NovoLog). About 3 days later he developed migratory joint pains and myalgias. After some weeks his insulin regimen was changed to insulin detemir (Levemir), and his myalgia symptoms briefly improved but then worsened. He experienced tingling of his feet that caused increasing difficulty sleeping. His review of systems was remarkable for fatigue, weight loss, polydipsia, polyphagia, polyuria, myalgias and arthralgias, numbness and tingling of both feet, and difficulty sleeping.

Evidence-based interventional pain medicine according to clinical diagnoses. 18. Painful diabetic polyneuropathy.

In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM-induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second-line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.

Painful diabetic neuropathy: diagnosis and management.

The prevalence of painful diabetic peripheral neuropathy (PDN) is about 20% in patients with type 2 diabetes and 5% in those with type 1. Patients should be systematically questioned concerning suggestive symptoms, as they are not usually volunteers. As PDN is due to small-fibre injury, the 10 g monofilament pressure test as well as the standard electrophysiological procedures may be normal. Diagnosis is based on clinical findings: type of pain (burning discomfort, electric shock-like sensation, aching coldness in the lower limbs); time of occurrence (mostly at rest and at night); and abnormal sensations (such as tingling or numbness). The DN4 questionnaire is an easy-to-use validated diagnostic tool. Three classes of drugs are of equal value in treating PDN: tricyclic antidepressants; anticonvulsants; and selective serotonin-reuptake inhibitors. These compounds may be prescribed as first-line therapy following pain assessment using a visual analogue scale. If the initial drug at its maximum tolerated dose does not lead to a decrease in pain of at least 30%, another drug class should be prescribed; if the pain is decreased by 30% but remains greater than 3/10, a drug from a different class may be given in association.

Peripheral neuropathy

Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it was thought that many of the cases of small fiber peripheral neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in the prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes." The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.

InternalMed_Harrison

Polyneuropathy/Mononeuropathy The most common form of diabetic neuropathy is distal symmetric polyneuropathy. It most frequently presents with distal sensory loss and pain, but up to 50% of patients do not have symptoms of neuropathy. Hyperesthesia, paresthesia, and dysesthesia also may occur. Any combination of these symptoms may develop as neuropathy progresses. Symptoms may include a sensation of numbness, tingling, sharpness, or burning that begins in the feet and spreads proximally. Neuropathic pain develops in some of these individuals, occasionally preceded by improvement in their glycemic control. Pain typically involves the lower extremities, is usually present at rest, and worsens at night. Both an acute (lasting <12 months) and a chronic form of painful diabetic neuropathy have been described. The acute form is sometimes treatment-related, occurring in the context of improved glycemic control. As diabetic neuropathy progresses, the pain subsides and eventually disappears,

Top 20 Research Studies of 2021 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

A comparative double-blind randomized study on the effectiveness of Duloxetine and Gabapentin on painful diabetic peripheral polyneuropathy.

<bBackground:</b The most common cause of polyneuropathy is diabetes mellitus. Neuropathic pain is seen in 26% of diabetic population. Therapeutic techniques for this disease can become challenging. <bMethod:</b This study was a prospective comparative double-blind randomized study which was conducted during an eight-week period. Totally, 104 painful diabetic peripheral polyneuropathy (PDPP) patients who had a minimum Visual Analog Scale (VAS) of 40 millimeters, received no pain-controlling medication, and had no other severe disease at its final stage were randomly assigned to two groups (n=52) through the four block method. One group received Duloxetine and the other received Gabapentin. The effectiveness was measured through primary effectiveness (VAS scale) and secondary effectiveness (Sleep Interference Score, and Clinical Global Impression of Change (CGIC)). Medication compliance was assessed by enumerating the number of patients who refused treatment because of side effects. The Fisher's exact T-test and ANOVA were used for data analysis. This study was approved by the Ethics Committee of Jundishapur, University of Medical sciences Ahvaz, Iran, under reference number: IR.AJUMS.REC.1395.78. In addition, this study was registered and approved in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20161023030455N2) (http://irct.ir/). <bResults:</b VAS, Sleep Interference Score, and CGIC were significantly improved (P<0.05) through time in both groups, [For GBP: VAS<supBaseline</sup=64±20.03, VAS<supweek1</sup=55.32±18.76, VAS<supweek4</sup=44.68±15.82, VAS<supweek8</sup=39.43±14.32; For DLX: VAS<supBase-line</sup=62±21.18, VAS<supweek1</sup=58.76±20.37, VAS<supweek4</sup=45.84±16.21, VAS<supweek8</sup=36.78±15.62] while a significant difference between the two groups was not observed (P<0.05). However, such significant improvements were not observed in the Duloxetine group at the end of the first week (P=674). Improvement in Sleep Interference Score and CGIC were similar to the results for the VAS scale. Side effects in the Duloxetine group (n=2) compared to the Gabapentin group (n=9) were significantly less (P<0.001). As a result, medication acceptance in the Duloxetine group (n=47) was significantly better than the Gabapentin (n=41) group (P<0.001). <bConclusion:</b Both Duloxetine and Gabapentin are effective for the treatment of PDPP. On the one hand, Gabapentin shows the effect earlier while has more side effects. Conversely, Duloxetine has better medication compliance. <bTrial registration:</b The method of this study was approved by the Ethics Committee of Jundishapur University of Medical Sciences, Ahvaz, Iran, under reference number: IR.AJUMS.REC.1395.78. In addition, this study was registered and approved in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20161023030455N2) (http://irct.ir/).

Top 20 Research Studies of 2017 for Primary Care Physicians.

Based on systematic surveillance of more than 110 medical journals, 247 studies met criteria as POEMs (patient-oriented evidence that matters) in 2017. Members of the Canadian Medical Association identified 20 of these POEMs as most relevant to practice. This article reviews the clinical questions and bottom-line answers from these studies. Blood pressure should be measured after a period of rest, using a bare arm, and orthostatic blood pressure is more predictive when measured after one minute of standing rather than three minutes. Intensive blood pressure lowering results in cardiovascular benefits but also renal harms in high-risk patients with an average age of 68 years. The initiation of a statin for primary prevention does not reduce cardiovascular events in adults 65 years or older. Sterile gloves do not reduce the risk of infection for common outpatient skin procedures, and the preferred approach to managing onychomycosis is empiric oral terbinafine. Routine home glucose monitoring is not needed in patients with type 2 diabetes mellitus, and trying to achieve an A1C target level of 6.0% rather than 7.0% to 7.9% does not improve outcomes and may be harmful. Fasting blood glucose and A1C levels have limited accuracy for identifying glucose intolerance, and patients 65 years and older with thyroid-stimulating hormone levels between 4.6 and 10.0 mIU per mL should be rechecked before considering treatment. Gabapentin and pregabalin are not effective for acute or chronic low back pain, even in patients with sciatica. Physical therapy does not provide any additional benefit over usual care in patients with acute ankle sprain, and corticosteroid injections for knee osteoarthritis are ineffective and may damage cartilage. A two-question screening test can rule out depression in older adults; a large U.S. trial continued to find no benefit to prostate cancer screening; and clinicians need to be thoughtful about how they discuss recommendations to stop screening for cancer in older patients. Finally, ibuprofen, naproxen, and celecoxib have similar risks of adverse events, and continuous positive airway pressure in patients with obstructive sleep apnea does not reduce the risk of cardiovascular events.

InternalMed_Harrison

evidence of peripheral nerve disease. Presenting symptoms are usually painful burning sensations in the feet and lower extremities. Findings on examination include a stocking-type sensory loss to pinprick, temperature, and touch sensation and a loss of ankle reflexes. Motor changes are mild and are usually limited to weakness of the intrinsic foot muscles. Response of this condition to antiretrovirals has been variable, perhaps because antiretrovirals are responsible for the problem in some instances. When due to dideoxynucleoside therapy, patients with lower extremity peripheral neuropathy may complain of a sensation that they are walking on ice. Other entities in the differential diagnosis of peripheral neuropathy include diabetes mellitus, vitamin B12 deficiency, and side effects from metronidazole or dapsone. For distal symmetric polyneuropathy that fails to resolve following the discontinuation of dideoxynucleosides, therapy is symptomatic; gabapentin, carbamazepine, tricyclics,

Small Fiber Neuropathy in Children: Two Case Reports Illustrating the Importance of Recognition.

Small fiber neuropathy (SFN) is a debilitating condition that often leads to pain and autonomic dysfunction. In the last few decades, SFN has been gaining more attention, particularly in adults. However, literature about SFN in children remains limited. The present article reports the cases of 2 adolescent girls diagnosed with SFN. The first patient (14 years of age) complained about painful itch and tingling in her legs, as well as dysautonomia symptoms for years. She also reported a red/purple-type discoloration of her legs aggravated by warmth and standing, compatible with erythromelalgia. The diagnosis of SFN was confirmed by a reduced intraepidermal nerve fiber density (IENFD) in skin biopsy sample. No underlying conditions were found. Symptomatic neuropathic pain treatment was started with moderate effect. The second patient (16 years of age) developed painful sensations in both feet and hands 6 weeks after an ICU admission for diabetic ketoacidosis, which included dysautonomia symptoms. She also exhibited some signs of erythromelalgia. The patient was diagnosed with predominant SFN (abnormal IENFD and quantitative sensory testing) as well as minor large nerve fiber involvement. Treatment with duloxetine, combined with a rehabilitation program, resulted in a marked improvement in her daily functioning. Although the SFN diagnosis in these 2 cases could be established according to the definition of SFN used in adults, additional diagnostic tools are needed that may be more appropriate for children. Additional information about the course of SFN in children may result in better treatment options.

Treatment-induced diabetes neuropathy: reminder of an important clinical lesson.

Treatment-induced neuropathy of diabetes (TIND) is an acute, painful and rare complication of intensive glycaemic control in diabetes. We present a case of a 32-year-old man with sudden onset of severe lower limb pain. It worsened progressively and was refractory to analgesic and muscle relaxant therapies. It became so severe that the patient was impossible to stand, causing a marked impact on his daily life. He had a history of type 1 diabetes, diagnosed 3 years ago, and an episode of deep vein thrombosis of the left leg, 4 years ago. While completing an extensive workup, various analgesic adjustments were made, with no improvement. After careful revision of his medical data, a significant reduction of his A1C 6 months before the appearance of symptoms was noticed. A diagnosis of TIND was made. The patient was treated with amitriptyline and showed noticeable improvement after the first month.

Breathlessness with pulmonary metastases: a multimodal approach.

Case Study  Sarah is a 58-year-old breast cancer survivor, social worker, and health-care administrator at a long-term care facility. She lives with her husband and enjoys gardening and reading. She has two grown children and three grandchildren who live approximately 180 miles away. SECOND CANCER DIAGNOSIS  One morning while showering, Sarah detected a painless quarter-sized lump on her inner thigh. While she thought it was unusual, she felt it would probably go away. One month later, she felt the lump again; she thought that it had grown, so she scheduled a visit with her primary care physician. A CT scan revealed a 6.2-cm soft-tissue mass in the left groin. She was referred to an oncologic surgeon and underwent an excision of the groin mass. Pathology revealed a grade 3 malignant melanoma. She was later tested and found to have BRAF-negative status. Following her recovery from surgery, Sarah was further evaluated with an MRI scan of the brain, which was negative, and a PET scan, which revealed two nodules in the left lung. As Sarah had attended a cancer support group during her breast cancer treatment in the past, she decided to go back to the group when she learned of her melanoma diagnosis. While the treatment options for her lung lesions included interleukin-2, ipilimumab (Yervoy), temozolomide, dacarbazine, a clinical trial, or radiosurgery, Sarah's oncologist felt that ipilimumab or radiosurgery would be the best course of action. She shared with her support group that she was ambivalent about this decision, as she had experienced profound fatigue and nausea with chemotherapy during her past treatment for breast cancer. She eventually opted to undergo stereotactic radiosurgery. DISEASE RECURRENCE  After the radiosurgery, Sarah was followed every 2 months. She complained of shortness of breath about 2 weeks prior to each follow-up visit. Each time her chest x-ray was normal, and she eventually believed that her breathlessness was anxiety-related. Unfortunately, Sarah's 1-year follow-up exam revealed a 2 cm × 3 cm mass in her left lung, for which she had a surgical wedge resection. Her complaints of shortness of breath increased following the surgery and occurred most often with anxiety, heat, and gardening activities, especially when she needed to bend over. Sarah also complained of a burning "pins and needles" sensation at the surgical chest wall site that was bothersome and would wake her up at night. Sarah met with the nurse practitioner in the symptom management clinic to discuss her concerns. Upon physical examination, observable signs of breathlessness were lacking, and oxygen saturation remained stable at 94%, but Sarah rated her breathlessness as 7 on the 0 to 10 Borg scale. The nurse practitioner prescribed duloxetine to help manage the surgical site neuropathic pain and to assist with anxiety, which in turn could possibly improve Sarah's breathlessness. Several nonpharmacologic modalities for breathlessness were also recommended: using a fan directed toward her face, working in the garden in the early morning when the weather is cooler, gardening in containers that are at eye level to avoid the need to bend down, and performing relaxation exercises with pursed lip breathing to relieve anxiety-provoked breathlessness. One month later, Sarah reported relief of her anxiety; she stated that the fan directed toward her face helped most when she started to feel "air hungry." She rated her breathlessness at 4/10 on the Borg scale. SECOND RECURRENCE: MULTIPLE PULMONARY NODULES  Sarah's chest x-rays remained clear for 6 months, but she developed a chronic cough shortly before the 9-month exam. An x-ray revealed several bilateral lung lesions and growth in the area of the previously resected lung nodule. Systemic therapy was recommended, and she underwent two cycles of ipilimumab. Sarah's cough and breathlessness worsened, she developed colitis, and she decided to stop therapy after the third cycle. In addition, her coughing spells triggered bronchospasms that resulted in severe anxiety, panic attacks, and air hunger. She rated her breathlessness at 10/10 on the Borg scale during these episodes. She found communication difficult due to the cough and began to isolate herself. She continued to attend the support group weekly but had difficulty participating in conversation due to her cough. Sarah was seen in the symptom management clinic every 2 weeks or more often as needed. No acute distress was present at the beginning of each visit, but when Sarah began to talk about her symptoms and fear of dying, her shortness of breath and anxiety increased. The symptom management nurse practitioner treated the suspected underlying cause of the breathlessness and prescribed oral lorazepam (0.5 to 1 mg every 6 hours) for anxiety and codeine cough syrup for the cough. Opioids were initiated for chest wall pain and to control the breathlessness. Controlled-release oxycodone was started at 10 mg every 12 hours with a breakthrough pain (BTP) dose of 5 mg every 2 hours as needed for breathlessness or pain. Sarah noted improvement in her symptoms and reported a Borg scale rating of 5/10. Oxygen therapy was attempted, but subjective improvement in Sarah's breathlessness was lacking. END OF LIFE  Sarah's disease progressed to the liver, and she began experiencing more notable signs of breathlessness: nasal flaring, tachycardia, and restlessness. Opioid doses were titrated over the course of 3 months to oxycodone (40 mg every 12 hours) with a BTP dose of 10 to 15 mg every 2 hours as needed, but her breathlessness caused significant distress, which she rated 8/10. The oxycodone was rotated to IV morphine continuous infusion with patient-controlled analgesia (PCA) that was delivered through her implantable port. This combination allowed Sarah to depress the PCA as needed and achieve immediate control of her dyspneic episodes. Oral lorazepam was also continued as needed. Sarah's daughter moved home to take care of her mother, and hospice became involved for end-of-life care. As Sarah became less responsive, nurses maintained doses of morphine for control of pain and breathlessness and used a respiratory distress observation scale to assess for breathlessness since Sarah could no longer self-report. A bolus PCA dose of morphine was administered by Sarah's daughter if her mother appeared to be in distress. Sarah died peacefully in her home without signs of distress.

Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy.

To examine the efficacy and safety of tramadol/acetaminophen (APAP) for the management of painful diabetic peripheral neuropathy (DPN). Adults with painful DPN involving the lower extremities received 37.5 mg tramadol/325 mg APAP or placebo, up to 1-2 tablets four times daily, for 66 days. Subjects rated average daily pain and sleep interference from 0 ('none') to 10 ('pain as bad as you can imagine' or 'complete interference') every night. Baseline values were recorded for 7 days before starting study medication. The primary endpoint was change in mean of average daily pain scores from baseline to final week. Secondary efficacy outcomes included pain intensity, sleep interference, quality of life, mood, and global impression of change. Potential study limitations included permission to use serotonin reuptake inhibitors concomitantly (except venlafaxine or duloxetine) and the lack of a tramadol-alone or APAP-alone control group. A total of 160 subjects received tramadol/APAP and 153 received placebo. Tramadol/APAP reduced average daily pain significantly compared to placebo from baseline to the final week (-2.71 vs. -1.83, p = 0.001). Tramadol/APAP was associated with significantly greater improvement than placebo (p < or = 0.05) for all measures of pain intensity, sleep interference, and global impression, as well as several measures of quality of life and mood. The only adverse event reported by > 10% of subjects in either the tramadol/APAP or placebo group was nausea (11.9% and 3.3%, respectively). Adverse events resulted in early study discontinuation for 8.1% and 6.5% of subjects in the tramadol/APAP and placebo groups, respectively. Tramadol/APAP was more effective than placebo and was well tolerated in the management of painful DPN.

Oxycodone/ibuprofen

Oxycodone/ibuprofen (INNs, trade name Combunox) is an oral combination drug formulation of the opioid analgesic oxycodone and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen that is used in the treatment of chronic and acute pain. This particular drug is supplied in a fixed dose combination tablet which contains Oxycodone Hydrochloride, USP 5 mg with Ibuprofen, USP 400 mg. Adverse effects See also Oxycodone/paracetamol Oxycodone/aspirin Hydrocodone/ibuprofen References External links Combination analgesics

Clinical Approach to the Treatment of Painful Diabetic Neuropathy.

Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated.This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first, second and third line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions and cost. Additional topics of discussion include breakthrough pain, opioid use and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient.

Midthoracic Punctate Midline Myelotomy for Treatment of Chronic, Intractable, Nonmalignant, Abdominal Visceral Pain: 2-Dimensional Operative Video.

Punctate midline myelotomy (PMM) is a surgical procedure that damages the ascending fibers of the postsynaptic dorsal column (PSDC) pathway to interrupt visceral pain transmission.1-3 It can offer relief to patients with chronic visceral pain conditions that are refractory to other treatments. Here, we present a surgical video of midthoracic PMM in a patient with chronic, intractable, nonmalignant visceral abdominal pain that failed over a decade of medical treatment. We choose T7-8 as the level for laminectomy in patients with pelvic or lower abdominal pain, because the postsynaptic pain fibers transmitting visceral pain sensation from the lower abdominal organs will invariably be caudal to this level. The patient developed immediate and complete relief of her visceral pain after the procedure, which was sustained through the 11-wk follow-up period to date and was able to be weaned off narcotics. Postoperatively, she remained full strength and had no impairment of light touch or proprioception of her lower extremities. Detailed physical examination showed a reduced vibratory sensation on the glabrous skin of her great toes. Regarding patient-reported sensory changes (not detected on physical examination), she reported some numbness on the insides of her feet that had resolved by 11-wk follow-up. She also reported some numbness of the vulva, but not of the vagina. However, by 11-wk follow-up, she reported this had resolved and she had normal sexual function. The only persistent sensation at 11-wk follow-up was slight tingling in her toes that was not bothersome to her.4 The patient presented in the following video consented to both the surgical procedure and the publication of her clinical history and operative video.

[Primary hyperparathyroidism of chance, a case study].

The authors are reporting here a documented case of hyperparathyroidism leading to hypercalcemia diagnosed spontaneously. A 75-year old female patient with has been treated since 3-4 years with metformin and ramipiril fortype 2 diabetes and high blood pressure, respectively. She was seen in our endocrinology outpatient visit for tingling in the arms associated with cervical pain with increasing intensity over the last six months. The patient's mother was diabetic and her father had high blood pressure. The diagnostic of primary hyperparathyroidism, resulting from a diffuse hyperplasia of the parathyroid gland, was retained after medical, biological, chirurgical and anatomo-pathological investigations. The blood level of PTH1-84 was 916.60pg/ml Normal value=15-68.3pg/ml. Diffuse poly-arthralgia in the neck and the lower limbs may not always be due to arthrosis in elderlies. Further investigation such as the dosage of blood level of calcium and PTH are required.

Clinical and nerve conduction study correlation in patients of diabetic neuropathy.

1) To study types of neuropathy in Type 2 diabetes. 2) To correlate clinical features of peripheral neuropathy with nerve conduction study in Type 2 diabetes. A total of 50 diabetics, whose onset of diabetes after the age of 30 years were studied from Dr. D. Y. Patil hospital and research centre. Type 2 Diabetes mellitus with symptom suggestive of peripheral neuropathy were studied and included. Chronic alcoholic, peripheral neuropathy due to any other known cause were excluded. METHOD OF COLLECTION OF DATA: History of symptoms like paraesthesia like tingling sensation, burning feet, hyperaesthesia, foot ulcer, history of weakness and gait abnormality was noted. Complete central nervous system examination was performed to look for signs such as diminished ankle jerk, diminished power. Sensory examination for loss of light touch, superficial pain, temperature sense, vibration and joint position was done. Nerve conduction studies were performed using Clarity Octopus NCV/EMG machine. Written and informed consent from patient were taken. 1) 46 patients i.e. 92% presented with complaints of tingling sensation and 32 patients i.e. 64% had burning feet. 2) 29 patients i.e. 58% have diminished ankle jerk, 29 patients i.e. 58% have diminished or loss of vibration sense, in 21 patients i.e. 42% patients have diminished light touch and 20 patients i.e. 40% patients have loss of joint position senses. 3) NCV performed on 50 patients of diabetic neuropathy out of which all patients i.e. 100% had involvement of lower limb and only 24 patients i.e. 48% had involvement of upper limb also. 4) Involvement of tibial and sural nerve is more common i.e. 86% and 82% respectively. 5) 42 patients i.e. 84% found to have distal symmetrical polyneuropathy, 2 patients i.e. 4% had isolated tibial nerve involvement, 4 patients i.e. 8% had pure sensory sural nerve involvement, and only 1 patient each of isolated medial and plantar nerve involvement. Distal symmetrical polyneuropathy is most common form of diabetic neuropathy. Involvement of tibial and sural nerve is more common in diabetic neuropathy.

[Diabetic Neuropathy. Diagnosis and Treatment in the Physician's Office].

The most common form of diabetic neuropathy is the distal symmetrical sensorimotor variety. It is all the more likely to develop, the longer diabetes mellitus has been clinically manifest. Clinical signs of this neuropathy include the loss of the Achilles tendon reflex, sensory disorders beginning distally, distal muscle paresis and such signs of autonomic nerve involvement as erectile disorders, disordered bladder emptying, diaphoretic disorders or orthostatic hypotension. The diagnostic work-up should also include a number of laboratory investigations to exclude other causes of neuropathy. The basis of treatment is the earliest detection of diabetes mellitus and the establishment of normoglycemia. The individual manifestations are treated symptomatically. For the treatment of pain, it may become necessary to apply opioids if antidepressants and anticonvulsants fail to prove effective.

Paracetamol

Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior to ibuprofen in that respect, and the benefits of its use for fever are unclear. Paracetamol may relieve pain in acute mild migraine but only slightly in episodic tension headache. However, the aspirin/paracetamol/caffeine combination helps with both conditions where the pain is mild and is recommended as a first-line treatment for them. Paracetamol is effective for post-surgical pain, but it is inferior to ibuprofen. The paracetamol/ibuprofen combination provides further increase in potency and is superior to either drug alone. The pain relief paracetamol provides in osteoarthritis is small and clinically insignificant. The evidence in its favor for the use in low back pain, cancer pain and neuropathic pain is insufficient.

[Night headache: report of 2 cases].

The pathogenesis of hypnic headache is still unknown. Some authors supposed that the genesis of hypnic disorder is a decrease of melatonin secretion. It is a rare, moderately severe headache that occurs in middle-aged or elderly patients and affects both sexes. It appears exclusively during sleep and often with alarm clock regularity. The attack lasts from two to 6 hours, it may be unilateral or diffuse, pulsating or boring, without autonomic system features. Case 1. A 49 year old man reported the history of two week nocturnal headache that awakened him every night from sleep. The headache lasted two hours. There were no autonomic system features. Case 2. A 52 year old man suffered from nocturnal headaches for 6 weeks. The pain occurred between 2 and 5 almost every night and woke the patient. He suffered from diabetes mellitus too. Both patients were treated with flunarizine with good results.

Hand and foot syndrome secondary to capecitabine.

A 55-year-old woman on treatment with capecitabine and paclitaxel for breast carcinoma presented with history of a tingling sensation in her hands and feet with a progressive burning sensation. She also noted discomfort, minimal pain and stiffness while holding objects. On examination, there was patchy hyperpigmentation of both the palms and soles, and the dorsa of hands and feet. This was accompanied by a thickening of the skin more over the knuckles and toes. In addition there was a moist desquamation around the toes and over the palmar creases and a bluish discoloration of the lunulae of both thumbnails. She was diagnosed with hand and foot syndrome and started on pyridoxine and emollients. The finding of keratoderma noted in our patient is not seen commonly in hand and foot syndrome.

[Chronic pain in the diabetic patient: a quali-quantitative observational study].

The purpose of this study is to evaluate the prevalence and characteristics of pain in subjects affected by Diabetes Mellitus (DM), to assess approach and therapeutically valid outcomes as well as the knowledge of the Law n. 38/15/03/2010 of the Italian Government ("Dispositions to guarantee the access to the Palliative Cares and Pain Therapy"). We have enrolled 462 patients affected by DM [242 (52.4%) males, 209 (42.5%) females; while in 11 (5.1%) cases the gender has not been specified], with characteristics as follows: 62 patients (13.4%) affected by T1DM (37 males and 25 females) e 400 patients (86.6%) affected by T2DM (224 males e 176 females). The average age was of 65.2 years old (range 20-91). All the patients have been presented with an original questionnaires based on 10 questions. 221 subjects (48%) have claimed to have experienced pain; 60% within the females, 38% within the males (p<0.001). 31% of these are to be included among the patients with T1DM, 50.5% among those with T2DM (p<0.01). The presence of chronic pain has been acknowledged by 162 subjects (35%). As per chronic pain, this has been described as articular pain by 128 patients (80%), while 63 (38%) located the pain through the spine and 29 (18%) throughout the muscles. Chronic pain was described as moderate by 73 subjects (45%), intense by 59 (36%), feeble by 15 (9%), utterly intense by 5 (3%), moderate/intense by 1 (1%). The drugs for treating the chronic pain used by the patients have been enlisted as follows: FANS (41%), paracetamol (30%), glucocorticoids (3%), weak opioids (2%); 27% of subjects have received no therapy. As for the Law 38/2010, only 8% have said they have had news of it. The data gathered in this study have drawn attention on the fact that the presence of pain is higher in female gender, with a prevalence of 60% compared to the 38% of the male gender. It has been observed no relation with the age range, in particular no proportional increase level of pain has been observed, although the higher peak of prevalence has been experienced in the age range between 70-79, both for pain in general and for chronic pain. Speaking about efficacy of the treatment, almost 50% of the subjects have received no improvement from the therapy.

[Opioid combination of transdermal fentanyl and oral oxycodone for pain in a patient with giant-cell tumor of the sacrum].

We describe successful pain control in a patient suffering from severe pain, using an opioid combination of transdermal fentanyl and oral oxycodone. A woman in her 40s with a giant-cell tumor of the sacrum suffered from refractory 4-5/5 pain on the Wong-Baker faces pain rating scale in her sacrum, feet and legs. Despite administration of fentanyl (2,520 microg day(-1)), she could not sleep in the supine position due to pain and dysesthesia. We gradually changed her medication from transdermal fentanyl to oral oxycodone. However, the patient complained of constant drowsiness after the complete switch to oral oxycodone (120 mg x day(-1)). Hence, we reduced the oral oxycodone dose and began a combination of transdermal fentanyl and oral oxycodone in addition to increasing doses of pregabalin. With the combination of transdermal fentanyl (25 microg x hr(-1)) and oral oxycodone (60 mg x day(-1)) her pain decreased to 1-3/5 on the faces pain rating scale. Our experience suggests that an opioid combination may provide favorable pain control in patients with severe pain, while minimizing the side effects of each drug.

Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy.

Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately half of patients with diabetes. DPN is symmetric and predominantly sensory, starting distally and gradually spreading proximally in a glove-and-stocking distribution. It causes substantial morbidity and is associated with increased mortality. The unrelenting nature of pain in this condition can negatively affect a patient's sleep, mood, and functionality and result in a poor quality of life. The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN. A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. This review considers seminal and novel research in epidemiology; diagnosis, especially in relation to novel surrogate end points; and the treatment of neuropathic pain in DPN. We also consider potential new pharmacotherapies for painful DPN. DPN is often misdiagnosed and inadequately treated. Other than improving glycemic control, there is no licensed pathogenetic treatment for diabetic neuropathy. Management of painful DPN remains challenging due to difficulties in personalizing therapy and ascertaining the best dosing strategy, choice of initial pharmacotherapy, consideration of combination therapy, and deciding on defining treatment for poor analgesic responders. Duloxetine and pregabalin remain first-line therapy for neuropathic pain in DPN in all 5 of the major published guidelines by the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, National Institute of Clinical Excellence (United Kingdom), and the American Diabetes Association, and their use has been approved by the US Food and Drug Administration. Clinical recognition of DPN is imperative for allowing timely symptom management to reduce the morbidity associated with this condition.

[Abdominal migraine in adults].

A case of a 35-year-old woman with abdominal migraine is presented. For four years she had been suffering from abdominal pains occurring only at night, always between 1 and 3 a.m. The patient always woke with abdominal pains and nausea. Each time she had diarrhoea and vomited and found that this gave her relief from the pain. Sometimes she lost consciousness for 1-2 minutes. After the attack she felt very weak, her legs and feet became numb and she found it difficult to get to sleep. The attacks and the fainting fits increased in frequency until she had several a month. Numerous gastrological examinations did not reveal any deviations from the normal. At the anti- epileptic consulting unit, abdominal epilepsy was excluded (no abnormalities were found in the eeg and CT examinations of the cranium). As a child she had paroxysmal abdominal pains. When the patient was 10 years old, she had an attack lasting one week and though the pain was severe on the left side, appendectomy was performed. Her mother suffers from migraine with very severe head pains. The patient was referred to our consulting unit where she was treated with Pizotifen in doses of 0.5 mg morning and noon and 1 mg in the evening for three months during which time she had no attacks. A few weeks after discontinuing this treatment, the nocturnal attacks again occurred though the pains were not so severe. She was then prescribed Nitrendipine, 5 mg nightly, and the attacks ceased. However, the patient said that she had felt better when taking Pizotifen.

Tender neck in a diabetic patient.

A 45-year-old Indian patient with a history of type 2 diabetes mellitus presented with history of pain in the left side of the neck associated with sore throat of one month duration. The diagnosis of subacute granulomatous thyroiditis (de Quervains thyroiditis) was made which was confirmed radiologically by depressed radioactive iodine uptake. The patient showed marked clinical response and improvement within 24 hours on anti-inflammatory drugs and corticosteroid.

Infection in the diabetic foot.

A 56-year-old woman presented with a chronic infection of her right first toe. The woman had a 15-year history of diabetes mellitus and had been insulin dependent for the past five years. Her toe had been injured one month earlier when hit by a frozen chicken that fell out of the freezer. The accident caused a bruise and a small cut. Serous to purulent drainage then developed. When she presented, the toe was reddened and draining. Physical examination showed a nonobese woman with no fever or other evidence of systemic infection. The wound showed no evidence of necrotizing fasciitis. Peripheral pulses were 2+ and capillary refill was slow. Sensation in both feet was decreased. The transcutaneous oxygen tension in the feet was reduced at 20 mm Hg. Relevant laboratory findings included a serum glucose of 250 and creatinine of 1.5. X-rays of the foot were compatible with diffuse osteomyelitis of the distal phalanx of the great toe. Technetium and indium scans were positive, with increased uptake localized to the area of x-ray changes (Figure 1). The patient was admitted to the hospital.

Complaints of Upper Extremity Numbness and Tingling Relieved With Dry Needling of the Teres Minor and Infraspinatus: A Case Report.

Study Design Case report. Background Abnormal sensation, such as numbness or tingling, is traditionally thought to originate from neural compression. There is limited evidence to support reports of abnormal sensation arising from a trigger point. Case Description The patient was a 60-year-old woman with a primary complaint of right shoulder pain and secondary complaints of neck pain and right upper extremity numbness. Cervical spine neurological examination was unremarkable, and manual examination did not reproduce the patient's arm numbness or tingling symptoms. Compression of a trigger point in the infraspinatus and teres minor reproduced the patient's primary complaint of shoulder pain. The initial intervention included dry needling, which reproduced her upper extremity numbness. Subsequent treatment included manual therapy and exercise. Outcomes The patient was seen for a total of 3 visits, including the evaluation. Dry needling was utilized in 2 of her 3 visits. At discharge, she reported complete resolution of pain and altered sensation. Additionally, her scores on the Neck Disability Index, numeric pain-rating scale, and global rating of change exceeded the minimal clinically important difference. These outcomes were maintained at 2- and 12-month follow-up phone calls. Discussion This case report described the examination and use of dry needling in a case where the diagnosis was unclear. Clinicians may consider trigger point referral when examining patients with reports of abnormal sensation, especially when a more common cause cannot be identified. Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther 2017;47(4):287-292. Epub 3 Mar 2017. doi:10.2519/jospt.2017.7055.

Application of OpSite film: a new and effective treatment of painful diabetic neuropathy.

The aim of the study was to assess the effect of application of OpSite dressings on the pain and quality of life in 33 patients with chronic diabetic neuropathy. The effect of OpSite was compared with no treatment. After a run-in period of 2 weeks, OpSite was applied to one of the painful legs for 4 weeks. This was followed by another period of 4 weeks when OpSite was switched to the opposite leg. Pain was assessed by visual analogue scale and the primary analysis variable was within patient difference in pain between OpSite leg and no treatment leg at week 4 corrected for baseline. Secondary variables were paracetamol pill ingestion and the quality of life dimensions, sleep, mobility, contact discomfort, appetite, and mood. Changes in these variables from baseline to weeks 4 and 8 were analysed. There was a significantly greater reduction in pain in the OpSite treated limbs than the control limbs (p < 0.001). By week 4 paracetamol intake also declined significantly (p = 0.034) and patients experienced a significant improvement in contact discomfort, sleep, mood, appetite, and mobility (p < 0.002 for all 5 variables). OpSite appeared to alleviate the pain associated with diabetic painful neuropathy and thus improved patients' quality of life.

Multiple extremity necrosis in fatal calciphylaxis: Case report.

The clinical impact of vascular calcification is well established in the context of cardiovascular morbidity and mortality, but other clinical syndromes, such as calciphylaxis, although less frequent, have a significant impact on chronic kidney disease. Case report of a 27-year-old woman, who had complained of bilateral pain in her toes for 3 days, with the presence of small necrotic areas in the referred sites. She had a history of type 1 diabetes (25 years ago), with chronic kidney disease, on peritoneal dialysis, in addition to rheumatoid arthritis. She was admitted to the hospital, which preceded the current condition, due to exacerbation of rheumatoid arthritis, evolving with intracardiac thrombus due to venous catheter complications, when she started using warfarin. Ischemia progressed to her feet, causing the need for bilateral amputations. Her chirodactyls were also affected. Thrombophilia, vasculitis, endocarditis or other embolic sources were investigated and discarded. Her pathology report evidenced skin necrosis and superficial soft parts with recent arterial thrombosis, and Monckeberg's medial calcification. We started treatment with bisphosphonate and sodium thiosulfate, conversion to hemodialysis and replacement of warfarin with unfractionated heparin. Despite all the therapy, the patient died after four months of evolution. Calciphylaxis is a rare microvasculature calcification syndrome that results in severe ischemic injuries. It has pathogenesis related to the mineral and bone disorder of chronic kidney disease combined with the imbalance between promoters and inhibitors of vascular calcification, with particular importance to vitamin K antagonism. The preventive strategy is fundamental, since the therapy is complex with poorly validated effectiveness.