Oxaliplatin- and docetaxel-induced polyneuropathy: clinical and neurophysiological characteristics.

The aim of this study was to evaluate the presence and characterization of chemotherapy-induced neuropathy (CIPN) and neuropathic pain 5 years after adjuvant chemotherapy with docetaxel or oxaliplatin. Patients from an ongoing prospective study, who had received adjuvant chemotherapy with docetaxel or oxaliplatin in 2011 to 2012 were invited to participate. The patients underwent a thorough examination with interview, neurological examination, questionnaires, assessment tools, nerve conduction studies (NCS), quantitative sensory testing, MScan motor unit number estimation (MUNE), and corneal confocal microscopy (CCM). Patients were divided into no, possible, probable, and confirmed CIPN. Out of the 132 eligible patients, 63 agreed to participate: 28 had received docetaxel and 35 had received oxaliplatin. Forty-one percent had confirmed CIPN, 34% possible or probable CIPN, and 22% did not have CIPN. The CIPN was characterized mainly by sensory nerve fiber loss, with a more pronounced large fiber than small fiber loss but also some motor fiber loss identified on NCS and MUNE. In general, patients had mild neuropathy with relatively low scores on assessment tools and no association with mood and quality of life. CCM was not useful as a diagnostic tool. Of the patients with probable or confirmed CIPN, 30% experienced pain, which was most often mild, but still interfered moderately with daily life in 20% to 25% and was associated with lower quality of life. In conclusion CIPN was confirmed in 41% 5 years after chemotherapy. The neuropathy was generally mild, but in patients with neuropathic pain it was associated with lower quality of life.

Educational attainment and work disability in cancer survivors: Do diagnosis and comorbidity affect this association?

OBJECTIVES: To study whether educational attainment had less impact on work disability in cancer survivors than in individuals without cancer. To study whether comorbidity had a higher impact on work disability in low-educated cancer survivors than in high-educated and whether this impact differed when compared with individuals without cancer. METHODS: Linkage of population-based public health survey data and the Danish Cancer Registry formed two groups: cancer survivors (n = 3,514) and cancer-free individuals (n = 171,262). In logistic regression models, the risk of experiencing an 8-week sick leave spell and the granting of disability pension within a 3-year follow-up period was studied in three educational levels and whether these associations were modified by history of cancer and comorbidity. Odds ratios (OR) with 95% confidence intervals (CI) are reported. RESULTS: Non-stratified adjusted risk of experiencing an 8-week sick leave spell (OR: 1.41, 95% CI (1.33-1.49)) or being granted a disability pension (OR: 1.61, 95% CI (1.31-1.97)) was significantly higher in low-educated than in high-educated respondents. Cancer or comorbidity did not significantly interact with education on the risk of work disability. CONCLUSIONS: A moderate impact of low education on future work disability was found for all respondents, neither history of cancer nor comorbidity modified this association.

The utility of a point-of-care sural nerve conduction device for detection of diabetic polyneuropathy: A cross-sectional study.

INTRODUCTION: Rapid and accessible methods for diagnosing diabetic polyneuropathy (DPN) have been developed, but not validated, in large cohorts of people with diabetes. METHODS: The performance of a point-of-care device (POCD) was studied in 168 patients with type 2 diabetes, estimating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) compared with conventional sural nerve conduction studies (NCS). RESULTS: A POCD amplitude limit of 6 µV increased the sensitivity (96%) and NPV (98%), but decreased the specificity (71%) and PPV (54%) compared with the 4-µV limit, which had values of 78%, 92%, 89%, and 71%, respectively. POCD on both legs showed better performance than on 1 leg. POCD amplitudes and conduction velocities correlated significantly with conventional sural NCS, but POCD values were underestimated compared with NCS. DISCUSSION: The POCD may be used as a suitable screening tool for detection of DPN. Patients with abnormal and borderline results should undergo conventional NCS. Muscle Nerve 59:187-193, 2019.

Probiotics for chronic low back pain with type 1 Modic changes: a randomized double-blind, placebo-controlled trial with 1-year follow-up using Lactobacillus Rhamnosis GG.

PURPOSE: To investigate whether treatment by lactic acid bacteria for 100 days is associated with change of disability and pain in chronic low back pain (CLBP) patients with type 1 or mixed Modic changes (MC) during 1-year follow-up. METHODS: Eighty-nine patients with CLBP and type 1 MC or mixed MC were randomized to receive either one capsule Lactobacillus Rhamnosis GG (6 billion colony-forming unit per capsule) twice daily or placebo capsules for 100 days. RESULTS: Missing values at 1 year were 4% and 3% in the disability and pain variables, respectively. The predefined outcomes disability and back + leg pain only changed little during follow-up with no statistically significant differences between groups. At 1 year, back pain had on average decreased by 1.1 more on a 0-10 scale (95% confidence interval 0.20-1.97) in the group treated by lactic acid bacteria than in the control group. There were no differences regarding other predefined outcomes, i.e. global effect or percentage with minimal disability at 1 year. Nine per cent of the patients reported gastrointestinal side effects without difference between groups. CONCLUSIONS: No differences were found regarding the predefined outcomes. Overall, there was little improvement during the 1-year observation period. A small, though hardly clinically relevant, effect on back pain was seen after treatment by Lactobacillus Rhamnosis GG, and the treatment was without side effects in comparison with the control group.

Are fatigue, depression and anxiety associated with labour market participation among patients diagnosed with haematological malignancies? A prospective study.

OBJECTIVES: The objectives of this study are to examine levels of fatigue, depression and anxiety following diagnosis of a haematological malignancy, to determine the incidence of return to work (RTW) and long-term sickness absence (LTSA) during 1-year follow-up and to examine whether fatigue, depression and anxiety are associated with RTW and LTSA in this group of cancer patients. METHODS: Questionnaire-based data on fatigue, depression and anxiety were obtained at baseline. In all, 196 patients returned the questionnaire. Of these, 106 patients were on sick leave and 90 patients were working. They were all followed prospectively for 1 year using register-based data on labour market participation. RESULTS: At baseline, high levels of fatigue, depression and anxiety were more prevalent among sickness absent patients than in those working. Half of the sickness absent patients returned to work during follow-up, and only 10 (11%) working patients experienced LTSA. Sickness absent patients with highest scores of physical fatigue were less likely to RTW than those with lowest scores (RRadj 0.43, 95% CI 0.23-0.78). Similar, we found an association between symptoms of anxiety and RTW (p = 0.048). This association was though non-significant in multivariable analyses (p = 0.068). No significant association was found between depression and RTW. CONCLUSION: Half of sickness absent patients returned to work, and only a few of working patients experienced LTSA during follow-up. Patients reporting high levels of physical fatigue were less likely to RTW. There was a similar tendency for anxiety, whereas we found no association between depression and RTW. Larger prospective studies are needed.

Wage-subsidised employment as a result of permanently reduced work capacity in a nationwide cohort of patients diagnosed with haematological malignancies.

BACKGROUND: Patients with haematological malignancies have a poorer labour market prognosis than the general population. We have previously found that they have low rates of return to work, and a higher risk of being granted disability pension, than individuals without a history of these diseases. The aim of this study was to further investigate the labour market prognosis for these patients, by comparing the risk of being granted wage-subsidised (WS) employment as a result of permanently reduced work capacity among patients diagnosed with haematological malignancies to a reference cohort, and to determine if relative risks differ between subtypes of haematological malignancies. MATERIAL AND METHODS: We combined data from national registers on Danish patients diagnosed with haematological malignancies between 2000 and 2007 and a reference cohort without a history of these diseases. A total of 3194 patients and 28 627 reference individuals were followed until they were granted WS employment, disability pension, anticipatory pension, old age pension, emigration, death or until 26 February 2012, whichever came first. RESULTS: A total of 310 (10%) patients and 795 (3%) reference individuals had their work capacity permanently reduced to an extent that they were granted WS employment during the follow-up period. Age- and gender-adjusted relative risks differed significantly between the subgroups of haematological malignancies, and four years after diagnosis they ranged from 2.47 (95% CI 1.46-4.16) for patients with Hodgkin lymphoma to 10.83 (95% CI 7.15-16.40) for patients with chronic myeloid leukaemia. CONCLUSION: All eight subtypes of haematological malignancies were associated with an increased risk of being granted WS employment due to permanently reduced work capacity compared to the reference cohort. The relative risks differed according to haematological malignancy subtype, and the highest was found for patients with chronic myeloid leukaemia.

Local infiltration analgesia is not improved by postoperative intra-articular bolus injections for pain after total hip arthroplasty.

BACKGROUND AND PURPOSE: The effect of postoperative intra-articular bolus injections after total hip arthroplasty (THA) remains unclear. We tested the hypothesis that intra-articular bolus injections administered every 6 hours after surgery during the first 24 hours would significantly improve analgesia after THA. PATIENTS AND METHODS: 80 patients undergoing THA received high-volume local infiltration analgesia (LIA; 200 mg ropivacaine and 30 mg ketorolac) followed by 4 intra-articular injections with either ropivacaine (100 mg) and ketorolac (15 mg) (the treatment group) or saline (the control group). The intra-articular injections were combined with 4 intravenous injections of either saline (treatment group) or 15 mg ketorolac (control group). All patients received morphine as patient-controlled analgesia (PCA). The primary outcome was consumption of intravenous morphine PCA and secondary outcomes were consumption of oral morphine, pain intensity, side effects, readiness for hospital discharge, length of hospital stay, and postoperative consumption of analgesics at 3, 6, and 12 weeks after surgery. RESULTS: There were no statistically significant differences between the 2 groups regarding postoperative consumption of intravenous morphine PCA. Postoperative pain scores during walking were higher in the treatment group from 24-72 hours after surgery, but other pain scores were similar between groups. Time to readiness for hospital discharge was longer in the treatment group. Other secondary outcomes were similar between groups. INTERPRETATION: Postoperative intra-articular bolus injections of ropivacaine and ketorolac cannot be recommended as analgesic method after THA.

Risk of disability pension for patients diagnosed with haematological malignancies: a register-based cohort study.

UNLABELLED: Patients with haematological malignancies are at increased risk of experiencing work-related problems. The aims of this study were to compare the risk of disability pension (DP) among patients diagnosed with eight subtypes of haematological malignancies to a reference cohort, and to determine if relative risks differ between these subtypes; to evaluate the influence of socioeconomic factors, demographic factors, and clinical factors on the risk of DP; and to investigate if these associations differ between the reference cohort and the patient cohort. MATERIAL AND METHODS: We combined data from national registers on Danish patients diagnosed with haematological malignancies between 2000 and 2007 and a reference cohort without a history of these diseases. A total of 3194 patients and 28 627 reference individuals were followed until DP, emigration, old age pension or anticipatory pension, death or 26 February 2012, whichever came first. RESULTS: A total of 550 (17%) patients and 1511 (5%) reference individuals were granted DP. Age- and gender-adjusted relative risks differed significantly between the subgroups of haematological malignancies and ranged from 2.64 (95% CI 1.84-3.78) for patients with Hodgkin lymphoma to 12.53 (95% CI 10.57-14.85) for patients with multiple myeloma. In the patient cohort we found that gender, age, comorbidity, ethnicity, educational level, household income, history of long-term sick leave, and need of treatment with anxiolytics or antidepressants after diagnosis were associated with receiving DP. However, most of these associations were stronger in the reference cohort. CONCLUSION: All eight subtypes of haematological malignancies were associated with an increased risk of DP compared to the reference cohort. The relative risks differed according to subtype, and patients with multiple myeloma had the highest risk of DP. Furthermore, most socioeconomic, demographic and clinical factors had a stronger impact on the risk of DP in the reference cohort than in the patient cohort.

Patient satisfaction and esthetic outcome after immediate placement and provisionalization of single-tooth implants involving a definitive individual abutment.

OBJECTIVES: To assess patient satisfaction and esthetic outcome after immediate placement and provisionalization of single-tooth implants involving a definitive individual abutment and a provisional crown followed by later placement of a definitive crown. MATERIALS AND METHODS: In private practice, a single-tooth implant was placed immediately after tooth extraction in the esthetic zone of 54 patients. A definitive individual abutment and a provisional crown were mounted in the same visit. The definitive crown was placed after a mean period of 7 months. After a mean follow-up period of 33 months, the subjective and professional evaluation of the total implant treatment, peri-implant soft tissues, and implant crown were assessed on a 10-cm visual analog scale (VAS). The professional esthetic treatment outcome was also evaluated using pink esthetic score (PES), white esthetic score (WES), and total score of PES/WES. RESULTS: The evaluation of total implant treatment, peri-implant soft tissues, and implant crown demonstrated a significantly higher subjective than professional score for all 3 parameters (P < 0.001), for example, for the overall treatment, the mean scores were 9.4 and 7.0, respectively. A significant positive correlation was revealed between the professional VAS scores and the PESs and WESs. CONCLUSIONS: Immediate placement and provisionalization of single-tooth implants involving a definitive individual abutment and provisional crown followed by later placement of a definitive crown demonstrated high subjective and professional satisfaction. Generally, the professionals seem to be more critical than the patients. A strong correlation was observed between the professional VAS scores and the PES and WES scoring systems.

When cooling of the skin is perceived as warmth: Enhanced paradoxical heat sensation by pre-cooling of the skin in healthy individuals.

A paradoxical heat sensation (PHS) is the misperception of warmth when the skin is cooled. PHS is uncommon in healthy individuals but common in patients with neuropathy and is associated with reduced thermal sensitivity. Identifying conditions that contribute to PHS may indirectly help us understand why some patients experience PHS. We hypothesized that pre-warming increased the number of PHS and that pre-cooling had minimal effect on PHS. We tested 100 healthy participants' thermal sensitivity on the dorsum of their feet by measuring detection and pain thresholds to cold and warm stimuli and PHS. PHS was measured using the thermal sensory limen (TSL) procedure from the quantitative sensory testing protocol of the German Research Network on Neuropathic Pain and by using a modified TSL protocol (mTSL). In the mTSL we examined the participants' thermal detection and PHS after pre-warming of 38°C and 44°C and pre-cooling of 26°C and 20°C. Compared to a baseline condition, the number of PHS responders was significantly increased after pre-cooling (20°C: RR = 1.9 (1.1; 3.3), p = 0.023 and 26°C: RR = 1.9 (1.2; 3.2), p = 0.017), but not significantly after pre-warming (38°C: RR = 1.5 (0.86; 2.8), p = 0.21 and 44°C: RR = 1.7 (.995; 2.9), p = 0.078). Pre-warming and pre-cooling increased the detection threshold of both cold and warm temperatures. We discussed these findings in relation to thermal sensory mechanisms and possible PHS mechanisms. In conclusion, PHS and thermosensation are closely related and pre-cooling can induce PHS responses in healthy individuals.

Labor Market Attachment 2 Years After Colorectal Cancer Surgery: A Population-based Study.

Objectives: To investigate the association between clinical/sociodemographic factors and labor market attachment, and to estimate employment probability 2 years after colorectal cancer (CRC) surgery. Background: A rising prevalence of younger CRC survivors commands a stronger focus on labor market attachment. The association between clinical factors like type of surgery and CRC survivors' labor market attachment remains poorly investigated. Methods: National registries provided information on employment status and clinical/sociodemographic variables for all 20- to 60-year-old CRC patients without previous cancer diagnosed in Denmark from 2001 to 2014, undergoing surgery and being attached to the labor market. Associations between clinical/sociodemographic factors and labor market attachment were investigated in multiple logistic regression analyses. Results: A total of 5755 CRC patients were included. Two years after surgery, 59.7% were working. Factors significantly associated with a higher probability of working were being in the 46 to 50 years age group, male gender, higher educational level, no comorbidity, working at the time of diagnosis, lower Union for International Cancer Control stage, and undergoing surgery in the most recent of four time-periods. Two years after undergoing surgery, the probability of working was significantly higher for left-sided than for right-sided colon resections, higher for low anterior resection (LAR)/high tumor than for LAR/low tumor, and higher for abdominoperineal resection than for Hartmann's procedure. Of the 4798 (86.8%) patients alive 2 years after surgery, 68.8% were working, 7.8% had retired, whereas 23.4% were on temporary benefits, sick leave, or disability pension. Conclusions: Clinical/sociodemographic factors were associated with the probability of working 2 years after surgery. This knowledge can be used to inform patients and target interventions towards patients with low post-CRC probability of working.

Gait analysis after total hip replacement with hip resurfacing implant or Mallory-head Exeter prosthesis: a randomised controlled trial.

A key to the analysis of function after total hip replacement (THR) is the ability to identify gait adaptations specific to design features and surgical procedures. In a randomised controlled design, we evaluated the mechanics of gait after THR with a hip resurfacing system or conventional prosthesis. We also investigated whether gait adaptations returned to normal postoperatively. Similar improvements in mechanics of gait were found, except for peak abductor moments, which improved more in the conventional group. Gait speed increased significantly, but with no differences between groups. The increase in walking speed was reflected as significant improvement within groups in most kinematic and kinetic variables. Significant differences between the operated and non-operated hip were seen in all patients, but with no difference between groups. Mean curves of joint angle profiles and moments in all anatomical planes during a gait cycle revealed that gait impairment persisted with no differences between the conventional prosthesis and the resurfacing system.

Impact of papillary muscle relocation as adjunct procedure to mitral ring annuloplasty in functional ischemic mitral regurgitation.

BACKGROUND: The optimal surgical treatment in functional ischemic mitral regurgitation (FIMR) remains controversial. Recently, a posterior papillary muscle relocation (PMR) technique as adjunct procedure to ring annuloplasty has been proposed to prevent recurrent FIMR. In the present study, we used 3D cardiac MRI to assess the impact of relocating both papillary muscles as adjunct procedure to downsized ring annuloplasty on mitral leaflet coaptation geometry in FIMR pigs. METHODS AND RESULTS: Eleven FIMR pigs were randomized to downsized ring annuloplasty (RA; n=6) or RA combined with PMR (RA+PMR, n=5). In the RA+PMR group, a 2-0 Gore-Tex suture was attached to each trigone, exteriorized through the corresponding papillary muscle, mounted on an epicardial pad, and tightened to relocate the myocardium adjacent to the anterior and posterior papillary muscles 5 and 15 mm, respectively. Using 3D MRI, the impact from these interventions on leaflet geometry was assessed. The distance from the posterior papillary muscle to the anterior trigone was reduced significantly more (median values) in the RA+PMR compared with RA animals at end-diastole (-7.9% versus 3.8%, P<0.01) and end-systole (-9.7% versus 2.5%, P=0.02). Accordingly, lateral tethering of the coaptation point (median values) was reduced significantly more in RA+PMR compared with RA animals (-42.8% versus -29.1%, P<0.01). CONCLUSIONS: Adding papillary muscle relocation to downsized ring annuloplasty reduced lateral leaflet tethering in a porcine experimental model of FIMR. Therefore, this technique holds promise for reducing persistent and recurrent FIMR in patients.

Does down-sized ring annuloplasty induce papillary muscle relocation in ischemic mitral regurgitation?

BACKGROUND AND AIM OF THE STUDY: Down-sized ring annuloplasty has been shown to induce left ventricular remodeling in patients with functional ischemic mitral regurgitation (FIMR). To determine if this remodeling comprised papillary muscle (PM) relocation, a chronic FIMR porcine model was used to assess the impact on three-dimensional (3D) PM positioning, by implanting a down-sized rigid ring annuloplasty. METHODS: Six out of ten FIMR pigs that underwent a down-sized mitral ring annuloplasty (CE Classic size 26-28) survived for six weeks postoperatively. 3D cardiac magnetic resonance imaging was carried out at one week preoperatively, and repeated at one and six weeks postoperatively, to assess the direct distances (in mm) from the anterior papillary muscle (APM) and posterior papillary muscle (PPM) to each trigone. Three reference planes were also constructed to determine APM and PPM displacement in the lateral, anterioposterior, and apical directions. RESULTS: Relative to the preoperative situation, at one week postoperatively a reduced displacement of the APM was observed in an anterior direction (from 18.8 to 16.2 mm; p < 0.05) and from the posterior trigone (from 40.5 to 37.4 mm; p < 0.05) at end-diastole. Relative to one week postoperatively, at six weeks postoperatively a reduced PPM displacement was observed from the anterior trigone (43.0 versus 42.0 mm; p < 0.05) at end-systole. Relative to the preoperative situation, no overall tendency of surgically induced PM relocation was observed at one or six weeks postoperatively. CONCLUSION: A down-sized ring annuloplasty did not induce an overall pattern of PM relocation in pigs with chronic FIMR.

No effect of TETRA hand portable transmission signals on human cognitive function and symptoms.

Current radio frequency radiation exposure guidelines rest on well-established thermal effects. However, recent research into analogue and digital transmission fields at levels covered by the exposure guidelines has indicated possible detrimental effects on human cognitive performance. To investigate this, we conducted a controlled climate chamber study of possible changes in cognitive performance in healthy volunteers exposed to transmission signals from TETRA hand portables (TETRA handsets). The trial deployed a balanced, randomized, double-blinded cross-over design. Performance on different paper-and-pencil, auditory and computer-based cognitive tasks was monitored in 53 male volunteers (mean age 36.41 years, SD 8.35) during 45-min exposure to a TETRA handset and sham control signals remotely controlled from a laboratory more than 100 km away. The main cognitive outcome was the Trail Making B (TMB) test. In addition, the participants completed a computer-based questionnaire measuring self-reported psychological and physical symptoms. No statistically significant differences (P < 0.05) between the TETRA and sham conditions were found for either TMB (estimated difference 3.8%, confidence interval (CI) -1.6% to 9.2%) or any of the remaining cognitive tasks or symptoms. In conclusion, we found no evidence that brief exposure to hand-held TETRA transmitters' affects human cognitive function or subjective symptoms.

The final follow-up plain radiograph is sufficient for clinical evaluation of polyethylene wear in total hip arthroplasty. A study of validity and reliability.

BACKGROUND AND PURPOSE: Radiostereometric analysis (RSA) is a highly accurate tool for assessment of polyethylene (PE) wear in total hip arthroplasty (THA); however, PE wear measurements in clinical studies are often limited to plain radiographs. We evaluated the agreement between PE wear measured with PolyWare software, which uses plain radiographs, and by model-based RSA, which uses stereo radiographs. METHODS: Measurements of PE wear postoperatively and at final follow-up (after mean 6 years) on plain radiographs of 12 patients after cementless THA were evaluated with PolyWare software and the results were compared with those from RSA as the gold standard (Model-based RSA using elementary geometrical shape models; EGS-RSA). With PolyWare, we either used the final radiographic follow-up (PW1) only or both the postoperative follow-up and the final follow-up (PW2). RESULTS: The 2D mean wear measured (in mm) was 0.80, 1.07, and 0.60 for the PW2, PW1, and RSA method. 2D intra-method repeatability was similar for PW1 and RSA with limits of agreement (LOAs, in mm) of ± 0.22, and ± 0.23, respectively. 2D inter-method concurrent validity was best between PW1 and EGS-RSA with LOAs of ± 0.55. For 2D linear wear measurements, the PW1 method had a clinical repeatability similar to that of RSA. INTERPRETATION: PW1 is sufficient for retrospective determination of 2D wear from medium-term wear measurements above 0.5 mm, It alleviates the need for baseline plain radiographs, has a clinical precision similar to that of RSA, and is easy and inexpensive to use.

Long-term symptoms of polyneuropathy in breast and colorectal cancer patients treated with and without adjuvant chemotherapy.

BACKGROUND: The aim of this study was to assess chemotherapy-induced polyneuropathy (CIPN) 5 years after adjuvant chemotherapy in patients with breast and colorectal cancer. The association of CIPN with quality of life, anxiety, and depression was analyzed. METHODS: Of a set of 100 patients with breast cancer and of 74 with colorectal cancer who had undergone surgery and adjuvant chemotherapy in 2011-2012, 80 and 52 patients alive, respectively, were included together with two reference groups of 249 breast cancer patients and 83 colorectal cancer patients who had undergone surgery only. All patients were sent a questionnaire on alcohol consumption, smoking habits, comorbidity, medicine consumption, and oxaliplatin-specific questions, as well as the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), the Douleur Neuropathique 4 Questions (DN4q), the EQ-5D, and the Hospital Anxiety and Depression Scale. Possible polyneuropathy was defined as the presence of numbness and/or tingling in the feet, secondly as a score of ≥4 on the MNSIq. Possible painful polyneuropathy was defined as pain in both feet and a score ≥3 on the DN4q. RESULTS: The prevalence of possible polyneuropathy defined by numbness and/or tingling in the feet was 38.8% (28.1-50.3) after adjuvant docetaxel and 57.7% (43.2-71.3) after adjuvant oxaliplatin, with no significant difference from a previous 1-year follow-up (P >.35). Fewer had possible polyneuropathy as defined by the MNSIq. Patients with possible polyneuropathy after adjuvant chemotherapy reported significantly lower quality of life than patients treated with surgery only. CONCLUSION: Symptoms of polyneuropathy following adjuvant docetaxel and oxaliplatin persist 5 years after treatment and affect quality of life negatively.

Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial.

BACKGROUND: Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response. METHODS: This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients' daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety. DISCUSSION: We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03777956 . Registered on 18 December 2018.

Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy.

BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

The effect of pretreating morselized allograft bone with rhBMP-2 and/or pamidronate on the fixation of porous Ti and HA-coated implants.

BMPs stimulate new bone formation, but may also accelerate bone resorption. We added rhBMP-2 and pamidronate to morselized bone allograft packed around uncemented HA-coated and non-coated porous Ti implants in sixteen dogs. Each dog received four implants where the allograft was added (1) nothing, (2) BMP, (3) BP, and (4) BMP+BP. After four weeks, the untreated control implants had better mechanical fixation than all other treatment groups. The rhBMP-2-treated group had abundant formation of new bone on and around the implant. However, almost all allografts were resorbed, rendering the implant mechanically unstable. In the pamidronate-treated group the allograft was preserved, but the implants were covered by fibrous tissue and there was almost no new bone formation. This was also the case for the combined BMP+BP group, although fibrous tissue was absent on these implants. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The results warrant a conservative approach and emphasize the importance of identifying a therapeutic window for these substances prior to clinical use.