Nevin Manimala

Pain Physician. 2022 Nov;25(8):555-567.

ABSTRACT

BACKGROUND: An impaired immune system in the perioperative period has important clinical implications in patients with cancer. Despite the immunosuppressive properties of opioid therapy, it is still commonly utilized in the intrathecal or epidural space for the treatment of postoperative pain. Also, intrathecal dexmedetomidine has extended analgesic efficacy in postoperative pain; it can significantly affect immune function in perioperative patients.

OBJECTIVE: To investigate the effect of intrathecal morphine, dexmedetomidine, or both in combination with bupivacaine on cellular immunity and cytokine production in cancer surgical patients.

STUDY DESIGN: A prospective randomized clinical study.

SETTING: South Egypt Cancer Institute, Assiut University.

METHODS: Ninety patients were randomly assigned to receive intrathecal morphine 0.5 mg (Group M, n = 30), dexmedetomidine 0.5 µg/kg (Group D, n = 30) or morphine 0.5 mg with dexmedetomidine 0.5 µg/kg (Group MD n = 30); 2 mL bupivacaine 0.5% was added to injected drugs in all groups. Blood samples were collected preoperative (T0), immediate postoperative (T1), 4 hours postoperative (T2), and 24 hours postoperative (T3) for measurement of CD3, CD4, CD4/CD8 and CD16+56(NK), interleukin(IL)-1beta (IL-1beta), IL-6, IL-10 and tumor necrosis factor alpha (TNF-alpha).

RESULTS: A significant reduction in cellular immunity (CD3, CD4, CD8, CD4/CD8, CD 16+56) was noticed in the 24-hour postoperative period in all 3 studied groups, with a marked reduction in Group M in comparison to Group MD and Group D. Regarding inflammatory mediators, IL-10 and IL-1beta showed significant reduction in Group M in the first 24-hour postoperative period in comparison to Group MD and Group D, while IL-6 was significantly reduced in Group MD and Group D in comparison to Group M in the same period. TNF-alpha was significantly increased postoperative at T1 and T2 in the 3 studied groups, then at T3 it decreased without a statistically significant difference with the preoperative level.

LIMITATIONS: Our study has some limitations, such as the short period of follow-up and lack of postoperative clinical follow-up of patients to discover the association between immunity and patient outcomes.

CONCLUSION: Intrathecal dexmedetomidine has the least immunosuppressive effect than morphine and morphine-dexmedetomidine, in combination with bupivacaine.

PMID:36375185

Pain Physician. 2022 Nov;25(8):531-542.

ABSTRACT

BACKGROUND: Lumbar disc herniation (LDH) is the main cause of low back pain and/or radiculopathy. Currently, epidural intervention is a widely used and effective conservative treatment method for managing low back and radicular pain caused by LDH.

OBJECTIVES: To explore the effectiveness of different epidural injection approaches in adult patients with lumbosacral radicular pain.

STUDY DESIGN: Systematic review and network meta-analysis (NMA).

METHODS: An electronic literature search was performed in the Pubmed, Embase, Cochrane Library, and Web of Science databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was conducted to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Effect estimates from Bayesian NMA were presented as mean difference (MD) with 95% credible intervals (CrI).

RESULTS: This NMA assessed caudal (C), interlaminar (IL), transforaminal (TF) and parasagittal interlaminar (PIL) epidural injection approaches for lumbosacral radicular pain from 7 trials. A statistically significant treatment difference for pain relief was reported for midline interlaminar (MIL) vs PIL (MD, 1.16; 95%CrI, 0.31-2.06), MIL vs TF (MD, 1.12; 95%CrI, 0.51-1.85), C vs TF (MD, 1.07; 95%CrI, 0.01-2.18) in short-term follow-up and MIL vs TF (MD, 1.8; 95% CrI, 0.3-3.48) in intermediate-term follow-up. For functional improvement, a statistically significant difference was observed with MIL vs PIL (MD, 9.9; 95% CrI, 0.64-19.94) and MIL vs TF (MD, 1.08; 95% CrI, 1.08-17.08) in short-term follow-up. Moreover, the PIL approach and TF appeoach were ranked in the top 2 for pain relief and functional improvement, both in short-term and intermediate-term follow-up.

LIMITATIONS: 1) The number of studies included was small; 2) some treatments lacked direct comparisons; 3) only scores from the visual analog scale for pain and the Oswestry Disability Index were included in the result; 4) important outcomes, such as complications, were not included.

CONCLUSION: In short-term and intermediate-term follow-up, the PIL approach has the highest probability for pain relief and functional improvement.

PMID:36375181

Cochrane Database Syst Rev. 2022 Nov 14;11:CD012956. doi: 10.1002/14651858.CD012956.pub2.

ABSTRACT

BACKGROUND: Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods.

OBJECTIVES: To assess the effects of pharmacological treatment for people with BPD.

SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication.

SELECTION CRITERIA: Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events.

DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane’s risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis.

MAIN RESULTS: We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified.

AUTHORS’ CONCLUSIONS: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.

PMID:36375174 | DOI:10.1002/14651858.CD012956.pub2

Pain. 2022 Sep 15. doi: 10.1097/j.pain.0000000000002782. Online ahead of print.

ABSTRACT

This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent musculoskeletal pain (MSP) among adults presenting to the emergency department with acute MSP after trauma or injury. In this randomized, double-blind, placebo-controlled study, eligible participants (n = 78) were randomized to 2 weeks of a daily dose of one of the following: placebo (n = 27), 30 mg duloxetine (n = 24), or 60 mg duloxetine (n = 27). Tolerability, the primary outcome, was measured by dropout rate and adverse effects. Secondary outcomes assessed drug efficacy as measured by (1) the proportion of participants with moderate to severe pain (numerical rating scale ≥ 4) at 6 weeks (pain persistence); and (2) average pain by group over the six-week study period. We also explored treatment effects by type of trauma (motor vehicle collision [MVC] vs non-MVC). In both intervention groups, duloxetine was well tolerated and there were no serious adverse events. There was a statistically significant difference in pain over time for the 60 mg vs placebo group (P = 0.03) but not for the 30 mg vs placebo group (P = 0.51). In both types of analyses, the size of the effect of duloxetine was larger in MVC vs non-MVC injury. Consistent with the role of stress systems in the development of chronic pain after traumatic stress, our data indicate duloxetine may be a treatment option for reducing the transition from acute to persistent MSP. Larger randomized controlled trials are needed to confirm these promising results.

PMID:36375173 | DOI:10.1097/j.pain.0000000000002782

Ann Intern Med. 2022 Nov 15. doi: 10.7326/M22-2058. Online ahead of print.

ABSTRACT

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF).

OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events.

DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307).

SETTING: 17 National Health Service trusts across the United Kingdom.

PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure.

INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment.

MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible.

RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]).

LIMITATION: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques.

CONCLUSION: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%.

PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Heath Technology Assessment Programme.

PMID:36375147 | DOI:10.7326/M22-2058

Clin Exp Optom. 2022 Nov 14:1-8. doi: 10.1080/08164622.2022.2140031. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: The changes in various biomechanical and tomographic characteristics of the cornea associated with orthokeratology may allow us to identify potential mid- and long-term structural alterations, resulting in a better understanding of the governing mechanisms of this procedure and in its optimisation.

BACKGROUND: The study aimed at describing short and mid-term changes in CORVIS ST® parameters and indices in orthokeratology (ortho-k), and their diurnal variations.

METHODS: A prospective observational study was designed in which several CORVIS ST® parameters of 75 new adult participants successfully fitted with overnight ortho-k Seefree® (Conóptica – Hecht Contactlinsen) contact lenses were explored. Measurements were conducted in baseline (BL) conditions and in the morning and evening at the one-night (1 NM/1NT), one-week (1WM/1 WT) and 3-month (3 MM/3MT) follow-up visits.

RESULTS: Statistically significant differences were found in DARatio_2 mm, IntRad, ARTh, CBI and TBI following overnight ortho-k, when compared with BL values, with most values reaching stability at 1WM or reverting to BL values at 3 MM. The ARTh and CBI parameters showed some of the most significant temporal variations (both p < 0.001), probably reflecting the encountered differences in central corneal thickness between BL and 1WM (p = 0.010) and between BL and 3 MM (p = 0.016). In general, corneal rigidity was higher in the morning at all follow-up visits, and decreased during the day. No statistically significant changes in adjusted intraocular pressure values were found.

CONCLUSION: Ortho-k in adults may be considered a safe procedure in terms of short and mid-term changes in CORVIS ST® parameters. The observed alterations in most of the parameters provided by the Corvis ST® probably responded to the well-described changes in corneal pachymetry and tomography, rather than to actual alterations in corneal rigidity.

PMID:36375143 | DOI:10.1080/08164622.2022.2140031

Clin Exp Optom. 2022 Nov 14:1-8. doi: 10.1080/08164622.2022.2134763. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Horizontal fusional reserves are used in the diagnosis and monitoring of common vergence disorders, such as convergence insufficiency, which can cause asthenopia and impact near work. Infrared eyetracking technology shows promise for obtaining automated and objective measurements of fusional reserves, expanding options for screening, clinical testing, and at-home monitoring/vision training.

BACKGROUND: Current clinical tests for fusional reserves rely on subjective judgements made by patients (for diplopia) and clinicians (for eye movements). This paper describes an objective and automated “digital fusion-range test” pilot-tested in adults without current eye disease or binocular vision anomalies. This test combines a consumer-grade infrared eyetracker, a dichoptic display, and custom analyses programs to measure convergence and divergence reserves.

METHODS: Twenty-nine adult participants completed the study. Horizontal fusional reserves at 55 cm were measured using prism bars and with our computer-based digital fusion-range test. For the digital test, observers viewed dichoptic targets whose binocular disparity modulated over time (at speeds of 0.5, 1.0, or 2.0 Δ/s) while their eye movements were continuously recorded. Subjective reports of break and recovery (by keyboard button press) were compared to objective estimates extracted from eyetracking recordings (via automated analyses).

RESULTS: Objective and subjective measures of break and recovery agreed closely. Clinically small (0.3-2Δ) but statistically significant (p < 0.012) differences were found between measurement types for divergence breaks/recoveries and convergence recoveries. No significant differences were found for convergence breaks (p = 0.11). Such differences are consistent with an average 0.91 (SD 1.66) seconds delay between objective break/recovery and subjective responses. The digital test produced comparable results to the standard clinical prism bar method.

CONCLUSION: The digital fusion-range test supports an automated, reliable assessment of horizontal fusional reserves, which do not depend on subjective responses. This technology may prove useful in a variety of clinical and community-based settings.

PMID:36375141 | DOI:10.1080/08164622.2022.2134763

Rhinology. 2022 Nov 14. doi: 10.4193/Rhin22.329. Online ahead of print.

ABSTRACT

BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus.

METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated.

RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted.

CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.

PMID:36375133 | DOI:10.4193/Rhin22.329

Int J Urol. 2022 Nov 14. doi: 10.1111/iju.15100. Online ahead of print.

ABSTRACT

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation.

OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD.

METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively.

RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613).

CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

PMID:36375083 | DOI:10.1111/iju.15100

Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2118589119. doi: 10.1073/pnas.2118589119. Epub 2022 Nov 14.

ABSTRACT

As a ubiquitous paradigm of instabilities and mixing that occur in instances as diverse as supernovae, plasma fusion, oil recovery, and nanofabrication, the Rayleigh-Taylor (RT) problem is rightly regarded as important. The acceleration of the fluid medium in these instances often depends on time and space, whereas most past studies assume it to be constant or impulsive. Here, we analyze the symmetries of RT mixing for variable accelerations and obtain the scaling of correlations and spectra for classes of self-similar dynamics. RT mixing is shown to retain the memory of deterministic conditions for all accelerations, with the dynamics ranging from superballistic to subdiffusive. These results contribute to our understanding and control of the RT phenomena and reveal specific conditions under which Kolmogorov turbulence might be realized in RT mixing.

PMID:36375067 | DOI:10.1073/pnas.2118589119