BER analysis of an optimum MIMO linear receiver in optical SDM systems with mode-dependent loss.

Multiple-input multiple-output (MIMO) receivers designed to optimize the minimum mean square error (MMSE) are a common choice in coherent optical communication systems based on spatial division multiplexing (SDM). This kind of receivers naturally integrate both MIMO equalization and matched filtering functions. However, when the optical channel exhibits significant mode-dependent loss (MDL) and/or mode-dependent gain (MDG), the impact of inter-symbol interference (ISI) and crosstalk that arise, even using an ideal MIMO MMSE linear receiver, is barely analyzed. Moreover, due to the random nature of the MDL/MDG model, the resulting ISI, crosstalk, and bit error rate (BER) also become random variables and, hence the system performance is more unpredictable. In this paper, we first evaluate the residual distortion (ISI and crosstalk) after the MIMO receiver and then we study the validity of assuming it as an additional Gaussian noise term independent of the channel noise. Next, the probability density distribution (PDF) of the BER is analyzed, from both an analytical perspective and numerical simulations. For the latter, we use a single-carrier 2-PAM (pulse amplitude modulation) system, with pulse shaping, and the MIMO MMSE receiver implementation by means of a MIMO fractionally-spaced equalizer (FSE). We carry out simulations of the system under different conditions of MDL/MDG level and signal to noise ratio (SNR), measured at the receiver input. Additionally, we address possible fits of the BER PDF to known closed-form distributions, among which the Generalized Extreme Value (GEV) family of distributions is selected, and polynomial functions are proposed that relate the system parameters with the GEV PDF parameters. Finally, we present contour maps of BER according to a giving target of system outage probability (OP) that depend on the MDL/MDG and SNR conditions.

Post-FEC performance evaluation of optical SDM systems with mode-dependent loss.

This work is focused on the bit error rate (BER) performance of spatial division multiplexing (SDM) systems over an optical channel with mode-dependent loss or gain (collectively referred to in this paper as MDL). When the latter is non-negligible, the BER has a random nature that introduces the outage probability as an important performance metric for the system design and also impacts on the selection of a forward-error correction (FEC) scheme. In MDL-impaired SDM systems, the pre-FEC BER is a random variable whose probability density function (PDF) and coding gain depend on the signal-to-noise ratio (SNR) at the receiver input. Hence, the common and simple approach of adding a coding gain factor to the pre-FEC BER to obtain the post-FEC BER is not adequate, and numerical simulations are needed. In this paper, we simulate and analyze the performance in terms of post-FEC BER for two proposals of applying low-density parity check (LDPC) FEC encoder/decoder in a SDM system MDL-impaired and an optimal linear multiple input multiple output (MIMO) receiver. In the first one, the LDPC is applied independently to each mode, and in the second one, the LDPC is applied among all SDM modes. Simulation results indicate that the first proposal outperforms the second. Simplifications in the log-likelihood ratio (LLR) computations have also been considered.

Matched Filtering for MIMO Coherent Optical Communications with Mode-Dependent Loss Channels.

The use of digital signal processors (DSP) to equalize coherent optical communication systems based on spatial division multiplexing (SDM) techniques is widespread in current optical receivers. However, most of DSP implementation approaches found in the literature assume a negligible mode-dependent loss (MDL). This paper is focused on the linear multiple-input multiple-output (MIMO) receiver designed to optimize the minimum mean square error (MMSE) for a coherent SDM optical communication system, without previous assumptions on receiver oversampling or analog front-end realizations. The influence of the roll-off factor of a generic pulse-amplitude modulation (PAM) transmitter on system performance is studied as well. As a main result of the proposed approach, the ability of a simple match filter (MF) based MIMO receiver to completely eliminate inter-symbol interference (ISI) and crosstalk for SDM systems under the assumption of negligible MDL is demonstrated. The performance of the linear MIMO fractionally-spaced equalizer (FSE) receiver for an SDM system with a MDL-impaired channel is then evaluated by numerical simulations using novel system performance indicators, in the form of signal to noise and distortion ratio (SNDR) loss, with respect to the case without MDL. System performance improvements by increasing the transmitter roll-off factor are also quantified.

A Patient-Based National Survey and Prospective Evaluation of Postoperative Pain Management in Spain: Prevalent but Possibly Preventable.

OBJECTIVE: To evaluate the national general prevalence of postoperative pain and the associated organizational/structural factors related to the provision of health care services. DESIGN AND SETTING: Observational prospective cohort study performed in 46 tertiary hospitals that were randomly selected from the Spanish National Inventory of Hospitals through a two-stage balanced and stratified procedure. SUBJECTS AND METHODS: Nine-hundred surgical patients representing a wide spectrum of surgical procedures and anesthetic methods were recruited. Those suffering moderate or worse pain while in the postanesthesia care unit/surgery ward (PACU/SW) were followed for 72 hours. Site characteristics were also surveyed. Multilevel models were used to evaluate center- and patient-level factors associated with pain and quality of recovery (QoR). Weighted generalized estimating equations were used to analyze the evolution of pain intensity. RESULTS: The prevalence while in and at discharge from the PACU/SW was 48.7% (cluster-adjusted 95% confidence interval [CI] = 38.1-59.2%) and 21.6% (95% CI = 15.4-27.8%), respectively. Pain intensity decreased significantly over time. Less than 20% of the patients received systemic patient-controlled analgesia (PCA) or regional analgesic techniques. Age, preexisting pain, type of surgery, use of general anesthesia, and postoperative potent opioids were associated with pain risk and intensity, as were center-level factors such as patient information, protocol availability, and coordination of care. In turn, QoR was related to pain intensity and patient satisfaction with analgesia and side effects. CONCLUSIONS: Compared with previous reports, the prevalence of moderate/severe postoperative pain has decreased but remains excessive. Organizational improvements to deploy procedure-specific, opioid-sparing analgesic strategies including regional techniques are recommended.

Magnesium sulfate in pediatric anesthesia: the Super Adjuvant.

Magnesium is an essential chemical element in all organisms, intervening in most cellular enzymatic reactions; thus, its importance in homeostasis and as a therapeutic tool in highly challenging patients such as pediatrics. The primary purpose of this paper was to review the role of magnesium sulfate as an adjuvant drug in pediatric anesthesia. This compound already has the scientific backing in certain aspects such as analgesia or muscle relaxation, but only theoretical or empirical backing in others such as organ protection or inflammation, where it seems to be promising. The multitude of potential applications in pediatric anesthesia, its high safety, and low cost make magnesium sulfate could be considered a Super Adjuvant.

Global transcriptional analysis of Geobacter sulfurreducens gsu1771 mutant biofilm grown on two different support structures.

Electroactive biofilms formation by the metal-reducing bacterium Geobacter sulfurreducens is a step crucial for bioelectricity generation and bioremediation. The transcriptional regulator GSU1771 controls the expression of essential genes involved in electron transfer and biofilm formation in G. sulfurreducens, with GSU1771-deficient producing thicker and more electroactive biofilms. Here, RNA-seq analyses were conducted to compare the global gene expression patterns of wild-type and Δgsu1771 mutant biofilms grown on non-conductive (glass) and conductive (graphite electrode) materials. The Δgsu1771 biofilm grown on the glass surface exhibited 467 differentially expressed (DE) genes (167 upregulated and 300 downregulated) versus the wild-type biofilm. In contrast, the Δgsu1771 biofilm grown on the graphite electrode exhibited 119 DE genes (79 upregulated and 40 downregulated) versus the wild-type biofilm. Among these DE genes, 67 were also differentially expressed in the Δgsu1771 biofilm grown on glass (56 with the same regulation and 11 exhibiting counter-regulation). Among the upregulated genes in the Δgsu1771 biofilms, we identified potential target genes involved in exopolysaccharide synthesis (gsu1961-63, gsu1959, gsu1972-73, gsu1976-77). RT-qPCR analyses were then conducted to confirm the differential expression of a selection of genes of interest. DNA-protein binding assays demonstrated the direct binding of the GSU1771 regulator to the promoter region of pgcA, pulF, relA, and gsu3356. Furthermore, heme-staining and western blotting revealed an increase in c-type cytochromes including OmcS and OmcZ in Δgsu1771 biofilms. Collectively, our findings demonstrated that GSU1771 is a global regulator that controls extracellular electron transfer and exopolysaccharide synthesis in G. sulfurreducens, which is crucial for electroconductive biofilm development.

Long-term tolerability, efficacy and acceptability of fentanyl pectin nasal spray for breakthrough cancer pain.

PURPOSE: Previous studies show that fentanyl pectin nasal spray (FPNS) rapidly provides clinically meaningful pain relief in the treatment of breakthrough cancer pain (BTCP). This study assessed the long-term tolerability, acceptability and consistency of effect of FPNS in patients with BTCP. METHODS: Patients (new and rolled over from earlier controlled studies) with cancer experiencing one to four episodes per day of BTCP whilst taking ≥ 60 mg/day of morphine (or equivalent) given orally for cancer pain entered an open-label 16-week safety study. Safety and tolerability were assessed by adverse events (AEs), adverse drug reactions (ADRs), withdrawal due to AEs and by nasal assessments. Acceptability assessments included ratings of overall satisfaction with each treated episode and ease of use and convenience of FPNS. Additional rescue medication and dose stability were used to evaluate the consistency of effect. RESULTS: Four hundred three patients were included in the safety and intent-to-treat analysis (42,227 episodes), 356 entered the treatment phase and 110 completed 16 weeks. Overall, 24.6% of 403 patients reported treatment-related treatment-emergent AEs that were generally mild/moderate and typical of opioids; 20 patients discontinued treatment due to an AE (9 were ADRs). Nasal assessments revealed no clinically significant effects; 94% of FPNS-treated episodes required no additional rescue medication. More than 90% of patients did not have to increase their dose during the study. Patients reported overall satisfaction with FPNS for 90.1% of episodes. At week 12, 96.9% of patients were satisfied with the ease of use and 97.9% with the convenience of FPNS. CONCLUSIONS: FPNS was generally well tolerated and well accepted for the treatment of BTCP, and doses remained stable over the 4-month study period.

Current knowledge of buprenorphine and its unique pharmacological profile.

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other µ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full µ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.

[Nasopalatine duct cyst: case report]. / Quiste del conducto nasopalatino: a propósito de un caso.

Nasopalatine are the most prevalent of non-odontogenic cysts in the oral cavity. Their origin, however, is still a source of controversy. We report the case of a patient with a mass in the anterior half of the hard palate following months of evolution, with a review of the literature.

Towards an Inclusive and Evidence-Based Definition of the Maternal Mortality Ratio: An Analysis of the Distribution of Time after Delivery of Maternal Deaths in Mexico, 2010-2013.

Progress towards the Millennium Development Goal No. 5 was measured by an indicator that excluded women who died due to pregnancy and childbirth after 42 days from the date of delivery. These women suffered from what are defined as late deaths and sequelae-related deaths (O96 and O97 respectively, according to the International Classification of Diseases, 10th revision). Such deaths end up not being part of the numerator in the calculation of the Maternal Mortality Ratio (MMR), the indicator that governments and international agencies use for reporting. The issue is not trivial since these deaths account for a sizeable fraction of all maternal deaths in the world and show an upward trend over time in many countries. The aim of this study was to analyze empirical data on maternal deaths that occurred between 2010 and 2013 in Mexico, linking databases of the Deliberate Search and Reclassification of Maternal Deaths (BIRMM) and the Birth Information Subsystem (SINAC) of the Ministry of Health. Data were analyzed by negative binomial regression, survival analysis and multiple cause analysis. While the reported MMR decreased by 5% per year between 2010 and 2013, the MMR due to late and sequelae-related deaths doubled from 3.5 to 7 per 100,000 live-births in 2013 (p <0.01). A survival analysis of all maternal deaths revealed nothing particular around the 42 day threshold, other than the exclusion of 18% of women who died due to childbirth in 2013. The multiple cause analysis showed a strong association between the excluded deaths and obstetric causes. It is suggested to review the construction of the MMR to make it a more inclusive and dignified measurement of maternal mortality by including all deaths due to pregnancy and childbirth into the Maternal Death definition.

Relationship between onset of pain relief and patient satisfaction with fentanyl pectin nasal spray for breakthrough pain in cancer.

BACKGROUND: Satisfaction with pain relief in patients with breakthrough pain in cancer (BTPc) has typically been assessed by overall efficacy without consideration of the rapidity of that response. OBJECTIVE: To determine the relationship between speed of onset of pain relief and patient satisfaction for treated BTPc episodes overall and for individual treatments. DESIGN: Pooled data from two randomized, double-blinded crossover studies. SETTING/SUBJECTS: Patients having 1-4 BTPc episodes per day on ≥60 mg/day oral morphine or equivalent. Episodes treated with fentanyl pectin nasal spray (FPNS; 100-800 µg), immediate-release morphine sulfate (IRMS), or placebo. MEASUREMENTS: Pain intensity was measured on an 11-point scale (5-60 minutes posttreatment); satisfaction was measured on a 4-point scale (30 and 60 minutes). The primary analysis assessed the overall relationship of time to onset of pain relief (pain intensity difference [PID]≥1) or time to clinically meaningfully reduction in pain (PID≥2) versus patient satisfaction and overall pain intensity (summed pain intensity difference at 30 [SPID30] and 60 minutes [SPID60]) assessed by analysis of variance (ANOVA). A secondary analysis assessed whether satisfaction was different between treatments using a within-patient comparison. RESULTS: Eight hundred thirty-one FPNS-treated, 368 IRMS-treated, and 200 placebo-treated episodes were analyzed. Overall, within the pool there was a statistically significant relationship between time to onset of pain relief (PID≥1 and PID≥2) and patient satisfaction (both speed of relief and overall) at 30 and 60 minutes (p<0.001); this relationship was also true within individual treatment groups (p<0.01). Similar results were found for overall pain intensity reduction. When treatment groups were compared using within-patient data, FPNS provided earlier onset of pain relief than IRMS or placebo (p<0.05), which translated into better satisfaction at 60 minutes (p<0.01). CONCLUSIONS: Earlier onset of pain relief resulted in greater patient satisfaction and overall relief of pain; between-treatment comparisons showed that FPNS provided earlier pain relief and greater satisfaction than IRMS or placebo.

A report on the long-term use of fentanyl pectin nasal spray in patients with recurrent breakthrough pain.

CONTEXT: As patients with cancer are living longer, there is a need to ensure that treatments used for palliative care are well tolerated and effective during long-term use. OBJECTIVES: To investigate the long-term use of fentanyl pectin nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in patients receiving regular opioid therapy. METHODS: Adult patients (N = 401) taking at least 60 mg/day oral morphine or equivalent, experiencing one to four episodes of BTPc a day, entered an open-label long-term study (NCT00458510). Patients had either completed an FPNS randomized controlled trial or were newly identified. Of these, 171 patients continued into an extension study. Up to four episodes of BTPc a day were treated with FPNS at 100-800 µg titrated doses. During the extension study, patients visited the clinic every four weeks for assessment and reporting of adverse events (AEs). RESULTS: There were 163 patients with documented FPNS use. The mean duration of use was 325 days; 46 patients used FPNS for ≥360 days; the maximum duration was 44 months. Seventy percent of patients did not change their FPNS dose; 2% of patients withdrew from the study because of the lack of efficacy. The most common AEs, aside from disease progression, were insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and peripheral edema, 9.4%. The overall incidence of FPNS-related AEs was 11.1%, the most common being constipation (4.1%), with no apparent dose relationship. Ten patients (5.8%) experienced nasal AEs, most of which were mild or moderate. CONCLUSION: FPNS appeared to provide sustained benefit and was well tolerated during long-term treatment of BTPc.

[Recommendations on use of direct oral anticoagulants in the perioperative period]. / Recomendaciones de uso de los anticoagulantes orales directos en el período perioperatorio.

Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented.

Long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray for breakthrough cancer pain in opioid-tolerant patients.

OBJECTIVE: to assess the long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray (FPNS) in patients with breakthrough cancer pain (BTCP). DESIGN: a multicenter, open-label study. PATIENTS: patients with chronic cancer pain treated with > or = 60 mg/d oral morphine or equivalent experiencing 1-4 episodes per day of BTCP. INTERVENTION: all patients entered into a 16-week treatment phase after undergoing a dose-titration phase with FPNS. MAIN OUTCOME MEASURES: safety and tolerability were assessed by adverse events (AEs) and by nasal tolerability assessments. Consistency of effect was monitored through additional rescue medication use and FPNS dose change. RESULTS: four hundred three patients were included in the safety analyses. Of these, 356 patients entered the treatment phase and 110 patients completed the study. FPNS was self-administered for 42,227 episodes. During the treatment phase, 99 patients (24.6 percent) reported treatment-related AEs; most were mild or moderate and typical of opioids. Serious AEs were reported by 61 patients (15.1 percent), but only five were considered related to study drug. Of the 80 deaths that occurred during this study, one was assessed as possibly related to study drug. Nasal assessments revealed no significant local effects. No additional rescue medication was required after 94 percent of FPNS-treated episodes. More than 90 percent of patients required no increase in their initial dose of FPNS. CONCLUSIONS: FPNS use for BTCP was associated with AEs, typical of opioids, with no evidence of nasal toxicity. A large proportion of BTCP episodes were treated with a single dose, and doses remained stable over the 4-month period.

La mascarilla (que tanto necesitamos es la que hubiéramos necesitado) / The mask (which we need so much is the one we would have needed)

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Spinal Cord Stimulation and Thalamic Pain: Long-term Results of Eight Cases.

Objectives. We submit a retrospective analysis of results of eight patients suffering from intractable pain of established or suspected thalamic origin. These patients were treated with spinal cord stimulation (SCS) in the cervical or dorsal cord. No patient was suffering pain from a complete hemibody or facial area. Material and Methods. Five men and three women aged 27-67 years were treated in the Pain Unit of our institution between April 1993 and January 2006. The cause of pain in five cases was stroke (plus one suspected). Multiple sclerosis was responsible for pain in two cases. An upper or lower extremity was affected in six cases. Extension to adjacent trunk was common. Exclusive trunk pain was treated in two cases. Results. The follow-up period was 36-149 months. Two patients were not battery-implanted because pain relief was insufficient during the trial phase. Two patients had a further stroke: One died and one was cured from pain. Good-to-excellent results were attained in six patients; long-term good-to-excellent results were maintained in three patients. Conclusions. Despite previous adverse reports, certain cases of thalamic pain can be effectively alleviated through SCS.

Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naive patients with severe chronic noncancer pain.

BACKGROUND: Chronic noncancer pain is often undertreated. AIMS: To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain. METHODS: A total of 215 patients with chronic (> or =6 months), severe (VAS > or = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 microg/h fentanyl TTS was titrated in 25 microg/h increments to a visual analog scale (VAS) score < or = 4. OTFC was administered as single-unit doses of 400 microg. RESULTS: The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 microg/h dose in 48 percent of patients, the 75 microg/h dose in 18 percent, and the 100 microg/h dose in 5 percent (only two patients required >100 microg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two. CONCLUSIONS: Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain.