ABSTRACT

Fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP) are 2 techniques that can be used to correct distal femoral valgus deformities. The fixator aids in achieving an accurate adjustable initial reduction, which is then made permanent with either nail or plate insertion. FALP can be performed with the knee held in a neutral extended position, whereas FAN requires 30° to 90° of knee flexion to insert the nail, which may cause some alignment loss. We hypothesized that FAN may yield less accurate correction than FALP. Prospectively collected data of a consecutive cohort of patients who underwent valgus deformity femoral correction with FAN or FALP at a single institution over an 8-year period were retrospectively evaluated. Twenty extremities (18 patients) were treated using FAN (median follow-up, 5 years; range, 1-10 years), and 7 extremities (6 patients) were treated with FALP (median follow-up, 5 years; range, 1-8 years). In the FAN cohort, the mean preoperative and postoperative mechanical lateral distal femoral angles (mLDFAs) were 81° (range, 67°-86°) and 89° (range, 80°-100°), respectively (P = .009). In the FALP cohort, the mean preoperative and postoperative mLDFAs were 80° (range, 71°-87°) and 88° (range, 81°-94°), respectively (P < .001). Although the average mechanical axis deviation correction for the FALP group was greater than for the FAN group (32 mm and 27 mm, respectively), the difference was not significant (P = .66). Both methods of femoral deformity correction can be considered safe and effective. On the basis of our results, FAN and FALP are comparable in accuracy for deformity correction in the distal femur.

Multiple etiologies for distal femoral valgus deformity have been described in the literature.^1-3 These can be congenital, developmental, secondary to lateral compartmental arthritis, or posttraumatic.⁴ If not corrected, femoral deformities alter the axial alignment and orientation of the joints, and may lead to early degenerative joint disease and abnormal leg kinematics.^3,5 After correcting these deformities, the goal of treatment is to obtain anatomic distal femoral angles and neutral mechanical axis deviation (MAD), but without overcorrecting into varus. Numerous techniques to fix these deformities, such as progressive correction with external fixation or acute correction open reduction with internal fixation (ORIF), have been described.⁶ Modern external fixation allows for a gradual, adjustable, and more accurate correction but may produce discomfort and complications for patients.^7-10 In contrast, ORIF may be more tolerable for the patient, but to achieve a precise correction, considerable technical skills and expertise are required.^1,11-14

Two techniques used to correct these valgus femoral deformities in adults are fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP).¹ FAN and FALP combine the advantage of external fixation (accuracy, adjustability) with the benefits of internal fixation (patient comfort), because the osteotomy and correction are performed with the guidance of a temporary external fixator and then permanently fixated by an intramedullary (IM) nail or a locking plate.^{1,8,11-13,15-18} Both techniques have the possibility to correct varus and valgus deformities, but whenever correcting sagittal plane angulation, the FAN technique may be more challenging. The paucity of studies available involving FAN and FALP do not lead to a conclusive preference of one technique over the other relative to the accuracy and success of correction.^15,19,20

Continue to: In both FAN and FALP

In both FAN and FALP, the external fixator is applied and adjusted after the osteotomy for accurate alignment. In FALP, the plate is added without moving the leg from its straight position. However, in FAN, the knee must be flexed to 30° to 90° for insertion of the retrograde knee nail, and the alignment may be lost if the external fixation is not fully stable. Therefore, we hypothesized that FAN would be less accurate than FALP. Hence, the purposes of this study is to compare the correction achieved with FAN and FALP in patients with distal femoral valgus deformities and to describe the intraoperative complications associated with both techniques.

MATERIALS AND METHODS

After proper Institutional Review Board approval was obtained, a consecutive cohort of 35 patients who underwent femoral deformity correction with either FAN or FALP during an 8-year period (January 2002 to December 2010) was retrospectively reviewed. Eleven patients had to be excluded because of inadequate follow-up (<12 months) or because additional procedures were simultaneously performed. A total of 24 patients (27 femora) who had a mean age of 26 years (range, 14-68 years) were included in the final study cohort. Specifically, 20 femora (18 patients) were corrected using the FAN technique (7 males and 11 females; mean age, 36 years; range, 14-68 years), and 7 femora (6 patients) were fixed using the FALP technique (2 males and 4 females; mean age, 16 years; range, 15-19 years). The median follow-up in the FAN cohort was 5 years (range, 1-10 years), and the median follow-up in the FALP cohort was 5 years (range, 1-8 years) (Table 1).

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing

The specific measurements performed in all patients were MAD, mechanical lateral distal femoral angle (mLDFA), and medial proximal tibia angle (MPTA). These were measured from standing anteroposterior radiographs of the knee that included the femur.²¹ All outcome data were collected from the medical charts, operative reports, and radiographic evaluations. To ensure accuracy, all measurements were performed by 2 authors blinded to each other’s measurements. If a variation of <5% was obtained, the results were averaged and used for further analysis. Whenever a difference of >5% was obtained, the measurement was repeated by both authors for confirmation.

SURGICAL FAN TECHNIQUE

After measuring the deformity (Figure 1A) with the patient under general anesthesia on a radiolucent table, the involved lower limb is prepared and draped. Two half-pins are inserted medially, 1 proximal and 1 distal to the planned osteotomy site (Figure 1B), and then connected loosely with a monolateral external fixator. Special care is taken while placing the half-pins, not to interfere with the insertion path of the IM rod. When performing the preoperative planning, the level of osteotomy is chosen to enable the placement of at least 2 interlocking screws distal to the osteotomy. Then, a percutaneous osteotomy is performed from a lateral approach, and the bone ends are manipulated (translation and then angulation) to achieve the desired deformity correction. The external fixator is then stabilized and locked in the exact position (Figure 1C). Subsequently, retrograde reaming, nail insertion, and placement of proximal and distal locking screws are performed (Figure 1D). Blocking screws may give additional stability. The removal of the external fixator is the final step (Figure 1E).²⁰

Continue to: When using the FAN technique...

SURGICAL FALP TECHNIQUE

Preoperatively, a decision concerning the planned osteotomy and the correct locking plate size is made. In addition, the outline of the plate is marked on the skin. Under general anesthesia, the patients are prepared and draped. A tourniquet is elevated around the upper thigh. Then, 2 half-pins are medially inserted, 1 proximal and 1 distal to the planned osteotomy site, and are then connected loosely with a monolateral external fixator (Figure 2A). A lateral approach to the distal femur is done, preserving the periosteum, except at the level of the osteotomy. After the osteotomy is performed (through an open lateral incision), both segments are translated (Figure 2B) and then the distal segment is angulated to achieve the desired deformity correction, and the desired position is then stabilized by tightening the external fixator connectors (Figure 2C). Subsequently, a locking plate is inserted in the submuscular-extraperiostal plane. The plate does not require being in full contact (flush) with the bone. At least 3 screws are placed on both sides of the osteotomy through a long lateral incision (Figure 2D). Bone graft may be added to the osteotomy site to encourage healing. Then, the external fixator is removed, and all incisions are closed (Figure 2E).^15,19 

During each of the procedures, we aimed at having “perfect alignment” with a MAD of 0 mm, in which a Bovie cord is used and passed through the center of the femoral head, knee, and ankle. However, to confirm that the surgery was successful, the actual measurements were performed on standing long-leg films. These films were obtained preoperatively and at latest follow-up. They were performed with the patella aiming forward, the toes straight ahead, feet separated enough for good balance, knees fully extended, and weight equally distributed on the feet. Postoperatively, in both cohorts, partial weight-bearing was encouraged immediately with crutches; physical therapy was instituted daily for knee range of motion. Radiographs were scheduled every 4 weeks to monitor callus formation. Full weight-bearing was allowed when at least 3 cortices were consolidated.^{1,15,19,20,25,26}

All statistical analyses were performed with the aid of the SPSS statistical software package (SPSS). Average values and standard error of the mean were assigned to each variable. A nonparametric Mann-Whitney U test was used, and a 2-tailed P < .05 was considered significant. Correlation of continuous variables was determined by Spearman’s correlation coefficient. Also, multivariate Cox regression analyses after adjustment for age, sex, and deformity correction were used to detect associations within the study population. To evaluate whether our data were normally distributed, Shapiro-Wilk tests were performed.

Continue to: Results...

RESULTS

The mLDFA significantly improved in the FAN cohort from a mean of 81° to a mean of 89° (ranges, 67°-86° and 80°-100°; respectively; P = .001) (Figures 3A, 3B). 

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing; mLDFA, mechanical lateral distal femoral angle

After evaluating the MPTA, in the FAN cohort, we found that the mean pre- and postoperative MPTAs were not modified. These patients had a mean preoperative angle of 88° (range, 62°-100°), which was kept postoperatively to a mean of 88° (range, 78°-96°). In the FALP cohort, a slight change from 90° to 88° was observed (ranges, 82°-97° and 83°-94°, respectively). None of these changes in MPTA were significant (P > .05).

When evaluating correction of the MAD, we observed that the FAN cohort changed from a preoperative MAD of 32 mm (range, 6-64 mm) to a postoperative mean of 10 mm (range, 0-22 mm), and this correction was statistically significant. (P = .001). The FALP cohort changed from a mean of 34 mm (range, 17-62 mm) preoperatively to 4 mm (range, 0-11 mm) postoperatively, and this was also statistically significant (P = .002). The mean MAD correction for the FAN group vs FALP group was 27 mm vs 32 mm, respectively (Table 2).

In patients with valgus femoral deformity, the MAD is usually lateralized; however, in the FAN cohort, we included 3 patients with medial MADs (10 mm, 13 mm, and 40 mm). This is justified in these patients because a complex deformity of the distal femur and the proximal tibia was present. In the extreme case of a 40-mm medial MAD, the presurgery mLDFA was 76°, and the presurgery MPTA was 62°. The amount of deformity correction in this patient was 16°.

During the follow-up period, 2 complications occurred in the FAN group. One patient developed gait disturbance that resolved with physical therapy. Another had an infection at the osteotomy site. This was addressed with intravenous antibiotic therapy, surgical irrigation and débridement, hardware removal, and antegrade insertion of an antibiotic-coated nail. In the FALP group, 1 patient developed a persistent incomplete peroneal nerve palsy attributed to a 17° correction from valgus to varus, despite prophylactic peroneal nerve decompression. Nonetheless, the patient was satisfied with the result, recovered partial nerve function, and returned for correction of the contralateral leg deformity. When comparing the complications between both cohorts, no significant differences were found: 2 of 18 cases (11%) in the FAN group vs 1 of 6 cases (17%) in the FALP group (P = .78).

Continue to: The goal of this study...

DISCUSSION

The goal of this study was to compare the accuracy of deformity corrections achieved with either FAN or FALP. A number of authors have described results after deformity correction with several plating and nailing techniques; however, the information derived from comparing these 2 techniques is limited. We hypothesized that FALP would be more accurate, because less mobilization during fixation is required. However, we found no significant differences between these 2 techniques.

This study has several limitations. First, the small size of our cohort had to be further reduced owing to limited data; nevertheless, this pathology and the treatment methods used are not commonly performed, which make this cohort 1 of the largest of its type described in the literature. Also, the procedures were performed by multiple surgeons in a population with a wide age range, creating multiple additional variables that complicate the comparison of the sole differences between FAN and FALP. However, owing to these variables, the generalizability of this study may be increased, and similar outcomes can potentially be obtained by other institutions/surgeons. In addition, the variability of our follow-up period is another limitation; however, these patients were all assessed until bony union after skeletal maturity was achieved. Hence, the development of additional deformity is not expected. The lack of clinical outcome with a standardized questionnaire may also be seen as a limitation. However, because the purpose of our study was to assess both surgeries in terms of their ability to achieve angular correction, the addition of patient-reported outcomes may have increased the variability of our data.

The foremost objective in valgus deformity correction is to establish joint orientation angles within anatomic range to prevent overloading of the lateral joint and thereby prevent lateral compartmental osteoarthritis.^2,20,27-29 There are 2 categories of fixation: internal and external. With FAN and FALP, we strive to have the adjustability and accuracy of external fixation with the comfort (for the patient) of internal fixation. Accurate osteotomy correction requires an accurate preoperative analysis and osteotomy close to the apex of the deformity.^16,21,30-33 The most commonly used osteotomy techniques are drill-hole,³¹ focal dome,³⁴ rotation, and open- or closed-wedge osteotomies.^35,36 After the osteotomy, the resultant correction has to be stabilized. In recent years, the popularity of plates instead of an IM nail for internal fixation has been driven by the rapid development of low contact locking plates.^{16,19,26,30,37-40}

There are certain advantages of using FAN over FALP. In older patients who may require a subsequent total knee arthroplasty (TKA), the midline incision used for retrograde FAN technique is identical to that made for TKA. In contrast, in a younger and more active population, with a longer life expectancy, the extra-articular FALP approach has the advantage of not violating the knee joint. In addition, locking plates may achieve a more rigid fixation than IM nails; however, the stability of IM nails can be augmented with blocking screws.

Continue to: In 20 patients, including children...

In their comparative study, Seah and colleagues¹¹ described monolateral frame vs FALP deformity correction in a series of 34 extremities (26 patients) that required distal femoral osteotomy. No differences related to knee range of motion or the ability to correct the deformity between internal and external fixation were reported (P > .05). Similarly, Eidelman and colleagues¹ evaluated the outcomes of 6 patients (7 procedures) who underwent surgery performed with the FALP technique for distal femoral valgus deformity. They concluded that this technique is minimally invasive and can provide a precise deformity correction with minimal morbidity.

Other methods of fixation while performing FAN have been described by Jasiewicz and colleagues,²² who evaluated possible differences between the classic Ilizarov device and monolateral fixators in 19 femoral lengthening procedures. The authors concluded that there is no difference between concerning complication rate and treatment time. The use of FAN has also been described in patients with metabolic disease who required deformity correction. In this regard, Kocaoglu and colleagues¹² described the use of a monolateral external fixator in combination with an IM nail in a series of 17 patients with metabolic bone disease. The authors concluded that the use of the IM nail prevented recurrence of deformity and refracture.¹² Kocaoglu and colleagues¹⁴ also published a series of 25 patients treated with the FAN and LON (lengthening over a nail) technique for lengthening and deformity correction. The mean MAD improved from 33.9 mm to11.3 mm (range, 0-30 mm). In contrast, Erlap and colleagues¹³ compared FAN with circular external fixator for bone realignment of the lower extremity for deformities in patients with rickets. Although no significant difference was found between both groups, FAN was shown to be accurate and to provide great comfort to patients, and it also shortened the total treatment time.¹³ Finally, the advent of newer technologies could also provide alternatives for correcting valgus deformities. For example, Saragaglia and Chedal-Bornu⁶ performed 29 computer-assisted valgus knees osteotomies (27 patients) and reported that the goal hip-knee angle was achieved in 86% of patients and that the goal MPTA was achieved in 100% of patients.⁶

CONCLUSION

Both the FALP and FAN methods of femoral deformity correction are safe and effective surgical techniques. In our opinion, the advantages of the FALP technique result from the easy lateral surgical approach under medial external fixation and stabilization of the osteotomy without bending the knee. Ultimately, the decision to use FAN may be influenced by the surgeon’s perception of the potential need for future TKA. In such cases, a midline anterior approach with nailing is very compatible with subsequent TKA. The surgeon’s experience and preference, while keeping in mind the patient’s predilection, will play an important role in the decision-making process. Larger prospective clinical trials with larger cohorts have to be conducted to confirm our findings.

ABSTRACT

Fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP) are 2 techniques that can be used to correct distal femoral valgus deformities. The fixator aids in achieving an accurate adjustable initial reduction, which is then made permanent with either nail or plate insertion. FALP can be performed with the knee held in a neutral extended position, whereas FAN requires 30° to 90° of knee flexion to insert the nail, which may cause some alignment loss. We hypothesized that FAN may yield less accurate correction than FALP. Prospectively collected data of a consecutive cohort of patients who underwent valgus deformity femoral correction with FAN or FALP at a single institution over an 8-year period were retrospectively evaluated. Twenty extremities (18 patients) were treated using FAN (median follow-up, 5 years; range, 1-10 years), and 7 extremities (6 patients) were treated with FALP (median follow-up, 5 years; range, 1-8 years). In the FAN cohort, the mean preoperative and postoperative mechanical lateral distal femoral angles (mLDFAs) were 81° (range, 67°-86°) and 89° (range, 80°-100°), respectively (P = .009). In the FALP cohort, the mean preoperative and postoperative mLDFAs were 80° (range, 71°-87°) and 88° (range, 81°-94°), respectively (P < .001). Although the average mechanical axis deviation correction for the FALP group was greater than for the FAN group (32 mm and 27 mm, respectively), the difference was not significant (P = .66). Both methods of femoral deformity correction can be considered safe and effective. On the basis of our results, FAN and FALP are comparable in accuracy for deformity correction in the distal femur.

Multiple etiologies for distal femoral valgus deformity have been described in the literature.^1-3 These can be congenital, developmental, secondary to lateral compartmental arthritis, or posttraumatic.⁴ If not corrected, femoral deformities alter the axial alignment and orientation of the joints, and may lead to early degenerative joint disease and abnormal leg kinematics.^3,5 After correcting these deformities, the goal of treatment is to obtain anatomic distal femoral angles and neutral mechanical axis deviation (MAD), but without overcorrecting into varus. Numerous techniques to fix these deformities, such as progressive correction with external fixation or acute correction open reduction with internal fixation (ORIF), have been described.⁶ Modern external fixation allows for a gradual, adjustable, and more accurate correction but may produce discomfort and complications for patients.^7-10 In contrast, ORIF may be more tolerable for the patient, but to achieve a precise correction, considerable technical skills and expertise are required.^1,11-14

Two techniques used to correct these valgus femoral deformities in adults are fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP).¹ FAN and FALP combine the advantage of external fixation (accuracy, adjustability) with the benefits of internal fixation (patient comfort), because the osteotomy and correction are performed with the guidance of a temporary external fixator and then permanently fixated by an intramedullary (IM) nail or a locking plate.^{1,8,11-13,15-18} Both techniques have the possibility to correct varus and valgus deformities, but whenever correcting sagittal plane angulation, the FAN technique may be more challenging. The paucity of studies available involving FAN and FALP do not lead to a conclusive preference of one technique over the other relative to the accuracy and success of correction.^15,19,20

Continue to: In both FAN and FALP

In both FAN and FALP, the external fixator is applied and adjusted after the osteotomy for accurate alignment. In FALP, the plate is added without moving the leg from its straight position. However, in FAN, the knee must be flexed to 30° to 90° for insertion of the retrograde knee nail, and the alignment may be lost if the external fixation is not fully stable. Therefore, we hypothesized that FAN would be less accurate than FALP. Hence, the purposes of this study is to compare the correction achieved with FAN and FALP in patients with distal femoral valgus deformities and to describe the intraoperative complications associated with both techniques.

MATERIALS AND METHODS

After proper Institutional Review Board approval was obtained, a consecutive cohort of 35 patients who underwent femoral deformity correction with either FAN or FALP during an 8-year period (January 2002 to December 2010) was retrospectively reviewed. Eleven patients had to be excluded because of inadequate follow-up (<12 months) or because additional procedures were simultaneously performed. A total of 24 patients (27 femora) who had a mean age of 26 years (range, 14-68 years) were included in the final study cohort. Specifically, 20 femora (18 patients) were corrected using the FAN technique (7 males and 11 females; mean age, 36 years; range, 14-68 years), and 7 femora (6 patients) were fixed using the FALP technique (2 males and 4 females; mean age, 16 years; range, 15-19 years). The median follow-up in the FAN cohort was 5 years (range, 1-10 years), and the median follow-up in the FALP cohort was 5 years (range, 1-8 years) (Table 1).

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing

The specific measurements performed in all patients were MAD, mechanical lateral distal femoral angle (mLDFA), and medial proximal tibia angle (MPTA). These were measured from standing anteroposterior radiographs of the knee that included the femur.²¹ All outcome data were collected from the medical charts, operative reports, and radiographic evaluations. To ensure accuracy, all measurements were performed by 2 authors blinded to each other’s measurements. If a variation of <5% was obtained, the results were averaged and used for further analysis. Whenever a difference of >5% was obtained, the measurement was repeated by both authors for confirmation.

SURGICAL FAN TECHNIQUE

After measuring the deformity (Figure 1A) with the patient under general anesthesia on a radiolucent table, the involved lower limb is prepared and draped. Two half-pins are inserted medially, 1 proximal and 1 distal to the planned osteotomy site (Figure 1B), and then connected loosely with a monolateral external fixator. Special care is taken while placing the half-pins, not to interfere with the insertion path of the IM rod. When performing the preoperative planning, the level of osteotomy is chosen to enable the placement of at least 2 interlocking screws distal to the osteotomy. Then, a percutaneous osteotomy is performed from a lateral approach, and the bone ends are manipulated (translation and then angulation) to achieve the desired deformity correction. The external fixator is then stabilized and locked in the exact position (Figure 1C). Subsequently, retrograde reaming, nail insertion, and placement of proximal and distal locking screws are performed (Figure 1D). Blocking screws may give additional stability. The removal of the external fixator is the final step (Figure 1E).²⁰

Continue to: When using the FAN technique...

SURGICAL FALP TECHNIQUE

Preoperatively, a decision concerning the planned osteotomy and the correct locking plate size is made. In addition, the outline of the plate is marked on the skin. Under general anesthesia, the patients are prepared and draped. A tourniquet is elevated around the upper thigh. Then, 2 half-pins are medially inserted, 1 proximal and 1 distal to the planned osteotomy site, and are then connected loosely with a monolateral external fixator (Figure 2A). A lateral approach to the distal femur is done, preserving the periosteum, except at the level of the osteotomy. After the osteotomy is performed (through an open lateral incision), both segments are translated (Figure 2B) and then the distal segment is angulated to achieve the desired deformity correction, and the desired position is then stabilized by tightening the external fixator connectors (Figure 2C). Subsequently, a locking plate is inserted in the submuscular-extraperiostal plane. The plate does not require being in full contact (flush) with the bone. At least 3 screws are placed on both sides of the osteotomy through a long lateral incision (Figure 2D). Bone graft may be added to the osteotomy site to encourage healing. Then, the external fixator is removed, and all incisions are closed (Figure 2E).^15,19 

During each of the procedures, we aimed at having “perfect alignment” with a MAD of 0 mm, in which a Bovie cord is used and passed through the center of the femoral head, knee, and ankle. However, to confirm that the surgery was successful, the actual measurements were performed on standing long-leg films. These films were obtained preoperatively and at latest follow-up. They were performed with the patella aiming forward, the toes straight ahead, feet separated enough for good balance, knees fully extended, and weight equally distributed on the feet. Postoperatively, in both cohorts, partial weight-bearing was encouraged immediately with crutches; physical therapy was instituted daily for knee range of motion. Radiographs were scheduled every 4 weeks to monitor callus formation. Full weight-bearing was allowed when at least 3 cortices were consolidated.^{1,15,19,20,25,26}

All statistical analyses were performed with the aid of the SPSS statistical software package (SPSS). Average values and standard error of the mean were assigned to each variable. A nonparametric Mann-Whitney U test was used, and a 2-tailed P < .05 was considered significant. Correlation of continuous variables was determined by Spearman’s correlation coefficient. Also, multivariate Cox regression analyses after adjustment for age, sex, and deformity correction were used to detect associations within the study population. To evaluate whether our data were normally distributed, Shapiro-Wilk tests were performed.

Continue to: Results...

RESULTS

The mLDFA significantly improved in the FAN cohort from a mean of 81° to a mean of 89° (ranges, 67°-86° and 80°-100°; respectively; P = .001) (Figures 3A, 3B). 

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing; mLDFA, mechanical lateral distal femoral angle

After evaluating the MPTA, in the FAN cohort, we found that the mean pre- and postoperative MPTAs were not modified. These patients had a mean preoperative angle of 88° (range, 62°-100°), which was kept postoperatively to a mean of 88° (range, 78°-96°). In the FALP cohort, a slight change from 90° to 88° was observed (ranges, 82°-97° and 83°-94°, respectively). None of these changes in MPTA were significant (P > .05).

When evaluating correction of the MAD, we observed that the FAN cohort changed from a preoperative MAD of 32 mm (range, 6-64 mm) to a postoperative mean of 10 mm (range, 0-22 mm), and this correction was statistically significant. (P = .001). The FALP cohort changed from a mean of 34 mm (range, 17-62 mm) preoperatively to 4 mm (range, 0-11 mm) postoperatively, and this was also statistically significant (P = .002). The mean MAD correction for the FAN group vs FALP group was 27 mm vs 32 mm, respectively (Table 2).

In patients with valgus femoral deformity, the MAD is usually lateralized; however, in the FAN cohort, we included 3 patients with medial MADs (10 mm, 13 mm, and 40 mm). This is justified in these patients because a complex deformity of the distal femur and the proximal tibia was present. In the extreme case of a 40-mm medial MAD, the presurgery mLDFA was 76°, and the presurgery MPTA was 62°. The amount of deformity correction in this patient was 16°.

During the follow-up period, 2 complications occurred in the FAN group. One patient developed gait disturbance that resolved with physical therapy. Another had an infection at the osteotomy site. This was addressed with intravenous antibiotic therapy, surgical irrigation and débridement, hardware removal, and antegrade insertion of an antibiotic-coated nail. In the FALP group, 1 patient developed a persistent incomplete peroneal nerve palsy attributed to a 17° correction from valgus to varus, despite prophylactic peroneal nerve decompression. Nonetheless, the patient was satisfied with the result, recovered partial nerve function, and returned for correction of the contralateral leg deformity. When comparing the complications between both cohorts, no significant differences were found: 2 of 18 cases (11%) in the FAN group vs 1 of 6 cases (17%) in the FALP group (P = .78).

Continue to: The goal of this study...

DISCUSSION

The goal of this study was to compare the accuracy of deformity corrections achieved with either FAN or FALP. A number of authors have described results after deformity correction with several plating and nailing techniques; however, the information derived from comparing these 2 techniques is limited. We hypothesized that FALP would be more accurate, because less mobilization during fixation is required. However, we found no significant differences between these 2 techniques.

This study has several limitations. First, the small size of our cohort had to be further reduced owing to limited data; nevertheless, this pathology and the treatment methods used are not commonly performed, which make this cohort 1 of the largest of its type described in the literature. Also, the procedures were performed by multiple surgeons in a population with a wide age range, creating multiple additional variables that complicate the comparison of the sole differences between FAN and FALP. However, owing to these variables, the generalizability of this study may be increased, and similar outcomes can potentially be obtained by other institutions/surgeons. In addition, the variability of our follow-up period is another limitation; however, these patients were all assessed until bony union after skeletal maturity was achieved. Hence, the development of additional deformity is not expected. The lack of clinical outcome with a standardized questionnaire may also be seen as a limitation. However, because the purpose of our study was to assess both surgeries in terms of their ability to achieve angular correction, the addition of patient-reported outcomes may have increased the variability of our data.

The foremost objective in valgus deformity correction is to establish joint orientation angles within anatomic range to prevent overloading of the lateral joint and thereby prevent lateral compartmental osteoarthritis.^2,20,27-29 There are 2 categories of fixation: internal and external. With FAN and FALP, we strive to have the adjustability and accuracy of external fixation with the comfort (for the patient) of internal fixation. Accurate osteotomy correction requires an accurate preoperative analysis and osteotomy close to the apex of the deformity.^16,21,30-33 The most commonly used osteotomy techniques are drill-hole,³¹ focal dome,³⁴ rotation, and open- or closed-wedge osteotomies.^35,36 After the osteotomy, the resultant correction has to be stabilized. In recent years, the popularity of plates instead of an IM nail for internal fixation has been driven by the rapid development of low contact locking plates.^{16,19,26,30,37-40}

There are certain advantages of using FAN over FALP. In older patients who may require a subsequent total knee arthroplasty (TKA), the midline incision used for retrograde FAN technique is identical to that made for TKA. In contrast, in a younger and more active population, with a longer life expectancy, the extra-articular FALP approach has the advantage of not violating the knee joint. In addition, locking plates may achieve a more rigid fixation than IM nails; however, the stability of IM nails can be augmented with blocking screws.

Continue to: In 20 patients, including children...

In their comparative study, Seah and colleagues¹¹ described monolateral frame vs FALP deformity correction in a series of 34 extremities (26 patients) that required distal femoral osteotomy. No differences related to knee range of motion or the ability to correct the deformity between internal and external fixation were reported (P > .05). Similarly, Eidelman and colleagues¹ evaluated the outcomes of 6 patients (7 procedures) who underwent surgery performed with the FALP technique for distal femoral valgus deformity. They concluded that this technique is minimally invasive and can provide a precise deformity correction with minimal morbidity.

Other methods of fixation while performing FAN have been described by Jasiewicz and colleagues,²² who evaluated possible differences between the classic Ilizarov device and monolateral fixators in 19 femoral lengthening procedures. The authors concluded that there is no difference between concerning complication rate and treatment time. The use of FAN has also been described in patients with metabolic disease who required deformity correction. In this regard, Kocaoglu and colleagues¹² described the use of a monolateral external fixator in combination with an IM nail in a series of 17 patients with metabolic bone disease. The authors concluded that the use of the IM nail prevented recurrence of deformity and refracture.¹² Kocaoglu and colleagues¹⁴ also published a series of 25 patients treated with the FAN and LON (lengthening over a nail) technique for lengthening and deformity correction. The mean MAD improved from 33.9 mm to11.3 mm (range, 0-30 mm). In contrast, Erlap and colleagues¹³ compared FAN with circular external fixator for bone realignment of the lower extremity for deformities in patients with rickets. Although no significant difference was found between both groups, FAN was shown to be accurate and to provide great comfort to patients, and it also shortened the total treatment time.¹³ Finally, the advent of newer technologies could also provide alternatives for correcting valgus deformities. For example, Saragaglia and Chedal-Bornu⁶ performed 29 computer-assisted valgus knees osteotomies (27 patients) and reported that the goal hip-knee angle was achieved in 86% of patients and that the goal MPTA was achieved in 100% of patients.⁶

CONCLUSION

Both the FALP and FAN methods of femoral deformity correction are safe and effective surgical techniques. In our opinion, the advantages of the FALP technique result from the easy lateral surgical approach under medial external fixation and stabilization of the osteotomy without bending the knee. Ultimately, the decision to use FAN may be influenced by the surgeon’s perception of the potential need for future TKA. In such cases, a midline anterior approach with nailing is very compatible with subsequent TKA. The surgeon’s experience and preference, while keeping in mind the patient’s predilection, will play an important role in the decision-making process. Larger prospective clinical trials with larger cohorts have to be conducted to confirm our findings.

ABSTRACT

Fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP) are 2 techniques that can be used to correct distal femoral valgus deformities. The fixator aids in achieving an accurate adjustable initial reduction, which is then made permanent with either nail or plate insertion. FALP can be performed with the knee held in a neutral extended position, whereas FAN requires 30° to 90° of knee flexion to insert the nail, which may cause some alignment loss. We hypothesized that FAN may yield less accurate correction than FALP. Prospectively collected data of a consecutive cohort of patients who underwent valgus deformity femoral correction with FAN or FALP at a single institution over an 8-year period were retrospectively evaluated. Twenty extremities (18 patients) were treated using FAN (median follow-up, 5 years; range, 1-10 years), and 7 extremities (6 patients) were treated with FALP (median follow-up, 5 years; range, 1-8 years). In the FAN cohort, the mean preoperative and postoperative mechanical lateral distal femoral angles (mLDFAs) were 81° (range, 67°-86°) and 89° (range, 80°-100°), respectively (P = .009). In the FALP cohort, the mean preoperative and postoperative mLDFAs were 80° (range, 71°-87°) and 88° (range, 81°-94°), respectively (P < .001). Although the average mechanical axis deviation correction for the FALP group was greater than for the FAN group (32 mm and 27 mm, respectively), the difference was not significant (P = .66). Both methods of femoral deformity correction can be considered safe and effective. On the basis of our results, FAN and FALP are comparable in accuracy for deformity correction in the distal femur.

Multiple etiologies for distal femoral valgus deformity have been described in the literature.^1-3 These can be congenital, developmental, secondary to lateral compartmental arthritis, or posttraumatic.⁴ If not corrected, femoral deformities alter the axial alignment and orientation of the joints, and may lead to early degenerative joint disease and abnormal leg kinematics.^3,5 After correcting these deformities, the goal of treatment is to obtain anatomic distal femoral angles and neutral mechanical axis deviation (MAD), but without overcorrecting into varus. Numerous techniques to fix these deformities, such as progressive correction with external fixation or acute correction open reduction with internal fixation (ORIF), have been described.⁶ Modern external fixation allows for a gradual, adjustable, and more accurate correction but may produce discomfort and complications for patients.^7-10 In contrast, ORIF may be more tolerable for the patient, but to achieve a precise correction, considerable technical skills and expertise are required.^1,11-14

Two techniques used to correct these valgus femoral deformities in adults are fixator-assisted nailing (FAN) and fixator-assisted locked plating (FALP).¹ FAN and FALP combine the advantage of external fixation (accuracy, adjustability) with the benefits of internal fixation (patient comfort), because the osteotomy and correction are performed with the guidance of a temporary external fixator and then permanently fixated by an intramedullary (IM) nail or a locking plate.^{1,8,11-13,15-18} Both techniques have the possibility to correct varus and valgus deformities, but whenever correcting sagittal plane angulation, the FAN technique may be more challenging. The paucity of studies available involving FAN and FALP do not lead to a conclusive preference of one technique over the other relative to the accuracy and success of correction.^15,19,20

Continue to: In both FAN and FALP

In both FAN and FALP, the external fixator is applied and adjusted after the osteotomy for accurate alignment. In FALP, the plate is added without moving the leg from its straight position. However, in FAN, the knee must be flexed to 30° to 90° for insertion of the retrograde knee nail, and the alignment may be lost if the external fixation is not fully stable. Therefore, we hypothesized that FAN would be less accurate than FALP. Hence, the purposes of this study is to compare the correction achieved with FAN and FALP in patients with distal femoral valgus deformities and to describe the intraoperative complications associated with both techniques.

MATERIALS AND METHODS

After proper Institutional Review Board approval was obtained, a consecutive cohort of 35 patients who underwent femoral deformity correction with either FAN or FALP during an 8-year period (January 2002 to December 2010) was retrospectively reviewed. Eleven patients had to be excluded because of inadequate follow-up (<12 months) or because additional procedures were simultaneously performed. A total of 24 patients (27 femora) who had a mean age of 26 years (range, 14-68 years) were included in the final study cohort. Specifically, 20 femora (18 patients) were corrected using the FAN technique (7 males and 11 females; mean age, 36 years; range, 14-68 years), and 7 femora (6 patients) were fixed using the FALP technique (2 males and 4 females; mean age, 16 years; range, 15-19 years). The median follow-up in the FAN cohort was 5 years (range, 1-10 years), and the median follow-up in the FALP cohort was 5 years (range, 1-8 years) (Table 1).

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing

The specific measurements performed in all patients were MAD, mechanical lateral distal femoral angle (mLDFA), and medial proximal tibia angle (MPTA). These were measured from standing anteroposterior radiographs of the knee that included the femur.²¹ All outcome data were collected from the medical charts, operative reports, and radiographic evaluations. To ensure accuracy, all measurements were performed by 2 authors blinded to each other’s measurements. If a variation of <5% was obtained, the results were averaged and used for further analysis. Whenever a difference of >5% was obtained, the measurement was repeated by both authors for confirmation.

SURGICAL FAN TECHNIQUE

After measuring the deformity (Figure 1A) with the patient under general anesthesia on a radiolucent table, the involved lower limb is prepared and draped. Two half-pins are inserted medially, 1 proximal and 1 distal to the planned osteotomy site (Figure 1B), and then connected loosely with a monolateral external fixator. Special care is taken while placing the half-pins, not to interfere with the insertion path of the IM rod. When performing the preoperative planning, the level of osteotomy is chosen to enable the placement of at least 2 interlocking screws distal to the osteotomy. Then, a percutaneous osteotomy is performed from a lateral approach, and the bone ends are manipulated (translation and then angulation) to achieve the desired deformity correction. The external fixator is then stabilized and locked in the exact position (Figure 1C). Subsequently, retrograde reaming, nail insertion, and placement of proximal and distal locking screws are performed (Figure 1D). Blocking screws may give additional stability. The removal of the external fixator is the final step (Figure 1E).²⁰

Continue to: When using the FAN technique...

SURGICAL FALP TECHNIQUE

Preoperatively, a decision concerning the planned osteotomy and the correct locking plate size is made. In addition, the outline of the plate is marked on the skin. Under general anesthesia, the patients are prepared and draped. A tourniquet is elevated around the upper thigh. Then, 2 half-pins are medially inserted, 1 proximal and 1 distal to the planned osteotomy site, and are then connected loosely with a monolateral external fixator (Figure 2A). A lateral approach to the distal femur is done, preserving the periosteum, except at the level of the osteotomy. After the osteotomy is performed (through an open lateral incision), both segments are translated (Figure 2B) and then the distal segment is angulated to achieve the desired deformity correction, and the desired position is then stabilized by tightening the external fixator connectors (Figure 2C). Subsequently, a locking plate is inserted in the submuscular-extraperiostal plane. The plate does not require being in full contact (flush) with the bone. At least 3 screws are placed on both sides of the osteotomy through a long lateral incision (Figure 2D). Bone graft may be added to the osteotomy site to encourage healing. Then, the external fixator is removed, and all incisions are closed (Figure 2E).^15,19 

During each of the procedures, we aimed at having “perfect alignment” with a MAD of 0 mm, in which a Bovie cord is used and passed through the center of the femoral head, knee, and ankle. However, to confirm that the surgery was successful, the actual measurements were performed on standing long-leg films. These films were obtained preoperatively and at latest follow-up. They were performed with the patella aiming forward, the toes straight ahead, feet separated enough for good balance, knees fully extended, and weight equally distributed on the feet. Postoperatively, in both cohorts, partial weight-bearing was encouraged immediately with crutches; physical therapy was instituted daily for knee range of motion. Radiographs were scheduled every 4 weeks to monitor callus formation. Full weight-bearing was allowed when at least 3 cortices were consolidated.^{1,15,19,20,25,26}

All statistical analyses were performed with the aid of the SPSS statistical software package (SPSS). Average values and standard error of the mean were assigned to each variable. A nonparametric Mann-Whitney U test was used, and a 2-tailed P < .05 was considered significant. Correlation of continuous variables was determined by Spearman’s correlation coefficient. Also, multivariate Cox regression analyses after adjustment for age, sex, and deformity correction were used to detect associations within the study population. To evaluate whether our data were normally distributed, Shapiro-Wilk tests were performed.

Continue to: Results...

RESULTS

The mLDFA significantly improved in the FAN cohort from a mean of 81° to a mean of 89° (ranges, 67°-86° and 80°-100°; respectively; P = .001) (Figures 3A, 3B). 

Abbreviations: FALP, fixator assisted locked plating; FAN, fixator assisted nailing; mLDFA, mechanical lateral distal femoral angle

After evaluating the MPTA, in the FAN cohort, we found that the mean pre- and postoperative MPTAs were not modified. These patients had a mean preoperative angle of 88° (range, 62°-100°), which was kept postoperatively to a mean of 88° (range, 78°-96°). In the FALP cohort, a slight change from 90° to 88° was observed (ranges, 82°-97° and 83°-94°, respectively). None of these changes in MPTA were significant (P > .05).

When evaluating correction of the MAD, we observed that the FAN cohort changed from a preoperative MAD of 32 mm (range, 6-64 mm) to a postoperative mean of 10 mm (range, 0-22 mm), and this correction was statistically significant. (P = .001). The FALP cohort changed from a mean of 34 mm (range, 17-62 mm) preoperatively to 4 mm (range, 0-11 mm) postoperatively, and this was also statistically significant (P = .002). The mean MAD correction for the FAN group vs FALP group was 27 mm vs 32 mm, respectively (Table 2).

In patients with valgus femoral deformity, the MAD is usually lateralized; however, in the FAN cohort, we included 3 patients with medial MADs (10 mm, 13 mm, and 40 mm). This is justified in these patients because a complex deformity of the distal femur and the proximal tibia was present. In the extreme case of a 40-mm medial MAD, the presurgery mLDFA was 76°, and the presurgery MPTA was 62°. The amount of deformity correction in this patient was 16°.

During the follow-up period, 2 complications occurred in the FAN group. One patient developed gait disturbance that resolved with physical therapy. Another had an infection at the osteotomy site. This was addressed with intravenous antibiotic therapy, surgical irrigation and débridement, hardware removal, and antegrade insertion of an antibiotic-coated nail. In the FALP group, 1 patient developed a persistent incomplete peroneal nerve palsy attributed to a 17° correction from valgus to varus, despite prophylactic peroneal nerve decompression. Nonetheless, the patient was satisfied with the result, recovered partial nerve function, and returned for correction of the contralateral leg deformity. When comparing the complications between both cohorts, no significant differences were found: 2 of 18 cases (11%) in the FAN group vs 1 of 6 cases (17%) in the FALP group (P = .78).

Continue to: The goal of this study...

DISCUSSION

The goal of this study was to compare the accuracy of deformity corrections achieved with either FAN or FALP. A number of authors have described results after deformity correction with several plating and nailing techniques; however, the information derived from comparing these 2 techniques is limited. We hypothesized that FALP would be more accurate, because less mobilization during fixation is required. However, we found no significant differences between these 2 techniques.

This study has several limitations. First, the small size of our cohort had to be further reduced owing to limited data; nevertheless, this pathology and the treatment methods used are not commonly performed, which make this cohort 1 of the largest of its type described in the literature. Also, the procedures were performed by multiple surgeons in a population with a wide age range, creating multiple additional variables that complicate the comparison of the sole differences between FAN and FALP. However, owing to these variables, the generalizability of this study may be increased, and similar outcomes can potentially be obtained by other institutions/surgeons. In addition, the variability of our follow-up period is another limitation; however, these patients were all assessed until bony union after skeletal maturity was achieved. Hence, the development of additional deformity is not expected. The lack of clinical outcome with a standardized questionnaire may also be seen as a limitation. However, because the purpose of our study was to assess both surgeries in terms of their ability to achieve angular correction, the addition of patient-reported outcomes may have increased the variability of our data.

The foremost objective in valgus deformity correction is to establish joint orientation angles within anatomic range to prevent overloading of the lateral joint and thereby prevent lateral compartmental osteoarthritis.^2,20,27-29 There are 2 categories of fixation: internal and external. With FAN and FALP, we strive to have the adjustability and accuracy of external fixation with the comfort (for the patient) of internal fixation. Accurate osteotomy correction requires an accurate preoperative analysis and osteotomy close to the apex of the deformity.^16,21,30-33 The most commonly used osteotomy techniques are drill-hole,³¹ focal dome,³⁴ rotation, and open- or closed-wedge osteotomies.^35,36 After the osteotomy, the resultant correction has to be stabilized. In recent years, the popularity of plates instead of an IM nail for internal fixation has been driven by the rapid development of low contact locking plates.^{16,19,26,30,37-40}

There are certain advantages of using FAN over FALP. In older patients who may require a subsequent total knee arthroplasty (TKA), the midline incision used for retrograde FAN technique is identical to that made for TKA. In contrast, in a younger and more active population, with a longer life expectancy, the extra-articular FALP approach has the advantage of not violating the knee joint. In addition, locking plates may achieve a more rigid fixation than IM nails; however, the stability of IM nails can be augmented with blocking screws.

Continue to: In 20 patients, including children...

In their comparative study, Seah and colleagues¹¹ described monolateral frame vs FALP deformity correction in a series of 34 extremities (26 patients) that required distal femoral osteotomy. No differences related to knee range of motion or the ability to correct the deformity between internal and external fixation were reported (P > .05). Similarly, Eidelman and colleagues¹ evaluated the outcomes of 6 patients (7 procedures) who underwent surgery performed with the FALP technique for distal femoral valgus deformity. They concluded that this technique is minimally invasive and can provide a precise deformity correction with minimal morbidity.

Other methods of fixation while performing FAN have been described by Jasiewicz and colleagues,²² who evaluated possible differences between the classic Ilizarov device and monolateral fixators in 19 femoral lengthening procedures. The authors concluded that there is no difference between concerning complication rate and treatment time. The use of FAN has also been described in patients with metabolic disease who required deformity correction. In this regard, Kocaoglu and colleagues¹² described the use of a monolateral external fixator in combination with an IM nail in a series of 17 patients with metabolic bone disease. The authors concluded that the use of the IM nail prevented recurrence of deformity and refracture.¹² Kocaoglu and colleagues¹⁴ also published a series of 25 patients treated with the FAN and LON (lengthening over a nail) technique for lengthening and deformity correction. The mean MAD improved from 33.9 mm to11.3 mm (range, 0-30 mm). In contrast, Erlap and colleagues¹³ compared FAN with circular external fixator for bone realignment of the lower extremity for deformities in patients with rickets. Although no significant difference was found between both groups, FAN was shown to be accurate and to provide great comfort to patients, and it also shortened the total treatment time.¹³ Finally, the advent of newer technologies could also provide alternatives for correcting valgus deformities. For example, Saragaglia and Chedal-Bornu⁶ performed 29 computer-assisted valgus knees osteotomies (27 patients) and reported that the goal hip-knee angle was achieved in 86% of patients and that the goal MPTA was achieved in 100% of patients.⁶

CONCLUSION

Both the FALP and FAN methods of femoral deformity correction are safe and effective surgical techniques. In our opinion, the advantages of the FALP technique result from the easy lateral surgical approach under medial external fixation and stabilization of the osteotomy without bending the knee. Ultimately, the decision to use FAN may be influenced by the surgeon’s perception of the potential need for future TKA. In such cases, a midline anterior approach with nailing is very compatible with subsequent TKA. The surgeon’s experience and preference, while keeping in mind the patient’s predilection, will play an important role in the decision-making process. Larger prospective clinical trials with larger cohorts have to be conducted to confirm our findings.

Most prescribers of buprenorphine view diversion or misappropriation of the drug as a concern, and most assess their patients for diversion, according to Lewei (Allison) Lin, MD, and her associates.

In a survey of 1,174 buprenorphine prescribers conducted from July 2014 to January 2017, 79% of the prescribers reported assessing all their patients for diversion of the drug, and 79.1% reported conducting urine tests for the presence of buprenorphine. In addition, 85% of prescribers viewed diversion as a problem in their community, and 80.3% of prescribers were willing to terminate treatment because of diversion, reported Dr. Lin of the department of psychiatry at the University of Michigan, Ann Arbor, and her associates in Drug and Alcohol Dependence.

Diversion was defined as “unauthorized rerouting or misappropriation of prescribed buprenorphine to someone other than the person for whom it was intended.”

Dr. Lin and her associates found that prescribers were more likely to assess all of their patients for diversion if they viewed diversion as a problem in their community, had fewer years of experience, or were white. Urine testing was more likely if prescribers viewed diversion as a problem in their community, had more patients, had less experience, had a 100-patient waiver, or were nonpsychiatrists. Treatment termination was more likely for prescribers who had a greater percentages of patients with medication counts, viewed diversion as a problem in their community, or practiced in nonaddiction/nonpsychiatric specialties.

“Although we did not include detailed questions about termination, the high proportion of prescribers who would terminate patients for diversion is important to note,” wrote Dr. Lin, also a research investigator at the VA Center for Clinical Management Research, Ann Arbor, and her associates. Addiction medicine specialists and psychiatrists were less likely to terminate patients because of concerns about diversion – which suggests that additional training in addiction might make clinicians more comfortable managing patients with high-risk behaviors, the investigators said.

They cited several limitations. For example, the survey’s cross-sectional design makes causal inferences difficult. In addition, when the survey was conducted, physicians were the only buprenorphine prescribers. It is therefore unclear whether the study results are generalizable to physician assistants or nurse practitioners, who now are able to prescribe buprenorphine after meeting certain requirements.

Still, the study uncovered new information about the steps that prescribers take to mitigate diversion. “Addressing diversion is a complex clinical dilemma and contextual factors, including availability of services, may need to be explored in the future alongside provider practices addressing diversion,” the investigators wrote.

[email protected]

SOURCE: LA Lin et al. Drug Alcohol Depend. 2018 May 1. doi: 10.1016/j.drugalcdep.2018.01.015.

Most prescribers of buprenorphine view diversion or misappropriation of the drug as a concern, and most assess their patients for diversion, according to Lewei (Allison) Lin, MD, and her associates.

In a survey of 1,174 buprenorphine prescribers conducted from July 2014 to January 2017, 79% of the prescribers reported assessing all their patients for diversion of the drug, and 79.1% reported conducting urine tests for the presence of buprenorphine. In addition, 85% of prescribers viewed diversion as a problem in their community, and 80.3% of prescribers were willing to terminate treatment because of diversion, reported Dr. Lin of the department of psychiatry at the University of Michigan, Ann Arbor, and her associates in Drug and Alcohol Dependence.

Diversion was defined as “unauthorized rerouting or misappropriation of prescribed buprenorphine to someone other than the person for whom it was intended.”

Dr. Lin and her associates found that prescribers were more likely to assess all of their patients for diversion if they viewed diversion as a problem in their community, had fewer years of experience, or were white. Urine testing was more likely if prescribers viewed diversion as a problem in their community, had more patients, had less experience, had a 100-patient waiver, or were nonpsychiatrists. Treatment termination was more likely for prescribers who had a greater percentages of patients with medication counts, viewed diversion as a problem in their community, or practiced in nonaddiction/nonpsychiatric specialties.

“Although we did not include detailed questions about termination, the high proportion of prescribers who would terminate patients for diversion is important to note,” wrote Dr. Lin, also a research investigator at the VA Center for Clinical Management Research, Ann Arbor, and her associates. Addiction medicine specialists and psychiatrists were less likely to terminate patients because of concerns about diversion – which suggests that additional training in addiction might make clinicians more comfortable managing patients with high-risk behaviors, the investigators said.

They cited several limitations. For example, the survey’s cross-sectional design makes causal inferences difficult. In addition, when the survey was conducted, physicians were the only buprenorphine prescribers. It is therefore unclear whether the study results are generalizable to physician assistants or nurse practitioners, who now are able to prescribe buprenorphine after meeting certain requirements.

Still, the study uncovered new information about the steps that prescribers take to mitigate diversion. “Addressing diversion is a complex clinical dilemma and contextual factors, including availability of services, may need to be explored in the future alongside provider practices addressing diversion,” the investigators wrote.

[email protected]

SOURCE: LA Lin et al. Drug Alcohol Depend. 2018 May 1. doi: 10.1016/j.drugalcdep.2018.01.015.

Most prescribers of buprenorphine view diversion or misappropriation of the drug as a concern, and most assess their patients for diversion, according to Lewei (Allison) Lin, MD, and her associates.

In a survey of 1,174 buprenorphine prescribers conducted from July 2014 to January 2017, 79% of the prescribers reported assessing all their patients for diversion of the drug, and 79.1% reported conducting urine tests for the presence of buprenorphine. In addition, 85% of prescribers viewed diversion as a problem in their community, and 80.3% of prescribers were willing to terminate treatment because of diversion, reported Dr. Lin of the department of psychiatry at the University of Michigan, Ann Arbor, and her associates in Drug and Alcohol Dependence.

Diversion was defined as “unauthorized rerouting or misappropriation of prescribed buprenorphine to someone other than the person for whom it was intended.”

Dr. Lin and her associates found that prescribers were more likely to assess all of their patients for diversion if they viewed diversion as a problem in their community, had fewer years of experience, or were white. Urine testing was more likely if prescribers viewed diversion as a problem in their community, had more patients, had less experience, had a 100-patient waiver, or were nonpsychiatrists. Treatment termination was more likely for prescribers who had a greater percentages of patients with medication counts, viewed diversion as a problem in their community, or practiced in nonaddiction/nonpsychiatric specialties.

“Although we did not include detailed questions about termination, the high proportion of prescribers who would terminate patients for diversion is important to note,” wrote Dr. Lin, also a research investigator at the VA Center for Clinical Management Research, Ann Arbor, and her associates. Addiction medicine specialists and psychiatrists were less likely to terminate patients because of concerns about diversion – which suggests that additional training in addiction might make clinicians more comfortable managing patients with high-risk behaviors, the investigators said.

They cited several limitations. For example, the survey’s cross-sectional design makes causal inferences difficult. In addition, when the survey was conducted, physicians were the only buprenorphine prescribers. It is therefore unclear whether the study results are generalizable to physician assistants or nurse practitioners, who now are able to prescribe buprenorphine after meeting certain requirements.

Still, the study uncovered new information about the steps that prescribers take to mitigate diversion. “Addressing diversion is a complex clinical dilemma and contextual factors, including availability of services, may need to be explored in the future alongside provider practices addressing diversion,” the investigators wrote.

[email protected]

SOURCE: LA Lin et al. Drug Alcohol Depend. 2018 May 1. doi: 10.1016/j.drugalcdep.2018.01.015.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

To the Editor:

A 13-year-old white adolescent girl presented with asymptomatic discrete hyperpigmented papules on the chest, back, arms, and upper legs of 7 months’ duration. The patient otherwise was in good health; her weight and height were on the 40th percentile on growth curves and she had no history of any medications. Treatments for the skin condition prescribed by outside dermatologists included minocycline 75 mg twice daily for 2 months, lactic acid lotion 12% daily, and ketoconazole 400 mg administered twice 1 week apart.

Physical examination revealed more than 50 scattered hyperpigmented papules on the chest, back, arms, and upper legs ranging in size from 2 to 3.5 cm (Figure 1). Stroking of lesions failed to elicit Darier sign. A potassium hydroxide preparation and fungal culture were negative for pathogenic fungal organisms. The plasma insulin level was within reference range. A punch biopsy from the abdomen was obtained and sent for histopathologic examination. Histopathology showed mild hyperkeratosis, subtle papillomatosis, and interanastomosing acanthosis comprising squamoid cells with mild basilar hyperpigmentation (Figure 2). Sparse superficial perivascular lymphocytic infiltrate and increased pigmentation was seen in the basal layer. The dermis showed a few scattered dermal melanophages. A periodic acid–Schiff with diastase stain was negative. Giemsa and Leder stains highlighted a normal number and distribution of mast cells. Based on the histologic findings, the patient was diagnosed with idiopathic eruptive macular pigmentation (IEMP).

Idiopathic eruptive macular pigmentation is a rare condition that was described in 1978 by Degos et al.¹ Sanz de Galdeano et al² established the following diagnostic criteria: (1) eruption of brownish black, nonconfluent, asymptomatic macules involving the trunk, neck, and proximal arms and legs in children or adolescents; (2) absence of preceding inflammatory lesions; (3) no prior drug exposure; (4) basal cell layer hyperpigmentation of the epidermis and prominent dermal melanophages without visible basal layer damage or lichenoid inflammatory infiltrate; and (5) normal mast cell count.

Idiopathic eruptive macular pigmentation with papillomatosis (IEMPwP) is a variant of IEMP.³ It is undecided if IEMP and IEMPwP are variants of the same entity or distinct conditions. Until a clear etiology of these entities is established, we prefer to separate them on purely morphologic grounds. Marcoux et al⁴ labeled IEMPwP as a variant of acanthosis nigricans. Although morphologically the 2 conditions appear similar, our patient’s plasma insulin level essentially ruled out acanthosis nigricans.

Idiopathic eruptive macular pigmentation is a rare condition with the majority of cases reported in the Asian population with some reports in white, Hispanic, and black individuals.⁵ Idiopathic eruptive macular pigmentation with papillomatosis was reported by Joshi³ in 2007 in 9 Indian children with the classic findings of IEMP along with a velvety rash that correlated with papillomatosis. Diagnosis of IEMPwP is important, as the disease generally is self-limited and resolves over the course of a few weeks to a few years.

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.

In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.

“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.

The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.

Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.

“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.

The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.

“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.

However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.

“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.

In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].

“With good sound science like this we continue to inch closer to the answers we need,” he concluded.

Dr. Epstein reported having no disclosures.

CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.

In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.

“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.

The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.

Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.

“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.

The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.

“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.

However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.

“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.

In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].

“With good sound science like this we continue to inch closer to the answers we need,” he concluded.

Dr. Epstein reported having no disclosures.

CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.

In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.

“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.

The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.

Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.

“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.

The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.

“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.

However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.

“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.

In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].

“With good sound science like this we continue to inch closer to the answers we need,” he concluded.

Dr. Epstein reported having no disclosures.

Recent increases in nonmedical exemptions (NMEs) to vaccination have created metropolitan “hotspots” with large numbers of unvaccinated children, according to a report published June 12 in PLoS Medicine.

Since 2009, NMEs based on philosophical beliefs have increased in 12 of the 18 states that currently allow them, although rates seem to have plateaued in some states since 2014. As a result of those increases, there were, during the 2016-2017 school year, 15 metro areas with kindergarten NME populations over 400, reported Jacqueline K. Olive, and her associates at Baylor College of Medicine. Their report was based on data from state health departments and the Centers for Disease Control and Prevention.

Leading the way was Maricopa County, Ariz., home of Phoenix and 2,947 unvaccinated kindergartners, which was more than triple the number in county/city No. 2, Salt Lake County/Salt Lake City (NME total: 956). Close behind in third was King County, Wash. (Seattle) at 940, followed by Multnomah County, Ore. (Portland) at 711 and Oakland County, Mich. (Troy) at 686, the investigators said.

[email protected]

SOURCE: Olive JK et al. PLoS Med. 2018 Jun 12;15(6): e1002578. doi: 10.1371/journal.pmed.1002578.

Recent increases in nonmedical exemptions (NMEs) to vaccination have created metropolitan “hotspots” with large numbers of unvaccinated children, according to a report published June 12 in PLoS Medicine.

Since 2009, NMEs based on philosophical beliefs have increased in 12 of the 18 states that currently allow them, although rates seem to have plateaued in some states since 2014. As a result of those increases, there were, during the 2016-2017 school year, 15 metro areas with kindergarten NME populations over 400, reported Jacqueline K. Olive, and her associates at Baylor College of Medicine. Their report was based on data from state health departments and the Centers for Disease Control and Prevention.

Leading the way was Maricopa County, Ariz., home of Phoenix and 2,947 unvaccinated kindergartners, which was more than triple the number in county/city No. 2, Salt Lake County/Salt Lake City (NME total: 956). Close behind in third was King County, Wash. (Seattle) at 940, followed by Multnomah County, Ore. (Portland) at 711 and Oakland County, Mich. (Troy) at 686, the investigators said.

[email protected]

SOURCE: Olive JK et al. PLoS Med. 2018 Jun 12;15(6): e1002578. doi: 10.1371/journal.pmed.1002578.

Recent increases in nonmedical exemptions (NMEs) to vaccination have created metropolitan “hotspots” with large numbers of unvaccinated children, according to a report published June 12 in PLoS Medicine.

Since 2009, NMEs based on philosophical beliefs have increased in 12 of the 18 states that currently allow them, although rates seem to have plateaued in some states since 2014. As a result of those increases, there were, during the 2016-2017 school year, 15 metro areas with kindergarten NME populations over 400, reported Jacqueline K. Olive, and her associates at Baylor College of Medicine. Their report was based on data from state health departments and the Centers for Disease Control and Prevention.

Leading the way was Maricopa County, Ariz., home of Phoenix and 2,947 unvaccinated kindergartners, which was more than triple the number in county/city No. 2, Salt Lake County/Salt Lake City (NME total: 956). Close behind in third was King County, Wash. (Seattle) at 940, followed by Multnomah County, Ore. (Portland) at 711 and Oakland County, Mich. (Troy) at 686, the investigators said.

[email protected]

SOURCE: Olive JK et al. PLoS Med. 2018 Jun 12;15(6): e1002578. doi: 10.1371/journal.pmed.1002578.

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Mind and body cognitive behavioral therapy (CBT‐HA) relaxation skills emerged as popular and effective for pediatric migraine sufferers, based on patient and parent reports in a recent study. Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT‐HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were ranged in age from 13 to 17.5 years (median=15.4, standard deviation=1.63) and had undergone CBT‐HA about 1 to 2 years prior to participating in the study. Researchers found:

• Overall, patients and their parents reported that CBT‐HA was helpful in reducing headache frequency and related disability.
• Although patients provided mixed reports on the effectiveness of different CBT‐HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT‐HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills.
• Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable.

CBT for pediatric migraine: A qualitative study of patient and parent experience. Headache. 2018;58(5):661-675. doi:10.1111/head.13285.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Visual quality of life (QOL) is significantly adversely affected in migraine sufferers, according to a recent study. In fact, patients with chronic migraine may have visual QOL impacts that are as significant as those associated with other common neuro‐ophthalmic disorders. In this cross‐sectional quantitative survey, visual QOL in individuals with chronic and episodic migraine was assessed using the National Eye Institute Visual Function Questionnaire‐25, and the 10‐item National Eye Institute Visual Function Questionnaire‐25 Neuro‐Ophthalmic Supplement. Overall headache severity and impact was assessed using the Migraine‐specific Quality of Life Questionnaire and the Headache Impact Test‐6. Researchers found:

• Among 29 participants with chronic migraine, vision‐specific QOL scores were all statistically significantly decreased compared to disease‐free controls.
• Among 37 participants with episodic migraine, vision‐specific QOL scores were also decreased compared to disease‐free controls.
• Chronic migraineurs had decreased visual QOL scores compared to those with episodic migraines.
• Participants with chronic migraine had visual QOL scores that were as poor as those previously published for patients with other neuro‐ophthalmic disorders, such as multiple sclerosis, myasthenia gravis, and ischemic optic neuropathy.
   

Patients with migraine have substantial reductions in measures of visual quality of life. [Published online ahead of print June 7, 2018]. Headache. doi:10.1111/head.13330.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.

Less than one-third of eligible migraineurs were referred for behavioral treatment and only about half initiated behavioral migraine treatment in a recent prospective cohort study. Researchers compared patients who initiated behavioral migraine treatment following a provider recommendation with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. They found:

• Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment.
• 53 (76.8%) patients referred for behavioral treatment were reached by phone.
• The mean duration from time of referral to follow-up was 76 (median 76, SD=45) days.
• 30 (56.6%) patients initiated behavioral migraine treatment.
• There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control.
• Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not.
• Time constraints were the most common barrier cited for not initiating behavioral migraine treatment.

Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: A prospective observational study. [Published online ahead of print June 5, 2018]. Pain Medicine. doi:10.1093/pm/pny028.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.

The Supreme Court decision to overturn the federal law that prohibited state-sanctioned college and professional sports betting is bad news for clinicians who treat patients with addictions.

On May 14, the high court ruled 7-2 that the 1992 law, called the Professional and Amateur Sports Protection Act (PASPA), was unconstitutional. Now every state is free to operate, sponsor, promote, license, advertise, or authorize gambling for any college or professional sport–based event.

Optimistic outlooks on the death of PASPA include the foreseen opportunity by the states to tax and generate revenue on such gambling. Proponents of the ruling also argue that illegal activity that thrived on sports betting will now end.

But to what extent will either of those scenarios benefit the public?

If passage of various state marijuana laws is any example, assumptions that legal avenues will usurp illegal enterprises are flawed. Also, taxation likely will generate a large sum of revenue for each state. But those revenues might be offset by subsequent changes that will be needed in mental health, addiction, and wellness programs – a difficult proposition given the opioid epidemic already overburdening the country. Remember the tobacco cases and promise of state support for education, treatment, and other noble activities? Addiction medicine specialists worry that taxes collected by the states, and promises to prevent and treat gambling problems – and prevent addiction – will not end up in those coffers.

As clinicians, perhaps our most important contribution to the debates on this ruling lies in raising awareness of pathological gambling as an addiction disorder.
 

Redefining the act of gambling

Breaking down previous barriers to access and increasing convenience to gambling undoubtedly will be associated with increased pathological engagement in gambling. This conclusion is clear, based on past national experiments with substances of addiction (such as alcohol prohibition).

Since the cocaine epidemic of the 1980s, and our increased understanding that addictions need not have prominent withdrawal syndromes, we have focused on addiction as a fatal attraction. Psychiatrists and other clinicians made the case – in some quarters, at least – for sugar, sex, and Internet compulsivity as addictions. Compared with those addictions, the evidence was clearest and most compelling for pathological gambling as an addiction disorder. Indeed, gambling disorder was introduced in 2013 to the DSM-5 as the very first non–substance-based addictive disorder. This was a decisive change, as it recognizes that gambling is more than an environmental hazard for those suffering from dopamine-driven obsessive-compulsive-like dysfunction (the DSM section where it had lived previously). Instead, gambling acts as an agent that can initiate a usurpation of the brain’s reward circuitry. (In addition, this change has reopened the door for other increasingly recognized non–substance-based disorder categories such as video game and pornography addiction, and others.)

Gambling disorder certainly fits well into what many experts view as the essential phenotype of any addiction: Continued use despite harm, waning self-control over engagement, a craving state, and compulsive use. Current research is expanding rapidly and filling in the theoretical framework, strongly supporting gambling disorder based on biological evidence. Much of what we now know about the biology of addiction has been through the efforts of the Yale University–based research group, led by psychiatrist Marc N. Potenza. Dr. Potenza and his colleagues have been investigating gambling disorder in a thorough manner (Harv Rev Psychiatry. 2015 Mar-Apr;23[2]:134-46) and (Curr Treat Options Psychiatry. 2014 Jun 1;1[2]:189-203). Indeed, gambling disorder is much like the other substance-use disorders in which it is grouped, in that it has been found to share some similarities/pathways common to all addictions while also carrying its own specific nuances.

Twin studies have unearthed a wealth of information, such as knowledge that environmental factors seem to be the predominant source of the comorbid development of gambling disorder with the more socially acceptable substances as associated use disorders (alcohol, tobacco, and marijuana) through mechanisms such as peer association and place preference conditioning. Similarly, genetic influences also might be meaningful to treatment. For example, one finding showed that patients with gambling disorder and a family history of alcoholism were found to more preferentially respond to opioid-receptor antagonists as treatment for gambling disorder, compared with individuals without such family history (Psychopharmacology [Berl]. 2008;200[4]:521-7).

Explorations of neurotransmitter involvement and brain connectivity also have been conducted for gambling behaviors. Dopaminergic underpinnings of addiction have been particularly indicated in imaging studies focused on the ventral striatum and other components of reward circuitry. In addition, functional MRI studies have identified both overlapping and discordant brain imaging findings between gambling and many other substance use disorders such as cocaine. All these indicate that gambling seems, like its use-disorder counterparts, to follow a similar but distinct course of hijacking reward systems and priming the brain to seek out further gambling in a pathological manner.
 

Vulnerable populations

Another key finding of recent research exploring the biological foundations of gambling disorder is gender dimorphism. In numerous studies, women have been found to experience a “telescoping effect” from gambling, compared with their male counterparts, where they seem to more quickly advance from first exposure to problematic use. This phenomenon also is seen in women who use cocaine. Also, functional MRI studies also have found that women appear to have alternative signal changes in regions germane to addiction, compared with their male counterparts. One such example was greater activity in the hippocampus and middle temporal gyrus in women, suggestive of stronger activation of regions key for memory retrieval used in craving/urge-related emotions. These data highlight the need for not only understanding how gambling and other addictions diverge between men and women, but also for how prevention and treatment of these disorders might differ based on sex.

Adolescents also get special consideration: How will they be affected by this expected growth in gambling avenues? Adolescence and young adulthood are periods of development defined by increased impulsivity and risk taking, making this population particularly vulnerable to addiction that can then persist into adulthood. It is expected that age laws will persist and prevent the legal access adults might enjoy, but shifts in opinions of harm and ease of access are likely to contribute to increased gambling exposure. To use another addictive phenomena as an example, data from the Substance Abuse and Mental Health Services Administration show a clear correlation between marijuana use, marijuana legal status, and perceptions of risk. Specifically, areas with unfettered/loosened marijuana regulation have much lower levels of perceived risk among youth and much higher levels of use. Gambling could follow a similar course.

Perhaps the most crucial observation is that the most severe pathological gamblers began gambling before adulthood. Many factors have been identified that seem to increase rates of gambling in youth: Receiving scratch-off lotto cards as gifts, gambling on school grounds, and even smoking status (quite significant given the advent of e-cigarettes now common to many high school students). All of these essentially boil down to the common pathway of proximity and social referencing. As such, the notion that an increased social presence of (what will likely be) large scale, polished, mass televised sports gambling events will be associated with increased gambling behavior (and other mental health comorbidities) among youth is not far-fetched. What also is known for gambling, as well as for other addictive disorders, is that earlier age of onset is correlated to a worse prognosis of gambling disorder in adulthood. In other words, the earlier an addiction strikes, the deeper and more severe it is in the individual – further highlighting the impetus to focus concerns about the PASPA ruling toward the impact on youth.
 

Prevention and treatment

Lastly, it is important to consider the ground gained in preventing and treating gambling addiction. Many groups focused on treating and preventing gambling already are well established, such as Gamblers Anonymous, and these groups have produced favorable results. More targeted interventions such as cognitive-behavioral therapy adjusted for addiction disorders also have proved effective, as they often not only tackle the gambling disorder but also the collection of conditions it is so often comorbid with (affective illnesses, anxiety disorders).

Pharmacotherapy also has a role, further justifying the view of gambling disorder, and indeed all addiction disorders, as biological processes with biological solutions. Examinations into opiate antagonism and glutamatergic modulation (N-acetylcysteine) also have shown some promise. Prevention programs offer perhaps the best cost-effective ratio in reducing the societal burden of gambling, which is about $7 billion annually, according to 2013 estimates by the National Council on Problem Gambling). These programs have been conducted in schools through parent-teacher groups as well as publicly through distribution of informative psychoeducation via TV and advertising channels.

All available research conducted on treatment shows that further research and validation are needed. We should not pretend that increasing access to sports betting and normalizing the activity will not have an effect on gambling prevalence and problems. Prevention, even simple cautionary public warnings, requires time, money, and planning for effective execution.

Dr. Wenzinger is a clinical fellow, PGY-4, in the department of child and adolescent psychiatry at St. Louis Children’s Hospital. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health.