Facial aging is the result of the interplay between loss of skin elasticity, changes in subcutaneous fat and other soft-tissue layers, and skeletal remodeling with chronological age.¹ Dermal fillers are effective for the treatment of rhytides, facial scars, and lipoatrophy, as well as facial contouring and augmentation. Given that multiple filler options exist, updated reviews are necessary to inform clinicians of the choices that are available. We provide a detailed review of the clinical efficacy and safety of the dermal fillers with the most recent approvals by the US Food and Drug Administration (FDA).

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) microspheres suspended in bovine collagen and lidocaine 0.3% were approved in 2006 for use in nasolabial folds (NLFs) and in 2014 for acne scars. Now branded as Bellafill (Suneva Medical, Inc), it is the only permanent injectable filler currently available. Once injected, the particles are not reabsorbed and can only be removed by procedural extraction (eg, liposuction of the surrounding fat); however, the permanence of PMMA does not extend to facial rejuvenation, which can last up to 5 years. Prior to use, skin testing for bovine collagen reaction is necessary. In a clinical trial of 147 patients with moderate to severe acne scarring, patients were randomized to receive PMMA in collagen (n=97) or saline (n=50).² Injections were administered using a linear threading or serial puncture technique, and patients were reevaluated after 4 weeks for touch-up injections. After 6 months, 64% of patients treated with PMMA in collagen achieved improvement in acne scars by 2 points or more on the acne scar rating scale versus 33% of the control group (P=.0005).²

Treatment-related adverse events (AEs) include injection-site pain, bruising, swelling, erythema, and more rarely pruritus and lumps/granulomas.³ A 5-year longitudinal safety investigation of 871 patients initially treated with PMMA in collagen for NLF correction revealed that 17 patients (2.0%) had biopsy-confirmed granulomas with half of these retained at study end.⁴ Fifteen of these patients were treated with intralesional corticosteroids alone or in combination with intralesional 5-fluorouracil, oral antibiotics, or topical calcineurin inhibitors; 1 patient was untreated and another used topical corticosteroids. The authors noted no correlation between treatment method and granuloma response.⁴ Polymethylmethacrylate in collagen is contraindicated in patients with lidocaine or bovine collagen sensitivity and is not indicated for use in lip augmentation due to high rates of nodule formation.³

Hyaluronic Acid

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan polymer found in the extracellular matrix of the dermis. Hyaluronic acid fillers are bacteria derived and come in gel form. A useful advantage of HA fillers compared to other dermal fillers is the commercial availability of hyaluronidase to correct injections. Preinjection skin testing is not necessary.⁵

This category of nonpermanent dermal fillers has the most robust market choices. Older HA dermal fillers with reliable and proven efficacy are Restylane (Galderma Laboratories, LP)(facial rhytides, lip augmentation), Juvéderm (Ultra/Ultra XC/Ultra Plus/Ultra Plus XC [Allergan, Inc])(facial rhytides, lip augmentation), Hydrelle (Anika Therapeutics, Inc)(facial rhytides), and Prevelle Silk (Mentor Corporation)(facial rhytides); they will not be reviewed here. Newer agents include Belotero Balance (Merz Aesthetics), Juvéderm Voluma XC (Allergan, Inc), Restylane Silk (Galderma Laboratories, LP), and Restylane Lyft (Galderma Laboratories, LP).

Belotero Balance

Belotero Balance is used to treat fine lines and wrinkles, especially NLFs.⁶ The initial pivotal studies that led to FDA approval in 2011 demonstrated noninferiority and superiority to bovine collagen for use in the treatment of NLFs.^7,8 One hundred eighteen patients with bilateral NLFs that were rated as 2 (moderate) or 3 (severe) on the wrinkle severity rating scale (WSRS) were randomized to split-face injection of Belotero Balance in one NLF and bovine collagen in the contralateral NLF.⁷ An additional injection at week 2 was allowed for optimal correction. Belotero Balance was noninferior to bovine collagen at week 2, with mean improvement in WSRS of 1.52 versus 1.57 (P=.50). Belotero Balance was superior to bovine collagen in mean WSRS improvement at weeks 12 (1.25 vs 0.26; P<.001), 16 (1.09 vs 0.66; P<.001), and 24 (1.08 vs 0.50; P<.001).⁷ In a subsequent open-label extension study, which included 95 of 118 patients who received Belotero Balance injections in both NLFs at week 24, 80.2% of patients showed sustained improvement in WSRS from baseline for 48 weeks without further injection.⁸

The first comparative study of Belotero Balance with other established HA fillers at the time—Restylane and Juvéderm Ultra 3/Ultra Plus XC—to treat NLFs demonstrated noninferiority.⁹ Forty patients with bilateral, moderate to severe NLFs (rated 3 or 4 on the Merz severity scale) were randomized to split-face groups of Belotero Balance versus Restylane or Belotero Balance versus Juvéderm. At 12 months, NLF severity improved from 2.3 to 1.5 in the Restylane group and from 2.3 to 1.6 in the Juvéderm group.⁹

Belotero Balance has been compared to Juvéderm Ultra XC for use in perioral lines.¹⁰ The study included 136 patients with moderate to severe perioral lines, according to the perioral lines severity scale, who were randomized (1:1 ratio) to receive injections of Belotero Balance or Juvéderm Ultra XC to correct upper and lower perioral lines, with assessment at week 2 for optimization. After 6 months, 87% of Juvéderm-treated patients compared to 72% of Belotero Balance–treated patients had 1-point improvement in perioral lines (P<.04). Juvéderm-treated patients also reported significantly less pain than Belotero Balance–treated patients (P<.001).¹⁰

Treatment-related AEs are described in the Table, with the majority occurring at lower rates compared to a collagen control group and self-resolving within 2 weeks.⁷

Juvéderm Voluma XC was FDA approved in 2013 for cheek augmentation to correct age-related volume deficit restoration by subcutaneous or subperiosteal injections. In its landmark multicenter investigation, 282 patients with moderate to severe midface (eg, zygomaticomalar, anteromedial cheek, submalar regions) volume deficit measured on a validated midface volume deficit scale (MFVDS) were treated with Juvéderm Voluma XC (n=235) or control (n=47).¹¹ Patients were reevaluated at 30 days and 81.9% received touch-up injections. At a 6-month primary evaluation, 86% of the Juvéderm-treated patients versus 39% of the control patients showed 1-point improvement on the MFVDS (P<.001). At 24-months’ follow-up, 44.6% of patients sustained efficacy.¹¹ Of these aforementioned patients, 167 received repeat treatment due to lost correction or patient request and 91.1% improved by 1 point or more on the MFVDS on evaluation 12 months after repeat treatment.¹² For this same population of patients, a 2-year extended follow-up of patient-reported outcomes revealed that 49% of patients felt fulfilled in their treatment goals 2 years after treatment and 79% of patients rated improvement from baseline based on the global aesthetic improvement scale.¹³ Efficacy studies involving Juvéderm Voluma XC are currently ongoing for facial temporal aging (registered at www.clinicaltrials.gov with the identifier NCT02437903) and recruiting for mandibular hypoplasia (NCT02330016).

Common treatment-related AEs are detailed in the Table. Two patients required treatment with hyaluronidase for chronic lumpiness and nodularity following non–treatment-related cellulitis.¹¹ The product is contraindicated in patients with allergy to lidocaine.

Restylane Silk

Restylane Silk was approved in 2014 for lip augmentation and perioral rhytides. Efficacy and safety was demonstrated in a large multicenter randomized investigation in which 221 patients seeking lip augmentation received either Restylane Silk (n=177) injected submucosally for treatment of the upper and lower lips and/or intradermally for perioral rhytides or no treatment (n=44).¹⁴ Restylane treatment group patients optionally received touch-up at 2 weeks for optimization. All patients, including the control group, received injections at 6 months. At the 2-month primary end point, 80.2% of the treatment group exhibited at least 1-point improvement in upper lip fullness on the Medicis lip fullness scale compared to 11.9% (P<.001) of the control group; response rates for the lower lips were 84.2% versus 18.4% (P<.001). Patients in the treatment group receiving injections for perioral rhytides showed significant improvement in perioral rhytides through week 24 compared to patients treated for lip augmentation only (P<.001).¹⁴ Restylane Silk currently is undergoing investigation for cheek rejuvenation (NCT02636894, NCT02679924) and treatment of hand photoaging (NCT02780258).

The most common AEs are listed in the Table. No lip disorders were considered clinically concerning on evaluation. Concomitant lip augmentation and treatment of perioral rhytides yielded similar rates of AEs.¹⁴ Restylane Silk is not to be used in patients with known lidocaine allergy.

Restylane Lyft

Restylane Lyft (formerly known as Perlane-L) was approved in 2010 for use in facial rhytides, including NLFs, and gained approval in 2015 for use in cheek augmentation and midface contouring. Only its efficacy and safety for the more recent indication will be reviewed here.

In an evaluator-blinded investigation of 200 patients with mild to substantial bilateral midface deficiency based on the Medicis midface volume scale (MMVS), patients were randomized to receive supraperiosteal and subcutaneous treatment with Restylane Lyft (n=150) or no treatment (n=50).¹⁵ Touch-up injections at week 2 or month 12 were available to treatment group patients and all patients were given either an initial treatment or retreatment at 12 months. Primary end point evaluation at week 8 showed that 89% of treatment group patients had at least 1 grade MMVS improvement compared to 16% of the control group (P<.001). Although the percentage of these MMVS responders in the treatment group decreased with each follow-up period to 54.3% at month 12, retreatment was effective in reproducing a similar MMVS response rate as with initial treatment.¹⁵ Restylane Lyft is under ongoing investigation for dorsal hand rejuvenation (NCT02650921).

In addition to the common treatment-related AEs listed in the Table, 2 patients reported serious AEs, including bilateral implant-site inflammation and unilateral implant-site hematoma and infection (organism not described), all of which resolved with unspecified treatment.¹⁵ Lidocaine allergies are contraindications for use.

Conclusion

Several new options in dermal fillers have been approved in recent years and have demonstrated efficacy and acceptable safety in various cosmetic rejuvenation applications. Restylane Silk and Restylane Lyft are undergoing further studies to evaluate use in hand rejuvenation, an area that currently has few cosmetic filler treatment options. As technology continues to progress and new formulations of dermal fillers with varied properties and benefits are available, clinicians should expect multiple options for use in rhytides, volume deficits, and contouring.

ADDENDUM

After the manuscript was accepted for publication, Juvéderm Volbella XC (Allergan, Inc) was approved by the FDA for use in lip augmentation and thus is not included in this review.

Facial aging is the result of the interplay between loss of skin elasticity, changes in subcutaneous fat and other soft-tissue layers, and skeletal remodeling with chronological age.¹ Dermal fillers are effective for the treatment of rhytides, facial scars, and lipoatrophy, as well as facial contouring and augmentation. Given that multiple filler options exist, updated reviews are necessary to inform clinicians of the choices that are available. We provide a detailed review of the clinical efficacy and safety of the dermal fillers with the most recent approvals by the US Food and Drug Administration (FDA).

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) microspheres suspended in bovine collagen and lidocaine 0.3% were approved in 2006 for use in nasolabial folds (NLFs) and in 2014 for acne scars. Now branded as Bellafill (Suneva Medical, Inc), it is the only permanent injectable filler currently available. Once injected, the particles are not reabsorbed and can only be removed by procedural extraction (eg, liposuction of the surrounding fat); however, the permanence of PMMA does not extend to facial rejuvenation, which can last up to 5 years. Prior to use, skin testing for bovine collagen reaction is necessary. In a clinical trial of 147 patients with moderate to severe acne scarring, patients were randomized to receive PMMA in collagen (n=97) or saline (n=50).² Injections were administered using a linear threading or serial puncture technique, and patients were reevaluated after 4 weeks for touch-up injections. After 6 months, 64% of patients treated with PMMA in collagen achieved improvement in acne scars by 2 points or more on the acne scar rating scale versus 33% of the control group (P=.0005).²

Treatment-related adverse events (AEs) include injection-site pain, bruising, swelling, erythema, and more rarely pruritus and lumps/granulomas.³ A 5-year longitudinal safety investigation of 871 patients initially treated with PMMA in collagen for NLF correction revealed that 17 patients (2.0%) had biopsy-confirmed granulomas with half of these retained at study end.⁴ Fifteen of these patients were treated with intralesional corticosteroids alone or in combination with intralesional 5-fluorouracil, oral antibiotics, or topical calcineurin inhibitors; 1 patient was untreated and another used topical corticosteroids. The authors noted no correlation between treatment method and granuloma response.⁴ Polymethylmethacrylate in collagen is contraindicated in patients with lidocaine or bovine collagen sensitivity and is not indicated for use in lip augmentation due to high rates of nodule formation.³

Hyaluronic Acid

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan polymer found in the extracellular matrix of the dermis. Hyaluronic acid fillers are bacteria derived and come in gel form. A useful advantage of HA fillers compared to other dermal fillers is the commercial availability of hyaluronidase to correct injections. Preinjection skin testing is not necessary.⁵

This category of nonpermanent dermal fillers has the most robust market choices. Older HA dermal fillers with reliable and proven efficacy are Restylane (Galderma Laboratories, LP)(facial rhytides, lip augmentation), Juvéderm (Ultra/Ultra XC/Ultra Plus/Ultra Plus XC [Allergan, Inc])(facial rhytides, lip augmentation), Hydrelle (Anika Therapeutics, Inc)(facial rhytides), and Prevelle Silk (Mentor Corporation)(facial rhytides); they will not be reviewed here. Newer agents include Belotero Balance (Merz Aesthetics), Juvéderm Voluma XC (Allergan, Inc), Restylane Silk (Galderma Laboratories, LP), and Restylane Lyft (Galderma Laboratories, LP).

Belotero Balance

Belotero Balance is used to treat fine lines and wrinkles, especially NLFs.⁶ The initial pivotal studies that led to FDA approval in 2011 demonstrated noninferiority and superiority to bovine collagen for use in the treatment of NLFs.^7,8 One hundred eighteen patients with bilateral NLFs that were rated as 2 (moderate) or 3 (severe) on the wrinkle severity rating scale (WSRS) were randomized to split-face injection of Belotero Balance in one NLF and bovine collagen in the contralateral NLF.⁷ An additional injection at week 2 was allowed for optimal correction. Belotero Balance was noninferior to bovine collagen at week 2, with mean improvement in WSRS of 1.52 versus 1.57 (P=.50). Belotero Balance was superior to bovine collagen in mean WSRS improvement at weeks 12 (1.25 vs 0.26; P<.001), 16 (1.09 vs 0.66; P<.001), and 24 (1.08 vs 0.50; P<.001).⁷ In a subsequent open-label extension study, which included 95 of 118 patients who received Belotero Balance injections in both NLFs at week 24, 80.2% of patients showed sustained improvement in WSRS from baseline for 48 weeks without further injection.⁸

The first comparative study of Belotero Balance with other established HA fillers at the time—Restylane and Juvéderm Ultra 3/Ultra Plus XC—to treat NLFs demonstrated noninferiority.⁹ Forty patients with bilateral, moderate to severe NLFs (rated 3 or 4 on the Merz severity scale) were randomized to split-face groups of Belotero Balance versus Restylane or Belotero Balance versus Juvéderm. At 12 months, NLF severity improved from 2.3 to 1.5 in the Restylane group and from 2.3 to 1.6 in the Juvéderm group.⁹

Belotero Balance has been compared to Juvéderm Ultra XC for use in perioral lines.¹⁰ The study included 136 patients with moderate to severe perioral lines, according to the perioral lines severity scale, who were randomized (1:1 ratio) to receive injections of Belotero Balance or Juvéderm Ultra XC to correct upper and lower perioral lines, with assessment at week 2 for optimization. After 6 months, 87% of Juvéderm-treated patients compared to 72% of Belotero Balance–treated patients had 1-point improvement in perioral lines (P<.04). Juvéderm-treated patients also reported significantly less pain than Belotero Balance–treated patients (P<.001).¹⁰

Treatment-related AEs are described in the Table, with the majority occurring at lower rates compared to a collagen control group and self-resolving within 2 weeks.⁷

Juvéderm Voluma XC was FDA approved in 2013 for cheek augmentation to correct age-related volume deficit restoration by subcutaneous or subperiosteal injections. In its landmark multicenter investigation, 282 patients with moderate to severe midface (eg, zygomaticomalar, anteromedial cheek, submalar regions) volume deficit measured on a validated midface volume deficit scale (MFVDS) were treated with Juvéderm Voluma XC (n=235) or control (n=47).¹¹ Patients were reevaluated at 30 days and 81.9% received touch-up injections. At a 6-month primary evaluation, 86% of the Juvéderm-treated patients versus 39% of the control patients showed 1-point improvement on the MFVDS (P<.001). At 24-months’ follow-up, 44.6% of patients sustained efficacy.¹¹ Of these aforementioned patients, 167 received repeat treatment due to lost correction or patient request and 91.1% improved by 1 point or more on the MFVDS on evaluation 12 months after repeat treatment.¹² For this same population of patients, a 2-year extended follow-up of patient-reported outcomes revealed that 49% of patients felt fulfilled in their treatment goals 2 years after treatment and 79% of patients rated improvement from baseline based on the global aesthetic improvement scale.¹³ Efficacy studies involving Juvéderm Voluma XC are currently ongoing for facial temporal aging (registered at www.clinicaltrials.gov with the identifier NCT02437903) and recruiting for mandibular hypoplasia (NCT02330016).

Common treatment-related AEs are detailed in the Table. Two patients required treatment with hyaluronidase for chronic lumpiness and nodularity following non–treatment-related cellulitis.¹¹ The product is contraindicated in patients with allergy to lidocaine.

Restylane Silk

Restylane Silk was approved in 2014 for lip augmentation and perioral rhytides. Efficacy and safety was demonstrated in a large multicenter randomized investigation in which 221 patients seeking lip augmentation received either Restylane Silk (n=177) injected submucosally for treatment of the upper and lower lips and/or intradermally for perioral rhytides or no treatment (n=44).¹⁴ Restylane treatment group patients optionally received touch-up at 2 weeks for optimization. All patients, including the control group, received injections at 6 months. At the 2-month primary end point, 80.2% of the treatment group exhibited at least 1-point improvement in upper lip fullness on the Medicis lip fullness scale compared to 11.9% (P<.001) of the control group; response rates for the lower lips were 84.2% versus 18.4% (P<.001). Patients in the treatment group receiving injections for perioral rhytides showed significant improvement in perioral rhytides through week 24 compared to patients treated for lip augmentation only (P<.001).¹⁴ Restylane Silk currently is undergoing investigation for cheek rejuvenation (NCT02636894, NCT02679924) and treatment of hand photoaging (NCT02780258).

The most common AEs are listed in the Table. No lip disorders were considered clinically concerning on evaluation. Concomitant lip augmentation and treatment of perioral rhytides yielded similar rates of AEs.¹⁴ Restylane Silk is not to be used in patients with known lidocaine allergy.

Restylane Lyft

Restylane Lyft (formerly known as Perlane-L) was approved in 2010 for use in facial rhytides, including NLFs, and gained approval in 2015 for use in cheek augmentation and midface contouring. Only its efficacy and safety for the more recent indication will be reviewed here.

In an evaluator-blinded investigation of 200 patients with mild to substantial bilateral midface deficiency based on the Medicis midface volume scale (MMVS), patients were randomized to receive supraperiosteal and subcutaneous treatment with Restylane Lyft (n=150) or no treatment (n=50).¹⁵ Touch-up injections at week 2 or month 12 were available to treatment group patients and all patients were given either an initial treatment or retreatment at 12 months. Primary end point evaluation at week 8 showed that 89% of treatment group patients had at least 1 grade MMVS improvement compared to 16% of the control group (P<.001). Although the percentage of these MMVS responders in the treatment group decreased with each follow-up period to 54.3% at month 12, retreatment was effective in reproducing a similar MMVS response rate as with initial treatment.¹⁵ Restylane Lyft is under ongoing investigation for dorsal hand rejuvenation (NCT02650921).

In addition to the common treatment-related AEs listed in the Table, 2 patients reported serious AEs, including bilateral implant-site inflammation and unilateral implant-site hematoma and infection (organism not described), all of which resolved with unspecified treatment.¹⁵ Lidocaine allergies are contraindications for use.

Conclusion

Several new options in dermal fillers have been approved in recent years and have demonstrated efficacy and acceptable safety in various cosmetic rejuvenation applications. Restylane Silk and Restylane Lyft are undergoing further studies to evaluate use in hand rejuvenation, an area that currently has few cosmetic filler treatment options. As technology continues to progress and new formulations of dermal fillers with varied properties and benefits are available, clinicians should expect multiple options for use in rhytides, volume deficits, and contouring.

ADDENDUM

After the manuscript was accepted for publication, Juvéderm Volbella XC (Allergan, Inc) was approved by the FDA for use in lip augmentation and thus is not included in this review.

Facial aging is the result of the interplay between loss of skin elasticity, changes in subcutaneous fat and other soft-tissue layers, and skeletal remodeling with chronological age.¹ Dermal fillers are effective for the treatment of rhytides, facial scars, and lipoatrophy, as well as facial contouring and augmentation. Given that multiple filler options exist, updated reviews are necessary to inform clinicians of the choices that are available. We provide a detailed review of the clinical efficacy and safety of the dermal fillers with the most recent approvals by the US Food and Drug Administration (FDA).

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) microspheres suspended in bovine collagen and lidocaine 0.3% were approved in 2006 for use in nasolabial folds (NLFs) and in 2014 for acne scars. Now branded as Bellafill (Suneva Medical, Inc), it is the only permanent injectable filler currently available. Once injected, the particles are not reabsorbed and can only be removed by procedural extraction (eg, liposuction of the surrounding fat); however, the permanence of PMMA does not extend to facial rejuvenation, which can last up to 5 years. Prior to use, skin testing for bovine collagen reaction is necessary. In a clinical trial of 147 patients with moderate to severe acne scarring, patients were randomized to receive PMMA in collagen (n=97) or saline (n=50).² Injections were administered using a linear threading or serial puncture technique, and patients were reevaluated after 4 weeks for touch-up injections. After 6 months, 64% of patients treated with PMMA in collagen achieved improvement in acne scars by 2 points or more on the acne scar rating scale versus 33% of the control group (P=.0005).²

Treatment-related adverse events (AEs) include injection-site pain, bruising, swelling, erythema, and more rarely pruritus and lumps/granulomas.³ A 5-year longitudinal safety investigation of 871 patients initially treated with PMMA in collagen for NLF correction revealed that 17 patients (2.0%) had biopsy-confirmed granulomas with half of these retained at study end.⁴ Fifteen of these patients were treated with intralesional corticosteroids alone or in combination with intralesional 5-fluorouracil, oral antibiotics, or topical calcineurin inhibitors; 1 patient was untreated and another used topical corticosteroids. The authors noted no correlation between treatment method and granuloma response.⁴ Polymethylmethacrylate in collagen is contraindicated in patients with lidocaine or bovine collagen sensitivity and is not indicated for use in lip augmentation due to high rates of nodule formation.³

Hyaluronic Acid

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan polymer found in the extracellular matrix of the dermis. Hyaluronic acid fillers are bacteria derived and come in gel form. A useful advantage of HA fillers compared to other dermal fillers is the commercial availability of hyaluronidase to correct injections. Preinjection skin testing is not necessary.⁵

This category of nonpermanent dermal fillers has the most robust market choices. Older HA dermal fillers with reliable and proven efficacy are Restylane (Galderma Laboratories, LP)(facial rhytides, lip augmentation), Juvéderm (Ultra/Ultra XC/Ultra Plus/Ultra Plus XC [Allergan, Inc])(facial rhytides, lip augmentation), Hydrelle (Anika Therapeutics, Inc)(facial rhytides), and Prevelle Silk (Mentor Corporation)(facial rhytides); they will not be reviewed here. Newer agents include Belotero Balance (Merz Aesthetics), Juvéderm Voluma XC (Allergan, Inc), Restylane Silk (Galderma Laboratories, LP), and Restylane Lyft (Galderma Laboratories, LP).

Belotero Balance

Belotero Balance is used to treat fine lines and wrinkles, especially NLFs.⁶ The initial pivotal studies that led to FDA approval in 2011 demonstrated noninferiority and superiority to bovine collagen for use in the treatment of NLFs.^7,8 One hundred eighteen patients with bilateral NLFs that were rated as 2 (moderate) or 3 (severe) on the wrinkle severity rating scale (WSRS) were randomized to split-face injection of Belotero Balance in one NLF and bovine collagen in the contralateral NLF.⁷ An additional injection at week 2 was allowed for optimal correction. Belotero Balance was noninferior to bovine collagen at week 2, with mean improvement in WSRS of 1.52 versus 1.57 (P=.50). Belotero Balance was superior to bovine collagen in mean WSRS improvement at weeks 12 (1.25 vs 0.26; P<.001), 16 (1.09 vs 0.66; P<.001), and 24 (1.08 vs 0.50; P<.001).⁷ In a subsequent open-label extension study, which included 95 of 118 patients who received Belotero Balance injections in both NLFs at week 24, 80.2% of patients showed sustained improvement in WSRS from baseline for 48 weeks without further injection.⁸

The first comparative study of Belotero Balance with other established HA fillers at the time—Restylane and Juvéderm Ultra 3/Ultra Plus XC—to treat NLFs demonstrated noninferiority.⁹ Forty patients with bilateral, moderate to severe NLFs (rated 3 or 4 on the Merz severity scale) were randomized to split-face groups of Belotero Balance versus Restylane or Belotero Balance versus Juvéderm. At 12 months, NLF severity improved from 2.3 to 1.5 in the Restylane group and from 2.3 to 1.6 in the Juvéderm group.⁹

Belotero Balance has been compared to Juvéderm Ultra XC for use in perioral lines.¹⁰ The study included 136 patients with moderate to severe perioral lines, according to the perioral lines severity scale, who were randomized (1:1 ratio) to receive injections of Belotero Balance or Juvéderm Ultra XC to correct upper and lower perioral lines, with assessment at week 2 for optimization. After 6 months, 87% of Juvéderm-treated patients compared to 72% of Belotero Balance–treated patients had 1-point improvement in perioral lines (P<.04). Juvéderm-treated patients also reported significantly less pain than Belotero Balance–treated patients (P<.001).¹⁰

Treatment-related AEs are described in the Table, with the majority occurring at lower rates compared to a collagen control group and self-resolving within 2 weeks.⁷

Juvéderm Voluma XC was FDA approved in 2013 for cheek augmentation to correct age-related volume deficit restoration by subcutaneous or subperiosteal injections. In its landmark multicenter investigation, 282 patients with moderate to severe midface (eg, zygomaticomalar, anteromedial cheek, submalar regions) volume deficit measured on a validated midface volume deficit scale (MFVDS) were treated with Juvéderm Voluma XC (n=235) or control (n=47).¹¹ Patients were reevaluated at 30 days and 81.9% received touch-up injections. At a 6-month primary evaluation, 86% of the Juvéderm-treated patients versus 39% of the control patients showed 1-point improvement on the MFVDS (P<.001). At 24-months’ follow-up, 44.6% of patients sustained efficacy.¹¹ Of these aforementioned patients, 167 received repeat treatment due to lost correction or patient request and 91.1% improved by 1 point or more on the MFVDS on evaluation 12 months after repeat treatment.¹² For this same population of patients, a 2-year extended follow-up of patient-reported outcomes revealed that 49% of patients felt fulfilled in their treatment goals 2 years after treatment and 79% of patients rated improvement from baseline based on the global aesthetic improvement scale.¹³ Efficacy studies involving Juvéderm Voluma XC are currently ongoing for facial temporal aging (registered at www.clinicaltrials.gov with the identifier NCT02437903) and recruiting for mandibular hypoplasia (NCT02330016).

Common treatment-related AEs are detailed in the Table. Two patients required treatment with hyaluronidase for chronic lumpiness and nodularity following non–treatment-related cellulitis.¹¹ The product is contraindicated in patients with allergy to lidocaine.

Restylane Silk

Restylane Silk was approved in 2014 for lip augmentation and perioral rhytides. Efficacy and safety was demonstrated in a large multicenter randomized investigation in which 221 patients seeking lip augmentation received either Restylane Silk (n=177) injected submucosally for treatment of the upper and lower lips and/or intradermally for perioral rhytides or no treatment (n=44).¹⁴ Restylane treatment group patients optionally received touch-up at 2 weeks for optimization. All patients, including the control group, received injections at 6 months. At the 2-month primary end point, 80.2% of the treatment group exhibited at least 1-point improvement in upper lip fullness on the Medicis lip fullness scale compared to 11.9% (P<.001) of the control group; response rates for the lower lips were 84.2% versus 18.4% (P<.001). Patients in the treatment group receiving injections for perioral rhytides showed significant improvement in perioral rhytides through week 24 compared to patients treated for lip augmentation only (P<.001).¹⁴ Restylane Silk currently is undergoing investigation for cheek rejuvenation (NCT02636894, NCT02679924) and treatment of hand photoaging (NCT02780258).

The most common AEs are listed in the Table. No lip disorders were considered clinically concerning on evaluation. Concomitant lip augmentation and treatment of perioral rhytides yielded similar rates of AEs.¹⁴ Restylane Silk is not to be used in patients with known lidocaine allergy.

Restylane Lyft

Restylane Lyft (formerly known as Perlane-L) was approved in 2010 for use in facial rhytides, including NLFs, and gained approval in 2015 for use in cheek augmentation and midface contouring. Only its efficacy and safety for the more recent indication will be reviewed here.

In an evaluator-blinded investigation of 200 patients with mild to substantial bilateral midface deficiency based on the Medicis midface volume scale (MMVS), patients were randomized to receive supraperiosteal and subcutaneous treatment with Restylane Lyft (n=150) or no treatment (n=50).¹⁵ Touch-up injections at week 2 or month 12 were available to treatment group patients and all patients were given either an initial treatment or retreatment at 12 months. Primary end point evaluation at week 8 showed that 89% of treatment group patients had at least 1 grade MMVS improvement compared to 16% of the control group (P<.001). Although the percentage of these MMVS responders in the treatment group decreased with each follow-up period to 54.3% at month 12, retreatment was effective in reproducing a similar MMVS response rate as with initial treatment.¹⁵ Restylane Lyft is under ongoing investigation for dorsal hand rejuvenation (NCT02650921).

In addition to the common treatment-related AEs listed in the Table, 2 patients reported serious AEs, including bilateral implant-site inflammation and unilateral implant-site hematoma and infection (organism not described), all of which resolved with unspecified treatment.¹⁵ Lidocaine allergies are contraindications for use.

Conclusion

Several new options in dermal fillers have been approved in recent years and have demonstrated efficacy and acceptable safety in various cosmetic rejuvenation applications. Restylane Silk and Restylane Lyft are undergoing further studies to evaluate use in hand rejuvenation, an area that currently has few cosmetic filler treatment options. As technology continues to progress and new formulations of dermal fillers with varied properties and benefits are available, clinicians should expect multiple options for use in rhytides, volume deficits, and contouring.

ADDENDUM

After the manuscript was accepted for publication, Juvéderm Volbella XC (Allergan, Inc) was approved by the FDA for use in lip augmentation and thus is not included in this review.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

VIENNA – They say that in hula dancing, it’s the expressive hands, not the quaking hips, that tell the story.

And in Dutch women, a relatively short index finger on the left hand bespeaks an increased risk for depression and stress.

That’s right: The ratio of the length of the index finger to the ring finger, or 2D:4D digit ratio, of the left hand shows potential as a quick and dirty biomarker that could be used to screen patients for increased risk for depression. But only in women, Deborah De Kruijff reported at the annual congress of the European College of Neuropsychopharmacology.

She and her coinvestigators measured the lengths of the index and ring fingers on both hands of 124 male and 146 female Dutch college students using Vernier calipers accurate to within 0.01 mm. Participants completed the 21-item version of the Depression, Anxiety, and Stress Scale (DASS-21) and correlated the 2D:4D digit ratios with the DASS-21 total scores as well as the scores on the depression, anxiety, and stress subscales.

The 2D:4D digit ratio didn’t correlate with DASS-21 scores in men. But in women, the lower the 2D:4D ratio on the left hand, the higher their overall DASS-21 score as well as their scores on the depression and stress subscales. Each of these associations was highly statistically significant at the P = .002 to .005 level, according to Ms. De Kruijff, a PhD candidate in neuroscience at Utrecht (the Netherlands) University.

Finding correlates between the 2D:4D digit ratio and predispositions to various diseases, personality traits, and other human characteristics was a popular scientific pastime in the 1800s. After a long dry spell, it rebounded as a research area several decades ago. The 2D:4D ratio is a sexually dimorphic trait. It is thought to depend upon prenatal exposure to sex hormones. A low 2D:4D ratio is associated with in utero exposure to relatively higher levels of fetal testosterone than fetal estrogen. Thus, a greater proportion of men than women have index fingers that are shorter than the ring finger.

Other investigators have linked a low 2D:4D ratio to increased risks of prostate cancer, attention-deficit/hyperactivity disorder, and autism spectrum disorder in men, and to greater assertiveness and increased risk of anorexia nervosa in women.

Ms. De Kruijff said more research is needed to understand why only the finger length on the left hand of the women was predictive of increased risk of depression and stress.

She reported having no financial conflicts of interest regarding this university-funded study.

[email protected]

VIENNA – They say that in hula dancing, it’s the expressive hands, not the quaking hips, that tell the story.

And in Dutch women, a relatively short index finger on the left hand bespeaks an increased risk for depression and stress.

That’s right: The ratio of the length of the index finger to the ring finger, or 2D:4D digit ratio, of the left hand shows potential as a quick and dirty biomarker that could be used to screen patients for increased risk for depression. But only in women, Deborah De Kruijff reported at the annual congress of the European College of Neuropsychopharmacology.

She and her coinvestigators measured the lengths of the index and ring fingers on both hands of 124 male and 146 female Dutch college students using Vernier calipers accurate to within 0.01 mm. Participants completed the 21-item version of the Depression, Anxiety, and Stress Scale (DASS-21) and correlated the 2D:4D digit ratios with the DASS-21 total scores as well as the scores on the depression, anxiety, and stress subscales.

The 2D:4D digit ratio didn’t correlate with DASS-21 scores in men. But in women, the lower the 2D:4D ratio on the left hand, the higher their overall DASS-21 score as well as their scores on the depression and stress subscales. Each of these associations was highly statistically significant at the P = .002 to .005 level, according to Ms. De Kruijff, a PhD candidate in neuroscience at Utrecht (the Netherlands) University.

Finding correlates between the 2D:4D digit ratio and predispositions to various diseases, personality traits, and other human characteristics was a popular scientific pastime in the 1800s. After a long dry spell, it rebounded as a research area several decades ago. The 2D:4D ratio is a sexually dimorphic trait. It is thought to depend upon prenatal exposure to sex hormones. A low 2D:4D ratio is associated with in utero exposure to relatively higher levels of fetal testosterone than fetal estrogen. Thus, a greater proportion of men than women have index fingers that are shorter than the ring finger.

Other investigators have linked a low 2D:4D ratio to increased risks of prostate cancer, attention-deficit/hyperactivity disorder, and autism spectrum disorder in men, and to greater assertiveness and increased risk of anorexia nervosa in women.

Ms. De Kruijff said more research is needed to understand why only the finger length on the left hand of the women was predictive of increased risk of depression and stress.

She reported having no financial conflicts of interest regarding this university-funded study.

[email protected]

VIENNA – They say that in hula dancing, it’s the expressive hands, not the quaking hips, that tell the story.

And in Dutch women, a relatively short index finger on the left hand bespeaks an increased risk for depression and stress.

That’s right: The ratio of the length of the index finger to the ring finger, or 2D:4D digit ratio, of the left hand shows potential as a quick and dirty biomarker that could be used to screen patients for increased risk for depression. But only in women, Deborah De Kruijff reported at the annual congress of the European College of Neuropsychopharmacology.

She and her coinvestigators measured the lengths of the index and ring fingers on both hands of 124 male and 146 female Dutch college students using Vernier calipers accurate to within 0.01 mm. Participants completed the 21-item version of the Depression, Anxiety, and Stress Scale (DASS-21) and correlated the 2D:4D digit ratios with the DASS-21 total scores as well as the scores on the depression, anxiety, and stress subscales.

The 2D:4D digit ratio didn’t correlate with DASS-21 scores in men. But in women, the lower the 2D:4D ratio on the left hand, the higher their overall DASS-21 score as well as their scores on the depression and stress subscales. Each of these associations was highly statistically significant at the P = .002 to .005 level, according to Ms. De Kruijff, a PhD candidate in neuroscience at Utrecht (the Netherlands) University.

Finding correlates between the 2D:4D digit ratio and predispositions to various diseases, personality traits, and other human characteristics was a popular scientific pastime in the 1800s. After a long dry spell, it rebounded as a research area several decades ago. The 2D:4D ratio is a sexually dimorphic trait. It is thought to depend upon prenatal exposure to sex hormones. A low 2D:4D ratio is associated with in utero exposure to relatively higher levels of fetal testosterone than fetal estrogen. Thus, a greater proportion of men than women have index fingers that are shorter than the ring finger.

Other investigators have linked a low 2D:4D ratio to increased risks of prostate cancer, attention-deficit/hyperactivity disorder, and autism spectrum disorder in men, and to greater assertiveness and increased risk of anorexia nervosa in women.

Ms. De Kruijff said more research is needed to understand why only the finger length on the left hand of the women was predictive of increased risk of depression and stress.

She reported having no financial conflicts of interest regarding this university-funded study.

[email protected]

Due to the increasing number of older adults, the annual number of new cases of Alzheimer disease and other types of dementia is projected to double by 2050.¹ The cost of caring for persons with dementia is rising as well. In 2015, the expected health care cost for persons with dementia in the U.S. is estimated to be $226 billion.¹ There is a growing awareness of the needs of persons with dementia and of the importance of providing caregivers with support and education that enables them to keep their loved ones at home as long as possible. Additionally, caregiver stress adversely affects health and increases mortality risk.^2-4 Efficacious interventions that teach caregivers to cope with challenging behaviors and functional decline are also available.^5,6 Yet many caregivers encounter barriers that prevent access to these interventions. Some may not be able to access interventions due to lack of insurance plan coverage; others may not have the time to participate in these programs.^7,8

The VA has requested that its VISNs and VAMCs develop dementia committees so that VA employees can establish goals focused on improving dementia care. The VA Palo Alto Health Care System (VAPAHCS) Dementia Committee determined that veterans, caregivers, and staff needed simple, clear information about dementia, based on consensus opinion. In 2013, one of the committee co-chairs, a clinical nurse specialist in the Geriatric Research Education and Clinical Center (GRECC), introduced the concept of a dementia resource fair. There is evidence supporting the use of interdisciplinary health fairs to educate allied health trainees (eg, nursing students and social workers) through service learning.⁹ But to the authors’ knowledge, the use of such a fair to provide dementia information has not been evaluated.

The fair drew from the evidence base for formal psychoeducational interventions for caregiversand for those with dementia or cognitive impairment.^10,11 The goal of the fair was to provide information about resources for and management of dementia to veterans, families, staff, caregivers, and the community, using printed material and consultation with knowledgeable staff. The GRECC staff also initiated a systematic evaluation of this new initiative and collaborated with the Stanford/VA Alzheimer’s Research Center staff on the evaluation process.

Initial Plan

A subcommittee, composed of interdisciplinary professionals who work with veterans diagnosed with dementia, planned the initial dementia resource fair. The subcommittee representatives included geriatric medicine, nursing, occupational therapy, pharmacy, psychology, recreational therapy, and social work. Subcommittee members were charged with developing VA-branded handouts as educational tools to address key issues related to dementia, such as advance directive planning, behavioral management, home safety, and medication management. The subcommittee met monthly for 6 months and focused on logistics, identification of resource tables, creation of educational materials, advertising, and development of an evaluation. Table 1 provides an overview of the planning time line for the 2013 fair held in San Jose. Findings from a systematic evaluation of the 2013 fair were used to improve the 2015 fair held in Menlo Park. A discussion about the evaluation method and results follows.

Methods

The first fair was held at a VA community-based outpatient clinic in a small conference room with 13 resource tables. Feedback from attendees in 2013 included suggestions for having more tables, larger event space, more publicity, and alternate locations for the fair. In response to the feedback, the 2015 fair was held at a division of the main VAMC in a large conference room and hosted 20 tables arranged in a horseshoe shape. The second fair included an activity table staffed by a psychology fellow and recreation therapist who provided respite to caregivers if their loved one with dementia accompanied them to the event. Both the 2013 and 2015 fairs were 4 hours long.

A 1-page, anonymous survey was developed to assess attendees’ opinions about the fair. The survey included information about whether attendees were caregivers, veterans, or VA staff but did not ask other demographic questions to preserve anonymity. In 2013, the survey asked attendees to choose the category that best described them, but in 2015, the survey asked attendees to indicate the number of individuals from each category in their party. The 2015 survey assessed 2 additional categories (family member, other) and added a question about the number of people in each party to better estimate attendance. Both surveys also asked attendees to check which resource tables they visited.

The following assessment questions were consistent across both fairs to allow for comparisons. The authors assessed attitudes and learning as a result of the fair, using 2 statements that were rated with a 5-point Likert scale. The authors asked 3 open-ended questions to ascertain the helpful aspects of the fair, unmet needs, and suggestions for improvement. The Stanford University Institutional Review Board (IRB) reviewed this program evaluation plan and determined that the program evaluation project did not require IRB approval.

When attendees arrived at the fair, they received a folder containing branded handouts, a reusable bag, and a survey. Committee members asked that 1 person per party complete the survey at the end of the visit. Attendees visited tables, obtained written materials, and spoke with subcommittee members who staffed the tables. Snacks and light refreshments were provided. The reusable bag was provided by the VAMC Suicide Prevention Program to increase awareness of the VAPAHCS Suicide Prevention Program. As attendees were leaving, they were reminded to complete the survey. Attendees deposited completed surveys in a box to ensure anonymity.

Results

Thirty-six individuals attended the 2013 fair, and 138 individuals attended the 2015 fair. Thirty-one surveys were completed in 2013, yielding an 86% response rate. One hundred six surveys were returned and represented responses for 129 individuals in 2015, yielding a 94% response rate in 2015. Most of the 2013 attendees were caregivers, followed by veterans, VA staff, and outside staff (Table 2). In contrast, most of the 2015 attendees were VA staff, followed by veterans, caregivers/family members, outside staff, and others. Distributions of attendees differed significantly across the fairs: χ²(4) = 12.66; P = .01.

The surveys assessed which tables attendees visited and their perceptions of the fair. The most frequently visited resource table for both 2013 and 2015 fairs was the Alzheimer’s Association table. Other popular resource tables were VA Benefits and VA Caregiver Support in 2013 and Home Safety and End of Life Care in 2015. Ninety-six percent of 2013 attendees and 100% of 2015 attendees strongly agreed or agreed that “attending the dementia fair was worth my time and effort.” Eighty-three percent of 2013 attendees and 100% of 2015 attendees felt that they had learned something useful at the fair. The proportion of individuals reporting that they had learned something useful significantly increased from 2013 to 2015: χ²(2) = 18.07; P = .0001.

To summarize the open-ended responses to the question “What was most helpful about the fair?” the authors constructed a word cloud that displays the 75 most frequently used words in attendees’ descriptions of the 2015 fair (Figure). Attendees provided suggestions about additional information and resources they desired, which included VA benefits enrollment, books and movies about dementia (eg, Still Alice), speech and swallowing disorders representatives, varied types of advance directives, class discussion, question-and-answer time with speakers, and resources for nonveteran older adults. General suggestions for future fairs included hosting the fair at the main division of the VA health care system, having more room between tables, inviting more vendors, using more visual posters at the tables, and additional advertising for VA services.

Discussion

Dementia is a costly disease with detrimental health and well-being effects on caregivers. The dementia resource fairs aimed to connect caregivers with resources for veterans with dementia in the VA and in the community. Given that nearly half the 2015 fair attendees were VA staff, there is an apparent need for increasing dementia education and access to care resource for this VAMC’s workforce. The high proportion of staff attendees at the 2015 fair may be attributed to the 2 VA community living centers at the VAMC site where the fair was held. This unexpected finding points to the importance of informal and interactive education opportunities for staff, particularly those working with veterans with dementia. The fair served an important role for VA staff seeking information on dementia for professional and personal reasons. This systematic evaluation of the fair demonstrated a need for improving access to information about dementia.

The idea of hosting a dementia resource fair was met with enthusiasm from attendees and subcommittee members in 2013. Feedback helped refine the second fair. The increase in self-reported learning from 2013 to 2015 suggests improvements may have been made between the first and second fair; however, this must be interpreted in light of the different compositions of the attendees at each fair and the absence of a control group. Attendees desired even more information about dementia at the second fair, as evidenced by suggestions to have presentations, speakers, and class discussions. These responses suggest that other sites may wish to consider holding similar events. Next steps include researching the effectiveness of low-cost, pragmatic educational initiatives for caregivers. In fact, randomized, controlled trials of dementia caregiver education and skill-building interventions are underway at VAPAHCS.

Conclusion

The primary lesson learned from the most recent fair was that marketing is the key to success. The authors created an efficient hospital publicity plan in 2015 that included (1) flyers posted throughout 2 main medical center campuses; (2) announcements on closed-circuit VA waiting room televisions; (3) e-mail announcements sent to staff; and (4) VA social media announcements. Flyers also were mailed to known caregivers, and announcements of the event were provided to local community agencies. This focus on publicity likely contributed to the substantial increase in participation from the 2013 to 2015 fair.

Future fairs may be improved by providing more detailed information about dementia through formal presentations. The authors aim to increase the number of family caregivers in attendance possibly through coordinating the fair to coincide with primary care clinic hours, advertising the availability of brief respite at the fair, and conducting additional outreach to veterans.

This systematic evaluation of the dementia resource fair confirmed that providing resources in a drop-in setting resulted in self-reported learning about resources available for veterans with dementia. VA dementia care providers are encouraged to use the authors’ time line and lessons learned to develop dementia resource fairs for their sites.

Acknowledgments

The authors wish to acknowledge the members of the 2013 and 2015 Dementia Resource Fair Committees, chaired by Betty Wexler and Kathleen McConnell, respectively. Dr. Gould is supported by the U.S. Department of Veterans Affairs (IK2 RX001478) and by Ellen Schapiro & Gerald Axelbaum through a 2014 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Dr. Scanlon is supported by the U.S. Department of Veterans Affairs (IK2 RX001240; I21 RX001710), U.S. Department of Defense (W81XWH-15-1-0246), Sierra-Pacific Mental Illness Research Education and Clinical Center, and Stanford/VA Alzheimer’s Research Center. Drs. Gould and Scanlon also receive support from Palo Alto Veterans Institute for Research.

Due to the increasing number of older adults, the annual number of new cases of Alzheimer disease and other types of dementia is projected to double by 2050.¹ The cost of caring for persons with dementia is rising as well. In 2015, the expected health care cost for persons with dementia in the U.S. is estimated to be $226 billion.¹ There is a growing awareness of the needs of persons with dementia and of the importance of providing caregivers with support and education that enables them to keep their loved ones at home as long as possible. Additionally, caregiver stress adversely affects health and increases mortality risk.^2-4 Efficacious interventions that teach caregivers to cope with challenging behaviors and functional decline are also available.^5,6 Yet many caregivers encounter barriers that prevent access to these interventions. Some may not be able to access interventions due to lack of insurance plan coverage; others may not have the time to participate in these programs.^7,8

The VA has requested that its VISNs and VAMCs develop dementia committees so that VA employees can establish goals focused on improving dementia care. The VA Palo Alto Health Care System (VAPAHCS) Dementia Committee determined that veterans, caregivers, and staff needed simple, clear information about dementia, based on consensus opinion. In 2013, one of the committee co-chairs, a clinical nurse specialist in the Geriatric Research Education and Clinical Center (GRECC), introduced the concept of a dementia resource fair. There is evidence supporting the use of interdisciplinary health fairs to educate allied health trainees (eg, nursing students and social workers) through service learning.⁹ But to the authors’ knowledge, the use of such a fair to provide dementia information has not been evaluated.

The fair drew from the evidence base for formal psychoeducational interventions for caregiversand for those with dementia or cognitive impairment.^10,11 The goal of the fair was to provide information about resources for and management of dementia to veterans, families, staff, caregivers, and the community, using printed material and consultation with knowledgeable staff. The GRECC staff also initiated a systematic evaluation of this new initiative and collaborated with the Stanford/VA Alzheimer’s Research Center staff on the evaluation process.

Initial Plan

A subcommittee, composed of interdisciplinary professionals who work with veterans diagnosed with dementia, planned the initial dementia resource fair. The subcommittee representatives included geriatric medicine, nursing, occupational therapy, pharmacy, psychology, recreational therapy, and social work. Subcommittee members were charged with developing VA-branded handouts as educational tools to address key issues related to dementia, such as advance directive planning, behavioral management, home safety, and medication management. The subcommittee met monthly for 6 months and focused on logistics, identification of resource tables, creation of educational materials, advertising, and development of an evaluation. Table 1 provides an overview of the planning time line for the 2013 fair held in San Jose. Findings from a systematic evaluation of the 2013 fair were used to improve the 2015 fair held in Menlo Park. A discussion about the evaluation method and results follows.

Methods

The first fair was held at a VA community-based outpatient clinic in a small conference room with 13 resource tables. Feedback from attendees in 2013 included suggestions for having more tables, larger event space, more publicity, and alternate locations for the fair. In response to the feedback, the 2015 fair was held at a division of the main VAMC in a large conference room and hosted 20 tables arranged in a horseshoe shape. The second fair included an activity table staffed by a psychology fellow and recreation therapist who provided respite to caregivers if their loved one with dementia accompanied them to the event. Both the 2013 and 2015 fairs were 4 hours long.

A 1-page, anonymous survey was developed to assess attendees’ opinions about the fair. The survey included information about whether attendees were caregivers, veterans, or VA staff but did not ask other demographic questions to preserve anonymity. In 2013, the survey asked attendees to choose the category that best described them, but in 2015, the survey asked attendees to indicate the number of individuals from each category in their party. The 2015 survey assessed 2 additional categories (family member, other) and added a question about the number of people in each party to better estimate attendance. Both surveys also asked attendees to check which resource tables they visited.

The following assessment questions were consistent across both fairs to allow for comparisons. The authors assessed attitudes and learning as a result of the fair, using 2 statements that were rated with a 5-point Likert scale. The authors asked 3 open-ended questions to ascertain the helpful aspects of the fair, unmet needs, and suggestions for improvement. The Stanford University Institutional Review Board (IRB) reviewed this program evaluation plan and determined that the program evaluation project did not require IRB approval.

When attendees arrived at the fair, they received a folder containing branded handouts, a reusable bag, and a survey. Committee members asked that 1 person per party complete the survey at the end of the visit. Attendees visited tables, obtained written materials, and spoke with subcommittee members who staffed the tables. Snacks and light refreshments were provided. The reusable bag was provided by the VAMC Suicide Prevention Program to increase awareness of the VAPAHCS Suicide Prevention Program. As attendees were leaving, they were reminded to complete the survey. Attendees deposited completed surveys in a box to ensure anonymity.

Results

Thirty-six individuals attended the 2013 fair, and 138 individuals attended the 2015 fair. Thirty-one surveys were completed in 2013, yielding an 86% response rate. One hundred six surveys were returned and represented responses for 129 individuals in 2015, yielding a 94% response rate in 2015. Most of the 2013 attendees were caregivers, followed by veterans, VA staff, and outside staff (Table 2). In contrast, most of the 2015 attendees were VA staff, followed by veterans, caregivers/family members, outside staff, and others. Distributions of attendees differed significantly across the fairs: χ²(4) = 12.66; P = .01.

The surveys assessed which tables attendees visited and their perceptions of the fair. The most frequently visited resource table for both 2013 and 2015 fairs was the Alzheimer’s Association table. Other popular resource tables were VA Benefits and VA Caregiver Support in 2013 and Home Safety and End of Life Care in 2015. Ninety-six percent of 2013 attendees and 100% of 2015 attendees strongly agreed or agreed that “attending the dementia fair was worth my time and effort.” Eighty-three percent of 2013 attendees and 100% of 2015 attendees felt that they had learned something useful at the fair. The proportion of individuals reporting that they had learned something useful significantly increased from 2013 to 2015: χ²(2) = 18.07; P = .0001.

To summarize the open-ended responses to the question “What was most helpful about the fair?” the authors constructed a word cloud that displays the 75 most frequently used words in attendees’ descriptions of the 2015 fair (Figure). Attendees provided suggestions about additional information and resources they desired, which included VA benefits enrollment, books and movies about dementia (eg, Still Alice), speech and swallowing disorders representatives, varied types of advance directives, class discussion, question-and-answer time with speakers, and resources for nonveteran older adults. General suggestions for future fairs included hosting the fair at the main division of the VA health care system, having more room between tables, inviting more vendors, using more visual posters at the tables, and additional advertising for VA services.

Discussion

Dementia is a costly disease with detrimental health and well-being effects on caregivers. The dementia resource fairs aimed to connect caregivers with resources for veterans with dementia in the VA and in the community. Given that nearly half the 2015 fair attendees were VA staff, there is an apparent need for increasing dementia education and access to care resource for this VAMC’s workforce. The high proportion of staff attendees at the 2015 fair may be attributed to the 2 VA community living centers at the VAMC site where the fair was held. This unexpected finding points to the importance of informal and interactive education opportunities for staff, particularly those working with veterans with dementia. The fair served an important role for VA staff seeking information on dementia for professional and personal reasons. This systematic evaluation of the fair demonstrated a need for improving access to information about dementia.

The idea of hosting a dementia resource fair was met with enthusiasm from attendees and subcommittee members in 2013. Feedback helped refine the second fair. The increase in self-reported learning from 2013 to 2015 suggests improvements may have been made between the first and second fair; however, this must be interpreted in light of the different compositions of the attendees at each fair and the absence of a control group. Attendees desired even more information about dementia at the second fair, as evidenced by suggestions to have presentations, speakers, and class discussions. These responses suggest that other sites may wish to consider holding similar events. Next steps include researching the effectiveness of low-cost, pragmatic educational initiatives for caregivers. In fact, randomized, controlled trials of dementia caregiver education and skill-building interventions are underway at VAPAHCS.

Conclusion

The primary lesson learned from the most recent fair was that marketing is the key to success. The authors created an efficient hospital publicity plan in 2015 that included (1) flyers posted throughout 2 main medical center campuses; (2) announcements on closed-circuit VA waiting room televisions; (3) e-mail announcements sent to staff; and (4) VA social media announcements. Flyers also were mailed to known caregivers, and announcements of the event were provided to local community agencies. This focus on publicity likely contributed to the substantial increase in participation from the 2013 to 2015 fair.

Future fairs may be improved by providing more detailed information about dementia through formal presentations. The authors aim to increase the number of family caregivers in attendance possibly through coordinating the fair to coincide with primary care clinic hours, advertising the availability of brief respite at the fair, and conducting additional outreach to veterans.

This systematic evaluation of the dementia resource fair confirmed that providing resources in a drop-in setting resulted in self-reported learning about resources available for veterans with dementia. VA dementia care providers are encouraged to use the authors’ time line and lessons learned to develop dementia resource fairs for their sites.

Acknowledgments

The authors wish to acknowledge the members of the 2013 and 2015 Dementia Resource Fair Committees, chaired by Betty Wexler and Kathleen McConnell, respectively. Dr. Gould is supported by the U.S. Department of Veterans Affairs (IK2 RX001478) and by Ellen Schapiro & Gerald Axelbaum through a 2014 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Dr. Scanlon is supported by the U.S. Department of Veterans Affairs (IK2 RX001240; I21 RX001710), U.S. Department of Defense (W81XWH-15-1-0246), Sierra-Pacific Mental Illness Research Education and Clinical Center, and Stanford/VA Alzheimer’s Research Center. Drs. Gould and Scanlon also receive support from Palo Alto Veterans Institute for Research.

Due to the increasing number of older adults, the annual number of new cases of Alzheimer disease and other types of dementia is projected to double by 2050.¹ The cost of caring for persons with dementia is rising as well. In 2015, the expected health care cost for persons with dementia in the U.S. is estimated to be $226 billion.¹ There is a growing awareness of the needs of persons with dementia and of the importance of providing caregivers with support and education that enables them to keep their loved ones at home as long as possible. Additionally, caregiver stress adversely affects health and increases mortality risk.^2-4 Efficacious interventions that teach caregivers to cope with challenging behaviors and functional decline are also available.^5,6 Yet many caregivers encounter barriers that prevent access to these interventions. Some may not be able to access interventions due to lack of insurance plan coverage; others may not have the time to participate in these programs.^7,8

The VA has requested that its VISNs and VAMCs develop dementia committees so that VA employees can establish goals focused on improving dementia care. The VA Palo Alto Health Care System (VAPAHCS) Dementia Committee determined that veterans, caregivers, and staff needed simple, clear information about dementia, based on consensus opinion. In 2013, one of the committee co-chairs, a clinical nurse specialist in the Geriatric Research Education and Clinical Center (GRECC), introduced the concept of a dementia resource fair. There is evidence supporting the use of interdisciplinary health fairs to educate allied health trainees (eg, nursing students and social workers) through service learning.⁹ But to the authors’ knowledge, the use of such a fair to provide dementia information has not been evaluated.

The fair drew from the evidence base for formal psychoeducational interventions for caregiversand for those with dementia or cognitive impairment.^10,11 The goal of the fair was to provide information about resources for and management of dementia to veterans, families, staff, caregivers, and the community, using printed material and consultation with knowledgeable staff. The GRECC staff also initiated a systematic evaluation of this new initiative and collaborated with the Stanford/VA Alzheimer’s Research Center staff on the evaluation process.

Initial Plan

A subcommittee, composed of interdisciplinary professionals who work with veterans diagnosed with dementia, planned the initial dementia resource fair. The subcommittee representatives included geriatric medicine, nursing, occupational therapy, pharmacy, psychology, recreational therapy, and social work. Subcommittee members were charged with developing VA-branded handouts as educational tools to address key issues related to dementia, such as advance directive planning, behavioral management, home safety, and medication management. The subcommittee met monthly for 6 months and focused on logistics, identification of resource tables, creation of educational materials, advertising, and development of an evaluation. Table 1 provides an overview of the planning time line for the 2013 fair held in San Jose. Findings from a systematic evaluation of the 2013 fair were used to improve the 2015 fair held in Menlo Park. A discussion about the evaluation method and results follows.

Methods

The first fair was held at a VA community-based outpatient clinic in a small conference room with 13 resource tables. Feedback from attendees in 2013 included suggestions for having more tables, larger event space, more publicity, and alternate locations for the fair. In response to the feedback, the 2015 fair was held at a division of the main VAMC in a large conference room and hosted 20 tables arranged in a horseshoe shape. The second fair included an activity table staffed by a psychology fellow and recreation therapist who provided respite to caregivers if their loved one with dementia accompanied them to the event. Both the 2013 and 2015 fairs were 4 hours long.

A 1-page, anonymous survey was developed to assess attendees’ opinions about the fair. The survey included information about whether attendees were caregivers, veterans, or VA staff but did not ask other demographic questions to preserve anonymity. In 2013, the survey asked attendees to choose the category that best described them, but in 2015, the survey asked attendees to indicate the number of individuals from each category in their party. The 2015 survey assessed 2 additional categories (family member, other) and added a question about the number of people in each party to better estimate attendance. Both surveys also asked attendees to check which resource tables they visited.

The following assessment questions were consistent across both fairs to allow for comparisons. The authors assessed attitudes and learning as a result of the fair, using 2 statements that were rated with a 5-point Likert scale. The authors asked 3 open-ended questions to ascertain the helpful aspects of the fair, unmet needs, and suggestions for improvement. The Stanford University Institutional Review Board (IRB) reviewed this program evaluation plan and determined that the program evaluation project did not require IRB approval.

When attendees arrived at the fair, they received a folder containing branded handouts, a reusable bag, and a survey. Committee members asked that 1 person per party complete the survey at the end of the visit. Attendees visited tables, obtained written materials, and spoke with subcommittee members who staffed the tables. Snacks and light refreshments were provided. The reusable bag was provided by the VAMC Suicide Prevention Program to increase awareness of the VAPAHCS Suicide Prevention Program. As attendees were leaving, they were reminded to complete the survey. Attendees deposited completed surveys in a box to ensure anonymity.

Results

Thirty-six individuals attended the 2013 fair, and 138 individuals attended the 2015 fair. Thirty-one surveys were completed in 2013, yielding an 86% response rate. One hundred six surveys were returned and represented responses for 129 individuals in 2015, yielding a 94% response rate in 2015. Most of the 2013 attendees were caregivers, followed by veterans, VA staff, and outside staff (Table 2). In contrast, most of the 2015 attendees were VA staff, followed by veterans, caregivers/family members, outside staff, and others. Distributions of attendees differed significantly across the fairs: χ²(4) = 12.66; P = .01.

The surveys assessed which tables attendees visited and their perceptions of the fair. The most frequently visited resource table for both 2013 and 2015 fairs was the Alzheimer’s Association table. Other popular resource tables were VA Benefits and VA Caregiver Support in 2013 and Home Safety and End of Life Care in 2015. Ninety-six percent of 2013 attendees and 100% of 2015 attendees strongly agreed or agreed that “attending the dementia fair was worth my time and effort.” Eighty-three percent of 2013 attendees and 100% of 2015 attendees felt that they had learned something useful at the fair. The proportion of individuals reporting that they had learned something useful significantly increased from 2013 to 2015: χ²(2) = 18.07; P = .0001.

To summarize the open-ended responses to the question “What was most helpful about the fair?” the authors constructed a word cloud that displays the 75 most frequently used words in attendees’ descriptions of the 2015 fair (Figure). Attendees provided suggestions about additional information and resources they desired, which included VA benefits enrollment, books and movies about dementia (eg, Still Alice), speech and swallowing disorders representatives, varied types of advance directives, class discussion, question-and-answer time with speakers, and resources for nonveteran older adults. General suggestions for future fairs included hosting the fair at the main division of the VA health care system, having more room between tables, inviting more vendors, using more visual posters at the tables, and additional advertising for VA services.

Discussion

Dementia is a costly disease with detrimental health and well-being effects on caregivers. The dementia resource fairs aimed to connect caregivers with resources for veterans with dementia in the VA and in the community. Given that nearly half the 2015 fair attendees were VA staff, there is an apparent need for increasing dementia education and access to care resource for this VAMC’s workforce. The high proportion of staff attendees at the 2015 fair may be attributed to the 2 VA community living centers at the VAMC site where the fair was held. This unexpected finding points to the importance of informal and interactive education opportunities for staff, particularly those working with veterans with dementia. The fair served an important role for VA staff seeking information on dementia for professional and personal reasons. This systematic evaluation of the fair demonstrated a need for improving access to information about dementia.

The idea of hosting a dementia resource fair was met with enthusiasm from attendees and subcommittee members in 2013. Feedback helped refine the second fair. The increase in self-reported learning from 2013 to 2015 suggests improvements may have been made between the first and second fair; however, this must be interpreted in light of the different compositions of the attendees at each fair and the absence of a control group. Attendees desired even more information about dementia at the second fair, as evidenced by suggestions to have presentations, speakers, and class discussions. These responses suggest that other sites may wish to consider holding similar events. Next steps include researching the effectiveness of low-cost, pragmatic educational initiatives for caregivers. In fact, randomized, controlled trials of dementia caregiver education and skill-building interventions are underway at VAPAHCS.

Conclusion

The primary lesson learned from the most recent fair was that marketing is the key to success. The authors created an efficient hospital publicity plan in 2015 that included (1) flyers posted throughout 2 main medical center campuses; (2) announcements on closed-circuit VA waiting room televisions; (3) e-mail announcements sent to staff; and (4) VA social media announcements. Flyers also were mailed to known caregivers, and announcements of the event were provided to local community agencies. This focus on publicity likely contributed to the substantial increase in participation from the 2013 to 2015 fair.

Future fairs may be improved by providing more detailed information about dementia through formal presentations. The authors aim to increase the number of family caregivers in attendance possibly through coordinating the fair to coincide with primary care clinic hours, advertising the availability of brief respite at the fair, and conducting additional outreach to veterans.

This systematic evaluation of the dementia resource fair confirmed that providing resources in a drop-in setting resulted in self-reported learning about resources available for veterans with dementia. VA dementia care providers are encouraged to use the authors’ time line and lessons learned to develop dementia resource fairs for their sites.

Acknowledgments

The authors wish to acknowledge the members of the 2013 and 2015 Dementia Resource Fair Committees, chaired by Betty Wexler and Kathleen McConnell, respectively. Dr. Gould is supported by the U.S. Department of Veterans Affairs (IK2 RX001478) and by Ellen Schapiro & Gerald Axelbaum through a 2014 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Dr. Scanlon is supported by the U.S. Department of Veterans Affairs (IK2 RX001240; I21 RX001710), U.S. Department of Defense (W81XWH-15-1-0246), Sierra-Pacific Mental Illness Research Education and Clinical Center, and Stanford/VA Alzheimer’s Research Center. Drs. Gould and Scanlon also receive support from Palo Alto Veterans Institute for Research.

Doctor evaluating a patient

Photo courtesy of the CDC

Patients with multiple myeloma (MM) are more likely to live longer if they are treated at a medical center where the staff has more experience with the disease, according to research published in the Journal of Clinical Oncology.

The study showed that patients treated at medical centers seeing 10 new MM patients per year had a 20% higher risk of death than patients treated at centers seeing 40 new MM patients per year.

Most cancer treatment centers in the US see fewer than 10 new MM patients per year.

“It is very difficult to be proficient when doctors are seeing only 1 or 2 new cases of multiple myeloma per year,” said study author Ronald Go, MD, of the Mayo Clinic in Rochester, Minnesota.

“Studies on cancer surgery have shown the more experience the center or practitioner has, the better the outcome. We wanted to see if volume matters when it comes to nonsurgical treatment of rare cancers such as multiple myeloma.”

To investigate, Dr Go and his colleagues used the National Cancer Database, examining outcomes for 94,722 newly diagnosed MM patients treated at 1333 facilities between 2003 and 2011.

The researchers grouped the facilities into quartiles according to the volume of MM patients treated there each year.

The mean number of MM patients treated per year was:

• Less than 3.6 for quartile 1 (Q1)
• 3.6 to 6.1 for Q2
• 6.1 to 10.3 for Q3
• More than 10.3 for Q4.

The majority of patients (60.3%) were treated in Q4 facilities. For all facilities, the median number of new MM patients per year was 6.1 (range, 3.6 to 10.3). The mean was 8.8 ± 9.9.

The researchers calculated the relationship between MM patient volume at these facilities and patient mortality, adjusting for demographic characteristics, socioeconomic factors, geographic factors, comorbidities, and year of diagnosis.

Outcomes

The unadjusted median overall survival was 26.9 months for patients treated at Q1 facilities, 29.1 months for Q2, 31.9 months for Q3, and 49.1 months for Q4 (P<0.001).

The 1-year mortality rate was 33.5% for patients treated at Q1 facilities, 32.3% for Q2, 30.7% for Q3, and 21.9% for Q4.

The researchers’ multivariable analysis showed that facility volume was independently associated with all-cause mortality.

Patients treated at the lower-quartile facilities had a higher risk of death than patients treated at Q4 facilities. The hazard ratios were 1.12 for patients at Q3 facilities, 1.12 for Q2, and 1.22 for Q1.

The researchers performed another analysis in which volume was treated as a continuous variable, and they compared various volume sizes to a reference volume of 10 patients per year.

Compared with facilities treating 10 new MM patients per year, facilities treating 20 MM patients per year had roughly 10% lower overall mortality rates.

Facilities treating 30 MM patients per year had about 15% lower mortality rates. And facilities treating 40 MM patients per year had 20% lower overall mortality rates.

Doctor evaluating a patient

Photo courtesy of the CDC

Patients with multiple myeloma (MM) are more likely to live longer if they are treated at a medical center where the staff has more experience with the disease, according to research published in the Journal of Clinical Oncology.

The study showed that patients treated at medical centers seeing 10 new MM patients per year had a 20% higher risk of death than patients treated at centers seeing 40 new MM patients per year.

Most cancer treatment centers in the US see fewer than 10 new MM patients per year.

“It is very difficult to be proficient when doctors are seeing only 1 or 2 new cases of multiple myeloma per year,” said study author Ronald Go, MD, of the Mayo Clinic in Rochester, Minnesota.

“Studies on cancer surgery have shown the more experience the center or practitioner has, the better the outcome. We wanted to see if volume matters when it comes to nonsurgical treatment of rare cancers such as multiple myeloma.”

To investigate, Dr Go and his colleagues used the National Cancer Database, examining outcomes for 94,722 newly diagnosed MM patients treated at 1333 facilities between 2003 and 2011.

The researchers grouped the facilities into quartiles according to the volume of MM patients treated there each year.

The mean number of MM patients treated per year was:

• Less than 3.6 for quartile 1 (Q1)
• 3.6 to 6.1 for Q2
• 6.1 to 10.3 for Q3
• More than 10.3 for Q4.

The majority of patients (60.3%) were treated in Q4 facilities. For all facilities, the median number of new MM patients per year was 6.1 (range, 3.6 to 10.3). The mean was 8.8 ± 9.9.

The researchers calculated the relationship between MM patient volume at these facilities and patient mortality, adjusting for demographic characteristics, socioeconomic factors, geographic factors, comorbidities, and year of diagnosis.

Outcomes

The unadjusted median overall survival was 26.9 months for patients treated at Q1 facilities, 29.1 months for Q2, 31.9 months for Q3, and 49.1 months for Q4 (P<0.001).

The 1-year mortality rate was 33.5% for patients treated at Q1 facilities, 32.3% for Q2, 30.7% for Q3, and 21.9% for Q4.

The researchers’ multivariable analysis showed that facility volume was independently associated with all-cause mortality.

Patients treated at the lower-quartile facilities had a higher risk of death than patients treated at Q4 facilities. The hazard ratios were 1.12 for patients at Q3 facilities, 1.12 for Q2, and 1.22 for Q1.

The researchers performed another analysis in which volume was treated as a continuous variable, and they compared various volume sizes to a reference volume of 10 patients per year.

Compared with facilities treating 10 new MM patients per year, facilities treating 20 MM patients per year had roughly 10% lower overall mortality rates.

Facilities treating 30 MM patients per year had about 15% lower mortality rates. And facilities treating 40 MM patients per year had 20% lower overall mortality rates.

Doctor evaluating a patient

Photo courtesy of the CDC

Patients with multiple myeloma (MM) are more likely to live longer if they are treated at a medical center where the staff has more experience with the disease, according to research published in the Journal of Clinical Oncology.

The study showed that patients treated at medical centers seeing 10 new MM patients per year had a 20% higher risk of death than patients treated at centers seeing 40 new MM patients per year.

Most cancer treatment centers in the US see fewer than 10 new MM patients per year.

“It is very difficult to be proficient when doctors are seeing only 1 or 2 new cases of multiple myeloma per year,” said study author Ronald Go, MD, of the Mayo Clinic in Rochester, Minnesota.

“Studies on cancer surgery have shown the more experience the center or practitioner has, the better the outcome. We wanted to see if volume matters when it comes to nonsurgical treatment of rare cancers such as multiple myeloma.”

To investigate, Dr Go and his colleagues used the National Cancer Database, examining outcomes for 94,722 newly diagnosed MM patients treated at 1333 facilities between 2003 and 2011.

The researchers grouped the facilities into quartiles according to the volume of MM patients treated there each year.

The mean number of MM patients treated per year was:

• Less than 3.6 for quartile 1 (Q1)
• 3.6 to 6.1 for Q2
• 6.1 to 10.3 for Q3
• More than 10.3 for Q4.

The majority of patients (60.3%) were treated in Q4 facilities. For all facilities, the median number of new MM patients per year was 6.1 (range, 3.6 to 10.3). The mean was 8.8 ± 9.9.

The researchers calculated the relationship between MM patient volume at these facilities and patient mortality, adjusting for demographic characteristics, socioeconomic factors, geographic factors, comorbidities, and year of diagnosis.

Outcomes

The unadjusted median overall survival was 26.9 months for patients treated at Q1 facilities, 29.1 months for Q2, 31.9 months for Q3, and 49.1 months for Q4 (P<0.001).

The 1-year mortality rate was 33.5% for patients treated at Q1 facilities, 32.3% for Q2, 30.7% for Q3, and 21.9% for Q4.

The researchers’ multivariable analysis showed that facility volume was independently associated with all-cause mortality.

Patients treated at the lower-quartile facilities had a higher risk of death than patients treated at Q4 facilities. The hazard ratios were 1.12 for patients at Q3 facilities, 1.12 for Q2, and 1.22 for Q1.

The researchers performed another analysis in which volume was treated as a continuous variable, and they compared various volume sizes to a reference volume of 10 patients per year.

Compared with facilities treating 10 new MM patients per year, facilities treating 20 MM patients per year had roughly 10% lower overall mortality rates.

Facilities treating 30 MM patients per year had about 15% lower mortality rates. And facilities treating 40 MM patients per year had 20% lower overall mortality rates.

Lab mouse

A new bypassing agent mimics the pro-clotting activity of factor V Leiden and might prove effective for treating hemophilia A and B, according to preclinical research published in Blood.

“We know that patients who have severe hemophilia and also have mutations that increase clotting, such as factor V Leiden, experience less severe bleeding,” said study author Trevor Baglin, MD, of Addenbrooke’s Hospital in Cambridge, UK.

In patients with factor V Leiden, defects in the anticoagulant activated protein C (APC) mechanism lead to an overactive production of thrombin.

The researchers set out to determine if they could exploit this phenomenon to treat hemophilia by developing a direct inhibitor of APC. They modified serine protease inhibitors, known as serpins, to make them specific and efficient inhibitors of APC.

“We hypothesized that if we targeted the protein C pathway we could prolong thrombin production,” said study author James Huntington, PhD, of the University of Cambridge in the UK.

“We engineered a serpin so that it could selectively prevent APC from shutting down thrombin production before the formation of a stable clot.”

The researchers administered the serpin to mice with hemophilia B and clipped their tails. In this model, the blood loss decreased as the dose increased, with the highest dose reducing bleeding to the level of healthy mice.

Further injury models underscored that the serpin helped the majority of mice form stable clots, with higher doses resulting in quicker clot formation.

The serpin was also able to accelerate clot formation when added to blood samples from patients with hemophilia A.

“It is our understanding that because we are targeting a general anticlotting process, our serpin could effectively treat patients with either hemophilia A or B, including those who develop inhibitors to more traditional therapy,” Dr Huntington said.

“Additionally, we have focused on engineering the serpin to be both subcutaneously delivered and long-acting. This will free patients from the cumbersome thrice-weekly infusions that are necessary under many contemporary therapy regimens.”

“Within 3 years, we hope to be conducting our first-in-man trials of a subcutaneously administered form of our serpin,” Dr Baglin added.

“It is important to remember that the majority of people in the world with hemophilia have no access to therapy. A stable, subcutaneous, long-acting, effective hemostatic agent could bring treatment to a great deal many more hemophilia sufferers.”

This study forms part of a patent application by the authors, and the serpin is being developed into a therapeutic by a start-up company known as ApcinteX, with funding from Medicxi.

Lab mouse

A new bypassing agent mimics the pro-clotting activity of factor V Leiden and might prove effective for treating hemophilia A and B, according to preclinical research published in Blood.

“We know that patients who have severe hemophilia and also have mutations that increase clotting, such as factor V Leiden, experience less severe bleeding,” said study author Trevor Baglin, MD, of Addenbrooke’s Hospital in Cambridge, UK.

In patients with factor V Leiden, defects in the anticoagulant activated protein C (APC) mechanism lead to an overactive production of thrombin.

The researchers set out to determine if they could exploit this phenomenon to treat hemophilia by developing a direct inhibitor of APC. They modified serine protease inhibitors, known as serpins, to make them specific and efficient inhibitors of APC.

“We hypothesized that if we targeted the protein C pathway we could prolong thrombin production,” said study author James Huntington, PhD, of the University of Cambridge in the UK.

“We engineered a serpin so that it could selectively prevent APC from shutting down thrombin production before the formation of a stable clot.”

The researchers administered the serpin to mice with hemophilia B and clipped their tails. In this model, the blood loss decreased as the dose increased, with the highest dose reducing bleeding to the level of healthy mice.

Further injury models underscored that the serpin helped the majority of mice form stable clots, with higher doses resulting in quicker clot formation.

The serpin was also able to accelerate clot formation when added to blood samples from patients with hemophilia A.

“It is our understanding that because we are targeting a general anticlotting process, our serpin could effectively treat patients with either hemophilia A or B, including those who develop inhibitors to more traditional therapy,” Dr Huntington said.

“Additionally, we have focused on engineering the serpin to be both subcutaneously delivered and long-acting. This will free patients from the cumbersome thrice-weekly infusions that are necessary under many contemporary therapy regimens.”

“Within 3 years, we hope to be conducting our first-in-man trials of a subcutaneously administered form of our serpin,” Dr Baglin added.

“It is important to remember that the majority of people in the world with hemophilia have no access to therapy. A stable, subcutaneous, long-acting, effective hemostatic agent could bring treatment to a great deal many more hemophilia sufferers.”

This study forms part of a patent application by the authors, and the serpin is being developed into a therapeutic by a start-up company known as ApcinteX, with funding from Medicxi.

Lab mouse

A new bypassing agent mimics the pro-clotting activity of factor V Leiden and might prove effective for treating hemophilia A and B, according to preclinical research published in Blood.

“We know that patients who have severe hemophilia and also have mutations that increase clotting, such as factor V Leiden, experience less severe bleeding,” said study author Trevor Baglin, MD, of Addenbrooke’s Hospital in Cambridge, UK.

In patients with factor V Leiden, defects in the anticoagulant activated protein C (APC) mechanism lead to an overactive production of thrombin.

The researchers set out to determine if they could exploit this phenomenon to treat hemophilia by developing a direct inhibitor of APC. They modified serine protease inhibitors, known as serpins, to make them specific and efficient inhibitors of APC.

“We hypothesized that if we targeted the protein C pathway we could prolong thrombin production,” said study author James Huntington, PhD, of the University of Cambridge in the UK.

“We engineered a serpin so that it could selectively prevent APC from shutting down thrombin production before the formation of a stable clot.”

The researchers administered the serpin to mice with hemophilia B and clipped their tails. In this model, the blood loss decreased as the dose increased, with the highest dose reducing bleeding to the level of healthy mice.

Further injury models underscored that the serpin helped the majority of mice form stable clots, with higher doses resulting in quicker clot formation.

The serpin was also able to accelerate clot formation when added to blood samples from patients with hemophilia A.

“It is our understanding that because we are targeting a general anticlotting process, our serpin could effectively treat patients with either hemophilia A or B, including those who develop inhibitors to more traditional therapy,” Dr Huntington said.

“Additionally, we have focused on engineering the serpin to be both subcutaneously delivered and long-acting. This will free patients from the cumbersome thrice-weekly infusions that are necessary under many contemporary therapy regimens.”

“Within 3 years, we hope to be conducting our first-in-man trials of a subcutaneously administered form of our serpin,” Dr Baglin added.

“It is important to remember that the majority of people in the world with hemophilia have no access to therapy. A stable, subcutaneous, long-acting, effective hemostatic agent could bring treatment to a great deal many more hemophilia sufferers.”

This study forms part of a patent application by the authors, and the serpin is being developed into a therapeutic by a start-up company known as ApcinteX, with funding from Medicxi.

Micrograph showing

mycosis fungoides

The National Organization for Rare Disorders (NORD) has published a guide for physicians treating patients with cutaneous T-cell lymphoma (CTCL).

The guide contains information about disease classification, signs and symptoms of CTCL, methods of diagnosing the disease, standard therapies, and investigational therapies for CTCL.

The guide also includes a list of resources for physicians and patients.

“The NORD Physician Guide to Cutaneous T-Cell Lymphoma (CTCL)” is available for free on the NORD Physician Guides website.

The guide was made possible by an educational grant from Therakos, now a part of Mallinckrodt Pharmaceuticals.

The guide was developed in collaboration with Oleg E. Akilov, MD, PhD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“Eczema and even some cases of psoriasis may look very similar to mycosis fungoides, the most common type of cutaneous T-cell lymphomas,” Dr Akilov noted.

“It is important to be aware of these similarities and to be ready to think about cutaneous lymphoma when a patient with ‘common dermatosis’ does not respond to regular treatments.”

About NORD guides

NORD established its physician guide series as part of a broader strategic initiative to promote earlier diagnosis and state-of-the-art care for people with rare diseases. Each online guide is written or reviewed by a medical professional with expertise on the topic.

Other recent guides in the series include:

• The NORD Physician Guide to Mitochondrial Myopathies
• The NORD Physician Guide to Paroxysmal Nocturnal Hemoglobinuria (PNH)
• The NORD Physician Guide to Atypical Hemolytic Uremic Syndrome (aHUS)
• The NORD Physician Guide to Nontuberculous Mycobacterial Lung Disease.

“People who have rare diseases often go for many years without a diagnosis,” said Marsha Lanes, a genetic counselor in NORD’s Educational Initiatives Department.

“The purpose of NORD’s free online physician guides is to reduce the time to diagnosis and encourage optimal treatment for patients with little-known and little-understood rare diseases.”

Micrograph showing

mycosis fungoides

The National Organization for Rare Disorders (NORD) has published a guide for physicians treating patients with cutaneous T-cell lymphoma (CTCL).

The guide contains information about disease classification, signs and symptoms of CTCL, methods of diagnosing the disease, standard therapies, and investigational therapies for CTCL.

The guide also includes a list of resources for physicians and patients.

“The NORD Physician Guide to Cutaneous T-Cell Lymphoma (CTCL)” is available for free on the NORD Physician Guides website.

The guide was made possible by an educational grant from Therakos, now a part of Mallinckrodt Pharmaceuticals.

The guide was developed in collaboration with Oleg E. Akilov, MD, PhD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“Eczema and even some cases of psoriasis may look very similar to mycosis fungoides, the most common type of cutaneous T-cell lymphomas,” Dr Akilov noted.

“It is important to be aware of these similarities and to be ready to think about cutaneous lymphoma when a patient with ‘common dermatosis’ does not respond to regular treatments.”

About NORD guides

NORD established its physician guide series as part of a broader strategic initiative to promote earlier diagnosis and state-of-the-art care for people with rare diseases. Each online guide is written or reviewed by a medical professional with expertise on the topic.

Other recent guides in the series include:

• The NORD Physician Guide to Mitochondrial Myopathies
• The NORD Physician Guide to Paroxysmal Nocturnal Hemoglobinuria (PNH)
• The NORD Physician Guide to Atypical Hemolytic Uremic Syndrome (aHUS)
• The NORD Physician Guide to Nontuberculous Mycobacterial Lung Disease.

“People who have rare diseases often go for many years without a diagnosis,” said Marsha Lanes, a genetic counselor in NORD’s Educational Initiatives Department.

“The purpose of NORD’s free online physician guides is to reduce the time to diagnosis and encourage optimal treatment for patients with little-known and little-understood rare diseases.”

Micrograph showing

mycosis fungoides

The National Organization for Rare Disorders (NORD) has published a guide for physicians treating patients with cutaneous T-cell lymphoma (CTCL).

The guide contains information about disease classification, signs and symptoms of CTCL, methods of diagnosing the disease, standard therapies, and investigational therapies for CTCL.

The guide also includes a list of resources for physicians and patients.

“The NORD Physician Guide to Cutaneous T-Cell Lymphoma (CTCL)” is available for free on the NORD Physician Guides website.

The guide was made possible by an educational grant from Therakos, now a part of Mallinckrodt Pharmaceuticals.

The guide was developed in collaboration with Oleg E. Akilov, MD, PhD, of the University of Pittsburgh School of Medicine in Pennsylvania.

“Eczema and even some cases of psoriasis may look very similar to mycosis fungoides, the most common type of cutaneous T-cell lymphomas,” Dr Akilov noted.

“It is important to be aware of these similarities and to be ready to think about cutaneous lymphoma when a patient with ‘common dermatosis’ does not respond to regular treatments.”

About NORD guides

NORD established its physician guide series as part of a broader strategic initiative to promote earlier diagnosis and state-of-the-art care for people with rare diseases. Each online guide is written or reviewed by a medical professional with expertise on the topic.

Other recent guides in the series include:

• The NORD Physician Guide to Mitochondrial Myopathies
• The NORD Physician Guide to Paroxysmal Nocturnal Hemoglobinuria (PNH)
• The NORD Physician Guide to Atypical Hemolytic Uremic Syndrome (aHUS)
• The NORD Physician Guide to Nontuberculous Mycobacterial Lung Disease.

“People who have rare diseases often go for many years without a diagnosis,” said Marsha Lanes, a genetic counselor in NORD’s Educational Initiatives Department.

“The purpose of NORD’s free online physician guides is to reduce the time to diagnosis and encourage optimal treatment for patients with little-known and little-understood rare diseases.”

Mouse bone marrow showing

MSPCs with mutant PTPN11

(red) and monocytes (green).

Image courtesy of

Dong et al, Nature 2016

New research published in Nature has shown how certain mutations drive the development of myeloproliferative neoplasms (MPNs) and leukemia.

Investigators discovered that PTPN11 activating mutations promote the development and progression of MPNs through “profound detrimental effects” on hematopoietic stem cells (HSCs).

The team also identified a potential method of treating MPNs in patients with Noonan syndrome.

Noonan syndrome can be caused by mutations in several genes, but the most common is PTPN11. Children with Noonan syndrome are known to have an increased risk of developing MPNs/leukemia.

Previous research had established that mutations in PTPN11 have a conventional cell-autonomous effect on HSC growth.

In the current study, investigators showed that PTPN11 mutations also affect mesenchymal stem/progenitor cells (MSPCs) and osteoprogenitors.

The mutations cause over-production of the CC chemokine CCL3, which attracts monocytes into the HSCs’ niches. The monocytes make inflammatory molecules that stimulate the HSCs to differentiate and proliferate, leading to MPNs and leukemia.

“We have identified CCL3 as a potential therapeutic target for controlling leukemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan syndrome-associated leukemias,” said study author Cheng-Kui Qu, MD, PhD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Qu and his colleagues began this research intending to investigate the effects of PTPN11 mutations in the nervous system. The team developed genetically engineered mice that had altered PTPN11 in neural cells.

The mice all developed a condition resembling an MPN at an early age. It turned out that the mice had changes in the PTPN11 gene in their MSPCs and osteoprogenitors (in addition to their neural cells) but not in their HSCs.

The investigators found the MPN in these PTPN11-mutant mice can be treated in the short-term by HSC transplant, but the condition comes back within months.

However, drugs counteracting CCL3 successfully reversed MPN phenotypes. One of the drugs is the CCR5 antagonist maraviroc, which is approved in the US to combat HIV infection, and another is the CCR1 antagonist BX471.

The investigators noted that other Noonan syndrome mutations, in genes besides PTPN11, need to be assessed for their effects on MPN/leukemia formation.

Mouse bone marrow showing

MSPCs with mutant PTPN11

(red) and monocytes (green).

Image courtesy of

Dong et al, Nature 2016

New research published in Nature has shown how certain mutations drive the development of myeloproliferative neoplasms (MPNs) and leukemia.

Investigators discovered that PTPN11 activating mutations promote the development and progression of MPNs through “profound detrimental effects” on hematopoietic stem cells (HSCs).

The team also identified a potential method of treating MPNs in patients with Noonan syndrome.

Noonan syndrome can be caused by mutations in several genes, but the most common is PTPN11. Children with Noonan syndrome are known to have an increased risk of developing MPNs/leukemia.

Previous research had established that mutations in PTPN11 have a conventional cell-autonomous effect on HSC growth.

In the current study, investigators showed that PTPN11 mutations also affect mesenchymal stem/progenitor cells (MSPCs) and osteoprogenitors.

The mutations cause over-production of the CC chemokine CCL3, which attracts monocytes into the HSCs’ niches. The monocytes make inflammatory molecules that stimulate the HSCs to differentiate and proliferate, leading to MPNs and leukemia.

“We have identified CCL3 as a potential therapeutic target for controlling leukemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan syndrome-associated leukemias,” said study author Cheng-Kui Qu, MD, PhD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Qu and his colleagues began this research intending to investigate the effects of PTPN11 mutations in the nervous system. The team developed genetically engineered mice that had altered PTPN11 in neural cells.

The mice all developed a condition resembling an MPN at an early age. It turned out that the mice had changes in the PTPN11 gene in their MSPCs and osteoprogenitors (in addition to their neural cells) but not in their HSCs.

The investigators found the MPN in these PTPN11-mutant mice can be treated in the short-term by HSC transplant, but the condition comes back within months.

However, drugs counteracting CCL3 successfully reversed MPN phenotypes. One of the drugs is the CCR5 antagonist maraviroc, which is approved in the US to combat HIV infection, and another is the CCR1 antagonist BX471.

The investigators noted that other Noonan syndrome mutations, in genes besides PTPN11, need to be assessed for their effects on MPN/leukemia formation.

Mouse bone marrow showing

MSPCs with mutant PTPN11

(red) and monocytes (green).

Image courtesy of

Dong et al, Nature 2016

New research published in Nature has shown how certain mutations drive the development of myeloproliferative neoplasms (MPNs) and leukemia.

Investigators discovered that PTPN11 activating mutations promote the development and progression of MPNs through “profound detrimental effects” on hematopoietic stem cells (HSCs).

The team also identified a potential method of treating MPNs in patients with Noonan syndrome.

Noonan syndrome can be caused by mutations in several genes, but the most common is PTPN11. Children with Noonan syndrome are known to have an increased risk of developing MPNs/leukemia.

Previous research had established that mutations in PTPN11 have a conventional cell-autonomous effect on HSC growth.

In the current study, investigators showed that PTPN11 mutations also affect mesenchymal stem/progenitor cells (MSPCs) and osteoprogenitors.

The mutations cause over-production of the CC chemokine CCL3, which attracts monocytes into the HSCs’ niches. The monocytes make inflammatory molecules that stimulate the HSCs to differentiate and proliferate, leading to MPNs and leukemia.

“We have identified CCL3 as a potential therapeutic target for controlling leukemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan syndrome-associated leukemias,” said study author Cheng-Kui Qu, MD, PhD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Qu and his colleagues began this research intending to investigate the effects of PTPN11 mutations in the nervous system. The team developed genetically engineered mice that had altered PTPN11 in neural cells.

The mice all developed a condition resembling an MPN at an early age. It turned out that the mice had changes in the PTPN11 gene in their MSPCs and osteoprogenitors (in addition to their neural cells) but not in their HSCs.

The investigators found the MPN in these PTPN11-mutant mice can be treated in the short-term by HSC transplant, but the condition comes back within months.

However, drugs counteracting CCL3 successfully reversed MPN phenotypes. One of the drugs is the CCR5 antagonist maraviroc, which is approved in the US to combat HIV infection, and another is the CCR1 antagonist BX471.

The investigators noted that other Noonan syndrome mutations, in genes besides PTPN11, need to be assessed for their effects on MPN/leukemia formation.

BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.

Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).

Brian Hoyle/Frontline Medical News

[email protected]

BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.

Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).

Brian Hoyle/Frontline Medical News

[email protected]

BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.

Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).

Brian Hoyle/Frontline Medical News

[email protected]

BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

—Brian Hoyle

BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

—Brian Hoyle

BALTIMORE—A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detects patients with multiple sclerosis (MS) who have an increased risk for relapse, according to a multicenter cohort study. The findings could have clinical significance in MS treatment and patient counseling, said Jennifer S. Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco, at the 141st Annual Meeting of the American Neurological Association.

Low vitamin D levels are associated with an increased risk of MS, but whether this association is causal has not been determined. Dr. Graves and her colleagues sought to gain insight into the association by focusing on 29 single nucleotide polymorphisms (SNPs) within genes that previously had been discovered to be involved in the manufacture of 25-OH vitamin D. The investigators analyzed the relationship of these SNPs to relapses in patients with MS.

They compared the SNP profiles of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) with those of a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level. Patients in the discovery cohort were enrolled at two pediatric MS centers in California between 2006 and 2011, and those in the replication cohort were enrolled at nine MS centers in the United States from 2011 to 2015.

Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. The lowest and highest risk scores had linear associations with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in the discovery and replication cohorts. The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score.

“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.

The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.

The study was funded by the Race to Erase MS, the National MS Society, and the National Institute of Neurological Disorders and Stroke.

—Brian Hoyle